Plant-inspired zwitterionic monomers, polymers and uses thereof

Abstract

Disclosed is a polymer comprising a plurality of monomers, at least a portion of which is a zwitterion comprising a betaine having a pyridinium group and a carboxylate group. Also disclosed are filtration membranes, coating materials, wound dressings, electrolytes, batteries, and formulations comprising such polymers. Also disclosed is a method for preparing such polymers.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 215,781, filed June 28, 2021; the contents of which are incorporated by reference. GOVERNMENT SUPPORT

[0002] This invention was made with Government support under Grant No. 1802729 awarded by the National Science Foundation. The Government has certain rights in this invention. [Background technology]

[0003] Zwitterionic (ZI) polymers are a diverse subclass of materials that are the focus of research in many areas such as drug delivery, bioimplants, antifouling materials, and electrochemical energy storage. There are several different types of zwitterionic chemicals and materials that highlight their unique properties and potential as battery electrolytes.

[0004] However, commercially available ZI monomers contain Li + There are very limited options for functional groups, including sulfobetaine types (e.g., sulfobetaine methacrylate, SBMA), which do not promote transport, and phosphorylcholine types (e.g., 2-methacryloyloxyethyl phosphorylcholine, MPC), which are expensive to produce.

[0005] Thus, a major drawback to the widespread use of zwitterions is the limited number of commercially available or easily synthesized chemicals, which necessitates a continued need for the development of novel zwitterionic chemicals, especially those containing carboxybetaine (CB) and phosphorylcholine (PC) motifs that lower the synthetic barrier and increase the availability of zwitterions for future applications. Summary of the Invention [Means for solving the problem]

[0006] In some aspects, the invention provides a polymer comprising a plurality of monomers, at least a portion of which are zwitterions comprising betaines having a pyridinium group and a carboxylate group.

[0007] In certain embodiments, the polymer is a hydrogel.

[0008] In certain embodiments, a carboxylate group is attached to C3 of said pyridinium group.

[0009] In certain embodiments, the zwitterion further comprises an alkyl, allyl, aryl, vinylbenzyl, acrylate, methacrylate, acrylamide, or methacrylamide group.

[0010] In certain embodiments, the zwitterion is [ka] [ka] or any combination thereof, R represents acrylate (-OC(O)CH=CH2), methacrylate (-OC(O)C(CH3)=CH2), acrylamide (-NHC(O)CH=CH2), or methacrylamide (-NHC(O)C(CH3)=CH2).

[0011] In certain embodiments, the polymer is a copolymer further comprising a hydrophobic monomer, a charged monomer, an ionic (or ionizable) monomer, or any combination thereof.

[0012] In another aspect, the invention provides a filtration membrane (eg, a water filtration membrane) comprising a polymer of the invention.

[0013] In other aspects, the present invention provides coating materials (eg, bioimplant coating materials, implant surface coating materials, biomedical device coating materials, antifouling materials) comprising the polymers of the present invention.

[0014] In another aspect, the present invention provides a wound-dressing material comprising a polymer of the present invention.

[0015] In another aspect, the present invention provides an ionic liquid-based electrolyte (eg, an ionogel electrolyte) or polymer electrolyte comprising a polymer of the present invention.

[0016] In another aspect, the present invention provides a Li-ion battery comprising an ionic liquid-based or polymer electrolyte of the present invention.

[0017] In another aspect, the present invention provides a drug delivery formulation comprising a polymer of the present invention.

[0018] In some embodiments, the present invention provides a method for preparing a carboxybetaine monomer, comprising reacting nicotinic acid with an electrophile to obtain a cationic intermediate; and reacting the cationic intermediate with a base to obtain a carboxybetaine monomer.

[0019] In certain embodiments, the method further comprises a solvent (eg, DMF).

[0020] In certain embodiments, the electrophile is a halide or an epoxide.

[0021] In certain embodiments, the electrophile is [ka] where R is substituted or unsubstituted alkyl, allyl, or vinyl, and X is a halogen (e.g., bromine, chlorine, fluorine, or iodine).

[0022] In certain embodiments, the electrophile is a halide, and the halide is allyl bromide, 4-vinylbenzyl chloride, or 2-chloroethyl acrylate.

[0023] In certain embodiments, the carboxybetaine monomer is [ka] and R is substituted or unsubstituted alkyl, allyl, or vinyl.

[0024] In certain embodiments, the cationic intermediate is [ka] It is.

[0025] In certain embodiments, the base is an alkali hydroxide (eg, sodium hydroxide).

[0026] In certain embodiments, the carboxybetaine monomer is [ka] It is.

[0027] In some embodiments, a method for preparing a polymer comprising a carboxybetaine monomer comprises polymerizing a plurality of carboxybetaine monomers obtained by reacting nicotinic acid with a halide to obtain a cationic intermediate and reacting the cationic intermediate with a base to obtain a carboxybetaine monomer.

[0028] These and other aspects of the disclosure will become evident upon consideration of the following detailed description and claims. [Brief description of the drawings]

