Phosphonoyl-phosphate-containing compounds and polymers

Abstract

Novel phosphono-phosphate containing compounds, monomers and polymeric compositions having targeted use for divalent cations and surfaces having divalent cations are disclosed. These compounds can be used to deliver active agents to surfaces such as calcium hydroxyapatite.

Description

Technical Field

[0001] This invention relates to novel compounds and polymers containing phosphono-phosphate groups. The invention also relates to methods for treating surfaces using these novel compounds and polymers. Background Technology

[0002] Chemical structures that interact with polyvalent cations in solution and with surfaces containing polyvalent cations can be used to treat these systems. For example, polyphosphates and pyrophosphates have been used as detergent builders in laundry detergents and dishwashing preparations to control calcium, and in drilling mud to prevent precipitation. They have also been used in the oral care industry to help control tartar and reduce the thickness of the plaque layer on teeth, resulting in a smoother feel. Similarly, bisphosphonates and hydroxybisphosphonates are active ingredients in osteoporosis medications due to their strong interaction with the surface of calcium hydroxyapatite, and are also used as crystal growth inhibitors in dishwashing liquids and boiler systems. Each of these examples has inherent limitations. Polyphosphates readily degrade in aqueous solutions over time at all pH levels, eventually leading to an increase in orthophosphate in the solution. Polyphosphates are also quite anionic and insoluble in nonpolar organic systems. However, polyphosphates are generally safe for consumption and can be used in various food products. In contrast, bisphosphonates and hydroxybisphosphonates are long-term stable in water and can be completely dissolved in organic systems depending on the nature of the organic groups attached to the carbon atom of the bisphosphonate. However, bisphosphonates have osteoactive properties and, due to their potent pharmacological effects, cannot be used in food or other systems where they may be accidentally ingested. Polymers containing bisphosphonates with insufficient molecular weight to cross the intestinal wall may lack osteoactive properties; however, any low-molecular-weight residual monomers or oligomers that can cross the intestinal wall render such polymers unsuitable for use in potentially ingestible environments. Furthermore, because bisphosphonates are not readily degraded, their activity persists in the environment after use.

[0003] Therefore, there is still a need for phosphate compositions that are not easily degraded and are safe for human consumption. Summary of the Invention

[0004] Surprisingly, the phosphono-phosphate chemical group has improved the focus on polyphosphates and bisphosphonates, while also revealing its practicality in similar systems. Specifically, compositions, monomers, and polymers containing phosphono-phosphate groups can be used in many applications where structures containing polyphosphates and bisphosphonates are employed, whether by incorporation of monomers containing phosphono-phosphate groups or by post-polymerization modification. Such applications typically include those where the binding interactions involve polyvalent cations in solution and on surfaces containing divalent cations. Phosphono-phosphate structures can also be used in applications where the use of polyphosphates and bisphosphonates is limited. The phosphono-phosphate group is conditionally stable and will release phosphate only under acidic or catalytic conditions. Therefore, the phosphono-phosphate group is more stable than polyphosphates but less stable than bisphosphonates. This makes it possible to formulate systems where food safety and water stability are essential requirements. Furthermore, organic groups or polymers attached to phosphono-phosphate groups can make the entire molecule soluble in organic solvents or can be used to add additional functionality to the entire molecule.

[0005] In one embodiment, the present invention relates to compounds having the structure of Formula 1:

[0006]

[0007] in:

[0008] R1 is selected from -H and -CH3;

[0009] R2 is selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cation salts and structures of formula 2:

[0010]

[0011] in:

[0012] δ is the connection point with Equation 1.

[0013] R5 and R6 are independently selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts;

[0014] R3 is selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cation salts and structures of formula 3:

[0015]

[0016] in:

[0017] δ is the connection point with Equation 1.

[0018] R7 and R8 are independently selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts; and

[0019] n is an integer from 1 to 22;

[0020] R4 is selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts; and

[0021] L is selected from chemical bonds, aryl dimethyl groups, and structures of formula 4:

[0022]

[0023] in:

[0024] α is the linking site to the alkenyl group;

[0025] β is the linking site to the phosphono-phosphate group;

[0026] X is selected from the structures shown in Equations 5 to 11;

[0027]

[0028]

[0029]

[0030]

[0031]

[0032]

[0033]

[0034] in:

[0035] R9 is selected from -H, alkyl (C1-8) Phosphonylalkyl and phosphonyl(phosphate)alkyl; and

[0036] Y is selected from alkyldiyl, alkoxydiyl, alkylaminodiyl, and alkenyldiyl.

[0037] In one embodiment of the compound, R1 of Formula 1 is H. In another embodiment of the compound, R1 of Formula 1 is CH3. In yet another embodiment of the compound, L of Formula 1 is a covalent bond.

[0038] In one embodiment of the compound, R2, R3, and R4 are independently selected from -H, Na salts, and K salts. In another embodiment of the compound, L has the structure of Formula 4, and X has the structure of Formula 5. In another embodiment of the compound, L has the structure of Formula 4, and X has the structure of Formula 8. In one embodiment of the compound, L has the structure of Formula 4, and X has the structure of Formula 10.

[0039] Another embodiment of the present invention is a novel polymer. This polymer comprises a phosphono-phosphate group, wherein the phosphono-phosphate group has the structure of Formula 12:

[0040]

[0041] in:

[0042] ε is the connection site with a carbon atom in the main chain, side group, or side chain of the polymer;

[0043] R 10 Selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cation salts and structures of formula 13:

[0044]

[0045] in:

[0046] θ is the connection point with Equation 12.

[0047] R 13 and R 14 Independently selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts;

[0048] R 11 Selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cation salts and structures of formula 14:

[0049]

[0050] in:

[0051] θ is the connection point with Equation 12.

[0052] R 15 and R 16Independently selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts; and

[0053] n is an integer from 1 to 22; and

[0054] R 12 Selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts.

[0055] In one embodiment, at least one monomer used to form the polymer comprises a phosphono-phosphate group. In another embodiment, the phosphono-phosphate group is added during a post-polymerization modification process.

[0056] In another embodiment, at least one monomer used to form the polymer has the structure of Formula 15:

[0057]

[0058] in:

[0059] ω is the connection site with the phosphono-phosphate group of Formula 12;

[0060] R 17 Selected from -H and -CH3;

[0061] L1 is selected from chemical bonds, aryl dimethyl groups, and structures of formula 4:

[0062]

[0063] in:

[0064] α is the linking site to the alkenyl group;

[0065] β is the linking site with the phosphono-phosphate group of Formula 12;

[0066] X is selected from the structures in Equations 5 to 11;

[0067]

[0068]

[0069]

[0070]

[0071]

[0072]

[0073]

[0074]

[0075] in:

[0076] R9 is selected from -H, alkyl (C1-8) Phosphonylalkyl and phosphonyl(phosphate)alkyl; and

[0077] Y is selected from alkyldiyl, alkoxydiyl, alkylaminodiyl, and alkenyldiyl.

[0078] In one embodiment, when at least one monomer used to form the polymer has a structure of formula 15, R 17 For H. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, R 17 The value is CH3. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 is a covalent bond.

[0079] In one embodiment, when at least one monomer used to form the polymer has a structure of formula 15, R 10 R 11 and R 12 The monomer is independently selected from -H, Na salt, and K salt. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 has the structure of Formula 4 and X has the structure of Formula 5. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 has the structure of Formula 4 and X has the structure of Formula 8. In one embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 has the structure of Formula 4 and X has the structure of Formula 10.

[0080] These and other features, aspects, and advantages of the present invention will become apparent to those skilled in the art upon reading this disclosure. Attached Figure Description

[0081] Figure 1 A graph showing the polymer properties.

[0082] Figure 2 A graph showing the polymer properties.

[0083] Figure 3 A graph showing the polymer properties.

[0084] Figure 4 A graph showing the polymer properties.

[0085] Figure 5 This is a GPC trace obtained from polymer analysis.

[0086] Figure 6 This is a GPC trace obtained from polymer analysis. Detailed Implementation

[0087] Although the invention is specifically pointed out and clearly claimed at the end of the specification by the claims, it is believed that the invention will be better understood by the following description.

[0088] Unless otherwise specified, all percentages in this document are in moles of the composition.

[0089] Unless otherwise specified, all ratios are molar ratios.

[0090] Unless otherwise specified, all percentages, ratios and contents of ingredients mentioned herein are based on the actual content of the ingredient on a molar basis and do not include solvents, fillers or other materials that may be used in combination with these ingredients in commercially available products.

[0091] As used herein, “includes / contains” means other steps and other components that may be added without affecting the final result. This term encompasses both “consisting of” and “substantially consisting of”.

[0092] All cited references are incorporated herein by reference in their entirety. Any citation of any reference is not an endorsement of its availability as prior art to the invention protected by the claims.

[0093] definition

[0094] The terms "site," "linkage site," or "connection point" refer to an atom with an open valence state within a chemical group or defined structural entity, designated by a symbol such as a simple hyphen (-) or a lowercase Greek letter followed by a hyphen or line (e.g., α-, β-, etc.) to indicate that the designated atom is connected via a chemical bond to another atom in a separate chemical group. Symbols When drawing vertical cross keys

[0095]

[0096] It also indicates the connection points of chemical groups. It should be noted that this method is typically used only to identify the connection points of larger chemical groups, to clearly help the reader identify the connection points with atoms from which the chemical bond extends. Connection sites or junctions on the first chemical group or defined structural entity are connected to connection sites or junctions on the second chemical group or defined structural entity via single, double, or triple covalent bonds to satisfy the normal valence of the connected atoms.

[0097] When used with chemical groups, the term "group" refers to any connected atomic group, such as a methyl group, a carboxyl group, or a phosphono-phosphate group that is part of a larger molecule.

[0098] When used in the context of chemical groups: "hydrogen" refers to -H; "hydroxyl" refers to -OH; "oxo" refers to =O; "carbonyl" refers to -C(=O)-; "carboxyl" and "carboxylate" refer to -C(=O)OH (also written as -COOH or -CO2H) or its deprotonated form; "amino" refers to -NH2; "hydroxyamino" refers to -NHOH; "nitro" refers to -NO2; "imino" refers to =NH; "amine oxide" refers to N + O - In this context, N has three covalent bonds with atoms other than O; "isohydroxamic acid" or "isohydroxamic acid ion" refers to -C(O)NHOH or its deprotonated form; in the context of monovalent, "phosphate" refers to -OP(O)(OH)2 or its deprotonated form; in the context of divalent, "phosphate" refers to -OP(O)(OH)O- or its deprotonated form; "phosphonate" refers to CP(O)(OH)2 or its deprotonated form, where C has a normal tetravalent and three covalent bonds connected to atoms other than P; "phosphonyl-phosphate group" refers to a phosphonate ion chemically bonded to at least one phosphate ion through a shared oxygen atom, such as, but not limited to, phosphonyl-monophosphate CP(O)(OH)OP(O)(OH)2, phosphonyl-diphosphate CP(O)(OP(O)(OH)2)OP(O)(OH)2, and phosphonyl-cyclodiphosphate. Phosphonoyl-pyrophosphate CP(O)(OH)OP(O)(OH)OP(O)(OH)2 and phosphonoyl-polyphosphate CP(O)(OH)(OP(O)(OH)) n OP(O)(OH)2 (where n is an integer between 1 and 100) or their deprotonated forms, wherein C has a normal tetravalent oxidation state and three covalent bonds connected to atoms other than P; "phosphonate" refers to CP(O)(OH)(C) or its deprotonated form, wherein both C atoms have a normal tetravalent oxidation state and three additional bonds connected to atoms other than P; "sulfate" refers to -OS(O)2OH or its deprotonated form; "sulfonate" refers to CS(O)2OH or its deprotonated form, wherein C has a normal tetravalent oxidation state and three additional bonds connected to atoms other than S; "sulfinate" refers to CS(O)OH or its deprotonated form, wherein C has a normal tetravalent oxidation state and three additional bonds connected to atoms other than S; "mercapto" refers to -SH; "thio" refers to =S; "sulfonyl" refers to -S(O)2-; and "sulfinyl" refers to -S(O)-.

[0099] For the following chemical groups and categories, the subscripts in parentheses further define the chemical group / category as follows: "(Cn)" defines the exact number (n) of carbon atoms in the chemical group / category. "(C≤n)" defines the maximum number (n) of carbon atoms that can be in the chemical group / category, where the minimum number of chemical groups considered is as small as possible. For example, it should be understood that the chemical group "alkenyl"... (C≤8) "or chemical category "alkene" (C≤8) The minimum number of carbon atoms in a 'alkoxy' is 2. For example, 'alkoxy'. (C≤8) "" indicates alkoxy groups having 1 to 8 carbon atoms. (Cn-n') defines both the minimum (n) and maximum (n') number of carbon atoms in a chemical group. Similarly, alkyl groups... (C2-8) This refers to alkyl groups having 2 to 8 (inclusive) carbon atoms.

[0100] The term "cation" refers to an atom, molecule, or chemical group having a net positive charge, including single-charged and multi-charged substances. A cation can be a single atom such as a metal (non-limiting examples include Na). + or Ca +2 ), single molecule (non-limiting examples include (CH3)4N + ) or chemical groups (non-limiting examples include -N(CH3)3 + The term "amine cation" refers to NR4. + A specific molecular cation in which the four substituted R moieties can be independently selected from H and alkyl groups; non-limiting examples include NH4. + (ammonium), CH3NH3 + (methylammonium), CH3CH2NH3 + (ethylammonium), (CH3)2NH2 + (dimethylammonium), (CH3)3NH + (trimethylammonium) and (CH3)4N + (Tetramethylammonium)

[0101] The term "anion" refers to an atom, molecule, or chemical group that has a net negative charge, including single-charged and multi-charged substances. Anions can be single atoms (e.g., but not limited to halogen F). - Cl - ,Br - ), single molecule (non-limiting examples include CO3) -2 H2PO4 - HPO4 -2 PO4 -3 HSO4 - SO4- 2The deprotonated form of a chemical group (non-limiting examples include sulfate, phosphate, sulfonate, phosphonate, hypophosphonate, sulfonate, mercapto, carboxylate, amine oxide, isohydroxamate, and hydroxyamino) is considered an anionic group if removing a proton results in a net negative charge. In solution, according to the Henderson-Hasselbach equation (pH = pKa + log...), the deprotonated form of the chemical group is considered an anionic group. 10 ([A - [A-] / [HA]; where [HA] is the molar concentration of the undissociated acid and [A-] is the molar concentration of the conjugate base of the acid), a chemical group can lose a proton to become an anion as a function of pH. When the pH of the solution equals the pKa value of the functional group, 50% of the functional groups will be anions, while the remaining 50% will have protons. Generally, if the pH is at or above the pKa of the functional group, the functional group in the solution can be considered anion.

[0102] The term "salt" refers to an electrically neutral combination of one or more anions and cations. For example, when R represents a salt of a carboxylate group -COOR, it should be understood that the carboxylate group (-COO-) is an anion with a negative charge of -1, and R is a cation with a positive charge of +1 to form an electrically neutral entity with an anion with a charge of -1, or R is a cation with a positive charge of +2 to form an electrically neutral entity with two anions, both with a charge of -1.

[0103] As used herein, the term "saturated" means that a chemical compound or group so modified does not have a carbon-carbon double bond and does not have a carbon-carbon triple bond, unless described below. With regard to the substitution pattern of a saturated chemical group, one or more carbon-oxygen double bonds or carbon-nitrogen double bonds may be present. When such bonds are present, it is not excluded that the carbon-carbon double bond may occur as part of a keto-enol tautomerism or an imine / enamine tautomerism.

[0104] When used without the modifier "substitution," the term "aliphatic" indicates that the modified chemical compound / group is acyclic or cyclic, but not aromatic. In aliphatic chemical compounds / groups, carbon atoms can be linked together in straight-chain, branched, or non-aromatic (alicyclic) form. Aliphatic chemical compounds / groups can be saturated, i.e., linked by single bonds (alkane / alkyl); or unsaturated, i.e., having one or more double bonds (alkene / alkenyl) or one or more triple bonds (alkynyl / alkynyl).

[0105] When used without the modifier "substituted," the term "alkyl" refers to a monovalent saturated aliphatic group with a carbon atom as the linking point, having a straight or branched, cyclic, cyclic, or acyclic structure, and containing no atoms other than carbon and hydrogen. Thus, as used herein, cycloalkyl is a subset of alkyl groups in which the carbon atom forming the linking point is also a member of one or more non-aromatic ring structures, wherein the cycloalkyl group does not contain atoms other than carbon and hydrogen. As used herein, the term does not exclude the presence of one or more alkyl groups (permitted by carbon number restrictions) attached to the ring or ring system. Non-limiting examples of alkyl groups including -CH3(Me), -CH2CH3(Et), -CH2CH2CH3(n-Pr or propyl), -CH(CH3)2(i-Pr, 'Pr or isopropyl), -CH(CH2)2(cyclopropyl), -CH2CH2CH2CH3(n-Bu), -CH(CH3)CH2CH3(sec-butyl), -CH2CH(CH3)2(isobutyl), -C(CH3)3(tert-butyl, t-butyl, t-Bu or tBu), -CH2C(CH3)3(neopentyl), cyclobutyl, cyclopentyl, cyclohexyl, and cyclohexylmethyl. The term "alkanediyl" when used without the modifier "substituted" refers to a divalent saturated aliphatic group with one or two saturated carbon atoms as connecting points, having a straight or branched, cyclic, cyclic or acyclic structure, without carbon-carbon double or triple bonds, and without atoms other than carbon and hydrogen. The groups -CH2(methylene), -CH2CH2-, -CH2C(CH3)2CH2-, and -CH2CH2CH2- are non-limiting examples of alkyl diester groups. When used without the modifier "substituted," the term "alkylidene" refers to a divalent group =CRR', where R and R' are independently hydrogen, alkyl, or R and R' together represent an alkyl diester having at least two carbon atoms. Non-limiting examples of alkylidene groups include: =CH2, =CH(CH2CH3), and =C(CH3)2. "Alkane" refers to the compound HR, where R is an alkyl group as defined above. When any of these terms is used with the modifier “substitution”, one or more hydrogen atoms have been independently substituted by -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, -S(O)2NH2, -P(O)(OH)2, -P(O)(OH)OP(O)(OH)2, -OP(O)(OH)2, -OP(O)(OH)OP(O)(OH)2, -S(O)2(OH) or -OS(O)2(OH).The following groups are non-limiting examples of substituted alkyl groups: -CH2OH, -CH2Cl, -CF3, -CH2CN, -CH2C(O)OH, -CH2C(O)OCH3, -CH2C(O)NH2, -CH2C(O)CH3, -CH2OCH3, -CH2OC(O)CH3, -CH2NH2, -CH2N(CH3)2, -CH2CH2Cl, -CH2P(O)(OH)2, -CH2P(O)(OH)OP(O)(OH)2, -CH2S(O)2(OH), and -CH2OS(O)2(OH). The term "halogenated alkyl" is a subset of substituted alkyl groups in which one or more hydrogen atoms have been replaced by a halogen group, and no atoms other than carbon, hydrogen, and halogen are present. The group -CH2Cl is a non-limiting example of a haloalkyl group. The term "fluoroalkyl" is a subset of substituted alkyl groups in which one or more hydrogen atoms have been replaced by a fluorine group, and no atoms other than carbon, hydrogen, and fluorine are present. The groups -CH2F, -CF3, and -CH2CF3 are non-limiting examples of fluoroalkyl groups.

[0106] The term "phosphonoalkyl" is a subset of substituted alkyl groups in which one or more hydrogen atoms are replaced by a phosphonate group and no atoms other than carbon, hydrogen, phosphorus, and oxygen are present. Non-limiting examples of the groups -CH2P(O)(OH)2 and -CH2CH2P(O)(OH)2, and their corresponding deprotonated forms, are phosphonoalkyl groups.

[0107] The term "phosphonoyl(phosphate)alkyl" is a subset of substituted alkyl groups in which one or more hydrogen atoms are replaced by a phosphono-phosphate group and no atoms other than carbon, hydrogen, phosphorus, and oxygen are present. Non-limiting examples of the groups -CH2P(O)(OH)OP(O)(OH)2 and -CH2CH2P(O)(OH)OP(O)(OH)2, and their corresponding deprotonated forms, are phosphonoyl(phosphate)alkyl groups.

[0108] The term "sulfonylalkyl" is a subset of substituted alkyl groups in which one or more hydrogen atoms are replaced by a sulfonate group and no atoms other than carbon, hydrogen, sulfur, and oxygen are present. Non-limiting examples of the groups -CH2S(O)2OH and -CH2CH2S(O)2OH, and their corresponding deprotonated forms, are sulfonylalkyl groups.

[0109] When used without the modifier "substitution," the term "alkenyl" refers to a monovalent unsaturated aliphatic group having one carbon atom as a connecting point, having a straight or branched, cyclic, cyclic or acyclic structure, at least one non-aromatic carbon-carbon double bond, no carbon-carbon triple bond, and no atoms other than carbon and hydrogen. Non-limiting examples of alkenyl groups include: -CH=CH2 (vinyl), -C(CH3)=CH2 (methyl vinyl), -CH=CHCH3, -CH=CHCH2CH3, -CH2CH=CH2 (allyl), -CH2CH=CHCH3, and -CH=CHCH=CH2. When used without the modifier "substitution," the term "alkenidyl" refers to a divalent unsaturated aliphatic group having two carbon atoms as connecting points, having a straight or branched, cyclic, cyclic or acyclic structure, at least one non-aromatic carbon-carbon double bond, no carbon-carbon triple bond, and no atoms other than carbon and hydrogen. The groups >C=CH2(vinylidene), -CH=CH-, -CH=C(CH3)CH2-, and -CH=CHCH2- are non-limiting examples of alkenyl groups. It should be noted that although alkenyl groups are aliphatic, once connected at both ends, it does not preclude the group from forming part of an aromatic structure. The terms "alkene" or "olefin" are synonymous and refer to compounds having the formula HR, where R is an alkenyl group as defined above. A "terminal alkene" is an alkene having only one carbon-carbon double bond, where this bond forms a vinyl group at one end of the molecule. When any of these terms is used with the modifier “substitution”, one or more hydrogen atoms have been independently substituted by -OH, -F, -Cl, -Br, -I, -NH, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, or -S(O)2NH2. The groups -CH=CHF, -CH=CHCl, and -CH=CHBr are non-limiting examples of substituted alkenyl groups.