[0029] [Figure 1]Synthetic schemes of bio-inspired zwitterionic monomers: (a) CBZ1, prepared by reacting nicotinic acid with allyl bromide, and (b) CBZ2, prepared by reacting nicotinic acid with 4-vinylbenzyl chloride. [Diagram 2] Photographs of monomer solutions containing novel CB-type zwitterions: CBZ1 (left) and CBZ2 (right) in 1M LiTFSI / BMP TFSI (ZI units:Li+ molar ratio of 0.3). At this molar ratio, the approximate concentrations were 22 mg CBZ1 and 33 mg CBZ2 in 500 μL of 1M LiTFSI / BMP TFSI. [Diagram 3] 7Li NMR spectra of 1M LiTFSI / BMP TFSI and zwitterionic monomer solutions. Plots include NMR spectra of 1M LiTFSI / BMP TFSI solution (bottom) and ZI monomer solutions containing CBMA, CBZ1, SB2VP, and CBZ2. [Figure 4] Proposed synthesis scheme of CBZ3 by reacting nicotinic acid with 2-chloroethyl acrylate. [Diagram 5] 1H NMR spectrum of CBZ1 monomer. Synthesized by reacting nicotinic acid with allyl bromide following the procedure outlined in the Experimental Methods. Peak assignments are shown in the inset and NMR was performed using DO as solvent. 1H NMR (DO, 500MHz): 9.14, 8.82, 8.79, 8.01 (m, Pr), 5.9-6.01 (1H, =CH), 5.35-5.4 (2H, =CH2), 5.14 (2H, -CH2N). [Figure 6] 1H NMR spectrum of CBZ2 monomer. Prepared by reacting nicotinic acid with 4-vinylbenzyl chloride. Peak assignments are shown in the inset, NMR was performed using DO as solvent. 1H NMR (DO, 500 MHz): 8.75, 8.41, 8.05, 7.89 (m, Pr), 7.18-7.33 (m, benzene), 6.49-6.55 (2H, =CH2), 5.6 (1H, =CH), 5.16 (2H, -CH2N). [Figure 7] 19F NMR spectra of 1M LiTFSI / BMP TFSI solution and zwitterionic monomer solutions. The figure includes NMR spectra of a 1M LiTFSI / BMP TFSI solution (bottom) and ZI monomer solutions containing CBMA, CBZ1, SB2VP, and CBZ2. All samples contain the specific ZI unit:Li+ mole fraction as indicated in the figure legend, and all samples are referenced to 0.5M LiTFSI in DO at -79.15 ppm. [Figure 8] Temperature dependence of ionic conductivity measured for 1M LiTFSI / BMP TFSI solution (green) and electrolyte samples containing zwitterions CBZ1 (purple) and pCBZ2 (pink) (ZI units: Li+ mole fraction of 0.3). The calculated activation energy of ionic conductivity for each electrolyte is shown in the legend next to the name. [Figure 9] Cell impedance response (Nyquist plots) before and after polarization of 1M LiTFSI / BMP TFSI-based electrolytes. Samples include (a) ionic liquid (IL) solution, (b) CBZ1 monomer solution, and (c) pCBZ2 gel. The concentration of zwitterion in (b) and (c) is in ZI units: Li+ mole fraction value of 0.3, and the inset shows the chronoamperometry response to an applied potential of 10 mV. [Figure 10] Synthetic scheme for the reaction of niacin with various monomer building blocks to make zwitterionic monomers CBZ4, CBZ5, CBZ6, CBZ7, and CBZ8. R = acrylate (HC=CHC(O)O-), methacrylate (HC=C(CH)C(O)O-), acrylamide (HC=CHC(O)NH-), or methacrylamide (HC=C(CH)C(O)NH-) groups; X = Cl or Br. Arrows generally represent a two-step process (reaction to quaternize the nitrogen of niacin, followed by reaction with base to deprotonate the carboxylate group to zwitterionize it). [Figure 11] 1H NMR spectrum of CBZ9 monomer (acid version). Prepared by reacting nicotinic acid with 2-bromoethyl methacrylate. Peak assignments are shown in the inset, NMR was performed using DO as solvent. 1H NMR (DO, 500MHz): 9.38, 9.00, 8.93, 8.11, (m,Pr), 5.60-5.96 (2H, =CH2), 4.96 (2H, -CH2O), 4.60 (2H, -CH2N), 1.73 (3H, -CH3). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0030] This disclosure relates to CB-type ZI monomers that have been synthesized for the first time in a simple two-step process (see, e.g., FIG. 1) from nicotinic acid as a precursor. The advantage of these materials is their simple synthesis using naturally occurring reagents (nicotinic acid, niacin). Another potential advantage is that they are strongly Li + - the hydrophobicity of the pyridinium cationic unit combined with a coordinating carboxylate anionic unit.

[0031] This disclosure describes a strategy for the chemical synthesis of a novel class of zwitterionic (ZI) monomers and their (co)polymers derived from a naturally occurring, non-toxic, and low-cost starting material: nicotinic acid, also known as niacin, or a form of vitamin B3. ZI monomers and their (co)polymers are of practical importance due to their antifouling properties, high degree of hydration, biocompatibility, and strong electrostatic interactions with ions. The disclosed experiments demonstrate the successful synthesis of various ZI monomers using nicotinic acid as a starting material, resulting in a novel ZI functional group inspired by trigonelline (1-methylpyridine-l-ium-3-carboxylate), an alkaloid ZI small molecule found in several plants, such as the coffee plant (e.g., coffea arabica). This particular ZI functional group has not been widely explored or reported in synthetic monomers / (co)polymers to date. It therefore represents an important new addition to the ZI monomer / polymer community. NMR spectroscopy has demonstrated that the carboxylate anion units of these ZI monomers are Li + It has been shown to strongly interact with cations, and in ionic liquid-based electrolytes (e.g., for Li-ion batteries), + In addition, the relatively hydrophobic pyridinium cationic units of these ZI monomers are predicted to enhance the tunability of nanopore properties in filtration membranes based on copolymer selective layers incorporating these ZI units.

[0032] The ZI monomers and (co)polymers disclosed herein represent a new class of carboxybetaine (CB)-type zwitterions. We demonstrate that one such novel homopolymer (pCBZ2) exhibits Li(II) transport properties in ionic liquid-based ionogel electrolytes that are comparable to another CB-type zwitterionic homopolymer (pCBMA), which is more expensive and difficult to synthesize. +We have already demonstrated the ability to improve conductivity (Table 1). This new class of monomers / (co)polymers can therefore provide benefits for non-volatile Li-ion battery gel electrolytes and possibly even solid polymer electrolytes. These materials also allow for fine tuning of copolymer selective layers for water filtration applications based on their CB type and combination of hydrophobic pyridinium motifs. More generally, these (co)polymers can be antifouling and biocompatible, leading to biomedical applications (such as wound dressings or implant surface coatings). The present disclosure is also useful for battery development, water purification, and biomedical devices.

[0033] In some embodiments, the polymer comprises a plurality of monomers, at least a portion of which are zwitterionic, including betaines having a pyridinium group and a carboxylate group.

[0034] In some embodiments, the polymer is a hydrogel. In some embodiments, the carboxylate group is attached to C3 of the pyridinium group. In some embodiments, the zwitterion further comprises an alkyl, allyl, aryl, vinylbenzyl, acrylate, methacrylate, acrylamide, or methacrylamide group. In some embodiments, the zwitterion comprises CBZ1 (shown in FIG. 1), CBZ2 (shown in FIG. 1), CBZ3 (shown in FIG. 4), CBZ4 (shown in FIG. 10), CBZ5 (shown in FIG. 10), CBZ6 (shown in FIG. 10), CBZ7 (shown in FIG. 10), CBZ8 (shown in FIG. 10), or a combination thereof. In certain embodiments, the polymer is a copolymer further comprising a hydrophobic monomer, a charged monomer, an ionic monomer, or a combination thereof.

[0035] In some embodiments, a filtration membrane (e.g., a water filtration membrane), a coating material (e.g., a bioimplant coating material, an implant surface coating material, a biomedical device coating material, an antifouling material), a wound dressing, an ionic liquid-based electrolyte (e.g., an ionogel electrolyte), a polymer electrolyte, a Li-ion battery having an ionic liquid-based or polymer electrolyte, or a drug delivery formulation comprises the disclosed polymers.

[0036] In some embodiments, a method for preparing a carboxybetaine monomer includes reacting nicotinic acid with a halide to obtain a cationic intermediate; and reacting the cationic intermediate with a base to obtain the carboxybetaine monomer.

[0037] In some embodiments, a method for preparing a polymer comprising a carboxybetaine monomer comprises polymerizing a plurality of carboxybetaine monomers obtained by reacting nicotinic acid with a halide to obtain a cationic intermediate and reacting the cationic intermediate with a base to obtain a carboxybetaine monomer.

[0038] definition Unless otherwise defined herein, scientific and technical terms used in this application shall have the meanings that are commonly understood by those skilled in the art. Generally, the nomenclature used in connection with, and techniques of, chemistry, cell and tissue culture, molecular biology, cell and cancer biology, neurobiology, neurochemistry, virology, immunology, microbiology, pharmacology, genetics, and protein and nucleic acid chemistry described herein are well known and commonly used in the art.

[0039] The methods and techniques of the present disclosure are generally carried out according to conventional methods well known in the art and described in various general and more specific references cited and discussed throughout this specification, unless otherwise indicated.See, for example, "Principles of Neural Science", McGraw-Hill Medical, New York, NY (2000); Motulsky, "Intuitive Biostatistics", Oxford University Press, Inc. (1995); Lodish et al., "Molecular Cell Biology, 4th ed.", WH Freeman & Co., New York (2000); Griffiths et al., "Introduction to Genetic Analysis, 7th ed.", WH Freeman & Co., NY (1999); and Gilbert et al., "Developmental Biology, 6th ed.", Sinauer Associates, Inc., Sunderland, MA (2000).

[0040] Chemical terms used herein, unless otherwise defined herein, are used according to conventional usage in the art as exemplified by "The McGraw-Hill Dictionary of Chemical Terms", Parker S., Ed., McGraw-Hill, San Francisco, Calif. (1985).

[0041] As used herein, the term "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes cases where the event or circumstance occurs as well as cases where it does not occur. For example, "optionally substituted alkyl" means that the alkyl may be substituted and also includes cases where the alkyl is not substituted.

[0042] It is understood that the substituents and substitution patterns on the compounds of the present invention can be selected by one of ordinary skill in the art to result in chemically stable compounds that can be readily synthesized from readily available starting materials by techniques known in the art as well as the methods described below. When a substituent is itself substituted with multiple groups, it is understood that these multiple groups can be on the same carbon or on different carbons as long as a stable structure results.

[0043] As used herein, the term "optionally substituted" refers to one to six hydrogen radicals in a given structure being replaced with the radical of a specified substituent, including, but not limited to, hydroxyl, hydroxyalkyl, alkoxy, halogen, alkyl, nitro, silyl, acyl, acyloxy, aryl, cycloalkyl, heterocyclyl, amino, aminoalkyl, cyano, haloalkyl, haloalkoxy, -OCO-CH2-O-alkyl, -OP(O)(O-alkyl)2, or -CH2-OP(O)(O-alkyl). Preferably, "optionally substituted" refers to one to four hydrogen radicals in a given structure being replaced with the above-mentioned substituents. More preferably, one to three hydrogen radicals are replaced by the above-mentioned substituents. It is understood that the substituents may be further substituted.

[0044] Articles such as "a," "an," and "the" can mean one or more, unless otherwise indicated or clear from the context. A claim or description containing "or" between one or more members of a group is considered to be satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process, unless indicated to the contrary or clear from the context. The invention includes embodiments in which exactly one member of a group is present in, employed in, or otherwise relevant to a given product or process. The invention also includes embodiments in which more than one or all of the group members are present in, employed in, or otherwise relevant to a given product or process.

[0045] As used herein, the term "alkyl" refers to a saturated aliphatic group, C1 to C 10 Straight chain alkyl group or C1-C 10 Including, but not limited to, branched alkyl groups. Preferably, the "alkyl" group refers to a C1-C6 straight chain alkyl group or a C1-C6 branched chain alkyl group. Most preferably, the "alkyl" group refers to a C1-C4 straight chain alkyl group or a C1-C4 branched chain alkyl group. Examples of "alkyl" include, but are not limited to, methyl, ethyl, 1-propyl, 2-propyl, n-butyl, sec-butyl, tert-butyl, 1-pentyl, 2-pentyl, 3-pentyl, neo-pentyl, 1-hexyl, 2-hexyl, 3-hexyl, 1-heptyl, 2-heptyl, 3-heptyl, 4-heptyl, 1-octyl, 2-octyl, 3-octyl or 4-octyl, and the like. The "alkyl" group may be substituted. EXAMPLES

[0046] The present disclosure is further described with reference to the following specific examples, which are offered by way of illustration and not by way of limitation of the scope of the disclosure or the claims that follow.