[0110] When used without the modifier "substitution," the term "alkynyl" refers to a monovalent unsaturated aliphatic group having a single carbon atom as a linker, having a straight or branched, cyclic, cyclic or acyclic structure, at least one carbon-carbon triple bond, and having no atoms other than carbon and hydrogen. As used herein, the term alkynyl does not exclude the presence of one or more non-aromatic carbon-carbon double bonds. The groups -C≡CH, -C≡CCH3, and -CH2C≡CCH3 are non-limiting examples of alkynyl groups. "Alkyne" refers to the compound HR, where R is an alkynyl group. When any of these terms is used with the modifier “substitution”, one or more hydrogen atoms have been independently substituted by -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, or -S(O)2NH2.

[0111] When used without the modifier "substituted," the term "aryl" refers to a monovalent unsaturated aromatic group having one aromatic carbon atom as a connecting point, said carbon atom forming part of one or more six-membered aromatic ring structures, wherein all ring atoms are carbon, and wherein the group does not contain atoms other than carbon and hydrogen. If more than one ring is present, the rings may be fused or unfused. As used herein, the term does not exclude the presence of one or more alkyl or aralkyl groups (permitted by the carbon number limit) attached to the first aromatic ring or any other aromatic ring present. Non-limiting examples of aryl groups include phenyl (-Ph), methylphenyl, (dimethyl)phenyl, -C6H4CH2CH3 (ethylphenyl), naphthyl, and monovalent groups derived from biphenyl. When used without the modifier "substituted," the term "aryl diaryl" refers to a divalent aromatic group having two aromatic carbon atoms as connecting points, said carbon atoms forming part of one or more six-membered aromatic ring structures, wherein all ring atoms are carbon, and wherein the monovalent group does not contain atoms other than carbon and hydrogen. As used herein, the term does not exclude the presence of one or more alkyl, aryl, or aralkyl groups (permitted by carbon number restrictions) attached to the first aromatic ring or any other present aromatic ring. If more than one ring is present, the rings may be fused or unfused. Unfused rings may be connected via one or more of the following (permitted by carbon number restrictions): covalent bonds, alkyl diel, or olefin diel groups. Non-limiting examples of aryl diel groups include:

[0112]

[0113] "Aromatic hydrocarbon" refers to the compound HR, where R is aryl as defined above. Benzene and toluene are non-limiting examples of aromatic hydrocarbons. When any of these terms is used with the modifier "substituted", one or more hydrogen atoms have been independently substituted by -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, or -S(O)2NH2.

[0114] When used without the modifier "substitution," the term "acyl" refers to the group -C(O)R, where R is hydrogen, alkyl, aryl, aralkyl, or heteroaryl, as defined above. The groups -CHO (formyl), -C(O)CH3 (acetyl, Ac), -C(O)CH2CH3, -C(O)CH2CH2CH3, -C(O)CH(CH3)2, -C(O)CH(CH2)2, -C(O)C6H5, -C(O)C6H4CH3, -C(O)CH2C6H5, and -C(O) (imidazolyl) are non-limiting examples of acyl groups. "Thioacyl" is defined similarly, except that the oxygen atom in the group -C(O)R has been replaced by a sulfur atom to become -C(S)R. As defined above, the term "aldehyde" corresponds to an alkane in which at least one hydrogen atom has been substituted by a -CHO group. When any of these terms is used with the modifier “substitution”, one or more hydrogen atoms (including hydrogen atoms directly attached to a carbonyl or thiocarbonyl group, if present) have been independently substituted with -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, or -S(O)2NH2. The groups -C(O)CH2CF3, -CO2H (carboxyl), -CO2CH3 (methylcarboxyl), -CO2CH2CH3, -C(O)NH2 (carbamoyl), and -CON(CH3)2 are non-limiting examples of substituted acyl groups.

[0115] When used without the modifier "substitution," the term "alkoxy" refers to the group -OR, where R is an alkyl group as defined above. Non-limiting examples of alkoxy groups include: -OCH3 (methoxy), -OCH2CH3 (ethoxy), -OCH2CH2CH3, -OCH(CH3)2 (isopropoxy), -O(CH3)3 (tert-butoxy), -OCH(CH2)2, -O-cyclopentyl, and -O-cyclohexyl. When used without the modifier "substitution," the terms "alkenoxy," "alkynoxy," "aryloxy," "arylalkoxy," "heteroaryloxy," "heterocyclic alkoxy," and "acyloxy" refer to groups defined as -OR, where R is alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heterocyclic alkyl, and acyl, respectively. The term "alkoxydiyl" refers to the divalent group -O-alkanediyl-, -O-alkanediyl-O-, or -alkanediyl-O-alkanediyl-. The term "alkanediyl-alkoxy" refers to -alkanediyl-O-alkyl. A non-limiting example of alkanediyl-alkoxy is -CH2-CH2-O-CH2-CH3. The terms "alkathioyl" and "acylthioyl" when used without the modifier "substituted" refer to the group -SR, where R is alkyl and acyl, respectively. The term "alcohol" corresponds to an alkane as defined above, wherein at least one hydrogen atom is substituted by a hydroxyl group. The term "ether" corresponds to an alkane as defined above, wherein at least one hydrogen atom is substituted by an alkoxy group. When any of these terms is used with the modifier “substitution”, one or more hydrogen atoms have been independently substituted by -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, or -S(O)2NH2.

[0116] When used without the modifier "substitution," the term "alkylamino" refers to the group -NHR, where R is alkyl as defined above. Non-limiting examples of alkylamino groups include -NHCH3 and -NHCH2CH3. When used without the modifier "substitution," the term "dialkylamino" refers to the group -NRR', where R and R' can be the same or different alkyl groups, or R and R' can be combined to represent an alkyl diel. Non-limiting examples of dialkylamino groups include -N(CH3)2, -N(CH3)(CH2CH3), and N-pyrrolidinyl. When used without the modifier "substitution," the terms "alkoxyamino," "alkenylamino," "alkynylamino," "aromaticamino," "aralkylamino," "heteroaromaticamino," "heterocyclic alkylamino," and "alkylsulfonylamino" refer to groups defined as -NHR, where R is alkoxy, alkenyl, alkynyl, aryl, aralkyl, heteroaromatic, heterocyclic alkyl, and alkylsulfonyl, respectively. A non-limiting example of an aromaticamino group is -NHC6H5. The term "acylamino" (or "acylamino") when used without the modifier "substitution" refers to the group -NHR, where R is an acyl group as defined above. A non-limiting example of an acylamino group is -NHC(O)CH3. The term "alkylimino" when used without the modifier "substitution" refers to the divalent group =NR, where R is an alkyl group as defined above. The term "alkylaminodiyl" refers to the divalent group -NH-alkanediyl-, -NH-alkanediyl-NH-, or -alkanediyl-NH-alkanediyl-. When any of these terms is used with the modifier “substitution”, one or more hydrogen atoms have been independently substituted by -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, or -S(O)2NH2. The groups -NHC(O)OCH3 and -NHC(O)NHCH3 are non-limiting examples of substituted amide groups.

[0117] When used without the modifier "substitution," the terms "alkylsulfonyl" and "alkylsulfinyl" refer to the groups -S(O)₂R and -S(O)R, respectively, where R is alkyl, as defined above. The terms "alkenylsulfonyl," "alkynylsulfonyl," "arylsulfonyl," "aralkylsulfonyl," "heteroarylsulfonyl," and "heterocyclic alkylsulfonyl" are defined similarly. When any of these terms is used with the modifier "substitution," one or more hydrogen atoms have been independently substituted with -OH, -F, -Cl, -Br, -I, -NH₂, -NO₂, -CO₂H, -CO₂CH₃, -CN, -SH, -OCH₃, -OCH₂CH₃, -C(O)CH₃, -NHCH₃, -NHCH₂CH₃, -N(CH₃)₂, -C(O)NH₂, -OC(O)CH₃, or -S(O)₂NH₂.

[0118] The term "alkyl phosphate" when used without the modifier "substitution" refers to the group -OP(O)(OH)(OR) or its deprotonated form, where R is alkyl as defined above. Non-limiting examples of alkyl phosphate groups include -OP(O)(OH)(OMe) and -OP(O)(OH)(OEt). The term "dialkyl phosphate" when used without the modifier "substitution" refers to the group -OP(O)(OR)(OR'), where R and R' can be the same or different alkyl groups, or R and R' can be combined to represent an alkyl dienylate. Non-limiting examples of dialkyl phosphate groups include -OP(O)(OMe)2, -OP(O)(OEt)(OMe), and -OP(O)(OEt)2. When any of these terms is used with the modifier “substitution”, one or more hydrogen atoms have been independently substituted by -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, or -S(O)2NH2.

[0119] A linking group is a covalent bond between two other defining groups, or a series of covalently bonded atoms connecting two other defining groups, wherein none of the covalently bonded atoms have an open valence state except at the sites where they are attached to the two other defining groups. Non-limiting examples of linking groups include covalent bonds, alkyl dienes, alkenyl dienes, aryl dienes, alkoxy dienes, and alkylamino dienes.

[0120] As used herein, "chiral auxiliaries" refers to removable chiral groups capable of influencing the stereoselectivity of a reaction. Such compounds are familiar to those skilled in the art, and many are commercially available.

[0121] Other abbreviations used in this article are as follows: DMSO, dimethyl sulfoxide; DMF, dimethylformamide; MeCN, acetonitrile; MeOH, methanol; EtOH, ethanol; EtOAc, ethyl acetate; tBuOH, tert-butanol; iPrOH, isopropanol; cHexOH, cyclohexanol; Ac2O, acetic anhydride; AcOOH, peracetic acid; HCO2Et, ethyl formate; THF, tetrahydrofuran; MTBE, methyl tert-butyl ether; DME, dimethoxyethane; NBS, N-bromosuccinimide; CDI, carbonyl diimidazole; DIEA, diisopropylethylamine; TEA, triethylamine; DMAP, dimethylaminopyridine; NaOH, sodium hydroxide; AAPH, 2,2'-azobis(2-methylpropanediamine) Dihydrochloride; CTA, 1-Octamethyl mercaptan; APS, Ammonium persulfate; TMP, Trimethyl phosphate; VPA, Vinylphosphonic acid; VPP, Vinylphosphonyl-monophosphate; VPPP, Vinylphosphonyl-pyrophosphate; MVPP, Methyl-vinylphosphonyl-monophosphate; SVS, Sodium vinyl sulfonate; AMPS, Sodium 2-Acryloylamino-2-methylpropanesulfonate; SPA, Potassium salt of 3-sulfopropyl acrylate; 22A2MPA2HCl, 2,2'-Azobis(2-methylpropanediamine) dihydrochloride; VBPP, (4-vinylbenzyl)monophosphonyl-phosphate; VSME, Methyl vinyl sulfonate; NaOMe, Sodium methoxide; NaCl, Sodium chloride; DMVP, Dimethylvinylphosphonate

[0122] The International Union of Pure and Applied Chemistry (IUPAC) defines a "monomer molecule" as "a molecule that can undergo polymerization to contribute structural units to the basic structure of a macromolecule." Polymers are macromolecules.

[0123] IUPAC defines a "polymer backbone" or "backbone" as "a linear chain in which all other chains (long or short, or both) can be considered as its side groups." It's important to note that "in cases where two or more chains can be considered equivalently as backbones, the chain that makes the molecular representation simplest is chosen." Backbones can have different chemical compositions depending on the raw materials used to prepare them. Common backbones from chemically and biosynthetically synthesized polymers include alkanes (typically from vinyl or methyl vinyl polymerization or cationic and anionic polymerization), polyesters (from condensation polymerization), polyamides (such as peptides from polymerizations involving amidation reactions), and polyethoxylates derived from ring-opening of epoxides.

[0124] IUPAC defines "side group" or "side branch" as "a branch derived from the main chain that is neither an oligomer nor a polymer." Such side groups do not include linear repeating units.

[0125] IUPAC defines "polymer side chain" or "side chain" as "an oligomeric or polymeric branch derived from a macromolecular chain." It should also be noted that "oligomeric branches can be referred to as short branches" and "polymer branches can be referred to as long branches."

[0126] "Post-polymerization modification" is defined as any reaction or treatment of the polymer that occurs after polymerization. Post-polymerization modification includes reactions on chemical groups within or attached to the polymer backbone, side groups, or polymer side chains.

[0127] When used with the term "comprising" in the claims and / or specification, the word "a" may mean "a," but it is also consistent with the meanings of "one or more," "at least one," and "one or more."

[0128] Throughout this application, the term “about” is used to indicate values ​​that include inherent variations in the equipment or method used to determine the value, or variations that exist between the subjects under study.

[0129] The terms “contains,” “has,” and “includes” are open-ended connecting verbs. Any form or tense of one or more of these verbs, such as “contains,” “has,” and “includes,” is also open-ended. For example, any method of “contains,” “has,” or “includes” one or more steps is not limited to having only those one or more steps and also covers other steps not listed.

[0130] The above definitions supersede any conflicting definitions in any references incorporated herein by reference. However, the fact that some terms are defined should not be construed as indicating that any undefined term is indeterminate. Rather, all terms used are intended to describe the invention in a way that allows those skilled in the art to understand its scope and practice.

[0131] Polymers containing phosphono-phosphate groups

[0132] In one embodiment, the present invention relates to compounds having the structure of Formula 1:

[0133]

[0134] in:

[0135] R1 is selected from -H and -CH3;

[0136] R2 is selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cation salts and structures of formula 2:

[0137]

[0138] in:

[0139] δ is the connection point with Equation 1.

[0140] R5 and R6 are independently selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts;

[0141] R3 is selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cation salts and structures of formula 3:

[0142]

[0143]

[0144] in:

[0145] δ is the connection point with Equation 1.

[0146] R7 and R8 are independently selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts; and

[0147] n is an integer from 1 to 22;

[0148] R4 is selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts; and

[0149] L is selected from chemical bonds, aryl dimethyl groups, and structures of formula 4:

[0150]

[0151] in:

[0152] α is the linking site to the alkenyl group;

[0153] β is the linking site to the phosphono-phosphate group;

[0154] X is selected from the structures shown in Equations 5 to 11;

[0155]

[0156]

[0157]

[0158]

[0159]

[0160]

[0161]

[0162] in:

[0163] R9 is selected from -H, alkyl (C1-8) Phosphonylalkyl and phosphonyl(phosphate)alkyl; and

[0164] Y is selected from alkyldiyl, alkoxydiyl, alkylaminodiyl, and alkenyldiyl.

[0165] In one embodiment of the compound, R1 of Formula 1 is H. In another embodiment of the compound, R1 of Formula 1 is CH3. In yet another embodiment of the compound, L of Formula 1 is a covalent bond.

[0166] In one embodiment of the compound, R2, R3, and R4 are independently selected from H, Na, and K salts. In another embodiment of the compound, R2, R3, and R4 are independently selected from H, Na, K, Zn, Ca, Sn, and amine cation salts.

[0167] In another embodiment of the compound, R2 has the structure of Formula 2. In another embodiment, R2 has the structure of Formula 2, and R5 and R6 are independently selected from H, Na salts, and K salts. In another embodiment, R2 has the structure of Formula 2, and R5 and R6 are independently selected from H, Na salts, K salts, Zn salts, Ca salts, Sn salts, and amine cation salts.

[0168] In another embodiment of the compound, R3 has the structure of Formula 3. In another embodiment of the compound, R3 has the structure of Formula 3, and n is an integer from 1 to 3. In another embodiment of the compound, R3 has the structure of Formula 3, and n is 1. In another embodiment of the compound, R3 has the structure of Formula 3, and R7 and R8 are independently selected from H, Na salts, and K salts. In another embodiment of the compound, R3 has the structure of Formula 3, and R7 and R8 are independently selected from H, Na salts, K salts, Zn salts, Ca salts, Sn salts, and amine cation salts. In another embodiment of the compound, R3 has the structure of Formula 3, and R7 and R8 are independently selected from H, Na salts, K salts, Zn salts, Ca salts, Sn salts, and amine cation salts, and n is 1.

[0169] In one embodiment, R1 is H, and L is covalently bonded. In another embodiment, R1 is CH3, and L is covalently bonded. In another embodiment, R1 is H, L is covalently bonded, and R2, R3, and R4 are independently selected from H, Na salts, and K salts. In another embodiment, R1 is CH3, L is covalently bonded, and R2, R3, and R4 are independently selected from H, Na salts, and K salts. In another embodiment, R1 is H, L is covalently bonded, and R2 has the structure of Formula 2. In another embodiment, R1 is CH3, L is covalently bonded, and R2 has the structure of Formula 2. In another embodiment, R1 is H, L is covalently bonded, and R3 has the structure of Formula 3. In another embodiment, R1 is CH3, L is covalently bonded, and R3 has the structure of Formula 3.

[0170] In one embodiment of the compound, L has the structure of Formula 4, and X has the structure of Formula 5. In another embodiment of the compound, L has the structure of Formula 4, and X has the structure of Formula 8. In one embodiment of the compound, L has the structure of Formula 4, and X has the structure of Formula 10. In one embodiment of the compound, L has the structure of Formula 4, and X has the structure of Formula 6. In another embodiment of the compound, L has the structure of Formula 4, X has the structure of Formula 5, and Y is an alkanediyl group. In another embodiment of the compound, L has the structure of Formula 4, X has the structure of Formula 8, and Y is an alkanediyl group. In one embodiment of the compound, L has the structure of Formula 4, X has the structure of Formula 10, and Y is an alkanediyl group. In one embodiment of the compound, L has the structure of Formula 4, X has the structure of Formula 6, and Y is selected from alkanediyl and alkoxydiyl groups.

[0171] Another embodiment of the present invention is a novel polymer. This polymer comprises a phosphono-phosphate group, wherein the phosphono-phosphate group has the structure of Formula 12:

[0172]

[0173] in:

[0174] ε is the connection site with a carbon atom in the main chain, side group, or side chain of the polymer;

[0175] R 10 Selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cation salts and structures of formula 13:

[0176]

[0177] in:

[0178] θ is the connection point with Equation 12.

[0179] R 13 and R 14 Independently selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts;

[0180] R 11 Selected from -H, alkyl, alkanedialkoxy, metal salts and amine cations having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and structures of Formula 14:

[0181]

[0182] in:

[0183] θ is the connection point with Equation 12.

[0184] R 15 and R 16 Independently selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts; and

[0185] n is an integer from 1 to 22; and

[0186] R 12 Selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts.

[0187] In one embodiment of the polymer, R 10 R 11 and R 12 Independently selected from H, Na, and K salts. In one embodiment of the polymer, R10 R 11 and R 12 It is independently selected from H, Na, K, Zn, Ca, Sn and amine cation salts.

[0188] In another embodiment of the polymer, R 10 It has the structure of Formula 13. In another embodiment, R 10 It has the structure of Equation 3, and R 13 and R 14 It is independently selected from H, Na, and K salts. In another embodiment, R 10 It has the structure of Equation 13, and R 13 and R 14 It is independently selected from H, Na, K, Zn, Ca, Sn and amine cation salts.

[0189] In another embodiment of the polymer, R 11 It has the structure of Formula 14. In another embodiment of the polymer, R 11 It has the structure of Formula 14, and n is an integer from 1 to 3. In another embodiment of the polymer, R 11 It has the structure of Formula 14, and n is 1. In another embodiment of the polymer, R 11 It has the structure of Equation 14, and R 15 and R 16 Independently selected from H, Na, and K salts. In another embodiment of the polymer, R 11 It has the structure of Equation 14, and R 15 and R 16 The salts are independently selected from H, Na, K, Zn, Ca, Sn, and amine cations. In another embodiment of the polymer, R 11 It has the structure of Equation 14, R 15 and R 16 It is independently selected from H, Na, K, Zn, Ca, Sn and amine cation salts, and n is 1.

[0190] In one embodiment, at least one monomer used to form the polymer comprises a phosphono-phosphate group. In another embodiment, the phosphono-phosphate group is added during a post-polymerization modification process.

[0191] In another embodiment, at least one monomer used to form the polymer has the structure of Formula 15:

[0192]

[0193] in:

[0194] ω is the connection site with the phosphono-phosphate group of Formula 12;

[0195] R 17 Selected from -H and -CH3;

[0196] L1 is selected from chemical bonds, aryl dimethyl groups, and structures of formula 4:

[0197]

[0198] in:

[0199] α is the linking site to the alkenyl group;

[0200] β is the linking site with the phosphono-phosphate group of Formula 12;

[0201] X is selected from the structures in Equations 5 to 11;

[0202]

[0203]

[0204]

[0205]

[0206]

[0207]

[0208]

[0209] in:

[0210] R9 is selected from -H, alkyl (C1-8) Phosphonylalkyl and phosphonyl(phosphate)alkyl; and

[0211] Y is selected from alkyldiyl, alkoxydiyl, alkylaminodiyl, and alkenyldiyl.

[0212] In one embodiment, when at least one monomer used to form the polymer has a structure of formula 15, R 17 For H. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, R 17 For CH3. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 is a covalent bond. In one embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, R 17H is present, and L1 is a covalent bond. In one embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, R 17 It is CH3, and L1 is a covalent bond. In one embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, R 10 R 11 and R 12 Independently selected from -H, Na salts, and K salts. In one embodiment, when at least one monomer used to form the polymer has a structure of Formula 15, R 17 H is a covalent bond, L1 is a covalent bond, and R is a covalent bond. 10 R 11 and R 12 Independently selected from -H, Na salts, and K salts. In one embodiment, when at least one monomer used to form the polymer has a structure of Formula 15, R 17 It is CH3, L1 is covalent, and R 10 R 11 and R 12 Independently selected from H, Na, and K salts. In one embodiment, when at least one monomer used to form the polymer has a structure of Formula 15, R 17 H is a covalent bond, L1 is a covalent bond, and R is a covalent bond. 10 It has the structure of Formula 13. In one embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, R 17 It is CH3, L1 is covalent, and R 10 It has the structure of Formula 13. In one embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, R 17 H is a covalent bond, L1 is a covalent bond, and R is a covalent bond. 11 It has the structure of Formula 14. In one embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, R 17 It is CH3, L1 is covalent, and R 11 It has the structure of Equation 14.

[0213] In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 has the structure of Formula 4 and X has the structure of Formula 5. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 has the structure of Formula 4 and X has the structure of Formula 8. In one embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 has the structure of Formula 4 and X has the structure of Formula 10. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 has the structure of Formula 4 and X has the structure of Formula 6. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 has the structure of Formula 4, X has the structure of Formula 5, and Y is a alkyldiyl group. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 has the structure of Formula 4, X has the structure of Formula 8, and Y is a alkyldiyl group. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 has the structure of Formula 4, X has the structure of Formula 10, and Y is an alkyl diester. In another embodiment, when at least one monomer used to form the polymer has the structure of Formula 15, L1 has the structure of Formula 4, X has the structure of Formula 6, and Y is selected from alkyl diesters and alkoxy diesters.

[0214] Another embodiment of the invention is a novel polymer, which in this context is intended to include oligomers such as dimers, trimers, and tetramers. The polymer comprises a phosphono-phosphate group having a structure of Formula 16:

[0215]

[0216] in:

[0217] R1 is selected from -H and -CH3;

[0218] R2 is selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cation salts and structures of formula 2:

[0219]

[0220] in:

[0221] δ is the connection point with Equation 16.

[0222] R5 and R6 are independently selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts;

[0223] R3 is selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cation salts and structures of formula 3:

[0224]

[0225] in:

[0226] δ is the connection point with Equation 16.

[0227] R7 and R8 are independently selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts; and

[0228] n is an integer from 1 to 22;

[0229] R4 is selected from -H, alkyl, alkanedialkoxy, metal salts having Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cation salts;

[0230] R 18 These are chemical groups generated by polymer initiation;

[0231] R 19 A chemical group that causes chain termination;

[0232] M2 is selected from chemical bonds and post-polymerization residues of one or more comonomers;

[0233] m is an integer from 2 to 450; and

[0234] L is selected from chemical bonds, aryl dimethyl groups, and structures of formula 4:

[0235]

[0236] in:

[0237] α is the linking site to the alkenyl group;

[0238] β is the linking site to the phosphono-phosphate group;

[0239] X is selected from the structures shown in Equations 5 to 11;

[0240]

[0241]

[0242]

[0243]

[0244]

[0245]

[0246]

[0247] in:

[0248] R9 is selected from -H, alkyl (C1-8) Phosphonylalkyl and phosphonyl(phosphate)alkyl; and

[0249] Y is selected from alkyldiyl, alkoxydiyl, alkylaminodiyl, and alkenyldiyl.

[0250] In one embodiment of the polymer, R1 in Formula 16 is H. In another embodiment of the polymer, R1 in Formula 16 is CH3. In yet another embodiment of the polymer, L in Formula 16 is a covalent bond.

[0251] In one embodiment of the polymer, R2, R3, and R4 are independently selected from H, Na, and K salts. In another embodiment of the polymer, R2, R3, and R4 are independently selected from H, Na, K, Zn, Ca, Sn, and amine cation salts.

[0252] In another embodiment of the polymer, R2 has the structure of Formula 2. In another embodiment, R2 has the structure of Formula 2, and R5 and R6 are independently selected from H, Na salts, and K salts. In another embodiment, R2 has the structure of Formula 2, and R5 and R6 are independently selected from H, Na salts, K salts, Zn salts, Ca salts, Sn salts, and amine cation salts.

[0253] In another embodiment of the polymer, R3 has the structure of Formula 3. In another embodiment of the polymer, R3 has the structure of Formula 3, and n is an integer from 1 to 3. In another embodiment of the polymer, R3 has the structure of Formula 3, and n is 1. In another embodiment of the polymer, R3 has the structure of Formula 3, and R7 and R8 are independently selected from H, Na salts, and K salts. In another embodiment of the polymer, R3 has the structure of Formula 3, and R7 and R8 are independently selected from H, Na salts, K salts, Zn salts, Ca salts, Sn salts, and amine cation salts. In another embodiment of the polymer, R3 has the structure of Formula 3, and R7 and R8 are independently selected from H, Na salts, K salts, Zn salts, Ca salts, Sn salts, and amine cation salts, and n is 1.

[0254] In one embodiment, R1 is H, and L is covalently bonded. In another embodiment, R1 is CH3, and L is covalently bonded. In another embodiment, R1 is H, L is covalently bonded, and R2, R3, and R4 are independently selected from H, Na salts, K salts, and amine cation salts. In another embodiment, R1 is CH3, L is covalently bonded, and R2, R3, and R4 are independently selected from H, Na salts, K salts, and amine cation salts. In another embodiment, R1 is H, L is covalently bonded, and R2 has the structure of Formula 2. In another embodiment, R1 is CH3, L is covalently bonded, and R2 has the structure of Formula 2. In another embodiment, R1 is H, L is covalently bonded, and R3 has the structure of Formula 3. In another embodiment, R1 is CH3, L is covalently bonded, and R3 has the structure of Formula 3.

[0255] In one embodiment of the polymer, L has the structure of Formula 4, and X has the structure of Formula 5. In another embodiment of the polymer, L has the structure of Formula 4, and X has the structure of Formula 8. In one embodiment of the polymer, L has the structure of Formula 4, and X has the structure of Formula 10. In one embodiment of the polymer, L has the structure of Formula 4, and X has the structure of Formula 6. In another embodiment of the polymer, L has the structure of Formula 4, X has the structure of Formula 5, and Y is an alkanediyl group. In another embodiment of the polymer, L has the structure of Formula 4, X has the structure of Formula 8, and Y is an alkanediyl group. In one embodiment of the polymer, L has the structure of Formula 4, X has the structure of Formula 10, and Y is an alkanediyl group. In one embodiment of the polymer, L has the structure of Formula 4, X has the structure of Formula 6, and Y is selected from alkanediyl and alkoxydiyl groups.

[0256] In one embodiment of the polymer, the chemical group R derived from the polymer-initiated group... 18 Structures selected from Equations 17 to 21:

[0257]

[0258]

[0259]

[0260]

[0261]

[0262] in:

[0263] R 20 Selected from -H, Na, K and amine cation salts;

[0264] τ is the connection site with the polymer backbone; and

[0265] Q represents the non-olefin residues of the monomer used for polymerization.

[0266] In another implementation, Q has the structure of Equation 22:

[0267]

[0268] in:

[0269] L, R2, R3, and R4 are as described above, and κ represents the connection site with Equation 21.

[0270] In one embodiment of the polymer, M2 is a polymeric residue of one or more comonomers having the structure of Formula 23:

[0271]

[0272] in:

[0273] R 21 Selected from -H or -CH3;

[0274] Q1 represents the non-olefin residues of the comonomer used for polymerization; and

[0275] p is an integer from 1 to 450.

[0276] In another embodiment, Q is phosphono-phosphate.

[0277] In one embodiment of the polymer, the chemical group R generated by polymer termination 19 Selected from -H. In one embodiment of the polymer, the chemical group R generated by polymer termination... 19 It is another polymer chain with head-to-head connections.

[0278] In a preferred embodiment of the polymer, R1 is H, L is a covalent bond, and R 2、 R3 and R4 are independently selected from H, Na, K, and amine cation salts, R 18 The structure is that of Equation 21, Q is the structure of Equation 22, and R... 19 For H.

[0279] Methods for preparing polymers

[0280] The embodiments of the present invention can be prepared using the following general methods.

[0281] The polymers of this invention can be prepared by a variety of techniques, including bulk polymerization, solution polymerization, emulsion polymerization, or suspension polymerization. A summary of polymerization methods and techniques used for polymerization is found in *Encyclopedia of Polymer Science and Technology* (Interscience Publishers, New York), Vol. 7, pp. 361-431 (1967), and *Kirk-Othmer Encyclopedia of Chemical Technology*, 3rd edition, Vol. 18, pp. 740-744 (John Wiley & Sons, New York, 1982), both of which are incorporated herein by reference. General reaction techniques applicable to this invention are also found in *Preparative Methods of Polymer Chemistry*, 2nd edition, by Sorenson, WP and Campbell, TW (Interscience Publishers, New York, 1968), pp. 248-251, which are also incorporated herein by reference. In one example, the polymer is prepared by free radical copolymerization using a water-soluble initiator. Suitable free radical initiators include, but are not limited to, thermal initiators, redox pairs, and photochemical initiators. Redox and photochemical initiators can be used for polymerization processes initiated at temperatures below about 30°C. Such initiators are outlined in the Kirk-Othmer Encyclopedia of Chemical Technology, 3rd edition (John Wiley & Sons, New York), Vol. 13, pp. 355-373 (1981), which is incorporated herein by reference. Typical water-soluble initiators that provide free radicals at 30°C or lower include redox pairs such as potassium persulfate / silver nitrate and ascorbic acid / hydrogen peroxide. In one example, the method uses a thermal initiator in a polymerization process carried out at temperatures above 40°C. Water-soluble initiators that provide free radicals at 40°C or higher can be used. These include, but are not limited to, hydrogen peroxide, ammonium persulfate, and 2,2'-azobis(2-amidinylpropane) dihydrochloride. In one example, ammonium persulfate was used as an initiator, and water-soluble starting monomers were polymerized in water at 60°C.

[0282] The type of chemical functional groups at the ends of linear polymers depends on how the polymerization of the polymer chain is initiated and terminated. For radical polymerization, any free radical in the system can initiate a new chain. This free radical can be a direct derivative of the initiator, such as a sulfate group from persulfate, or an alkyl group from an azo initiator (such as, but not limited to, 2,2'-azobis(2-amidinylpropane)dihydrochloride). The free radical can also be the result of a transfer reaction, such as between water and another free radical to generate a hydroxyl radical or between a phosphate group and another free radical to generate a phosphate radical. Non-limiting examples of these resulting structures are given below, where R represents H or a suitable counterion such as Na, K, or an amine, and τ represents the linking site with the polymer.

[0283]

[0284] Free radicals can also result from chain transfer reactions, in which free radicals transfer from growing polymer chains to start new chains. Chain transfer has been clearly demonstrated in the polymerization of vinyl phosphonate monomers. The polymerization of alkyl esters of vinyl phosphonates, Macromolecules, Vol. 41, pp. 1634-1639 (2008), describes how chain transfer occurs on the alkyl group during polymerization; this literature is incorporated herein by reference. This transfer ultimately initiates a new polymer chain with an olefin-containing chemical group at the starting end. A similar phenomenon appears to occur in polymerization reactions based on vinylphosphonyl-phosphates. Chain transfer stops the growth of one chain and begins a new one.

[0285] In polymers containing phosphono-phosphate groups, vinyl CH2 groups are observed in the final polymer composition. It is hypothesized that these vinyl groups are formed through one of two mechanisms. The first mechanism is related to... The observed phenomenon is similar to, however, the phenomenon is similar to Unlike phosphonates, alkenes do not originate from alkyl esters of phosphonates, but rather potentially from vinyl monomers on a newly initiated chain. Not wishing to be bound by theory, the following scheme is given as a possible pathway through which chain transfer can generate alkenes at the initiation site of a universally radical polymerizable monomer, where, for clarity, the non-alkene portion of the monomer is simply described as Q. Q can represent any number of chemical functional groups and is not limited to a single chemical entity. Alkene-terminated groups based on vinylphosphonates and vinylphosphonyl-phosphates have been observed.

[0286]

[0287] The second mechanism for introducing vinyl groups involves a bite-back reaction and β-cleavage. This mechanism has been extensively documented in the literature for acrylate polymers. β-cleavage yields vinyl groups and primary radicals.

[0288]

[0289] Using the previously used terminology of τ to denote the linking site with the polymer, the initial functional group can be written as follows. It should be noted that chain transfer and biting back, as well as the subsequent β-splitting mechanism, will generate vinyl groups with two protons on the same carbon atom.

[0290]

[0291] The chemical groups at the ends of polymer chains depend on how the chain terminates. The most common terminations are chain transfer and back-biting reactions mentioned earlier, as well as combination and disproportionation. In chain transfer and back-biting, the terminal group is typically hydrogen. In combination, chain-propagating radicals on both chains react to form a new chain. This reaction results in a "head-to-head" configuration at the junction.

[0292]

[0293] In disproportionation, hydrogen is exchanged from one free radical chain to another. The result is one chain that is unsaturated and the other saturated. Note that the resulting unsaturated group is not a vinyl group. Each carbon atom in the unsaturated group has only one hydrogen atom.

[0294]

[0295] Polymers containing phosphono-phosphate groups may have phosphono-phosphate groups directly attached to polymer side groups or side chains but not to the polymer backbone. The phosphono-phosphate groups can be added to the polymer through polymerization of monomers having phosphono-phosphate groups, or through polymerization of monomers not having phosphono-phosphate groups, followed by post-polymerization modification of the resulting polymer, thereby incorporating the phosphono-phosphate groups into the polymer. Although examples in subsequent paragraphs will show homopolymers for simplicity, it should be understood that polymers having monomers other than phosphonate or phosphono-phosphate-containing monomers can be prepared by including these other monomers during polymerization.

[0296] As an example of a polymer containing phosphono-phosphate groups attached to the polymer backbone, consider a polymer made from the monomers vinylphosphonate or methylvinylphosphonate. The vinylphosphonate or methylvinylphosphonate can be chemically reacted to form phosphono-phosphate monomers, as shown in reaction 1 of scheme 1. These phosphono-phosphate-containing monomers can then be polymerized, as shown in reaction 2 of the same scheme, to obtain a phosphono-phosphate-containing polymer with phosphono-phosphate groups directly attached to the polymer backbone. Alternatively, the vinylphosphonate or methylvinylphosphonate can be polymerized first, as shown in reaction 3, to obtain the polymer. After polymerization, the phosphono-phosphate groups can be generated by post-polymerization modification of the attached phosphonate portion, as shown in reaction 4, thereby producing phosphono-phosphate groups directly attached to the polymer backbone.

[0297]

[0298] A second approach to generating phosphonyl-phosphate groups directly attached to the main chain via post-polymerization modification can be illustrated by starting with polyethylene. For an example of the first reaction in such modification, see M. Anbar, G.A. St. John, and A.C. Scott, J. Dent Res, Vol. 53, No. 4, pp. 867-878, 1974. As shown in Scheme 2, polyethylene is first oxidatively phosphorylated with oxygen and PCl3 to form a random phosphonate polymer. This phosphonate polymer can then be modified to produce a randomly substituted phosphonyl-phosphate polymer. The reaction products shown are intended to illustrate the random nature of the phosphonyl-phosphate group attachment sites in the resulting polymer.

[0299]

[0300] As an example of preparing a polymer having phosphonoyl-phosphate groups attached to side groups, consider the vinylbenzyl chemical shown in Scheme 3. As with the previous examples, for simplicity, this scheme will show a homopolymer. However, a heteropolymer with additional monomer components can be prepared by including additional monomers during the polymerization process. 4-Vinylbenzyl chloride can react with diethyl phosphite to form vinylbenzylphosphonate, as shown in reaction 1 of Scheme 3. For an example of this reaction, see Frantz, Richard; Durand, Jean-Olivier; Carre, Francis; Lanneau, Gerard F.; Le Bideau, Jean; Alonso, Bruno; Massiot, Dominique, Chemistry—A European Journal, Vol. 9, No. 3, pp. 770-775, 2003. Vinylbenzylphosphonate can be reacted to form the vinylbenzylphosphonoyl-phosphate shown in reaction 2, as described in the Examples section below. The monomer can then be polymerized, as described in the Examples section below, to form a phosphono-phosphate-containing polymer as shown in Reaction 5, wherein the phosphono-phosphate group is attached to a side group on the polymer. Alternatively, the first intermediate vinylbenzylphosphonate can be polymerized as shown in Reaction 4 to prepare polyvinylbenzylphosphonate. For an example of this reaction, see M. Anbar, G.A. St. John, and A.C. Scott, J. Dent Res, Vol. 53, No. 4, pp. 867-878, 1974. The polyvinylbenzylphosphonate can then be reacted as shown in Reaction 7 to produce a phosphono-phosphate-containing polymer, wherein the phosphono-phosphate group is attached to a side group on the polymer via post-polymerization modification as described in the Examples section below. A second approach involving post-polymerization modification is also shown in the same scheme. 4-Vinylbenzyl chloride can be polymerized to provide the polyvinylbenzyl chloride shown in Reaction 3. The polymer can be phosphonated as shown in reaction 6 (see, for example, Sang Hun Kim, Young Chul Park, Gui Hyun Jung and Chang Gi Cho, Macromolecules Research, Vol. 15, No. 6, pp. 587-597, 2007), and then the resulting polyvinylbenzylphosphonate can be reacted to produce the phosphono-phosphate-containing polymer shown in reaction 7.

[0301]

[0302] As a first example of a polymer comprising a phosphono-phosphate group attached to a side chain, consider the polyethylene glycol (PEG) side chain shown in Scheme 4. The phosphonate-containing PEG chain can be reacted with acryloyl chloride to produce an acrylate with PEG-terminated phosphonate groups. After the reaction produces a phosphono-phosphate, the phosphono-phosphate monomer can be polymerized to produce a phosphono-phosphate-containing polymer, wherein the phosphono-phosphate group is attached to the side chain of the polymer.

[0303]

[0304] As a second example of a polymer comprising a phosphono-phosphate group attached to a side chain, consider the polyvinyl alcohol shown in Scheme 5. The hydroxyl groups can react with ethylene oxide to produce a polymer having PEG side chains. The capped hydroxyl groups on the side chains can react with vinylphosphonate groups, which then react to form phosphono-phosphate groups. Therefore, this example describes a polymer containing phosphono-phosphate groups, wherein the phosphono-phosphate groups are attached to the side chains of the polymer and added via post-polymerization modification.

[0305]

[0306] The schemes described are not exhaustive in nature, but rather aim to convey the various ways in which phosphono-phosphate polymers can be generated. These examples provide technical details of the synthesis and numerous variations of phosphono-phosphate polymers, both those with the phosphono-phosphate group directly attached to the polymer backbone and those with the phosphono-phosphate group attached to side groups. For further examples of phosphonate monomers and polymers that can be converted into phosphono-phosphate monomers and polymers, see Sophie Monge, Benjamin Canniccioni, Ghislain David, and Jean-Jacques Robin, RSC Polymer Chemistry Series No. 11, Phosphorus-Based Polymers: From Synthesis to Applications, edited by Sophie Monge and Ghislain David, The Royal Society of Chemistry 2014, published by the Royal Society of Chemistry, www.rsc.org.

[0307] Applications of polymers containing phosphonoyl-phosphate groups

[0308] The phosphonoyl-phosphate polymers according to the present invention can be incorporated into a variety of compositions. These compositions include both aqueous and non-aqueous compositions. These compositions can be used to treat teeth, hair, body, fabrics, paper, non-wovens, and hard surfaces. These compositions can be used in water treatment, boiler treatment, treatment of ship hulls, oil wells, batteries, baking, fermentation, ceramics, plastic stabilizers, glass manufacturing, cheese production, buffers in food, abrasives in dental cleaning agents, binders in meat, coffee creamer, antifreeze, dispersants in paint liquid soaps, metal cleaners, synthetic rubber, textiles, and flame retardants. These compositions can also be used to treat materials containing polyvalent metal cations, including but not limited to calcium, tin, magnesium, and iron. Examples of such materials include hydroxyapatite, calcium carbonate (amorphous, calcite, aragonite), calcium phosphate, calcium hydroxide, magnesium carbonate, magnesium phosphate, soap residue (a mixture of calcium, magnesium, and iron salts of stearic acid and carbonates), and hard water stains. In one embodiment, the composition comprising the phosphonoyl-phosphate polymer is non-aqueous. In another embodiment, the composition is aqueous.

[0309] Compounds and polymers containing phosphonyl-phosphate groups can be applied to a variety of substrates. Embodiments of the substrates include biomaterials, fabrics, nonwovens, paper products, and rigid surface materials. In one embodiment, the biomaterial includes teeth. In another embodiment, the biomaterial includes keratin, such as hair or skin.

[0310] Example

[0311] The following examples further describe and demonstrate preferred embodiments within the scope of the present invention. These examples are given for illustrative purposes only and should not be construed as limiting the invention, as many variations are possible without departing from the spirit and scope of the invention. Components can be determined by their chemical names, or in other words, as defined below.

[0312] Powdered antifouling model (PSPM)

[0313] Powder stain prevention model (PSPM) is a screening technique in which hydroxyapatite powder (HAP) is used as a substrate for stain buildup. The general purpose of this technique is to demonstrate and quantify the ability or likelihood of tooth discoloration by chemical agents used in oral care. Hydroxyapatite powder provides a large surface area for adsorption of chromogenic substrates. Pretreatment of HAP with oral care active ingredients in the form of mouthwash or dental floss results in varying degrees of stain buildup depending on the ability of the active ingredient to block or enhance the binding of these chromogenic substrates to the HAP surface. The size of the stain can then be quantified via image analysis. The steps involved in PSPM are described below.

[0314] 1. HAP Preprocessing

[0315] Measure 200mg to 210mg of HAP powder ( HTP-Gel catalog #130-0421, Bio-Rad Laboratories (Hercules, Calif.) Pour HAP into 50 mL centrifuge tubes. Add 20 mL of the treatment to each tube. For simple polymers, the treatment is 2% by weight of the polymer or control based on 100% active ingredient used. For dental floss formulations, weigh 8 g of each toothpaste and place it into a labeled 50 g round-bottom centrifuge tube. Add 24 g of deionized water to the tube (making the slurry ratio 1:3). Vortex for 1 minute to thoroughly mix and prepare a slurry free of toothpaste lumps. Centrifuge the slurry at 15,000 rpm for 15 minutes and use 20 mL of the supernatant as the treatment. Vortex the tube for 30 seconds to completely suspend the HAP in the treatment, then centrifuge at 15,000 rpm for 15 minutes. After centrifugation, decant the supernatant and redistribute the pellets by adding 25 mL of water, vortex, centrifuge at 15,000 rpm for 15 minutes, and then decant—ensuring the pellets are broken up during vortexing. Repeat the washing cycle twice more.

[0316] 2. HAP color change

[0317] After the final wash, add 20 mL of filtered tea (one Lipton tea bag per 100 mL of hot water, infuse for 5 minutes, filter, and use at 50°C) to each granule and vortex for 30 seconds to ensure complete HAP suspension in the tea. Centrifuge the powder suspension at 15,000 rpm for 15 minutes and decant. Add approximately 25 mL of water to the tube, vortex, and then centrifuge at 15,000 rpm for 15 minutes. Decant the liquid and repeat the washing cycle twice more.