[0047] Introduction Zwitterionic (ZI) polymers are a diverse subclass of materials that have been the focus of research in many areas, including drug delivery, bioimplants, antifouling materials, and electrochemical energy storage. 1-6 There are several different types of zwitterionic chemicals and materials that highlight their unique properties and potential as battery electrolytes. 7-11 However, a major drawback to the widespread use of zwitterions is the limited number of chemicals that are commercially available or easy to synthesize. 12Although a variety of chemistries can be found in the literature, only a handful are readily available commercially, most of which are sulfobetaine (SB) zwitterions. Even those available are very difficult to synthesize and have low yields. Therefore, there is a continuing need to develop novel zwitterionic chemistries, especially those containing carboxybetaine (CB) and phosphorylcholine (PC) motifs that lower the synthetic barrier and increase the availability of zwitterions for future applications.

[0048] Of the zwitterions that have been studied and synthesized in the literature, several have been motivated by existing structures found in nature. One of the best-known commercially available ZI monomers, 2-methacryloyloxyethyl phosphorylcholine (MPC), is inspired by phospholipids found in cell membranes. 13-15 Due to its high biocompatibility and hydrophilicity, over the years, MPC has been used in numerous biological applications such as antifouling coatings for implants. 16,17 Another recent example of a nature-inspired zwitterionic polymer is derived from trimethylamine N-oxide (TMAO). TMAO, an organic osmolyte found in saltwater fish, is a new class of zwitterionic material that does not fall into one of the three major categories (carboxybetaines, sulfobetaines, phosphorylcholines). Although characterized by only a single covalent bond between the cationic and anionic zwitterionic moieties, TMAO-derived zwitterionic polymers exhibit extremely high hydrophilicity and antifouling potential, which are important for the development of novel biomaterials. 18 The naturally occurring zwitterionic molecule known as trigonelline (N-methylnicotinic acid) contains a CB-type carboxylate anion and a pyridinium cation. 19 Trigonelline, found in coffee beans and other plant seeds, can be converted to nicotinic acid upon roasting at high temperatures and is a useful precursor material for the synthesis of novel CB-type zwitterionic monomers. 20 .

[0049] Two novel bioinspired CB-type zwitterions are synthesized from nicotinic acid with different polymerizable groups. The monomers are then mixed into lithium-containing ionic liquid electrolytes and their effects on ion transport performance are compared with several existing chemicals. 11 The first monomer, synthesized with allyl bromide, showed moderate yields slightly lower than those observed for CBMA. 7 The Li 1D NMR chemical shifts were observed. However, due to the difficulty in polymerizing the allyl groups by radical polymerization, it was not possible to form an ionogel, which resulted in only minimal changes in ion transport. In contrast, a second monomer made with 4-vinylbenzyl chloride (VBC) showed negligible chemical shifts but moderate improvements in lithium conductivity by DC polarization and AC impedance spectroscopy measurements. These results support the understanding of the mechanism of Li 1D NMR in an ionic liquid (IL) environment. + The importance of the interlocking polymer network and the solubility of polyzwitterions to transport is shown, and these factors should be considered when designing and synthesizing new zwitterionic monomers. Results using available chemistry demonstrated that zwitterions derived from nicotinic acid are easy to synthesize and can have a beneficial effect on the properties of ionogel electrolytes.

[0050] Experimental Method material N-Butyl-N-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMP TFSI) (high purity grade), lithium bis(trifluoromethylsulfonyl)imide (LiTFSI), and 2-hydroxy-2-methylpropiophenone (HOMPP) were purchased from MilliporeSigma and stored in a N2-filled glove box (H2O, O2 < 1 ppm). Synthesis reagents, nicotinic acid, allyl bromide, 4-vinylbenzyl chloride, anhydrous dimethylformamide (DMF), and tetrahydrofuran (THF) were purchased from Sigma Aldrich. Lithium foil (99.9%, 0.75 mm thick) was purchased from Alfa Aesar and stored in an Ar-filled glove box (H2O, O2 < 0.5 ppm) until coin cells were prepared. Celgard separators (25 μm thick) and stainless steel (SS) coin cell parts (CR2032) were purchased from MTI Corp.

[0051] Synthesis of CBZ1 Nicotinic acid was dissolved in anhydrous DMF in a 1:15 molar ratio and stirred at 50°C until completely dissolved. In low light conditions, allyl bromide was added in a 1:1 molar ratio to nicotinic acid and the reaction was run overnight (can be confirmed by the color change of the solution). The monomer product was recovered by precipitating the DMF solution in THF and cooled in an ice bath until a solid was formed. The monomer product was then washed with additional THF, reprecipitated, and dried at low temperature in vacuum overnight. To make the product zwitterionic, the monomer was added to a 5 wt% NaOH solution in H2O and stirred for at least 1 hour. The zwitterionic monomer (CBZ1) was finally recovered by precipitating in acetone in an ice bath and drying under vacuum. The final product was dried under vacuum at room temperature and stored in a refrigerator until use. NMR spectroscopy was performed on a Bruker AVANCE III 500MHz NMR spectrometer using DO as the solvent. 1 H NMR (D2O, 500MHz): 9.14,8.82,8.79,8.01(m,Pr),5.9-6.01(1H,=CH),5.35-5.4(2H,=CH2),5.14(2H,-CH2N).

[0052] Synthesis of CBZ2 For the synthesis of CBZ2, nicotinic acid is again dissolved in anhydrous DMF in a 1-15 molar ratio and stirred at 50 °C until completely dissolved. For monomer reactivity, the solution is first cooled to room temperature and then 4-vinylbenzyl chloride (VBC) is added to the solution in a 1:1 molar ratio. The reaction is run overnight and a visible change in the opacity of the solution (becoming milky white) can be observed. The monomer product is recovered by precipitating the DMF solution in tetrahydrofuran (THF) and cooled in an ice bath until a solid is formed. The monomer product is then washed with additional THF, reprecipitated, and dried in vacuum at low temperature overnight. Precipitation was also attempted in diethyl ether, but overall THF was found to be a better non-solvent that worked well even at room temperature. To make the product zwitterionic, the monomer is added to a 5 wt% NaOH solution in H2O and stirred for at least 1 hour. The zwitterionic monomer (CBZ2) is recovered by precipitation in acetone at low temperature and dried under vacuum. The final product is stored in a refrigerator until use. NMR spectroscopy of CBZ2 was performed on a Bruker AVANCE III 500 MHz NMR spectrometer using DO as the solvent. NMR (DO, 500 MHz): 8.75, 8.41, 8.05, 7.89 (m, Pr), 7.18-7.33 (m, benzene), 6.49-6.55 (2H, =CH2), 5.6 (1H, =CH), 5.16 (2H, -CH2N).

[0053] Synthesis of CBZ9 [ka]

[0054] Nicotinic acid was dissolved in anhydrous DMF in a 1:15 molar ratio and stirred at 60°C until completely dissolved. 2-Bromoethyl methacrylate was then slowly added dropwise to this mixture in a 1.1:1 molar ratio to nicotinic acid and allowed to react for 48 hours (as confirmed by a color change in the solution). The monomer product was recovered by cooling the reaction mixture in an ice bath and precipitating in THF (1:20 ratio) for at least one day. The precipitate was then filtered and dried at room temperature for one day, followed by drying under vacuum for an additional day. NMR spectroscopy was performed on the acid version of the monomer on a Bruker AVANCE III 500MHz NMR spectrometer using DO as the solvent. 1 H NMR (D2O, 500MHz):9.38,9.00,8.93,8.11,(m,Pr),5.60-5.96(2H,=CH2),4.96(2H,-CH2O),4.60(2H,-CH2N),1.73(3H,-CH3).

[0055] Preparation of lithium-containing ionic liquid electrolytes and ionogels A conventional IL / lithium salt solution electrolyte was prepared by dissolving LiTFSI in BMP TFSI at a concentration of 1 M and stirring overnight at 50 °C in a N2-filled glove box until a homogenous solution was obtained. The ZI monomer was converted to the desired ZI unit: Li + Monomer solutions were prepared by adding CBZ2 in a ratio of 0.2 to 0.4 ZI units / (ZI units+Li) in 1M LiTFSI / BMP TFSI electrolyte (i.e., ZI unit concentrations of 0.25 to 0.67M). + ) mole fractions in the range of 1:4 to 2:3, corresponding to ZI units: Li + Molar ratios were used. For clarity, ZI units: Li +Mole fraction values ​​are used to label the experimental data. To prepare the ionogels, HOMPP photoinitiator (2 wt% on monomer basis) was added to the monomer solution, which was stirred for 10 min, and then polymerization was achieved by UV irradiation at 365 nm for 10 min using a handheld lamp (Spectronic Corp., 8 W). The ionogel samples were stored in a glove box overnight before use.

[0056] 1. Preparation of Coin Cells Coin cells for DC polarization measurements were prepared by loading liquid electrolyte into the pores of a Celgard separator or polymerizing ionogel into the pores of a Celgard separator to standardize the geometry and thickness of the cell electrolyte layer. The electrolyte solution was allowed to infiltrate into the Celgard separator (17 mm diameter and 25 μm thickness) for at least 2 h under mild vacuum conditions (prior to UV irradiation, in the case of ionogel precursor solution). Lithium / electrolyte / Li coin cells were assembled in an Ar-filled glovebox and Li was charged into the coin cells using glass vials. + Disks of metal (approximately 15 mm in diameter) were rolled and the lithium metal surface was polished before use. To determine the temperature dependence of ionic conductivity, SS / electrolyte / SS coin cells were prepared using SS disk electrodes (15.5 mm in diameter); the electrolyte was confined using a ring-shaped Teflon spacer (7.6 mm inner diameter and 1.6 mm thickness) placed between the SS electrodes. All coin cells were sealed using a digital pressure-controlled electric crimper (MTI Corp.).

[0057] Nuclear magnetic resonance spectroscopy measurements 1D NMR spectra were obtained using a Bruker AVANCE III 500 MHz NMR spectrometer with a standard multinuclear broadband observe probe with z-gradient. Spectroscopic measurements were performed using a relaxation delay of 0.1 ms and a total of 32 scans at room temperature (20°C). The nuclei examined were 7 Li and 19 F and Li +and TFSI - The local environment was observed. A solution of 0.5 M LiTFSI in D2O was used as the reference and locking solution for all samples. All samples were prepared in glass capillary tubes (inner diameter 1.5 mm) which were placed in a standard NMR tube (inner diameter 5 mm) containing the reference solution for the measurements.

[0058] Electrochemical measurements All electrochemical measurements were performed using a VersaSTAT3 potentiostat with a built-in frequency analyzer (Princeton Applied Research). AC impedance spectroscopy was used to measure the ionic conductivity of the IL, SIL, and polyzwitterion-supported ionogels for both electrolyte systems. Room temperature ionic conductivity measurements were performed in a N2-filled glove box using a custom Teflon cell, and measurements were made over a frequency range of 1 Hz to 100 kHz using a sinusoidal voltage amplitude of 10 mV. Temperature-dependent ionic conductivity measurements were performed using a symmetric SS / electrolyte / SS coin cell fixed to a temperature-controlled microscope stage (Linkam Scientific Instruments, LTS 420). During heating and cooling cycles, a 10 min hold time at each temperature was utilized to ensure thermal equilibrium, and all temperature-dependent Arrhenius model trend lines had an R of 0.99 or greater. 2 Value matched.