[0318] 3. Preparation of HAP for color analysis

[0319] The granules were vortexed in approximately 10 mL of water until completely suspended, and then filtered under vacuum onto a Millipore filter disc (membrane filter 4.5 tm, 47 mm catalog #HAWPO4700, Millipore Corporation, Bedford, Mass.). A control disc was prepared using approximately 200 mg of untreated, undiscolored HAP. The filter discs were then dried overnight in a flat position and then laminated.

[0320] 4. Color analysis of color-changing HAPs

[0321] Whitelight System: The HAP disks (untreated HAP controls and treated HAP samples) were placed in a stable sample holder. Color was measured using a digital camera with a lens equipped with a polarizing filter (Canon Inc. (Melville, NY) camera model CANON EOS 70D with a NIKON 55mm micro-NIKKOR lens with an adapter). The lighting system was provided by Dedo lamps (model DLH2) equipped with 150-watt, 24V bulbs (Xenophot model HLX64640), positioned approximately 30cm apart (measured from the center of the outer circular surface of the glass lenses through which the light passes, one to the other), and aimed at a 45-degree angle so that the light paths intersect on the HAP disks. Image analysis was performed using Whitelight with Ultragrab, Optimas, and Giant Imaging software.

[0322] 5. Control material

[0323] Common controls for single polymer PSPM are water treated with tea and water not exposed to tea. Additionally, pyrophosphate and polyphosphate are used as internal controls.

[0324] 6. Results

[0325] The changes in L* (brightness), a* (red(+) / green(-)), b* (yellow(-) / blue(+)) and E (total color) are calculated as follows:

[0326]

[0327]

[0328]

[0329]

[0330] The results are reported as mean ΔL, Δa, Δb and / or ΔE relative to the negative control, as well as the percentage of antifouling (AL & AE).

[0331] Powder Removal Model (PSRM)

[0332] Powder Stain Removal Model (PSRM) is a screening technique in which hydroxyapatite powder (HAP) is used as a substrate for stain buildup. The aim of this technique is to demonstrate and quantify the stain-removing properties of chemical agents used in oral care. Hydroxyapatite powder provides a large surface area for adsorption of chromophore substrates. Treatment of the discolored HAP with oral care active ingredients in the form of mouthwash or dental floss yields different levels of stain removal effectiveness based on the active ingredient's ability to disrupt the binding of these chromophore substrates to the HAP surface. The degree of stain removal effectiveness can then be quantified via image analysis. The model can be tested within three days. The steps involved in PSRM are described below.

[0333] 1. HAP color change

[0334] A large batch of tea tar was prepared by stirring 10 g of HAP powder in 200 mL of filtered tea for 5 minutes. The tar was transferred to centrifuge tubes and centrifuged at 15,000 rpm for 15 minutes. The tar was washed with 25 mL of water, vortexed, and centrifuged at 15,000 rpm for 15 minutes, then the liquid was aspirated. Ensure the tar was broken up during vortexing. The washing process was repeated.

[0335] Centrifuge tubes were placed in a convection oven (55°C to 65°C) overnight to dry the discolored HAP. Once dried, the discolored HAP was collected together and ground into a fine powder using a pestle and mortar.

[0336] 2. HAP processing

[0337] Measure 200mg to 210mg of HAP powder ( HTP-Gel catalog #130-0421, Bio-Rad Laboratories (Hercules, Calif.) Pour HAP into 50 mL centrifuge tubes. Add 20 mL of the treatment to each tube. For simple polymers, the treatment is 2% by weight of the polymer or control based on 100% of the active ingredient used. For dental floss formulations, weigh 8 g of each toothpaste and place it into a labeled 50 g round-bottom centrifuge tube. Add 24 g of deionized water to the tube (making the slurry ratio 1:3). Vortex for 1 minute to thoroughly mix and prepare a slurry free of toothpaste lumps. Centrifuge the slurry at 15,000 rpm for 15 minutes and use 20 mL of the supernatant as the treatment. Vortex the tube for 1 minute to completely suspend the HAP in the treatment, then centrifuge at 15,000 rpm for 15 minutes. After centrifugation, decant the supernatant and redistribute the pellets by adding 25 mL of water, vortex, centrifuge at 15,000 rpm for 15 minutes, and then decant—ensuring the pellets are broken up during vortexing. Repeat the washing cycle once more.

[0338] 3. Preparation of HAP for color analysis

[0339] The granules were vortexed in approximately 10 mL of water until completely suspended, and then filtered under vacuum onto a Millipore filter disc (membrane filter 4.5 tm, 47 mm catalog #HAWPO4700, Millipore Corporation, Bedford, Mass.). A control disc was prepared using approximately 200 mg of untreated, discolored HAP. The filter discs were then dried overnight in a flat position and then laminated.

[0340] 4. Color analysis of color-changing HAPs

[0341] Whitelight System: The HAP disks (untreated HAP controls and treated HAP samples) were placed in a stable sample holder. Color was measured using a digital camera with a lens equipped with a polarizing filter (Canon Inc. (Melville, NY) camera model CANON EOS 70D with a NIKON 55mm micro-NIKKOR lens with an adapter). The lighting system was provided by Dedo lamps (model DLH2) equipped with 150-watt, 24V bulbs (Xenophot model HLX64640), positioned approximately 30cm apart (measured from the center of the outer circular surface of the glass lenses through which the light passes, one to the other), and aimed at a 45-degree angle so that the light paths intersect on the HAP disks. Image analysis was performed using Whitelight with Ultragrab, Optimas, and Giant Imaging software.

[0342] 5. Control material

[0343] Common controls for single polymer PSRMs are water treated with tea and water not exposed to tea. Additionally, pyrophosphate and polyphosphate are used as internal controls.

[0344] 6. Results

[0345] The changes in L* (brightness), a* (red(+) / green(-)), b* (yellow(-) / blue(+)) and E (total color) are calculated as follows:

[0346]

[0347]

[0348]

[0349]

[0350] The results are reported as mean ΔL, Δa, Δb and / or ΔE relative to the negative control, as well as the percentage of antifouling (AL & AE).

[0351] In vitro thin-film tea rust model (iPTSM)

[0352] Tooth discoloration is a common and undesirable side effect of using stannous fluoride compositions. More efficient delivery of stannous fluoride by binding with polymeric mineral surfactants allows the improved stannous fluoride cleaning agents described herein to reduce tooth staining. Discoloration of the tooth surface caused by stannous fluoride can usually be determined clinically using staining indices such as the Lobene or Meckel indices described in the literature. To rapidly screen technologies that may help mitigate stannous-induced tooth discoloration, an in vitro experimental method was used, which provides a quantitative assessment of the preventive potential of stannous fluoride formulations for tooth discoloration. This method, called iPTSM (in vitro thin-film tea stain model), has shown good correlation with clinical observations.

[0353] The in vitro thin-film tea stain model (iPTSM) is a technique in which in vitro dental plaque biomass grows on a glass rod over three days from self-accumulated human saliva. The plaque biomass is treated with reagents to determine the potential degree of tooth discoloration associated with various reagents. The aim of this technique is to provide a simple and rapid method to determine whether a compound has a direct effect on the amount of dental plaque staining. This method uses dental plaque grown from self-accumulated human saliva on a polished glass rod, treated for 5 minutes, followed by 10 minutes of tea treatment. The in vitro model can be tested over five days, during which up to 12 treatments can be evaluated, including control treatments.

[0354] 1. Roughen the glass rod

[0355] A new glass rod (5mm × 90mm) was polished on a lathe from approximately 25mm away from the blunt end using silicon carbide paper with grits of 240, 320, 400, and 600. After the initial polishing, the rod was polished only with 600 grit paper before each test.

[0356] 2. Saliva collection and preparation

[0357] Saliva samples were collected daily from groups of 5-10 people using paraffin stimulation and refrigerated at 4°C until needed. The saliva was carefully collected (without pouring in the wax / mucus) and thoroughly mixed.

[0358] 3. Day 1: Clean the glass rod by ultrasonic treatment with diluted HCl, rinse, dry, and polish with 600-grit silicon carbide paper. Rinse the rod again with DI water and dry. Insert the rod into the holder, adjust the depth using the depth gauge on the treatment frame, and secure the rod with rubber O-rings.

[0359] In the afternoon, 7 mL of saliva with 0.1% wt% sucrose added was pipetted into a 16×75 mm test tube on an immersion rack. Sucrose was added to the saliva only on the first day. The rod holder was placed in a modified 37°C incubator designed to immerse the roughened glass rod into the test tube to a depth of 1.5 cm at a rate of 1 rpm. The rod was allowed to soak overnight. The complete design of the incubator is shown in Annex 1. The above-mentioned plaque growth medium and autoclave were prepared for use on the second day (saliva was added before use on the second day).

[0360] 4. Day 2: In the morning, add saliva to the plaque growth medium and mix thoroughly. Use a pipette to transfer 7 mL of plaque growth medium into a new 16 / 75 mm test tube in a new impregnation rack. Remove the old rack with the used test tube, place the new impregnation rack in the incubator, and impregnate the stick for at least six hours. Then, replace the stick with fresh saliva and impregnate overnight.

[0361] 5. Day 3: On the morning of the third day, pipette 10 mL of DI water into 17×100 mm test tubes in the second and third rows of the treatment rack. This is only for the tooth powder treatment. A rinsing solution may or may not be provided on the treatment rack. Pipe fresh accumulated saliva into the immersion rack and set aside. Begin preparing the tea by adding 550 mL to a glass beaker and microwave it for 10 minutes. At the end of the ten minutes, carefully remove the beaker from the microwave and place it in a magnetic stir bar to dissipate any excess water wick. Place 5 Lipton tea bags and a Celsius thermometer in the water and stir on a hot plate. The solution needs to be monitored to ensure it does not exceed 50°C when the tea treatment begins. While heating and mixing the tea treatment, prepare the tooth powder suspension (1 part tooth powder to 3 parts water, also known as a quarter dilution) and homogenize it for 30 seconds using a hand homogenizer. Centrifuge the suspension at 10,000 rpm for 15 minutes. Prepare a simple treatment of the rinse or active ingredient solution. Using a pipette, transfer 7 mL of 50°C tea solution into a separate saliva soaking rack. Add 5 mL of supernatant / rinse solution to a 16×75 mm glass tube in the first row of the treatment rack. Turn off the incubator soaking machine and remove the old saliva soaking rack. Remove all rod holders from the incubator and immerse the rods in the old saliva soaking rack to prevent drying. Treat one rod holder at a time by soaking it in the treatment rack for 5 minutes. If applicable, wash the rods by soaking them in a tube containing DI water on the treatment rack for 2×10 seconds. Place the rod holders on the prepared tea solution soaking rack and soak for 10 minutes. Repeat this process for all four rod holders, returning the holders to the soaking rack to prevent drying. Place the fresh saliva soaking rack into the incubator. After treatment / tea soaking, return the rods to the incubator and soak them in fresh saliva for at least 1 hour. Repeat the treatment cycle twice more using fresh treatment material / tea / saliva solution, for a total of 3 treatments per day. After the final treatment, return the stick to the incubator and soak it in fresh saliva overnight.

[0362] 6. Day 4: On the morning of the fourth day, turn off the incubator's immersion mechanism and remove the swab from the saliva. Allow the swab to dry, then weigh it to the nearest 0.1 mg. Record the weight and calculate the average weight of dried plaque biomass and the standard deviation. Place the swab into a clean, sterile, capped test tube containing 3 mL of 0.5 M KOH, seal the tube tightly, and digest overnight at 37°C.

[0363] 7. Day 5: On day 5, remove the rods from the incubator and allow them to cool. Vortex the glass rods to ensure all deposits are homogenized. Remove the rods from the test tubes, filter the solution through a 0.45 μm cellulose acetate syringe filter, and read the absorbance value of each rod at 380 nm on a spectrophotometer. Record the results and calculate the average absorbance value for each treatment, the standard deviation for each treatment, the average absorbance per mg of plaque, the standard deviation of the average absorbance per mg of plaque, and the percentage increase in absorbance per mg of plaque relative to the control using the following formulas.

[0364] Potential stain % = ((Test product Abs / biomass - Non-tin control Abs / biomass) / (High tin control Abs / biomass - Non-tin control Abs / biomass)) * 100

[0365] Example 1 - Synthesis of vinylphosphono-monophosphate (VPP) or [vinylphosphonic anhydride]

[0366]

[0367] Vinylphosphonic acid (VPA, 25.0 g, 231.5 mmol) and 300 mL DMF were added to a dry, single-necked round-bottom flask under nitrogen atmosphere and magnetically stirred. The resulting mixture was stirred at room temperature for 10 minutes to obtain a homogeneous solution. Tributylamine (64.3 g, 82.7 mL, 1.5 equivalents) was added and the mixture was stirred at room temperature for 30 minutes to obtain a turbid solution. Upon standing, the turbid solution separated into a small upper layer and a large lower layer.

[0368] 45.1 g (1.2 equivalents) of 1,1'-carbonyldiimidazole (CDI) was added to a 1000 mL dry single-necked round-bottom flask equipped with a second magnetic stirrer and a feeding funnel under nitrogen atmosphere, followed by 300 mL of DMF. The resulting mixture was stirred at room temperature for 10 minutes to obtain a homogeneous solution. Next, a tributylamine / vinylphosphonic acid solution was added to the CDI solution via the feeding funnel over approximately two hours, and the resulting mixture was stirred at room temperature overnight to obtain a pale yellow homogeneous solution.

[0369] H3PO4 (56.7 g, 2.5 equivalents) was added to a 2000 mL three-necked round-bottom flask equipped with a third magnetic stirrer and a feeding funnel under nitrogen atmosphere, followed by 400 mL of DMF. The resulting mixture was stirred at room temperature for 15 minutes to obtain a homogeneous solution. Tributylamine (128.7 g, 165.4 mL, 3.0 equivalents) was added to the mixture, and the mixture was stirred for 30 minutes to obtain a turbid solution. The solution from the second flask was added to this turbid solution via the feeding funnel over approximately 2 hours. The mixture was stirred at room temperature overnight to obtain a pale yellow turbid solution. The solvent in the solution was removed under vacuum (13 Torr) until a final temperature of approximately 70 °C, yielding 226 g of a pale yellow slurry.

[0370] The resulting product was dissolved in 450 ml of water, and the pH was adjusted to 10.5 with 50% NaOH (approximately 110 g) to obtain a two-phase system. The lower aqueous phase was separated from the upper organic phase. Water was removed from the aqueous phase and the mixture was heated to a final temperature of approximately 70 °C and a vacuum of 13 Torr to obtain 212 g of a yellow oil. The oil was heated to approximately 60 °C, and 300 ml of MeOH was added over 5 minutes to obtain a white precipitate. The MeOH was decanted from the precipitate, and the precipitate was then dried in an oven to 150.6 g. P-NMR analysis of the precipitate showed a phosphono-monophosphate product with 1.22 mol equivalents of orthophosphate, 0.29 mol equivalents of pyrophosphate, and 0.05 mol equivalents of the starting vinylphosphonic acid. ¹H-NMR analysis also showed the product, starting material, residual solvent, and approximately 0.4 mol equivalents of imidazole.

[0371] To further purify the precipitate, it was dissolved in 300 ml of water. 400 ml of MeOH was added over 30 minutes with rapid stirring. The resulting white precipitate was collected by filtration, washed with 100 ml of MeOH, and dried overnight to give 102.4 g. P-NMR analysis of the precipitate showed that it was primarily composed of orthophosphate with 0.06 mol equivalents of phosphono-monophosphate and 0.29 mol equivalents of pyrophosphate.

[0372] The solvent was removed from the aqueous MeOH filtrate until a final temperature of approximately 70°C and a pressure of 13 Torr were reached, yielding 81.94 g of a white solid. This solid was predominantly a vinylphosphono-monophosphate with 0.077 mol equivalents of vinylphosphonate and 0.091 mol equivalents of orthophosphate. Residual imidazole was extracted from this white solid by rapidly stirring the solid in 300 mL of MeOH at 40°C for 1 hour, filtering out the insoluble solid while the solution was hot, washing the resulting solid twice with 50 mL of room temperature MeOH, and drying the solid overnight under high vacuum at room temperature to obtain 54.8 g of a white powder.

[0373] P-NMR analysis of the final sample revealed a vinylphosphono-monophosphate with 0.05 mol equivalents of orthophosphate, 0.04 mol equivalents of pyrophosphate, and 0.02 mol equivalents of vinylphosphonate. ¹H-NMR analysis was consistent with the vinylphosphono-monophosphate product with 0.02 mol equivalents of imidazole and 0.09 mol equivalents of methanol. Using an internal standard, the total active material was calculated to be 80.8%, representing an 82% yield.

[0374] Example 2 - Combination of methyl-vinylphosphono-monophosphate (MVPP) or [methylvinylphosphonic anhydride] become

[0375]

[0376] Following the procedure of Example 1, and at a 1 / 14 molar scale-up ratio of Example 1, methyl-vinylphosphonic acid was used instead of vinylphosphonic acid. The final purity was 71.9%, and the yield was 31.2%.

[0377] Example 3 - (methylenephosphono-monophosphate)-methacrylate [or ((methacryloyloxy)methyl)phosphine] Synthesis of phosphoric anhydride

[0378]

[0379] In a dry, single-necked round-bottom flask with nitrogen under magnetic stirring, add (methylenephosphonic acid)-methacrylate (0.5 g, 2.77 mmol) and 10 ml DMF. Stir the mixture at room temperature for 10 minutes to obtain a homogeneous solution. Add tributylamine (0.77 g, 1.0 ml, 1.5 equivalents) and stir at room temperature for 30 minutes to obtain a homogeneous solution.

[0380] 1,1'-carbonyldiimidazole (CDI) (0.54 g, 1.2 equivalents) was added to a 10 mL dry single-necked round-bottom flask under nitrogen atmosphere and a second magnetic stirrer, followed by 10 mL of DMF. The resulting mixture was stirred at room temperature for 10 minutes to obtain a homogeneous solution. Next, a tributylamine / (methylenephosphonic acid)-methacrylate solution was added to the CDI solution over 1 minute, and the resulting mixture was stirred at room temperature for 4 hours to obtain a pale yellow homogeneous solution.

[0381] H3PO4 (0.68 g, 2.5 equivalents) was added to a 50 mL single-necked round-bottom flask under nitrogen atmosphere and magnetically stirred in a third chamber, followed by 15 mL of DMF. The mixture was stirred at room temperature for 15 minutes to obtain a homogeneous solution. Tributylamine (1.54 g, 2.0 mL, 3.0 equivalents) was added to the mixture, and the mixture was stirred for 30 minutes to obtain a turbid solution. The solution from the second flask was added to the turbid solution over 1 minute. The mixture was stirred at room temperature overnight to obtain a pale yellow turbid solution. The solvent in the solution was removed under vacuum (13 Torr) until a final temperature of approximately 65 °C, yielding 24.5 g of a pale yellow slurry.

[0382] The obtained product was dissolved in 100 ml of water, and the pH was adjusted to 8 with 1N NaOH (approximately 14 g) to obtain a milky white system. This system was then concentrated at 65 °C and 13 Torr to a light yellow slurry of 24.5 g. This slurry was added to 50 ml of MeOH over 5 minutes, resulting in a white precipitate. The MeOH was decanted to remove the precipitate, and then the MeOH was removed under vacuum to give 7.4 g of a gel-like solid. P-NMR analysis of this gel-like solid showed the expected phosphono-monophosphate product, with one equivalent of the product containing 0.55 molar equivalents of orthophosphate and 0.40 molar equivalents of the anhydride of the starting phosphonate.

[0383] Most of the gel-like solid was stirred in 50 mL of EtOH at room temperature for 1 hour to obtain an insoluble precipitate. The precipitate was filtered, washed twice with 10 mL of fresh EtOH, and dried under an O / N hood to 238 mg of solid. P-NMR of the solid showed a product doublet (1.1 / 1.0 ppm and -8.4 / -8.5 ppm) with a ratio of 100:70:10, phosphate (2.04 ppm), product anhydride (2.9 ppm), and other trace unknowns. ¹H-NMR showed that the dried solid was consistent with the product containing approximately 12 mol% imidazole, residual EtOH, and other trace unknowns.

[0384] Example 4 - (ethylphosphono-monophosphate) (butyl)acrylamide or [(2-(N-butylacrylamide)ethyl] Synthesis of [phosphonic anhydride]

[0385]

[0386] To a dry, 25 mL double-necked round-bottom flask with magnetic stirring, n-butylamine (6.3 mL, 63 mmol) was added and heated to 78 °C under dry nitrogen. Diethylvinylphosphonate (1.0 mL, 6.3 mmol) was added and stirred overnight. The resulting mixture was rotary evaporated at approximately 45 °C and 20 mbar to recover 1.38 g of high-purity diethylethylphosphonate butylamine by P-NMR (92% recovery).

[0387] To a magnetically stirred, dry, double-necked round-bottom flask, add 1.1 g (4.6 mmol) of diethylethylphosphonic acid butylamine, 2 mL of dichloromethane, and 6 mL of 1N NaOH. Stir the mixture and cool it in an ice bath. Over 30 minutes, add dropwise a mixture of 2 mL of dichloromethane and 0.368 g of acryloyl chloride to the flask. Dilute the mixture with 10 mL of dichloromethane, extract it in a separatory funnel with 2 × 25 mL of 1N HCl and 1 × 25 mL of saturated NaCl, and wash the aqueous phase with 10 mL of dichloromethane. Dry the combined organic phases over anhydrous sodium sulfate and filter. Remove the solvent by rotary evaporation at approximately 35 °C to give 0.84 g (72%) of the product.

[0388] The entire batch was dissolved in 4 mL of dichloromethane in a magnetically stirred 100 mL double-necked flask under dry nitrogen in an ice bath. Then, over 20 minutes, a mixture of 1 mL dichloromethane and 2 mL trimethylbromosilane was added to remove the ethyl ester groups from the product. Another 1 mL of dichloromethane was then added, followed by the mixture of 1 mL dichloromethane and 1 mL trimethylbromosilane. After 2 hours, 30 mL of MeOH was added and the mixture was stirred for 10 minutes, followed by the addition of a 1 mL dichloromethane solution containing 0.21 mg of butylated hydroxytoluene. Volatiles were removed by rotary evaporation at approximately 40 °C. The product was purified by dissolving in 50 mL of dichloromethane and extracting with a mixture of 25 mL 0.1 N NaOH and 25 mL 1 N NaOH. The aqueous phase was extracted a second time with 25 mL of dichloromethane, acidified to pH 1 with 1 N HCl, and then rotary evaporated to near dryness. The resulting residue was diluted with 50 mL of EtOH and rotary evaporated to near dryness three times to remove water. The residue was then diluted with 10 mL of pentane and evaporated to near dryness twice to remove residual EtOH. The final recovery was close to quantitation.

[0389] The addition of phosphono-phosphate groups was performed as in Example 3. The purification procedure was slightly modified. The crude reaction mixture was extracted with diethyl ether (1 volume equivalent), and the solution was removed under vacuum at 30°C to 35°C. The residue was dissolved in 25 mL of water, and the pH was adjusted to 7 with 1N NaOH. The water was then removed under vacuum at 40°C to 45°C, leaving a liquid residue. Next, 100 mL of methanol was added to the residue, resulting in a precipitate. The precipitate was collected and dried under vacuum to give approximately 9.1 g of 80% active substance, as determined by P-NMR.

[0390] Example 5 - (4-vinylbenzyl)phosphono-monophosphate or [(4-vinylbenzyl)phosphonic anhydride] become

[0391]

[0392] (4-vinylbenzyl)phosphonic acid (4.0 g, 20.2 mmol) and 20 mL DMF were added to a 50 mL dry, single-necked round-bottom flask under nitrogen atmosphere and magnetically stirred. The resulting mixture was stirred at room temperature for 10 minutes to obtain a homogeneous solution. Tributylamine (5.6 g, 7.2 mL, 1.5 equivalents) was added and the mixture was stirred at room temperature for 30 minutes to obtain a homogeneous solution.

[0393] 4.9 g (1.2 equivalents) of 1,1'-carbonyldiimidazole (CDI) was added to a 10 mL dry single-necked round-bottom flask under nitrogen atmosphere with a second magnetic stirrer, followed by 25 mL of DMF. The resulting mixture was stirred at room temperature for 10 minutes to obtain a homogeneous solution. Next, a tributylamine / (4-vinylbenzyl)phosphonic acid solution was added to the CDI solution over 1 minute, and the resulting mixture was stirred at room temperature for 4 hours to obtain a pale yellow homogeneous solution.

[0394] H3PO4 (5.94 g, 3.0 equivalents) was added to a 100 mL single-necked round-bottom flask under nitrogen atmosphere and magnetically stirred in a third chamber, followed by 25 mL of DMF. The resulting mixture was stirred at room temperature for 15 minutes to obtain a homogeneous solution. Tributylamine (13.1 g, 16.8 mL, 3.5 equivalents) was added to the mixture, and the mixture was stirred for 30 minutes to obtain a turbid solution. The solution from the second flask was added to the turbid solution over 1 minute. The mixture was stirred at room temperature overnight to obtain a pale yellow solution. The solvent in the solution was removed under vacuum (13 Torr) until a final temperature of approximately 65 °C, yielding 49.8 g of a pale yellow slurry.

[0395] The resulting product was added to 30 ml of water, and the pH was adjusted to 8.5 with 1 N NaOH (approximately 127 g), yielding a milky white system. This system was then concentrated at 65 °C and 13 Torr to a light yellow slurry of 58.2 g. This slurry was added to 40 ml of MeOH over 20 minutes, resulting in a white precipitate. P-NMR analysis of this paste showed it to be approximately 95% phosphate. The MeOH was decanted to remove the precipitate, and then the MeOH was removed again, yielding 7.23 g of a white paste. P-NMR analysis of this white paste showed the expected phosphono-monophosphate product, with one equivalent of the product containing 0.16 mol equivalents of orthophosphate, 0.05 mol equivalents of pyrophosphate, 0.25 mol equivalents of the anhydride of the starting phosphonate, and 0.065 mol equivalents of the starting phosphonate.

[0396] Most of the white paste was stirred in 75 mL of MeOH at room temperature for 1 hour. Part of the paste dissolved, while a portion remained undissolved. The undissolved portion was filtered and washed twice with 10 mL of fresh MeOH. The resulting solid was dried under high vacuum (O / N) to give 1.97 g of solid. P-NMR analysis of the solid showed a product doublet (1.1 / 1.0 ppm and -8.4 / -8.5 ppm) with a ratio of 100:70:10, phosphate (2.04 ppm), product anhydride (2.9 ppm), and other trace unknowns. ¹H-NMR analysis showed that the dried solid was consistent with the product containing approximately 12 mol% imidazole, residual EtOH, and other trace unknowns. The final solid yield was 23.7% of the theoretical value.

[0397] Example 6 - (bis(methylenephosphonate anhydride)aminopropyl)-methacrylate polymer or [4-(3-(methacryloyloxy)propyl)-1,4,2,6-oxonitridine-2,6-bis(alkoxide)2,6-dioxide poly Synthesis of [compounds]

[0398]

[0399] In a dry, three-necked round-bottom flask with magnetic stirring under nitrogen atmosphere, 3.0 g (9.06 mmol) of bis(methylenephosphonic acid)aminopropyl)-methacrylate and 100 mL of DMF were added. The mixture was stirred at room temperature for 10 minutes to obtain a homogeneous solution. Tributylamine (5.03 g, 6.5 mL, 3.0 equivalents) was added and the mixture was stirred at room temperature for 30 minutes to obtain a homogeneous solution.

[0400] 2.2 g (1.5 equivalents) of 1,1'-carbonyldiimidazole (CDI) was added to a 100 mL dry single-necked round-bottom flask equipped with a second magnetic stirrer and a feeding funnel under nitrogen atmosphere, followed by 40 mL of DMF. The resulting mixture was stirred at room temperature for 10 minutes to obtain a homogeneous solution. Over approximately one hour, the CDI solution was added to a first flask via the feeding funnel, and the resulting mixture was stirred overnight at room temperature, then allowed to stand for one week to obtain a white precipitate. The precipitate was collected by filtration, slurried in 100 mL of water, and the pH was adjusted to approximately 9 with 1 N NaOH to obtain a turbid solution. This solution was evaporated overnight under flowing air to 2.4 g. ¹H NMR and ¹P NMR results showed that the precipitate was a polymer containing some monomers. ¹P NMR showed a polymer target anhydride (12–13 ppm) and an initial diacid (6–7 ppm) in a ratio of 36:53:11, as well as a monomer peak (11.8–12 ppm). Most of the precipitate was sonicated in 100 mL of water for 1 hour to obtain a turbid solution. This turbid solution was filtered through a 250 mL Stericup Durapore filter with a 0.22 μm PVDF filter plate to obtain a clear solution. This was added to a 250 mL volume and purified by dialyzing in a Thermo Scientific Slide-A-Lyzer dialysis flask (2K MWCO, 250 mL) with 5 gallons of RO water (pH adjusted to 8.5 with 1N NaOH) for 7 days. After freeze-drying, 1.29 g of white solid (17-DF-5835-5) was obtained. P-NMR showed a broad anhydride peak at 12–13 ppm and a diacid peak at 6.4–7.4 ppm, with a molar ratio of 39.2:60.8. The calculated activity was 87.8% polymer and 12.2% water / inactive substance.

[0401] Example 7 - (ethylphosphono-monophosphate)-methacrylate or [(2-(methacryloyloxy)ethyl)phosphine Synthesis of phosphoric anhydride

[0402]

[0403] In a dry, single-necked round-bottom flask under nitrogen atmosphere and with magnetic stirring, add (ethylphosphonic acid)-methacrylate (3 g, 15.5 mmol) and 30 ml DMF. Stir the mixture at room temperature for 10 minutes to obtain a homogeneous solution. Add tributylamine (4.3 g, 5.5 ml, 1.5 equivalents) and stir at room temperature for 30 minutes to obtain a homogeneous solution.

[0404] 3.76 g (1.5 equivalents) of 1,1'-carbonyldiimidazole (CDI) was added to a 25 mL dry single-necked round-bottom flask under nitrogen atmosphere and a second magnetic stirrer, followed by 20 mL of DMF. The resulting mixture was stirred at room temperature for 10 minutes to obtain a homogeneous solution. Next, a tributylamine / (ethylphosphonic acid)-methacrylate solution was added to the CDI solution, and the resulting mixture was stirred at room temperature for 4 hours to obtain a pale yellow homogeneous solution.

[0405] H3PO4 (4.55 g, 3.0 equivalents) was added to a 500 mL single-necked round-bottom flask under nitrogen atmosphere with a third magnetic stirrer, followed by 25 mL of DMF. The resulting mixture was stirred at room temperature for 15 minutes to obtain a homogeneous solution. Tributylamine (12 g, 15.4 mL, 4.2 equivalents) was added to this mixture, and the mixture was stirred for 30 minutes to obtain a turbid solution. The solution from the second flask was added to this turbid solution within 1 minute. After stirring for about 1 hour, a white precipitate began to form. The result was stirred overnight at room temperature to form another precipitate. P-NMR showed a product peak with a ratio of 100:427:12:15 (7.2 / 7.3 ppm and -8.75 / -8.84 ppm), phosphonate (2.14 ppm), product anhydride (8.9 ppm), and pyrophosphate (-9.26 ppm).

[0406] Under stirring, 200 mL of diethyl ether was added to the crude Rx solution (approximately 90.7 g) over 30 minutes, resulting in a white precipitate. This precipitate was collected by filtration, washed with additional ether, and dried under vacuum (<1 Torr) overnight at room temperature, yielding 7.85 g of white precipitate. Under stirring, another 200 mL of diethyl ether was added to the resulting filtrate over 30 minutes, resulting in a two-layer system with a free-flowing top layer and a lower viscous oily layer. The top layer was decanted, and the lower oily layer was dried under vacuum (<1 Torr) overnight at room temperature, yielding 2.33 g of waxy solids. Under stirring, another 400 mL of ether was added to the decanted layer over 30 minutes, resulting in a turbid solution. The turbid solution was placed in a freezer (-15°C) overnight, yielding a clear, free-flowing top layer and a lower viscous oily layer. The top layer was decanted, and the lower oily layer was dried under vacuum (<1 Torr) at room temperature overnight for 1 hour, yielding 1.19 g of waxy solids.

[0407] H-NMR showed that the white precipitate was a mixture of product:imidazolium:tributylamine with a molar ratio of 100:1150:220, while P-NMR showed that the product was a mixture of product:phosphate:pyrophosphate with a molar ratio of 100:625:35.

[0408] ¹H NMR showed that the first waxy solid was a mixture of imidazole and tributylamine in a molar ratio of 100:230:170. ¹²P NMR showed a mixture of phosphates in a molar ratio of 100:89.

[0409] ¹H-NMR showed that the second waxy solid was a mixture of imidazole and tributylamine in a molar ratio of 100:100:150. ¹²P-NMR showed a mixture of phosphates in a molar ratio of 100:79.

[0410] The waxy solids were combined and dissolved in 50 mL of deionized water. The pH of the resulting solution was adjusted from 2.9 to 8.6 with 19.3 g of 1N NaOH, resulting in a turbid solution. This solution was extracted once with 50 mL of diethyl ether. The pH of the resulting aqueous layer was adjusted from 7.5 to 8.0 with another 1N NaOH. The residual ether was removed from the aqueous layer by rotary evaporation at room temperature and 20 Torr. Water was removed from the aqueous layer by freeze-drying to give 2.61 g of brownish-red solid.

[0411] The results of H-NMR and P-NMR show a mixture of product:imidazolium:NBut3 with a molar ratio of 100:160:50. P-NMR shows a mixture of product:phosphate with a molar ratio of 100:101.

[0412] The brownish-brown solid was stirred in 50 mL of MeOH for 30 minutes to obtain an insoluble solid. The solid was collected by filtration, washed with 2 × 10 mL of fresh MeOH, and dried overnight at room temperature under <1 Torr to give 1.79 g of a milky-white solid. The 1H-NMR results were consistent with the product containing about 1 mol% imidazole. LC-MS showed a mass consistent with the protonated form of M+H at 273. The 1H-NMR of the methanol extract showed that it was mainly composed of imidazole containing about 3 mol% of the product.

[0413] The activity was calculated by combining H-NMR and P-NMR and found to be 74.4%.

[0414] Example 8 - (propylphosphono-monophosphate)-methacrylate or [(3-(methacryloyloxy)propyl)phosphine Synthesis of phosphoric anhydride

[0415]

[0416] Following the procedure of Example 7, 5.5 g (26.4 mmol) of (propylphosphonic acid)-methacrylate was used instead of (ethylphosphonic acid)-methacrylate. All reagents were scaled up to maintain the same molar equivalent. After final evaporation, 5.17 g of emulsion solid was collected, showing an activity of 67.8%.

[0417] Example 9 - (ethylphosphono-monophosphate)-acrylamide or [(2-acrylamidoethyl)phosphonic anhydride] Synthesis

[0418]

[0419] Following the procedure of Example 5, (acryloylamino)ethylphosphonic acid (37 mmol) was used instead of vinylbenzylphosphonate to form a crude yellow solution, with all reagents increased in the same molar ratio as in Example 5.

[0420] The purification process for the crude solution was modified from Example 5. DMF was partially removed at room temperature with flowing dry nitrogen, yielding 46.8 g of a viscous yellow oil. This oil was dissolved in approximately 75 mL of water, and the pH was adjusted to 8 by adding 1 N NaOH over 20 minutes. A small organic layer of 9.4 g of tributylamine was formed and decanted. The aqueous phase was further dried to 147.5 g under flowing dry nitrogen, and then 220 mL of MeOH was added over 30 minutes, resulting in a white precipitate. The precipitate was filtered, and the resulting filtrate was dried to give 22.7 g of a brown paste, the pNMR of which showed that it was mostly product. The brown paste was slurried in 100 mL of EtOH at room temperature with vigorous stirring for 6 hours. A solid was formed and collected by filtration, washed with 2 × 25 mL of fresh EtOH, and dried overnight at <1 Torr to give 10.94 g of a brown solid. NMR indicated that the solid contained 69% phosphono-monophosphate product.

[0421] Example 10 - (methylenephosphono-monophosphate)-acrylate or [((acryloyloxy)methyl)phosphonic acid phosphate] Synthesis of anhydride

[0422]

[0423] Following the procedure in Example 3, (methylenephosphonic acid)-acrylate was used instead of (methylenephosphonic acid)-methacrylate.

[0424] Example 11 - (ethylphosphono-monophosphate)-vinyl ether or [(2-(ethyleneoxy)ethyl)phosphonic anhydride] Synthesis

[0425]

[0426] Diethyl(2-(ethoxy)ethyl)phosphonate (3 g, 14.4 mmol) and 30 mL of CH₂Cl₂ were added to a dry, diaphragm-sealed, nitrogen-purged, magnetically stirred 250 mL flask and cooled to 0–5 °C. Trimethylbromosilane (5.7 mL, 43.2 mmol, 3.0 equivalent) was added to the flask over 1 minute. After addition, the solution was stirred at room temperature for 2 hours, and the solvent was removed at 30 °C and <1 Torr, yielding 4.59 g of a yellow oil. 15 g of triethylamine, 30 g of MeOH, and 60 mg of phenothiazine (inhibitor) pre-cooled on dry ice and acetone were added to this oil. The mixture was heated to room temperature with continuous stirring and then vacuum-treated at room temperature for 1 hour to remove the solvent and volatiles, yielding 3.84 g of a viscous, turbid, yellow oil. P-NMR and H-NMR were consistent with those of the amine monotriethylamine salt.

[0427] Following the procedure of Example 7, (ethylphosphono-monophosphate)-vinyl ether was produced and purified, yielding 4.04 g of a brownish-yellow solid after methanol extraction. The ¹H-NMR results were consistent with the product containing approximately 5 mol% imidazole. The ¹H-NMR showed a consistent ratio of phosphono-monophosphate to residual phosphate at a ratio of 100:112. LC-MS revealed a mass consistent with the M+H protonated form at 231. The activity was calculated by combining ¹H-NMR and ¹H-NMR and found to be 52%.

[0428] Example 12 - (ethylphosphono-monophosphate)-acrylate or [(2-(acryloyloxy)ethyl)phosphonic acid phosphate] Synthesis of anhydride

[0429]

[0430] To a dry, magnetically stirred 1L three-necked round-bottom flask, add dimethyl (24.7 g, 16 mmol) phosphonate, triethylamine (17.8 g, 176 mmol), and 400 mL of CH₂Cl₂, and cool to 0–5 °C. Over 1.5 hours, while maintaining the reaction temperature at 0–5 °C, add 100 mL of a CH₂Cl₂ solution of acryloyl chloride (14.95 g, 16.51 mmol). After the addition is complete, maintain the reaction temperature at 0–5 °C for another 2 hours, then raise the temperature to room temperature and stir overnight.

[0431] The resulting light brown turbid solution was extracted with 2 × 200 mL of deionized water. The oil layer was dried over anhydrous MgSO4 and then filtered. The solvent in the filtrate was removed, yielding 30.5 g of a brown oil. The results of H-NMR, C-NMR, and P-NMR were consistent with those of the first intermediate (ethyl, dimethylphosphonic acid)-acrylate. The yield was 91.4%.

[0432] The above-mentioned brown oily substance was placed into a 500 mL three-necked round-bottom flask equipped with 250 mL of dichloromethane and a dry magnetic stirrer. The flask and its contents were cooled to 10 °C, and 67.3 g (3 equivalents) of trimethylbromosilane was added over 30 minutes. The flask was then heated to room temperature and stirred overnight. The solvent in the resulting solution was removed at 30 °C, and then stirred overnight under high vacuum (<1 Torr) to give 37 g of a light oily substance. 200 mL of methanol was added to this oily substance over 10 minutes at room temperature, and then stirred for 3 hours at room temperature. The solvent in the resulting solution was removed at 30 °C, and then stirred overnight under high vacuum (<1 Torr) to give 26.1 g of a viscous brownish-red oily substance. The ¹H NMR and ¹P NMR were consistent with the product. The yield was 98.9%.

[0433] Following the procedure of Example 5, (acryloyloxy)ethylphosphonic acid was used instead of vinylbenzylphosphonate to form a crude yellow solution. P NMR and H NMR showed a desired product yield of 72%.

[0434] Example 13 - Synthesis of Mixed Vinylphosphono-phosphates

[0435]

[0436] Following the procedure of Example 1, at a 1 / 12 molar scale-up scale of Example 1, pyrophosphate was substituted for phosphoric acid. After removing the DMF solvent to obtain a yellow oily substance and adding 1N NaOH, the mixture was bubbled overnight under nitrogen and 24.1 g of white solid was collected. PNMR indicated that the sample contained vinylphosphono-pyrophosphate (VPPP), vinylphosphono-monophosphate, starting material, starting material anhydride, phosphate, pyrophosphate, and triphosphate. The ratio of vinylphosphono-pyrophosphate to vinylphosphono-monophosphate was 1:1.7.

[0437] Example 14 Synthesis of Vinyl sulfonate (VSME)

[0438]

[0439] 250 mL of methanol was added to a 500 mL dry three-necked round-bottom flask equipped with a feeding funnel and thermometer and a magnetic stirrer under nitrogen atmosphere, and the flask was cooled to 0 °C. 2-Chloroethanesulfonyl chloride (Aldrich) was added to the flask over 15 minutes; no exothermic reaction was observed. Next, 25% NaOMe / MeOH (Aldrich) was added at a controlled rate over 2 hours while maintaining the temperature at approximately 0 °C. A white precipitate (NaCl) formed during the addition. The result was stirred at 0 °C for another hour, then heated to room temperature and stirred overnight. The precipitate was removed by filtration, and the solvent in the filtrate was removed, yielding 20.33 g of a white gel. This gel was slurried in 200 mL of CH₂Cl₂ for 1 hour. The result was filtered, and the solvent in the filtrate was removed, yielding 9.47 g of a brownish-red oily substance.

[0440] 1 H-NMR and 13 C-NMR showed a mixture of the expected product VSMS and methyl 2-methoxyethane-1-sulfonate in a 3:0.6 ratio, with the product comprising 79.8% by weight. H-NMR also showed an acid peak at approximately 10 ppm. Testing of 0.05 g of the brownish oily substance in 1 ml of water with litmus revealed a pH of approximately 1.

[0441] Dissolve 8.8 g of a brownish-red oily substance in 100 ml of CH2Cl2 and stir with 5 g of sodium bicarbonate. Filter the resulting solution and remove the solvent from the filtrate to obtain 8.02 g of a pale yellow, clear oily substance.

[0442] A test of 0.05 g of a clear, yellow oily substance in 1 mL of litmus water showed a pH of approximately 6-7. The same ratio of VSME to methyl 2-methoxyethane-1-1 sulfonate yielded 79.8% active substance.

[0443] Example 15 Synthesis of Sodium Vinylbenzylsulfonate

[0444]

[0445] 9.5 g of sodium sulfite (75.5 mmol) and 100 mL of water were added to a 250 mL dry three-necked round-bottom flask equipped with a heating mantle, feeding funnel, and reflux condenser and magnetically stirred. The resulting solution was heated to 100 °C under nitrogen. Next, a 15 mL solution of 4-vinylbenzyl chloride (9.6 g, 62.9 mmol) in acetone was added over 30 minutes. The mixture was refluxed for 12 hours, cooled to room temperature, and allowed to stand overnight without precipitation. Next, 100 mL of acetone was added with rapid stirring to obtain a paste-like lower layer. The water / acetone supernatant was decanted. The paste was washed with 25 mL of fresh acetone and then decanted. The paste was dried overnight under vacuum at 14 Torr at room temperature to give 8.5 g of solid.1 ¹H-NMR showed that the dried layer was mainly a homopolymer. The water / acetone decanting layer was evaporated to about 75 ml, yielding a white precipitate. The precipitate was collected by filtration, washed with 2 × 25 ml of acetone, and dried overnight under vacuum at 14 Torr and room temperature to give 2.14 g of solid.

[0446] The second precipitate 1 H-NMR is consistent with the monomer product, which is close to 100% active.

[0447] Example 16 Copolymerization of vinylphosphonic acid (VPA) and sodium vinyl sulfonate (SVS)

[0448]

[0449] In a round-bottom flask, VPA (2.0 g, 18.5 mmol) and SVS (25% aqueous solution, 7.9 g, 15.2 mmol) were added, with an initial molar ratio of SVS to VPA of 45 to 55. The flask was purged with nitrogen for 15 minutes and heated to 90 °C. Separately, two separate aqueous solutions were prepared containing 2,2'-azobis(2-methylpropanediamine) dihydrochloride (AAPH, Aldrich, 25.8 mg in 1.2 mL of water, 0.3 mol% relative to the total monomers added) and 1-octylthiol (CTA, Aldrich, 55.6 mg in 1.2 mL of water, 1.1 mol% relative to the total monomers added). These two solutions were then added to a heated stirred flask containing the monomers every 30 minutes over a 6-hour period. After the final addition, the resulting solution was stirred overnight at 90 °C.