[0059] Using the method developed by Bruce and coworkers, DC polarization of a symmetric Li / electrolyte / Li coin cell resulted in Li + transference number(t Li+ ) was calculated. Before the measurement, -2 A 2-hour constant current charging period at 0.01 mAcm was followed by a 2-hour constant potential hold and finally a 2-hour constant current charging period at 0.01 mAcm -2The cells were preconditioned using a constant current discharge at 1000 mA. After the preconditioning step was completed, an additional 12 hour rest period was performed before any experiments were performed. Li was measured by DC polarization / chronoamperometry measurement using an applied potential of 10 mV for 2 hours. + Transference number determinations were performed and AC impedance spectra were recorded both before and after the measurements.

[0060] Results and Discussion Synthesis and characterization In this work, we designed and synthesized two carboxybetaine-based zwitterionic monomers starting from nicotinic acid. In both cases, nicotinic acid was dissolved in anhydrous DMF and reacted with alkyl halide monomers to generate intermediate cationic products. The monomers were then dissolved in 5 wt% aqueous NaOH to give COO - The anionic group was deprotonated to create the zwitterionic monomer. The synthesis and final chemical structures of both monomers are outlined in Figure 1. During the synthesis of the monomer in the first step, the formation of the product is visually confirmed by the solution turning opaque white. Additionally, a slight color change is observed upon rendering the monomer zwitterionic in NaOH solution.

[0061] The two monomers synthesized both have the same CB-type zwitterionic moiety (pyridinium cation and carboxylate anion), but have very different polymerizable groups that affect their solution behavior. In aqueous systems, both monomers are readily soluble (despite the large non-polar benzyl group on CBZ2), and little difference is observed between the two. However, significant differences are observed with regard to solubility in lithium-containing IL electrolytes, and are shown in Figure 2 for solutions of CBZ1 and CBZ2 in 1M LiTFSI / BMP TFSI. These solutions are characterized by the ZI unit: Li +The molar ratio was chosen to be 0.3, which is equivalent to about 3 wt. % for CBZ1 and 4.5 wt. % for CBZ2. At about 3 wt. %, CBZ1 shows moderate solubility in 1 M LiTFSI / BMP TFSI and a slight yellow color observable in solution. Lowering the concentration does not result in a clear solution, suggesting some degree of incompatibility between the pyridinium-based cationic group and the specific IL environment. In comparison, the CBZ2 monomer is even less soluble, likely due to the benzene ring, and forms an opaque white solution at all concentrations tested.

[0062] Another important difference between these monomers is the nature of the polymerizable group. The allyl groups on CBZ1 are known to be difficult to react by radical polymerization, and all attempts in ILs, organic and aqueous solvent environments using both thermal and photoinitiators were unsuccessful. As a result, ionogels could not be made with CBZ1, and all subsequent electrochemical measurements in this work were performed with monomer solutions at specific concentrations. In contrast, polymerization was achieved with CBZ2, which was 1 This was observed by the reduction of the vinyl peak in H NMR and the formation of a non-flowable ionogel. Notably, a similar concentration in neat BMP TFSI (without lithium salt) remained liquid and did not gel, which is due to Li complexed with the ZI monomer. + It can be suggested that ions may act as bridges to form physical crosslinks in the gel.

[0063] 1D NMR chemical shifts The monomer solutions were screened using 1D NMR chemical shifts to investigate the interaction between the ZI moiety and Li ions. 7By analyzing the Li chemical shifts, insight into changes in the local electronic environment can be gained. Several other monomer solutions tested were visually clear homogeneous solutions. In comparison, the nicotinic acid-based zwitterion showed lower solubility at comparable concentrations in 1M LiTFSI / BMP TFSI. Nevertheless, 1D NMR can still provide useful insights, and the spectra of the IL electrolyte, the two zwitterions synthesized in this experiment, as well as CBMA and SB2VP are shown in Figure 3.

[0064] In another study, compared with the peak IL electrolyte environment, 7 The largest downfield shift in the peak position of the Li NMR signal was observed in the monomer solution of CBMA. This shift suggests a significant Coulombic interaction between the CB-type zwitterionic moieties, and a similar effect is seen in the first newly synthesized ZI monomer, CBZ1. As can be seen in Figure 3, CBZ1 shows a moderate downfield shift, comparable to that of CBMA at a slightly lower concentration. 7 Li peak shift (ZI unit: Li + A mole fraction of 0.3 results in a Δδ of approximately 0.4 ppm. The difference in chemical shifts could be due to the lower solubility of CBZ1 in ILs or the result of different behavior of the cationic moiety. However, this result is consistent with the COO shift seen in CB-type zwitterions. - The anion group is Li + This supports our understanding that CBZ2 can have strong interactions with the SB zwitterion. In comparison, nothing similar is observed for CBZ2, which only shows a very small downfield shift more comparable to the SB zwitterion (ZI units: Li + (At a mole fraction of 0.3, Δδ is about 0.1 ppm.) This difference may result from the significantly lower solubility of CBZ2 due to the presence of a benzene ring. The large mass of undissolved monomer limits the accessibility of the zwitterionic moiety and the Li + This is thought to reduce the possibility of interaction with ions. 19The F peak chemical shift is also observed (see Figure 7). This is further supported by the flattening of the peak intensity resulting from the low solubility and increased viscosity of the solution. In an IL environment where both ZI monomers are well soluble, we speculate that the chemical shifts will be quite close since the zwitterionic motifs are identical.

[0065] Characterization of ion transport The temperature dependence of the total ionic conductivity near ambient conditions (approximately 0°C to 100°C) and the lithium ion transport number value (t Li+ , Li for the total current in the applied electric field + The percentage of current carried by the LiTFSI / BMP TFSI electrolyte (the percentage of current carried by the LiTFSI / BMP TFSI electrolyte) was measured using AC impedance spectroscopy and DC polarization, respectively, for the same electrolyte formulations. These values ​​are summarized in Table 1 for 1M LiTFSI / BMP TFSI and the corresponding zwitterionic samples. Same ZI units: Li + Data for ionogel samples containing pCBMA and pSB2VP for molar ratio comparison are also included. Temperature-dependent ionic conductivity data for novel CB-type monomers, as well as t Li+ DC polarization and AC impedance spectroscopy data used to determine σ values ​​were also obtained (see Figures 8 and 9). At room temperature, the zwitterion-containing samples exhibited ionic conductivity (σ) values ​​that were nearly identical to the neat liquid, suggesting that the ZI groups promote a higher degree of dissociation of ion clusters / pairs in the electrolyte.

[0066] More interestingly, despite having comparable total ionic conductivities, t Li+ and E a For CBZ1, the values ​​are almost equivalent to the neat liquid, and there is no improvement in lithium transport as observed for CBMA. This is due to the large downfield 7 This seems to contradict previous trends that showed that zwitterions with Li chemical shifts also exhibit improved Li-ion transport. Li+One possible explanation for why is not changed by the addition of CBZ1 is that it is not a polyzwitterionic sample. In a previous study, our group hypothesized that Li-ion hopping along the polyzwitterionic chains is the mechanism for improved Li-ion mobility in SBVI:MPC copolymer ionogels. 8 , which may be the reason why nonpolymerizable CBZ1 does not show the same benefit. This is due to the t measured for pCBZ2, which shows a moderate difference from neat IL and CBZ1. Li+ and E a This is further supported by the E a A slight decrease in and a moderate increase in lithium conductivity were observed for pCBZ2, suggesting that polyzwitterions are important for improving ion transport properties. Lithium conductivity (σ Li+ ) is lower than the highest value achieved with pCBMA, likely a result of the lower solubility of pCBZ2, which reduces the effective concentration of available zwitterion. Although a direct comparison between the two chemicals is currently difficult, the improved performance of pCBZ2 compared to the neat IL electrolyte demonstrates that nicotinic acid-derived zwitterions can be effective for use in ionogel electrolytes.

[0067] [Table 1]

[0068] These CB-type zwitterions, CBZ1 and CBZ2, were tested in 1M LiTFSI / BMP TFSI and compared with several other chemicals. Improved lithium conductivity was observed for pCBZ2-containing ionogels, and the low solubility due to the benzene ring limited the interaction between the zwitterion and the IL. This is despite the fact that they have the same zwitterionic motif. 7Highlighted by the chemical shift differences between CBZ1 and CBZ2 observed through Li 1D NMR chemical shifts, the shift for CBZ1 is closer to CBMA, while the shift for CBZ2 is minimal. The synthesis of a third nicotinic acid-based zwitterion using 2-chloroethyl acrylate as the polymerizable group is shown in Figure 4. Variations of the synthesis of several additional zwitterionic monomers are shown in Figure 10. Compared to the allyl groups found on CBZ1, acrylates react very readily via radical polymerization and are chemically similar to the functional groups found on several zwitterionic monomers. Additionally, due to the absence of large non-polar rings in the structure, we expect significant improvement in solubility from CBZ2 in 1M LiTFSI / BMP TFSI. Although there may be a lower solubility limit compared to CBMA, it is envisioned that this acrylate-based zwitterionic monomer (CBZ3) can form an ionogel that boosts Li-ion transport.

[0069] While various embodiments have been shown and described in detail herein, it will be apparent to those skilled in the art that various modifications, additions, substitutions, and the like, can be made without departing from the spirit of the disclosure, and therefore are deemed to be within the scope of the disclosure as defined in the following claims.