[0450] Running the crude reaction solution 1 H-NMR and 31 P-NMR. Typical monomer conversion of 95% to 99% was observed, with broad P polymer peaks at approximately 31 ppm for the phosphonate group.

[0451] The crude reaction solution was diluted in water to 1% by weight of polymer, and the pH was adjusted to 6. These solutions were then dialyzed against reverse osmosis water for 5 to 7 days using a dialysis membrane with a molecular weight cutoff of 2K.

[0452] The water in the resulting solution was removed under vacuum to obtain a white to milky white solid, which was then further dried overnight in a vacuum oven to obtain 2.74 g of solid.

[0453] The phosphonate content in the polymer was determined by preparing an NMR sample in D2O solution using purified polymer and trimethyl phosphate (TMP). (Run) 1 H and 31Phosphonate content was calculated using P-NMR based on the H and P peaks of the internal standard (TMP) relative to the polymer and water peaks. Based on this analysis, the polymer contained 55.7 mol% repeating units derived from SVS and 44.3 mol% repeating units derived from VPA. The water content was calculated to be 9.6 wt%. The total monomer recovery in the polymer after dialysis was calculated to be 57 mol%.

[0454] Example 17: Copolymerization of vinylphosphonic acid and sodium vinyl sulfonate (SVS)

[0455] The procedure of Example 16 was repeated for VSA and VPA with different starting ratios. The polymer compositions obtained with different starting ratios and total yields (including Example 16) are shown in Table 1 below. Polymer molecular weights were calculated using a Wyatt gel permeation chromatography (GPC) system with a Polymer Standard Service (PSS) MCX 1000A column and both a Wyatt HELEOS II light scattering detector and a Wyatt Optilab differential refractive index detector, using the in-house Wyatt Astra 6 software.

[0456]

[0457] Table 1

[0458] Example 18 Copolymerization of vinylphosphonic acid (VPA) and acrylic acid (AA)

[0459]

[0460] The procedure in Example X was repeated using a 1.5 mL aqueous solution of 19 mmol VPA as the initial feed. Every 30 minutes, 28.5 mmol acrylic acid (0.3 mL) dissolved in 1.6 mL of water, along with 0.1 mL of AAPH and CTA, was added. An additional 3 mL of water was added midway through the addition. The final polymer collected after dialysis was 2.87 g and was found to be 30% phosphonate and 70% acrylate.

[0461] Example 19: Copolymerization of vinylphosphono-monophosphate (VPP) and sodium vinyl sulfonate (SVS)

[0462]

[0463] VPP (Example 1, 2.05 g active material, 8.87 mmol) and SVS (25% aqueous solution, 3.77 g, 7.25 mmol) were placed in a round-bottom flask with an initial molar ratio of SVS to VPP of 45 to 55. The top space of the flask was purged with flowing nitrogen for 15 minutes. The flask was sealed and heated to 60°C, at which point ammonium persulfate (APS, Aldrich, 183 mg, 5% relative to total monomers) was added to 0.50 mL of water. The result was stirred at 60°C for 24 hours.

[0464] Running the crude reaction solution 1 H-NMR and 31 P-NMR. Typical monomer conversions of 95% to 99% were observed, with broad P-polymer peaks for phosphonate groups at approximately 18 ppm to 23 ppm, and broad P-polymer peaks for phosphate groups bonded to phosphonate groups at -6 ppm to -10 ppm.

[0465] The crude reaction solution was diluted in water to 1% by weight of polymer, and the pH was adjusted to 8.5. These solutions were then dialyzed against reverse osmosis water for 5 to 7 days using a dialysis membrane with a molecular weight cutoff of 2K.

[0466] Water was removed from the product by freeze drying to obtain 2.22 g of white solid.

[0467] The phosphonate content in the polymer was determined by preparing an NMR sample in D2O solution using purified polymer and trimethyl phosphate (TMP). (Run) 1 H-NMR and 31 Phosphonate content was calculated using p-NMR, based on the H and P peaks of the internal standard (TMP) relative to the polymer peak and water peak. P-NMR showed a broad phosphonoyl-phosphate peak with a ratio of approximately 1:1 at approximately 18–23 ppm and -6–10 ppm, and a phosphonate peak at approximately 26–28 ppm. The phosphonate content was calculated based on the peaks at 18–23 ppm and 26–28 ppm. 31 P-NMR area, phosphonyl-phosphate:phosphonate ratio 94.9:5.1. Based on this analysis, the polymer contains 56 mol% repeating units from SVS, 42 mol% repeating units from VPP, and 2 mol% repeating units from VPA. Water content is calculated to be 23% by weight. Total monomer recovery in the polymer after dialysis is calculated to be 65 mol%.

[0468] Example 20: Copolymerization of vinylphosphono-monophosphate (VPP) and sodium vinyl sulfonate (SVS)

[0469] The process of Example 19 was repeated for VSA and VPP with different starting ratios. The polymer compositions (including Example 19) obtained with different starting ratios and total yields are shown in Table 2 below.

[0470]

[0471] Table 2

[0472] Example 21: Copolymerization of methyl-vinylphosphono-monophosphate (MVPP) and sodium vinyl sulfonate (SVS)

[0473]

[0474] Using MVPP (Example 2) instead of VPP, and with the ratio of MVS to MVPP being 55 to 45, the process of Example 19 was repeated, but with the following changes.

[0475] During the 24-hour run, the MVPP monomer conversion by NMR was approximately 75%. Therefore, an additional 3 mol% APS aqueous solution was added, and the reaction mixture was stirred at 60°C for an additional 24 hours. At this point, the MVPP monomer conversion was approximately 95%.

[0476] Dialysis and freeze-drying were performed as described in Example 19.

[0477] Based on this NMR analysis, the polymer contained 62 mol% repeating units derived from SVS, 35 mol% repeating units derived from MVPP, and 3 mol% repeating units derived from methylvinylphosphonic acid. The water content was calculated to be 10.3 wt%. The total recovery of monomers in the polymer after dialysis was calculated to be 65 mol%.

[0478] Example 22 Homopolymerization of vinylphosphono-monophosphate

[0479]

[0480] A 25 mL round-bottom flask was filled with 6 mL of an aqueous solution of VPP (Example 1, 16.4 mmol) and sodium bicarbonate (0.69 g, 8.2 mmol), and purged with nitrogen for 15 minutes. Ammonium persulfate (APS, 186.6 mg) was dissolved in 0.50 mL of water and added to the mixture. The resulting solution was stirred at 60 °C for 6 hours. At this point, NMR showed 25% monomer content. Another 0.50 mL aqueous solution of 186.6 mg APS was added. The mixture was stirred at 60 °C for a total of 24 hours. NMR showed no remaining monomer.

[0481] The crude reaction solution was diluted with 500 mL of water to obtain a pH of 8.7. This solution was then dialyzed against reverse osmosis water adjusted to pH 8.5 using a dialysis membrane with a molecular weight cutoff of 2K.

[0482] Water was removed from the resulting solution under vacuum to obtain a white to milky white solid, which was further dried overnight in a vacuum oven to give 2.8 g of solid. P-NMR showed only VPP and no VPA. The product was 91% by weight of polymer, with the remainder being water and impurities. The total recovery of monomers in the polymer after dialysis was calculated to be 58 mol%.

[0483] Example 23 Vinylphosphono-monophosphate (VPP) and sodium 2-acryloylamino-2-methylpropanesulfonate (AMPS) copolymer

[0484]

[0485] VPP (Example 1, 6.55 mmol) and 2 mL of water were placed in a round-bottom flask, and the top space of the flask was purged with flowing nitrogen for 15 minutes. The flask was sealed and heated to 60°C and held for 15 minutes to obtain a homogeneous solution. Ammonium persulfate (APS, 149.3 mg) was dissolved in 1.2 g of water. Over a total of 6 hours, 0.1 mL of APS solution and 0.206 mL of AMPS (3 g 50% solution, 6.55 mmol) were added to the reaction every 30 minutes. The result was stirred at 60°C for 24 hours.

[0486] The crude reaction solution was diluted with 250 mL of water and the reverse osmosis water was dialyzed for 6 days using a dialysis membrane with a molecular weight cutoff of 2K.

[0487] Water was removed from the product by freeze drying to obtain 2.66 g of white solid.

[0488] The phosphonate content in the polymer was determined by preparing an NMR sample in D2O solution using purified polymer and trimethyl phosphate (TMP). (Run) 1 H-NMR and 31 Phosphonate content was calculated using p-NMR, based on the H and P peaks of the internal standard (TMP) relative to the polymer peak and water peak. P-NMR showed a broad phosphonoyl-phosphate peak with a ratio of approximately 1:1 at approximately 18–23 ppm and -6–10 ppm, and a phosphonate peak at approximately 26–28 ppm. The phosphonate content was calculated based on the peaks at 18–23 ppm and 26–28 ppm. 31 P-NMR area, phosphonyl-phosphate:phosphonate ratio 98:2. Based on this analysis, the polymer contains 64.2 mol% repeating units from AMPS, 35.1 mol% repeating units from VPP, and 0.7 mol% repeating units from VPA. Water content is calculated to be 13.3% by weight.

[0489] Example 24 Copolymerization of vinylphosphono-monophosphate (VPP) and potassium 3-sulfopropyl acrylate (SPA)

[0490]

[0491] Following the procedure of Example 23, SPA (Aldrich) is used instead of AMPS.

[0492] The product was freeze-dried to give 2.04 g of white solid.

[0493] Based on NMR analysis, the polymer contains 62 mol% repeating units from SPA, 36 mol% repeating units from VPP, and 2 mol% repeating units from VPA. The water content is calculated to be 15.5% by weight.

[0494] Example 25: Copolymerization of VPP and Acrylamide

[0495]

[0496] VPP (Example 1, 9.9 mmol) and 3 mL of water were placed in a round-bottom flask, and the top space of the flask was purged with flowing nitrogen for 15 minutes. The flask was sealed and heated to 60°C and held for 15 minutes to obtain a homogeneous solution. Ammonium persulfate (APS, 225.9 mg) was dissolved in 1.2 g of water. Acrylamide (Aldrich, 9.9 mmol) was dissolved in 1.5 g of water every 30 minutes, and 0.1 mL of APS solution and 0.125 mL of acrylamide solution were added to the reaction over a total of 6 hours. The resulting product was stirred at 60°C for 24 hours. Progress was monitored by NMR.

[0497] The crude reaction solution was diluted with 250 mL of water, and the reverse osmosis water was dialyzed for 5 days using a dialysis membrane with a molecular weight cutoff of 2K.

[0498] Water was removed from the product by freeze drying to obtain 2.85 g of white solid.

[0499] The phosphonate content in the polymer was determined by preparing an NMR sample in D2O solution using purified polymer and trimethyl phosphate (TMP). (Run) 1 H-NMR and 31 Phosphonate content was calculated using p-NMR based on the H and P peaks of the polymer and water relative to the internal standard (TMP). P-NMR showed broad phosphonoyl-phosphate peaks with a ratio of approximately 1:1 at approximately 18 ppm to 23 ppm and at -6 ppm to -10 ppm. No phosphonate peaks were observed at approximately 26–28 ppm. Based on this analysis, the polymer contained 53 mol% repeating units derived from acrylamide and 47 mol% repeating units derived from VPP. The water content was calculated to be 16% by weight.

[0500] Example 26: Copolymerization of VPP and VSMS

[0501]

[0502] VPP (Example 1, 7.67 mmol), bicarbonate (Aldrich 11.5 mmol), and 5 mL of water were placed in a round-bottom flask, and the top space of the flask was purged with flowing nitrogen for 15 minutes. The flask was sealed and heated to 60°C and held for 15 minutes to obtain a homogeneous solution. Ammonium persulfate (APS, 174.9 mg) was dissolved in 1.2 g of water. Over a total of 3 hours, 0.1 mL of the APS solution and 0.084 mL of VSME (methyl vinyl sulfonate (Example 14, 79.8% active material, total 7.67 mmol)) were added to the reaction every 15 minutes. The resulting product was stirred at 60°C for an additional 3 hours. The crude reaction solution was diluted with 250 mL of water and dialyzed against reverse osmosis water at pH 8.5 for 5 days using a 2K molecular weight cutoff dialysis membrane.

[0503] Water was removed from the product by freeze drying to obtain 2.05 g of white solid.

[0504] The phosphonate content in the polymer was determined by preparing an NMR sample in D2O solution using purified polymer and trimethyl phosphate (TMP). (Run) 1 H-NMR and 31 Phosphonate content was calculated using P-NMR based on the H and P peaks of the internal standard (TMP) relative to the polymer peak and water peak. P-NMR showed broad phosphonoyl-phosphate peaks with a ratio of approximately 1:1.1 from about 18 ppm to 23 ppm and from -4 ppm to -10 ppm, but no phosphonate peaks from about 26–28 ppm. The total phosphorus content was 40.8%. Methyl protons from MSME were present in… 1 Visible in ¹H NMR, allowing for quantitative analysis of VSME hydrolysis. Based on total analysis, the polymer contained 39 mol% repeating units from VSME, 20 mol% from VSA, and 41 mol% repeating units from VPP. The result was 73 wt% polymer, with the remainder being water and impurities.

[0505] Example 27: Copolymerization of (phosphono-monophosphate ethyl) (butyl)acrylamide with AMPS

[0506]

[0507] (phosphono-monophosphate ethyl)(butyl)acrylamide (Example 4, 21.6 mmol) and AMPS (23.6 mmol) were polymerized as in Example 23. The crude reaction solution was dialyzed against reverse osmosis water overnight using a 1K molecular weight cutoff dialysis membrane, then swelled with 0.5 M NaCl for 2 hours, followed by swelling with 0.05 M NaCl for 1 hour. After freeze-drying, 11.5 g of material was collected. As found by NMR in other examples, the polymer was approximately 67 mol% repeating units derived from AMPS and 33% repeating units derived from (phosphono-monophosphate ethyl)(butyl)acrylamide. The solid contained approximately 16 wt% water and 55 wt% polymer.

[0508] Example 28 Copolymerization of VPP and VPA

[0509]

[0510] VPA (1.2 g, 11.1 mmol) and 6 mL of water were placed in a 25 mL round-bottom flask. Sodium bicarbonate (2.8 g, 33.3 mmol) was added over 60 minutes, and the flask was then purged with nitrogen and stirred overnight at room temperature. VPP (Example 1, 11.1 mmol) was added, the solution was purged with nitrogen and heated to 60 °C, resulting in a turbid solution. Ammonium persulfate (APS, 253.5 mg) was dissolved in 0.75 mL of water and added to the mixture. The resulting solution was stirred at 60 °C for 6 hours. At this point, NMR showed 40% polymerization of all monomers. Another 253.3 mg of APS in 0.75 mL of aqueous solution was added. The result was stirred at 60 °C for a total of 24 hours. NMR showed the remaining 10% monomers.

[0511] The crude reaction solution was diluted with 500 mL of water to obtain a pH of 8.7. This solution was then dialyzed against reverse osmosis water adjusted to pH 8.5 using a dialysis membrane with a molecular weight cutoff of 2K.

[0512] The water in the resulting solution was removed under vacuum to obtain a white to milky white solid, which was further dried overnight in a vacuum oven to obtain 2.66 g of solid. P-NMR showed that the VPP:VPA ratio in the polymer was 61:39. The resulting product was 88% by weight of polymer.

[0513] Example 29: Copolymerization of VPP and Methyl Acrylate

[0514]

[0515] VPP (Example 1, 9.9 mmol) and 4 mL of water were placed in a round-bottom flask, and the top space of the flask was purged with flowing nitrogen for 15 minutes. The flask was sealed and heated to 60°C and held for 15 minutes to obtain a homogeneous solution. Ammonium persulfate (APS, 225.7 mg) was dissolved in 1.2 g of water. Over a total of 6 hours, 0.1 mL of APS solution and 0.073 mL of methyl acrylate (Aldrich, 9.9 mmol, total 0.88 mL) solution were added to the reaction every 30 minutes. At 3 hours, a milky white solution began to form. The result was stirred at 60°C for 24 hours to obtain a milky white solution. Progress was monitored by NMR and showed that 20% of VPP remained and no methyl acrylate remained at 24 hours.

[0516] Add the reaction solution to 20 mL of additional water, and then add 5 mL of MeOH over 5 minutes with rapid stirring. Allow the mixture to stand at room temperature for 10 minutes to obtain a white precipitate. Filter the precipitate and remove the MeOH from the filtrate.

[0517] The filtrate was diluted with 250 mL of water and the reverse osmosis water was dialyzed for 5 days at a pH of approximately 6.5 using a dialysis membrane with a molecular weight cutoff of 2K.

[0518] Water was removed from the product by freeze drying to obtain 1.4 g of white solid.

[0519] The phosphonate content in the polymer was determined by preparing an NMR sample in D2O solution using purified polymer and trimethyl phosphate (TMP). (Run) 1 H and 31 P-NMR was used to calculate the phosphonate content based on the H and P peaks of the internal standard (TMP) relative to the polymer peak and water. Analysis showed that the obtained polymer consisted of 29% methyl acrylate, 16% acrylate, 50% VPP, and 5% vinyl phosphonate. The resulting solids comprised 77% by weight of the polymer.

[0520] Example 30: Copolymerization of (4-vinylbenzyl)phosphono-monophosphate with SVS

[0521]

[0522] (4-Vinylbenzyl)phosphono-monophosphate (VBPP, Example 5, 4.35 mmol), bicarbonate (Aldrich 183 mg, 8.2 mmol), and SVS (Aldrich, 25% aqueous solution, 8.1 mmol) were added to a round-bottom flask, and the top space of the flask was purged with flowing nitrogen for 15 minutes. The flask was sealed and heated to 60°C, at which point the gas was released. Additional bicarbonate (total 300 mg) was added incrementally until no further purging was observed. Ammonium persulfate (APS, Aldrich, 284 mg, 10% relative to all monomers) was added to 0.5 mL of water. The result was stirred at 60°C for 24 hours.

[0523] Running the crude reaction solution 1 H-NMR and 31 P-NMR. The polymer composition is approximately 25 / 75 SVS / VBPP.

[0524] The crude reaction solution was diluted with 500 mL of water, and the pH was adjusted to 8.5 with 1 N NaOH. The solution was dialyzed against reverse osmosis water for 6 days using a dialysis membrane with a molecular weight cutoff of 2 K. Water was removed from the product by freeze drying to obtain 1.85 g of white solid.

[0525] The phosphonate content in the polymer was determined by preparing an NMR sample in D2O solution using purified polymer and trimethyl phosphate (TMP). (Run) 1 H and 31 Phosphonate content was calculated using p-NMR, based on the H and P peaks of the polymer and water relative to the internal standard (TMP). P-NMR showed broad phosphonoyl-phosphate peaks with a ratio of approximately 1:1 at about 13–15 ppm and -5–7 ppm, and a phosphonate peak at about 21–23 ppm. The phosphonate content was calculated based on the peaks at 13–15 ppm and 21–23 ppm. 31 P-NMR area, phosphonyl-phosphate:phosphonate ratio 93:7. Based on this analysis, the polymer contains 30 mol% repeating units derived from SVS, 65 mol% repeating units derived from VBPP, and 5 mol% repeating units derived from (4-vinylbenzyl)phosphonate. Water content is calculated to be 18% by weight.

[0526] Example 31: Copolymerization of (phosphono-monophosphate ethyl)-acrylamide with SVS

[0527]

[0528] SVS (Aldrich, 25% aqueous solution, 4.73 mmol) was placed in a round-bottom flask, and the top space of the flask was purged with flowing nitrogen for 15 minutes. The flask was sealed and heated to 60°C. Ammonium persulfate (APS, Aldrich, 141 mg, 5% relative to all monomers) was added to 1.0 g of water. Phosphono-monophosphate (ethyl)-acrylamide (Example 9, 4.95 mmol) was added to 5.25 g of water. Over 3 hours, SVS, 0.1 mL of APS solution, and 1.0 mL of (phosphono-monophosphate ethyl)-acrylamide were added to the flask every 20 minutes. The resulting mixture was stirred and stirred at 60°C for an additional 4 hours.

[0529] The crude reaction solution was diluted with 500 mL of water, and the pH was adjusted to 8.5 with 1 N NaOH. The solution was dialyzed against reverse osmosis water for 6 days using a dialysis membrane with a molecular weight cutoff of 2 K. Water was removed from the product by freeze-drying to give 3.4 g of a brownish-yellow solid. The crude reaction solution was subjected to 1H NMR and 1P NMR. The polymer composition was approximately 62:36:2: SVS:(phosphono-monophosphate ethyl)-acrylamide:(phosphonate ethyl)-acrylamide.

[0530] Example 32: Post-polymerization modification of copolymers of VPA and AA

[0531]

[0532] The polymer obtained from Example 18 was esterified by reflux of 2.3 g in 150 mL of MeOH in a 250 mL single-necked round-bottom flask equipped with a heater and magnetic stirrer. After reflux for 1 hour, a short-path distillation head was added to remove approximately 1 / 3 of the MeOH. This MeOH was then replaced with fresh anhydrous MeOH, a total of 4 times. This process yielded a methyl ester conversion of approximately 47% of the repeating acrylic acid unit. Next, 2 drops of concentrated sulfuric acid were added, and the solution was refluxed for 48 hours. By ¹H NMR, the process increased the total methyl ester content to 83%. Furthermore, by ¹P NMR, approximately 9% of the phosphonate was converted to monomethylphosphonate.

[0533] In a dry, single-necked round-bottom flask under nitrogen atmosphere and with magnetic stirring, 0.5 mL of methyl ester-containing polymer (1.63 mmol P) and 15 mL of DMF were added. The mixture was stirred overnight at room temperature to obtain swollen polymer spheres. Next, 0.78 mL of tributylamine (2.0 equivalents relative to P monomer) was added and stirred overnight at room temperature to obtain a homogeneous solution. CDI (330 mg, 1.25 equivalents relative to P monomer) and 5 mL of DMF were premixed and added to the solution. The mixture was stirred overnight to obtain a homogeneous solution.

[0534] H3PO4 (479 mg, 3 equivalents), tributylamine (1.26 mL, 3.5 equivalents), and 5 mL DMF were mixed and sonicated, then added to the polymer-containing solution. The result was stirred overnight at room temperature. The solvent in the resulting solution was removed under vacuum (9 Torr) until a final temperature of approximately 60 °C was reached.

[0535] The obtained product was dissolved in 50 mL of 1N NaOH to obtain a solution with pH 13.15, and stirred overnight. The water in the product was removed with flowing dry nitrogen to obtain a white paste. The paste was dissolved in 60 mL of MeOH over 1 hour, and the resulting solid was collected and dried to 2.52 g.

[0536] The crude solid was dissolved in water, the pH was adjusted to 9, and the resulting solution was dialyzed as described in the previous examples. After lyophilization, 0.67 g of a white, fluffy solid was collected. P NMR showed that the yield of phosphono-monophosphonate groups was approximately 20% of the initial phosphonate groups.

[0537] Example 33: Copolymerization of (phosphono-monophosphate ethyl)-methacrylate with SVS

[0538]

[0539] Following the procedure of Example 31, 5.7 mmol of SVS and 3.79 mmol of (phosphono-monophosphate ethyl)-methacrylate obtained from Example 7 were used. After freeze-drying, 1.5 g of white solid was collected, with a polymer content of 86% and a water / inactive substance content of 14%. The polymer composition was approximately 63:35:2 of SVS:(phosphono-monophosphate ethyl)-methacrylate:(phosphonate ethyl)-methacrylate.

[0540] Example 34: Copolymerization of (propylphosphono-monophosphate)-methacrylate with SVS

[0541]

[0542] Following the procedure of Example 31, 3.7 mmol of SVS and 3.5 mmol of (propylphosphono-monophosphate)-methacrylate obtained from Example 8 were used. After freeze-drying, 1.84 g of white solid was collected, with a polymer content of 86% and a water / inactive substance content of 14%. The polymer composition was approximately 56:44 SVS:(propylphosphono-monophosphate)-methacrylate.

[0543] Example 35 Post-polymerization modification of VPA homopolymer

[0544]

[0545] Poly(vinylphosphonic acid) (500 mg) was added to a 100 mL round-bottom flask, followed by methanol (20 mL). Tributylamine (1.1 mL) was added to the mixture and stirred for 30 minutes until homogeneous. The resulting solution was concentrated under vacuum, and then pyridine (10 mL) was added and removed under vacuum three times. The resulting solid was dissolved in 10 mL of pyridine. Diphenylphosphochloride (956 μL, 1 equivalent) was slowly added; however, a precipitate formed in the reaction mixture, so it was diluted with another pyridine (50 mL). After 1 hour, mono(tributylamine) phosphate (3.3 mL, 3 equivalent) was added and stirred overnight.

[0546] The solvent was removed under vacuum, and the resulting solid was dissolved in water and dialyzed. After dialyzing, the water was removed by freeze-drying to obtain a viscous solid. PNMR analysis showed that 87.7% of the phosphonates formed anhydrides with adjacent phosphonates, while 12.3% were phosphonyl monophosphates.

[0547] Example 36 Post-polymerization modification of polymethyl-vinylphosphonate

[0548] Following a procedure similar to that in Example 32, polymethyl-vinylphosphonate and DMF were added to a magnetically stirred, dry round-bottom flask and purged with nitrogen. Next, tributylamine (2.0 equivalents relative to the P monomer) was added and stirred overnight at room temperature to obtain a homogeneous solution. CDI (1.25 equivalents relative to the P monomer) and DMF were premixed and added to the overnight stirred solution. H3PO4 (3 equivalents), tributylamine (3.5 equivalents), and DMF were mixed and sonicated, then added to the polymer-containing solution. The result was stirred overnight at room temperature. The solvent in the resulting solution was removed under vacuum (9 Torr) to a final temperature of approximately 60°C to obtain a phosphono-phosphate-containing polymer.

[0549] Example 37 Post-polymerization modification of polymers containing atactic phosphonates

[0550] Phosphonopolyethylene was synthesized according to the descriptions of Anbar (M. Anbar, G.A. St. John, and A.C. Scott, J. Dent Res., Vol. 53, No. 4, pp. 867-878, 1974) or Schroeder and Sopchak (J.P. Schroeder and W.P. Sopchak, Journal of Polymer Science, Vol. 47, No. 149, p. 417, 1960). Briefly, 10 g of polyethylene was refluxed with 200 g of PCl3 in a dry flask until the polymer dissolved. Next, dry oxygen was passed through the dissolved solution. The resulting solution was distilled to reduce the total volume by half and poured onto camphor to form phosphonopolyethylene. This phosphonopolyethylene was reacted according to the procedure of Example 36.

[0551] Example 38 Post-polymerization modification of polymers containing poly(vinylbenzylphosphonic acid)

[0552] Poly(vinylbenzylphosphonic acid) is synthesized by heating (4-vinylbenzyl)phosphonic acid in methanol as described by Anbar et al., or by using an initiator such as ammonium persulfate (loaded at 5-10% relative to the monomer). The resulting polymer is reacted according to the procedure of Example 36.

[0553] Example 39 Synthesis of phosphonophosphate monomers and polymers with side chains

[0554]

[0555] Following the procedure of Example 12, dimethyl (2-hydroxyethyl) phosphonate is replaced with an ethylene glycol dimer, trimer, tetramer, or polymer having a primary hydroxyl group, such as diethyl (2-hydroxyethoxy)ethoxyethyl phosphonate. The phosphonate-terminated ethylene glycol unit can be manufactured according to Brunet et al. (Ernesto Brunet, * a Jose′de la Mata, HusseinM.H.Alhendawi, Carlos Cerro, Marina Alonso, Olga Juanes and Juan Carlos Synthesized using the process described in Guez-Ubis, Chem. Mater., 2005, Vol. 17, pp. 1424-1433. In short, the desired ethylene glycol dimer, trimer, tetramer, or polymer (1 equivalent) is added to a mixture of Cs₂CO₃ (1.2 equivalent) and diethylvinylphosphonic acid (12.5 equivalent) at 90°C over 2-4 days. Extraction with water and dichloromethane is followed by purification using rapid chromatography. Homopolymers are obtained by polymerization of phosphono-phosphate monomers as described in Example 22, or copolymers are obtained by polymerization with comonomers as described in Examples 19, 20, 23, 24, 25, or 26.

[0556] Example 40: Synthesis of phosphonophosphate polymers with side chains via post-polymerization modification.

[0557]

[0558] As described in Example 38, ethoxylated polyvinyl alcohol is reacted to form a phosphonate-terminated ethoxylated polyvinyl alcohol polymer. The ethoxylated polyvinyl alcohol is synthesized by reacting polyvinyl alcohol with ethylene oxide, added slowly over several hours, in a sealed reactor at a temperature of 85-120°C and a pressure of 20-200 psig. This phosphonate-terminated polymer is then reacted as described in Example 36 to form a phosphonyl-phosphate-containing polymer, wherein the phosphonyl-phosphate is attached to the side chain of the polymer via post-polymerization modification.

[0559] Example 41 Copolymerization of dimethylvinylphosphonate (DMVP) and SVS

[0560]

[0561] SVS (Aldrich, 25% aqueous solution, 11.0 mmol) was placed in a round-bottom flask, and the top space of the flask was purged with flowing nitrogen for 15 minutes. The flask was sealed and heated to 60°C and held for 15 minutes. Ammonium persulfate (APS, 225 mg) was added to 1.0 g of water. Over a total of 6 hours, 0.1 mL of APS solution and 0.1 mL of DMVP (Aldrich, 1.5 g, 1.3 mL, 11.0 mmol) were added to the reaction every 30 minutes. The result was stirred at 60°C for 24 hours.

[0562] The crude reaction solution was diluted with 250 mL of water, and the reverse osmosis water was dialyzed for 4 days using a dialysis membrane with a molecular weight cutoff of 2K. The initial pH of the dialysate was 5.8, but it decreased to 2.5.

[0563] Water was removed from the product by freeze drying to obtain 2.4 g of white solid.

[0564] Based on NMR analysis, the polymer contained 56.9 mol% repeating units derived from SVS and 43.1 mol% DMVP. The water content was calculated to be 10.4% by weight.

[0565] Example 42: Copolymerization of (ethylphosphono-monophosphate)-vinyl ether and (AMPS) according to Example 23 Gather

[0566]

[0567] Add (ethylphosphono-monophosphate)-vinyl ether (Example 11, 4.7 mmol), 5 mL of water, and AMPS (4 g 50% solution, 8.7 mmol) to a round-bottom flask, and purge the headspace of the flask with flowing nitrogen for 15 minutes. Seal the flask and heat to 60°C and maintain for 15 minutes to obtain a homogeneous solution. Dissolve ammonium persulfate (APS, 306 mg) in 1.1 g of water. Add 0.1 mL of APS solution to the reaction every 30 minutes over a total of 4 hours. Stir the reaction mixture at 60°C for 4 hours.

[0568] The crude reaction solution was diluted with 750 mL of water and the reverse osmosis water was dialyzed for 8 days using a dialysis membrane with a molecular weight cutoff of 2K.

[0569] Water was removed from the product by freeze drying to obtain 2.12 g of brownish-red solid.

[0570] Based on NMR analysis, the polymer contained 90.8 mol% repeating units derived from AMPS and 9.2 mol% repeating units derived from (ethylphosphono-monophosphate)-vinyl ether. The solid was found to contain 77% water by weight.

[0571] Example 43 PSPM on VPA SVS copolymer .

[0572] Homopolymers of the polymer from Example 17, as well as polyvinyl sulfonate and polyvinyl phosphonate purchased from PolySciences Inc., were tested according to the PSPM model. Results were obtained in conjunction with pyrophosphate and polyphosphate... Figure 1 As shown in Table 3 (below).

[0573]

[0574] Table 3

[0575] Example 44 PSRM on VPA SVS copolymer .

[0576] The homopolymers from Example 17, along with polyvinyl sulfonate and polyvinyl phosphonate homopolymers purchased from PolySciences Inc., were tested according to the PSRM model. Results were compared with those from pyrophosphate, polyphosphate, and water treatment. Figure 2 As shown in Table 4 (below).

[0577]

[0578] Table 4

[0579] Example 45 PSPM on VPP SVS copolymer .

[0580] The polymer from Example 20 was tested according to the PSPM model. The results are shown together with those of pyrophosphate and polyphosphate. Figure 3 And in Table 5 (below).

[0581]

[0582] Table 5

[0583] Example 46 PSRM on VPP SVS copolymer .

[0584] The polymer from Example 20 was tested according to the PSRM model. The results are shown together with those for pyrophosphate, polyphosphate, and water treatment. Figure 4 And in Table 6 (below).

[0585]

[0586] Table 6

[0587] Example 47 PSRM and PSPM on the mixed copolymer .

[0588] Polymers from the previous embodiments described below were tested according to PSRM and PSPM models. The results of Δl, along with pyrophosphate, polyphosphate, and water treatment products, are shown in Table 7 below.

[0589]

[0590]

[0591]

[0592] Table 7

[0593] General chemical schemes of Examples 48 to 52 - Synthesis of vinylphosphono-monophosphate (VPP) by removing water Or [vinylphosphonic anhydride] and other extended vinylphosphono-phosphates (eVPP)

[0594] The following chemical schemes illustrate the general reaction protocols used in Examples 48 through 52 to form the main desired products VPP and VPPP, along with some other products observed in some, but not all, of the experiments described below. For the final determined product distribution, please refer to the individual examples.

[0595]

[0596] Example 48 - Synthesis of VPP and eVPP by evaporation using a purge gas containing 3 equivalents of PA

[0597] 1 g of vinylphosphonic acid (VPA) and 2.72 g (3 equivalents) of 99% phosphoric acid (PA) were added to a 50 mL three-necked round-bottom flask equipped with a magnetic stirrer and a short-path distillation head located in the central neck. One side neck was plugged, and nitrogen was purged through the other side neck and expelled through the distillation head. The flask was placed in an oil bath heated to 105 °C and stirred at this temperature for 27 hours. At the desired time point, a sample (approximately 1 drop) was taken out, dissolved in 1 mL of D7-DMF containing 0.25 mL of tributylamine, and evaluated by p-NMR. The final product was found to contain VPA, vinylphosphono-monophosphate (VPP), vinylphosphono-pyrophosphate (VPPP), vinylphosphonic anhydride (VPPV), phosphoric acid (PA), pyrophosphate (PP), and triphosphate (PPP). Substance identification was confirmed using LCMS. Furthermore, the final 27-hour sample was subjected to ¹H-NMR, thus confirming that no polymerization occurred during the reaction.

[0598] The final molar distribution of all vinyl-containing substances in the melt after 27 hours was found to be 43% VPA, 38% VPP, 9% VPPP and 10% VPPV.

[0599] Example 49 - Synthesis of VPP and eVPP by evaporation using vacuum and a purge gas containing 3 equivalents of PA

[0600] The procedure of Example 48 was followed, with the following changes. Instead of venting to the atmosphere, a short-path distillation head was connected to the Buchi vacuum pump. During the experiment, the round-bottom flask was evacuated to 50-60 Torr with a constant nitrogen flow from one side neck. At sampling times of 32 and 48 hours, there was little variation between time points where the vinyl content distribution was 31-32% VPA, 40-41% VPP, 14% VPPP, and 13-14% VPPV. A signal corresponding to VPPPV was also observed in p-NMR, but it was not quantified as overlapping with other peaks.

[0601] Example 50 - Synthesis of VPP and eVPP by evaporation using vacuum and a purge gas having 6 equivalents of PA.

[0602] Following the procedure of Example 49, PA with a concentration of 6 equivalents relative to VPA was used. The distribution of the vinyl-containing material at 72 hours was 31% VPA, 40% VPP, 21% VPPP, and 8% VPPV. A signal corresponding to VPPPV was also observed in P-NMR, but it was not quantified as overlapping with other peaks.

[0603] Example 51 - Synthesis of VPP and eVPP by reaction with phosphorous anhydride (P2O5, phosphorus pentoxide)

[0604] Add 2.24 g of 85% wt% aqueous phosphoric acid, 1.01 g of 90% vinylphosphonic acid, and 2.5 g of phosphorus pentoxide (in that order) to a magnetically stirred 20 mL scintillation vial. The molar ratio of vinylphosphonate to total phosphate (calculated as the sum of the number of moles of phosphate plus twice the number of moles of P2O) was 6. The vial was heated to 175 °C, and samples were taken for PNMR after 1 hour using the procedure of Example X. The identified molar composition of the vinyl-containing substances was 34% VPA, 41% VPP, 19% VPPP, and 5% VPPV. Additional vinyl peaks were visible in the PNMR, which may correspond to larger substances, including VPPPP and VPPPPP. LCMS confirmed the presence of higher phosphono-phosphates, with peaks of VPP, VPPP, VPPPP, VPPPPP, VPPPPPP, and VPPPPPPP visible in negative ion mode.

[0605] Scale-up and purification of Examples 52-49

[0606] Following the process of Example 49, the total material was increased fivefold. A 32-hour sampling showed a distribution of vinyl-containing substances of 35% VPA, 37% VPP, 12% VPPP, 12% VPPV, and 4% VPPPV.

[0607] After cooling, most of the crude reaction mixture was dissolved in 40 mL of anhydrous DMF. The dissolved solution was added to 100 mL of anhydrous DMF solution containing 28.1 g of triethylamine (based on a total starting acid of 1.5 equivalents), while stirring rapidly for 5 minutes. The resulting solution was subjected to P-NMR, and the results were consistent with the distribution of the crude reaction mixture.

[0608] DMF was removed from the resulting solution at 70 °C and 25 Torr, yielding 38.4 g of a viscous yellow oil. This was dissolved in 100 mL of H₂O to obtain a solution with pH 2.5. The pH was adjusted to 11.0 with 110 g of 10% NaOH, resulting in a clear solution. P-NMR analysis of the resulting solution showed a product distribution consistent with the previous sample, but with a decrease in VPPV of approximately 20%. After standing at room temperature for 1 hour, a white precipitate formed, which was collected by filtration and dried overnight in ambient air to 4.65 g. The precipitate was found to be approximately 90% pyrophosphate, with 4% phosphate and less than 3% each of VPA, VPP, and PPP. Removal of the solvent from the filtrate yielded 49.4 g of a clear, viscous oil. The pH of the resulting oil was checked with litmus and found to be approximately 7. Additional water was added to bring the pH to approximately 125 g, resulting in pH 7.5, which was then adjusted to 11.0 with 15.2 g of 1N NaOH. At room temperature, 250 mL of MeOH was added to the pH 11 solution over 30 minutes with rapid stirring. A white precipitate formed within one hour. The precipitate was collected by filtration, washed once with 50 mL of 2:3H₂O:MeOH, and dried overnight in ambient air to 17.9 g. The precipitate was found to contain approximately 43% pyrophosphate, 39% phosphoric acid, 10% PPP, 3% VPP, and 4% VPPP. The aqueous MeOH solution was concentrated overnight at room temperature under flowing nitrogen to give 31.1 g of a viscous oil. The oil was found to have a molar phosphorus distribution of approximately 33% VPA, 33% VPP, 8% VPPP, 11% PA, 10% VPPV, and 3% VPPPV. The oil was also found to contain residual water and DMF.

[0609] Adding 300 mL of MeOH to the oily substance at room temperature for 1 hour yielded a white precipitate. This precipitate was collected by filtration, washed with 1 x 50 mL of MeOH, and vacuum dried at room temperature for 2 hours to obtain 4.3 g of white powder. The powder was found to have a molar phosphorus distribution of 49% VPP, 26% PA, 6% PP, 15% VPPP, and 3% VPA. Concentrating the MeOH solution at room temperature under flowing nitrogen gave 7.0 g of a white paste. The composition of the white paste was found to be approximately 73% VPA, 23% VPP, and 5% VPPP.

[0610] Example 53 - Polymerization to form a polymer containing VPPP, and testing using PSPM and PSRM.

[0611] Following the procedures of Examples 19 and 20, the white powder of Example 52, containing 49% VPP, 26% PA, 6% PP, 15% VPPP, and 3% VPA, was polymerized using a 50 / 50 mixture (total molar vinyl) of white powder containing VPPP (8.6 mmol vinyl) and SVS (8.6 mmol vinyl). After dialyzing and freeze-drying, 3.6 g of polymer was collected and found to contain 57% monomer as SVS and 43% monomer as phosphonates. The phosphonate distribution was 3% from VPA, 78% from VPP, and 18% from VPPP. By weight, the polymer was 78% active material and 22% impurities / water. The polymer was tested in PSPM and PSRM models, with ΔL values ​​of 5.5 and 11.0, respectively. The controls for PSPM were: water 28.0, HAP blank 0.0, pyrophosphate 18.0, and polyphosphate 4.0; and the controls for PSRM were: water 24.2, HAP blank 0.0, pyrophosphate 12.4, and polyphosphate 8.6.

[0612] Examples 54 to 57 - Scale-up and testing of oral care formulations

[0613] The following examples illustrate the formulation of a dental cleaning agent from a polymer containing phosphonophosphate and subsequent testing in a stain model.

[0614] 20g-30g scale-up of Examples 54-19 and 20

[0615] The processes of Examples 19 and 20 were scaled up using 96.7 mmol of VPP and 96.7 mmol of VSA, along with equal increments of other reagents and solvents. After dialysis and lyophilization, 27.1 g of polymer was collected and found to contain 59% monomer as SVS, 40% monomer as VPP, and 2% monomer as VPA. By weight, the polymer was 83% active material and 17% impurities / water.

[0616] The polymer was tested in the PSPM and PSRM models, with ΔL values ​​of 6.8 and 13.0, respectively. The controls for PSPM were: water 28.0, HAP blank 0.0, pyrophosphate 14.3, and polyphosphate 3.1; and the controls for PSRM were: water 25.0, HAP blank 0.0, pyrophosphate 13.5, and polyphosphate 10.7.

[0617] 20g-30g scale-up of Examples 55-16 and 17

[0618] The processes of Examples 16 and 17 were scaled up using 148 mmol VPP and 122 mmol VSA, along with equal increments of other reagents and solvents. After dialysis and lyophilization, 26.8 g of polymer was collected, and it was found to contain 54% monomer based on SVS and 46% monomer based on VPA. By weight, the polymer was 90% active material and 10% impurities / water. The polymer was tested in PSPM and PSRM models, with ΔL values ​​of 10.2 and 20.2, respectively. The PSPM controls were: water 28.0, HAP blank 0.0, pyrophosphate 14.3, and polyphosphate 3.1; and the PSRM controls were: water 25.0, HAP blank 0.0, pyrophosphate 13.5, and polyphosphate 10.7.

[0619] 100g scale-up of Examples 56-19 and 20

[0620] The processes of Examples 19 and 20 were scaled up using 354.5 mmol VPP and 433 mmol VSA, along with equal increments of other reagents and solvents. After neutralization, the bulk solution was replenished with water to 9819 g, and the pH was adjusted to 10 with 1 N NaOH. Low molecular weight impurities in the resulting solution were reduced by tangential flow filtration (TFF) using a Tami Industries 1000 MWCO column (E190613N001). The solution was pumped from the reservoir through the column and then returned to the reservoir. The effluent through the column orifices was collected in a flask on a balance. In the first run, the solution was pumped until 3.5 kg of effluent was collected. The remaining solution in the reservoir was then replenished to approximately 9 kg. This process was repeated, removing 4.8 kg and replenishing the reservoir to 11 kg. In the final run, 6 kg of effluent was removed. After final TFF, the concentrated solution is filtered through a 0.22 μm filter (Stericup 500 ml filter unit, Aldrich).

[0621] Evaporation was carried out at room temperature under flowing nitrogen for 5 days. After filtration, water was removed from the final TFF concentrate, yielding 173 g of a brownish paste. This paste was further dried under a vacuum of >1 Torr for 48 hours, yielding 137.2 g of a light brownish solid. The solid was found to contain 66% monomer based on SVS and 34% monomer based on VPP. By weight, the polymer was 80% active material and 20% impurities / water. The polymer was tested in PSPM and PSRM models, with ΔL values ​​of 6.5 and 11.5, respectively. The PSPM controls were: water 28.0, HAP blank 0.0, pyrophosphate 18.0, and polyphosphate 4.0; and the PSRM controls were: water 24.2, HAP blank 0.0, pyrophosphate 12.4, and polyphosphate 8.6.

[0622] Formulations and tests of Examples 57-54 to 56

[0623] Unless otherwise specified, all percentages in this embodiment are by weight.

[0624] The composition is prepared as follows:

[0625] Composition #1 is a commercially available Crest Cavity Protection Regular Flavor.

[0626] Composition #2 is a commercially available Crest ProHealth Clean Mint Smooth Formula.

[0627] Composition #3 is the same as composition #2, which incorporates the polymer from Example 54.

[0628] Composition #2 was weighed into a Speedmix flask. The polymer from Example 54 was then added to the Speedmix flask and mixed in the Speedmixer until homogeneous. The pH was then measured using a pH electrode, and 2N HCl was added to the Speedmixer and mixed to adjust the pH to a target value of approximately 6.

[0629] Composition #4 is identical to Composition #2, which incorporates the polymer of Example 55. Composition #2 was weighed into a Speedmix flask. The polymer of Example 55 was then added to the Speedmix flask and mixed in the Speedmixer until homogeneous. The pH was then measured using a pH electrode, and a 50% NaOH solution was added to the Speedmixer and mixed to adjust the pH to a target value of approximately 6.

[0630] Composition #5 was prepared in a pilot-scale mixer by adding approximately half of the sorbitol, heating to 65°C using the heating / cooling jacket on the tank, and evacuating. In a separate vessel, 1% by weight of silica and all of the hydroxyethyl cellulose were dry-mixed until homogeneous, and then vacuum-drawn into the mixing vessel. An anchor stirrer and a high-shear rotor / stator were used to mix and homogenize the mixture to ensure homogeneity and hydration of the hydroxyethyl cellulose. Once homogeneous, the rotor / stator was shut off. The remaining sorbitol, approximately 25% of the water, and all of the blue dye were added and mixed using an anchor stirrer until homogeneous. In a separate vessel, 1% by weight of silica, all of the saccharin, and all of the carrageenan were dry-mixed and vacuum-drawn into the main mixing vessel while the high-shear rotor / stator and anchor stirrer were running. Once homogeneous, the rotor / stator was shut off. Next, the remaining silica was vacuum-drawn into the main mixing vessel and mixed using an anchor stirrer under a vacuum of not less than 26 inches of mercury. The batch is then cooled to approximately 49°C using a heating / cooling jacket while continuing to mix with an anchor stirrer. Once the batch reaches 49°C, the anchor stirrer is stopped, the mixer is turned on, and the flavoring agent and sodium lauryl sulfate solution are added to the top of the batch. Vacuum is then applied to 24 inches of mercury, and the anchor stirrer and rotor / stator are turned on until the batch is homogeneously mixed. After mixing, the rotor / stator is turned off, and vacuum is applied to 27 inches of mercury to remove air. In a separate container, the remaining 75% of the water is heated to 65°C. Sodium gluconate is added to the water and mixed until dissolved. Stannous fluoride is then added to the gluconate solution and mixed until dissolved. Stannous chloride is then added to the gluconate solution and mixed until dissolved. Once this solution is prepared, it is added to the main mixing vessel under vacuum and mixed using an anchor stirrer until homogeneous. After mixing, sodium hydroxide is added to the main mixing vessel under vacuum and mixed homogeneously using an anchor stirrer and rotor / stator. Once homogenized, shut off the rotor / stator and reduce the heating / cooling jacket to 30°C, then evacuate to 26 inches of mercury. Mix the batch under vacuum until the temperature reaches 35°C, then pump it out of the main mixing vessel.

[0631] Composition #6 is identical to Composition #5, which incorporates the polymer of Example 56. Composition #5 was weighed into a Speedmix flask. The polymer of Example 56 was then added to the Speedmix flask and mixed in a Speedmixer until homogeneous. The pH was then measured using a pH electrode, and no further adjustment was required to achieve a pH of approximately 6.

[0632] Composition #7 is identical to Composition #2, which incorporates the polymer of Example 56. Composition #2 was weighed into a Speedmix flask. The polymer of Example 56 was then added to the Speedmix flask and mixed in the Speedmixer until homogeneous. The pH was then measured using a pH electrode, and a 50% NaOH solution was added to the Speedmixer and mixed to adjust the pH to a target value of approximately 6.

[0633]

[0634]

[0635] Example 58 - Synthesis of VPP and eVPP by reaction with phosphoric acid and urea

[0636] For all samples in the examples, the following general procedure is followed:

[0637] Add VPA, 85% or 99% H3PO4, urea, and water to scintillation vials as shown in Table 1 below. Stir the resulting mixture at 60°C for approximately 15 minutes until a homogeneous solution is obtained. Transfer the resulting solution to an 800 mL beaker. Place the beaker in a programmable laboratory oven with circulating airflow and external ventilation. Heat all samples as follows:

[0638] 1) The temperature rises from room temperature to 110°C within 15 minutes.

[0639] 2) Keep at 110℃ for 3 hours.

[0640] 3) The temperature rises from 110°C to 150°C within 15 minutes.

[0641] 4) As shown in the table below, keep at 150℃ for 15 or 60 minutes.

[0642] 5) Cool to room temperature and let stand overnight.

[0643] P-NMR was performed on the crude reaction products (approximately 50 mg of reaction product in 1 mL of D₂O solution with 5 drops of 30% NaOD). These products were found to contain VPA, vinylphosphono-phosphate (VPPA), vinylphosphono-pyrophosphate (VPPPA), vinylphosphonic anhydride (SM-An), phosphoric acid (PA), pyrophosphate, and triphosphate (PPP). The areas from the P-NMR are shown in Table 3 below. ¹H-NMR was also performed on the reaction products to examine the polymerization of VPA during heating. No polymer was observed.

[0644]

[0645] Example 59 - Synthesis of a polymer containing VPP and eVPP by reacting the polymer with phosphoric acid and urea.

[0646]

[0647] Dimethyl vinylphosphonate (DMVP, 10.6 g, 77.9 mmol) and sodium vinyl sulfonate solution (SVS, 25% aqueous solution, 40.5 g, 77.9 mmol) were added to a 100 mL round-bottom flask. The flask was purged with nitrogen for 15 minutes and heated to 60 °C. 888 mg of ammonium persulfate (APS, 2.55% of the total monomers) was added to 4 g of water and degassed with nitrogen for 5 minutes. The APS solution was added to the solution containing DMVP and SVS, and the resulting solution was stirred at 60 °C under nitrogen for 24 hours.

[0648] Running the crude reaction solution 1 H-NMR and 31 P-NMR was performed, and a monomer conversion of approximately 99% was observed, with a broad P polymer peak at approximately 37 ppm of the phosphonate group.

[0649] The crude reaction solution was diluted with 207 g of water to a polymer concentration of 10% by weight. 300 mL of acetone was added, and the mixture was stirred continuously at room temperature for over 30 minutes to obtain a turbid solution. After standing for 30 minutes in a separatory funnel, a lower layer of viscous polymer-rich slurry and an upper layer of fluid organic matter were formed. The lower layer was collected, and the solvent was evaporated overnight under nitrogen, followed by vacuum evaporation at 1 Torr for 2 hours to obtain 15.3 g of a viscous, brownish-red solid. The solid was tested with the internal standard trimethyl phosphate. 1 H-NMR and 31 P-NMR showed that the ratio of DMVP:SVS derivative groups was 50:50.

[0650] A viscous, brownish-red solid was mixed with 30 g of water and 45 g of concentrated HCl (approximately 37%) to obtain a milky white solution. The mixture was refluxed for 48 hours to yield a pale brown, transparent solution. Water and HCl were stripped from the solution to approximately 20 mL using a rotary evaporator operating at 60 °C and 20 Torr. 100 mL of water was added to the remaining fraction, and the stripping was repeated. Then, 200 mL of water was added, and the sample was frozen and lyophilized to obtain 11.8 g of brownish-red solid. 31 P-NMR showed that the polymer peak shifted from approximately 37 ppm to approximately 32 ppm, while 1 ¹H-NMR showed that the polymer peak disappeared at approximately 3.8 ppm, corresponding to the methyl ester peak. Internal standard analysis indicated that the ratio of P-containing groups to sulfur-containing groups was approximately 47 to 53, and the gravimetric activity was 82.4%.

[0651] Add 4.85 g of 85% phosphoric acid and 2.77 g of urea to a 100 mL beaker and heat at 60 °C for 15 minutes, then cool to room temperature to obtain a clear solution. Dissolve 5 g of 82.4% active polymer (calculated P / S ratio of 47:53) in 15 mL of water and add it to the phosphoric acid / urea mixture in the 100 mL beaker. Place the beaker in a programmable laboratory oven with circulating airflow and external ventilation and heat as follows:

[0652] 1) The temperature rises from room temperature to 110°C within 15 minutes.

[0653] 2) Keep at 110℃ for 3 hours.

[0654] 3) The temperature rises from 110°C to 150°C within 15 minutes.

[0655] 4) Keep at 150℃ for 15 minutes.

[0656] 5) Cool to room temperature and let stand overnight.

[0657] 11.4 g of a spongy white product was collected. The crude reaction product (approximately 150 mg of the reaction product in 1 mL of D₂O solution with 2 drops of 30% NaOD) was subjected to P-NMR. The P-NMR showed a broad peak at approximately -5 ppm, corresponding to phosphonyl-phosphate groups on the polymer chain. Part of this peak overlapped with pyrophosphate, making quantification difficult.

[0658] Most of the crude product, 11.4 g, was dissolved in 50 mL of water and added to a round-bottom flask with stirring. 50 mL of methanol was added over 30 minutes to obtain a turbid solution. After standing for 30 minutes in a separatory funnel, a polymer-rich slurry layer with lower viscosity was obtained, which was then separated (9.5 g). The ratio of polymer to phosphate to pyrophosphate was evaluated by P-NMR and found to be 161:43:113.

[0659] The above 9.5 g slurry was repeatedly precipitated using 50 mL of water and 50 mL of methanol. 2.13 g of slurry was obtained. P-NMR showed that the polymer to phosphate to pyrophosphate ratio was 158:3:18.

[0660] The resulting slurry was added to 250 mL of reverse osmosis (RO) water and further purified by dialyzing with RO water (pH adjusted to 8.5 with saturated sodium bicarbonate solution) in a Thermo Scientific Slide-A-Lyzer dialysis flask (2K MWCO) for 6 days. Water was removed by freeze-drying to give 1.59 g of white solid. 1 H-NMR and 31P-NMR analysis showed that the collected polymer contained approximately 41% P monomers and 59% S monomers. Analysis of the P-containing groups revealed approximately 22% phosphono-phosphate groups and a small amount of phosphono-pyrophosphate groups. The remaining P-containing groups appeared to be a mixture of phosphonate and phosphonate anhydride structures. The polymer was calculated to be 87.4% by weight of active material.

[0661] Example 60: Copolymerization and purification of vinylphosphono-monophosphate (VPP) and sodium vinyl sulfonate (SVS)

[0662]

[0663] VPP (prepared on a larger scale as described in Example 1, 64.6 g of active material, 254 mmol) and SVS (25% aqueous solution, 161.6 g, 310 mmol) were placed in a 500 mL round-bottom flask, with an initial molar ratio of SVS to VPP of 55 to 45. The mixture was then stirred and the top space of the flask was purged with flowing nitrogen for 60 minutes. The pH of the solution was raised from 8.5 to 10.5 by adding 9.5 mL of 1M NaOH. The flask was purged with flowing nitrogen and heated to 60 °C, at which point ammonium persulfate (APS, Aldrich, 7.73 mL of 10% aqueous solution, mg, 0.6% relative to the total monomers) was added. The result was stirred at 60 °C for 24 hours.

[0664] Running the crude reaction solution 1 H-NMR and 31 P-NMR. The total monomer conversion was observed to be 78%, with broad P polymer peaks for phosphonate groups at approximately 18 ppm to 23 ppm, and broad P polymer peaks for phosphate groups bonded to phosphonate groups at -6 ppm to -10 ppm.

[0665] The polymer was purified by adding an aliquot of methanol to a stirred solution containing 10% active polymer over 15 minutes. The resulting turbid solution was transferred to a separatory funnel and allowed to stand for another 15 minutes to completely separate into a lower, viscous polymer-rich slurry and an upper, fluid layer. The lower polymer layer was collected, and the same process was repeated using additional aliquots of methanol to allow the upper layer to reprecipitate. All samples were then dried under vacuum for two days, and the final mass is recorded in Table 4 below.

[0666]

[0667] Table 4

[0668] In addition, approximately 50 ml of the remaining upper H₂O / MeOH layer was concentrated overnight under N₂ at room temperature, and then vacuum dried for 24 hours at room temperature to obtain 2.5 g of white solid. Size exclusion chromatography / gel permeation chromatography (SEC or GPC, 3 columns in series, Polymer Standards Service MCX1000A, MCX500A and MCX100A all 5 μm, with guard columns, 0.2 M NaNO₃ mobile phase 1 mL / min) showed that the molecular weight decreased sequentially from the highest molecular weight fraction 1 to the lowest molecular weight fraction 6. The GPC trace obtained from polymer analysis is shown below. Figure 5 As shown. Higher molecular weights are represented by shorter retention times, while lower molecular weights have longer retention times. The large peak after 22.5 minutes indicates non-polymeric substances, such as residual monomers and salt impurities in the sodium vinyl sulfate solution.

[0669] Example 61 yielded vinylphosphono-monophosphate (VPP) and sodium vinyl sulfonate (SVS) samples from Example 60. Additional purification of the product

[0670] Further purification was performed on fractions 1-3 and 4-6. A 15 wt% polymer aqueous solution was formed from the combined fractions 1-3. Methanol, equal to 20% of the total water fraction mass over 60 minutes, was added to this solution with stirring. Stirring was stopped, and the solution phase was separated to obtain a lower layer rich in viscous polymer. This fraction was collected and dried. This process was repeated three more times, each time adding 10% methanol relative to the initial mass of the solution. All samples were oven-dried, and the original mass percentages are recorded in the table below. Fractions 1-4 contained 77-81% active material, as well as less than 0.5% phosphate, less than 0.2% vinyl phosphate or vinylphosphonophosphate, and no vinyl sulfonate was detected.

[0671]

[0672] Table 5

[0673] A 20% by weight polymer solution was formed from the combined fractions 4-6. Methanol, equal to 60% of the total mass of the solution, was added to this solution. The resulting precipitate was vacuum dried for two days. The recovered polymer was 93% of its initial mass, with 83% active material, less than 0.5% phosphate, less than 0.1% vinyl sulfonate, and less than 0.1% vinyl phosphonate or vinyl phosphonate.

[0674] The GPC trace of the obtained refractory material is illustrated in the figure. Figure 6 middle.

[0675] In addition to RI detection, light scattering was also performed. Samples with low retention times provided good light scattering, while samples with higher retention times did not. This phenomenon was independently confirmed using a separate light scattering instrument not connected to the GPC. Low molecular weight fractions appeared to aggregate, which manifested as high molecular weight and high error after processing the light scattering signal into molecular weight. For this reason, only the molecular weight of the material with less retention is given. For fractions with more retention, the increasing trend of calculated Mn and Mw continues, with uncertainty close to 50%. Polymers with Mw of 60,000 Daltons were detected in the refraction fraction 1-3-1. This corresponds to polymers with 250 to 450 repeating units, depending on the composition of vinyl sulfonate and vinylphosphono-phosphate derived units.

[0676]

[0677] Table 6

[0678] Example 62: Identification of end groups using different analytical techniques

[0679] The HNMR from the refractories of Example 61 showed broad polymer peaks in the olefin region of 6.5–5 ppm. The integrals of these peaks relative to the non-olefin peaks of 4.0–1.0 ppm can be used to estimate the amount of olefins present. Assuming ethylene-like groups, the olefin area is divided by 2, while assuming CH2-CHX, the non-olefin area is divided by 3, where X is P or S. Based on the composition of each fraction, Mn can be approximated using internal standards combined with HNMR and PNMR under the assumption that each olefin corresponds to a terminal group. The closeness of this calculation to the light scattering (LS) results of Mn can then be used to assess whether each polymer contains an olefin at the terminal position. The comparative results are given in Table 7.

[0680]

[0681] Table 7

[0682] For substances with lower retention and potentially higher molecular weights, the matching was very close, with values ​​of 5.6 vs. 6.8 and 3.5 vs. 2.7 for the redistribution fractions 1-3-1 and 1-3-2, respectively. Unlike light scattering, olefin-based analysis also showed that Mn indeed decreased with increasing column retention. To confirm the CH2 nature of the olefins, edited heteronuclear single quantum coherence (edited HSQC) NMR was run on the sample redistribution fraction 4-6-1. The olefin peaks were confirmed to have CH2 characteristics.

[0683] Fractions 1-3-4 of the sample were also analyzed by ion chromatography (Dionex IonPac AS 16-4 μm) followed by high-resolution mass spectrometry. In addition to large, broad polymer peaks with numerous signals, sharp early elution (lower total charge) peaks were observed. These early elution peaks were found to contain multiple masses of a phosphono-phosphate "trimer," and these masses were matched to include proton form, sodium form, a mixture of protons and sodium, and masses corresponding to the loss or increase of water and the loss of phosphate groups. The substance was found to contain alkene or cyclic unsaturated groups. The structure in its fully proton form was shown based on the edited HSQC results.

[0684]

[0685] Assuming the presence of other end groups besides olefins, an initiator of 0.6% relative to the total molar amount of polymerizable monomers was used during the synthesis of the refractionated sample. Typical initiator efficiencies are below 100%, but this value will be used for calculation purposes. Each persulfate can cleave to form two radicals. If each radical initiates one polymer chain and the reaction proceeds to completion, 83 repeating units are expected per chain. According to HNMR data, the initial combined fractions 1–3 had an average of 19 repeating units, while combined fractions 4–6 had 6 repeating units. Therefore, assuming each initiator radical fully initiates the polymer, at least four chain transfers or bite-back and β-splitting combinations occur on that chain, each potentially yielding an olefin. Assuming only 40% initiation efficiency, 208 repeating units are expected, implying 11 chain transfers or bite-back and β-splitting combinations from each initiator radical.

[0686] It should be understood that the embodiments and implementations described herein are for illustrative purposes only, and various modifications or changes can be made thereto by those skilled in the art without departing from the spirit and scope of this application.

Claims

1. A polymer comprising a phosphono-phosphate group, wherein the phosphono-phosphate group has the structure of Formula 12: Formula 12 in: ε is the connection site with a carbon atom in the main chain, side group, or side chain of the polymer; R 10 Selected from -H, Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cations and structures of formula 13: Formula 13 in: θ is the connection point with Equation 12. R 13 and R 14 It is independently selected from -H, Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cations; R 11 Selected from -H, Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cations and structures of formula 14: Formula 14 in: θ is the connection point with Equation 12. R 15 and R 16 Independently selected from -H, Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cations; and n is an integer from 1 to 3; and R 12 Selected from -H, Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cations; The polymer is formed using monomers, and at least one monomer used to form the polymer contains the phosphono-phosphate group. The monomer described herein has the structure of Formula 15: Formula 15 in: ω is the connection site with the phosphono-phosphate group of Formula 12; R 17 Selected from -H and -CH3; L1 is selected from chemical bonds and the structure of Formula 4: Formula 4 in: α is the connection site with the alkenyl group; β is the connection site with the phosphono-phosphate group of Formula 12; X is selected from the following structures; Formula 5 Formula 6 Formula 8 Formula 10 in: R9 is selected from -H and alkyl groups. （C1-8） ;and Y is selected from alkyldiyl and alkoxydiyl.

2. The polymer according to claim 1, wherein the phosphono-phosphate group is added during post-polymerization modification.

3. The polymer according to claim 1, wherein R 17 For H.

4. The polymer according to claim 1, wherein R 17 It is CH3.

5. The polymer according to claim 1, wherein L1 is a covalent bond.

6. The polymer according to claim 1, wherein R 10 R 11 and R 12 It is independently selected from -H, Na cations and K cations.

7. The polymer according to claim 1, wherein L1 has the structure of Formula 4 and X has the structure of Formula 5.

8. The polymer according to claim 1, wherein L1 has the structure of Formula 4 and X has the structure of Formula 8.

9. The polymer according to claim 1, wherein L1 has the structure of Formula 4 and X has the structure of Formula 10.

10. Polymers having the following structures: Formula 16 in: R1 is selected from -H and -CH3; R2 is selected from -H, Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, amine cations and structures of formula 2: Formula 2 in: δ is the connection point with Equation 16. R5 and R6 are independently selected from -H, Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cations; R3 is selected from -H, Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cations; R4 is selected from -H, Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cations; R 18 These are chemical groups generated by polymer initiation, selected from the following structures: Formula 17 Formula 19 Formula 21 in: R 20 Selected from -H, Na, K and amine cations; τ is the connection site with the polymer backbone; and Q has the following structure: Formula 22 Where κ represents the connection site with Equation 21; R 19 -H; M2 is a polymeric residue of one or more comonomers having the following structure: Formula 23 in: R 21 Selected from -H or -CH3; Q1 represents the non-olefin residues of the comonomer used for polymerization; and p is an integer from 1 to 450; m is an integer from 2 to 450; and L is selected from chemical bonds and the structure of Formula 4: Formula 4 in: α is the connection site with the alkenyl group; β is the connection site with the phosphono-phosphate group; X is selected from the following structures; Formula 5 Formula 6 Formula 7 Formula 8 Formula 10 in: R9 is selected from -H, alkyl （C1-8） Phosphonylalkyl and phosphonyl(phosphate)alkyl; and Y is selected from alkyldiyl, alkoxydiyl, alkylaminodiyl, and alkenyldiyl.

11. The polymer according to claim 10, wherein R2 has the following structure: Formula 2 in: δ is the connection point with Equation 16; and R5 and R6 are independently selected from -H, Na, K, Ca, Mg, Mn, Zn, Fe or Sn cations, and amine cations.

12. The polymer according to claim 10, wherein L has the following structure: Formula 4 in: α is the connection site with the alkenyl group; β is the connection site with the phosphono-phosphate group; X is selected from the following structure: Formula 5; Formula 6; Equation 8; and Formula 10; in: R9 is selected from -H, alkyl （C1-8） Phosphonylalkyl and phosphonyl(phosphate)alkyl; and Y is selected from alkyldiyl, alkoxydiyl, alkylaminodiyl, and alkenyldiyl.

13. The polymer according to claim 10, wherein: R1 is H; L represents a covalent bond; R2, R3, and R4 are independently selected from H, Na, K, and amine cations; R 18 It has the following structure: Formula 21 in: τ is the connection site with the polymer backbone; and Q has the following structure: Formula 22 Where κ represents the connection site with Equation 21; and R 19 For H.

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