[0070] (1) Blackman, LD; Gunatillake, PA; Cass, P.; Locock, KES An Introduction to Zwitterionic Polymer Behavior and Applications in Solution and at Surfaces. Chem. Soc. Rev. 2019, 48, 757-770. (2) Xuan, F.; Liu, J. Preparation, Characterization and Application of Zwitterionic Polymers Andmembranes: Current Developments and Perspective. Polym. Int. 2009, 58, 1350-1361. (3) Sun, J.; MacFarlane, D. R.; Byrne, N.; Forsyth, M. Zwitterion Effect in Polyelectrolyte Gels Based on Lithium Methacrylate-N,N-Dimethyl Acrylamide Copolymer. Electrochim. Acta 2006, 51, 4033-4038. (4) Bengani-Lutz, P.; Converse, E.; Cebe, P.; Asatekin, A. Self-Assembling Zwitterionic Copolymers as Membrane Selective Layers with Excellent Fouling Resistance: Effect of Zwitterion Chemistry. ACS Appl. Mater. Interfaces 2017, 9, 20859-20872. (5) Leigh, B. L.; Cheng, E.; Xu, L.; Derk, A.; Hansen, M. R.; Guymon, C. A. Antifouling Photograftable Zwitterionic Coatings on PDMS Substrates. Langmuir 2019, 35, 1100-1110. (6) Lin, X.; Boit, M. O. K.; Wu, K.; Jain, P.; Liu, E. J.; Hsieh, Y. F.; Zhou, Q.; Li, B.; Hung, H. C.; Jiang, S. Zwitterionic Carboxybetaine Polymers Extend the Shelf-Life of Human Platelets. Acta Biomater. 2020, 109, 51-60. (7) Qin, H.; Panzer, M. J. Zwitterionic Copolymer-Supported Ionogel Electrolytes Featuring a Sodium Salt / Ionic Liquid Solution. Chem. Mater. 2020, 32, 7951-7957. (8) D'Angelo, A. J.; Panzer, M. J. Decoupling the Ionic Conductivity and Elastic Modulus of Gel Electrolytes: Fully Zwitterionic Copolymer Scaffolds in Lithium Salt / Ionic Liquid Solutions. Adv. Energy Mater. 2018, 8, 1801646. (9) Taylor, M. E.; Panzer, M. J. Fully-Zwitterionic Polymer-Supported Ionogel Electrolytes Featuring a Hydrophobic Ionic Liquid. J. Phys. Chem. B 2018, 122, 8469-8476. (10) Taylor, M. E.; Lounder, S. J.; Asatekin, A.; Panzer, M. J. Synthesis and Self-Assembly of Fully Zwitterionic Triblock Copolymers. ACS Mater. Lett. 2020, 2, 261-265. (11) Taylor, M. E.; Clarkson, D.; Greenbaum, S. G.; Panzer, M. J. Examining the Impact of Polyzwitterion Chemistry on Lithium Ion Transport in Ionogel Electrolytes. 2021, 3, 2635-2645. (12) Damodaran, V. B.; Murthy, S. N. Bio-Inspired Strategies for Designing Antifouling Biomaterials. Biomater. Res. 2016, 20, 1-11. (13) Shaplov, A. S.; Marcilla, R.; Mecerreyes, D. Recent Advances in Innovative Polymer Electrolytes Based on Poly(Ionic Liquid)S. Electrochim. Acta 2015, 175, 18-34. (14) Ueda, T.; Oshida, H.; Kurita, K.; Ishihara, K.; Nakabayashi, N. Preparation of 2-Methacryloyloxyethyl Phosphorylcholine Copolymers with Alkyl Methacrylates and Their Blood Compatibility. Polym. J. 1992, 24, 1259-1269. (15) Ishihara, K.; Ueda, T.; Nakabayashi, N. Preparation of Phospholipid Polylners and Their Properties as Polymer Hydrogel Membranes. Polym. J. 1990, 22, 355-360. (16) Feng, W.; Brash, J.; Zhu, S. Atom-Transfer Radical Grafting Polymerization of 2-Methacryloyloxyethyl Phosphorylcholine from Silicon Wafer Surfaces. J. Polym. Sci. Part A Polym. Chem. 2004, 42, 2931-2942. (17) Ma, Y.; Tang, Y.; Billingham, N. C.; Armes, S. P.; Lewis, A. L. Synthesis of Biocompatible, Stimuli-Responsive, Physical Gels Based on ABA Triblock Copolymers. Biomacromolecules 2003, 4, 864-868. (18) Li, B.; Jain, P.; Ma, J.; Smith, J. K.; Yuan, Z.; Hung, H. C.; He, Y.; Lin, X.; Wu, K.; Pfaendtner, J.; Jiang, S. Trimethylamine N-Oxide-Derived Zwitterionic Polymers: A New Class of Ultralow Fouling Bioinspired Materials. Sci. Adv. 2019, 5, eaaw9562. (19) Ashihara, H.; Ludwig, I. A.; Katahira, R.; Yokota, T.; Fujimura, T.; Crozier, A. Trigonelline and Related Nicotinic Acid Metabolites: Occurrence, Biosynthesis, Taxonomic Considerations, and Their Roles in Planta and in Human Health. Phytochem. Rev. 2015, 14, 765-798. (20) Kalaska, B.; Piotrowski, L.; Leszczynska, A.; Michalowski, B.; Kramkowski, K.; Kaminski, T.; Adamus, J.; Marcinek, A.; Gebicki, J.; Agric. Food Chem. 2014, 62, 2853-2860.

[0071] Incorporation by Reference All U.S. patents and U.S. and PCT patent application publications referred to herein are incorporated herein by reference in their entirety as if each individual patent or patent application publication was specifically and individually indicated to be incorporated by reference. In the case of conflict, the present application, including any definitions herein, will control.

[0072] Equivalent Those skilled in the art will recognize or be able to ascertain, using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims. The scope of the embodiments described herein is not intended to be limited to the above description, but is as set forth in the appended claims. Those skilled in the art will appreciate that various changes and modifications to this description can be made without departing from the spirit or scope of the invention, as defined in the following claims.

Claims

1. A polymer comprising a plurality of monomers, wherein at least a part of the monomers is an zwitterion comprising a betaine having a pyridinium group and a carboxylate group.

2. The polymer according to Claim 1, which is a hydrogel.

3. The polymer according to Claim 1, wherein the carboxylate group is bonded to C3 of the pyridinium group.

4. The polymer according to Claim 1, wherein the zwitterion further comprises an alkyl, allyl, aryl, vinylbenzyl, acrylate, methacrylate, acrylamide, or methacrylamide group.

5. The zwitterion is 【Chemical Formula 1-1】 【Chemical Formula 1-2】 or any combination thereof, and R represents acrylate (-OC(O)CH=CH ２ ), methacrylate (-OC(O)C(CH ３ )=CH ２ ), acrylamide (-NHC(O)CH=CH ２ ), or methacrylamide (-NHC(O)C(CH ３ )=CH ２ ), the polymer according to claim 1.

6. The polymer according to Claim 1, which is a copolymer further comprising a hydrophobic monomer, a charged monomer, an ionic monomer, or any combination thereof.

7. A filtration membrane comprising the polymer according to any one of Claims 1 to 6.

8. The filtration membrane according to Claim 7, which is a water filtration membrane.

9. A coating material comprising the polymer according to any one of Claims 1 to 6.

10. The coating material according to Claim 9, which is a bioimplant coating material.

11. The coating material according to Claim 9, which is an implant surface coating material.

12. The coating material according to Claim 9, which is a biomedical device coating material.

13. The coating material according to Claim 9, which is an anti-fouling material.

14. A wound dressing comprising the polymer according to any one of Claims 1 to 6.

15. An electrolyte comprising the polymer according to any one of Claims 1 to 6, which is an ionic liquid-based electrolyte or a polymer electrolyte.

16. The electrolyte according to Claim 15, which is an ionogel electrolyte.

17. A lithium ion battery comprising the electrolyte according to Claim 15.

18. A drug delivery formulation comprising the polymer according to any one of Claims 1 to 6.

19. A method for preparing a carboxybetaine monomer, comprising: reacting nicotinic acid with an electrophile to obtain a cation intermediate; and reacting the cation intermediate with a base to obtain a carboxybetaine monomer. The method comprising the above steps.

20. The method according to Claim 19, further comprising a solvent.

21. The method according to claim 20, wherein the solvent is DMF.

22. The method according to claim 19, wherein the electrophile is a halide or an epoxide.

23. The electrophile is [Chemical 2] wherein R is substituted or unsubstituted alkyl, allyl or vinyl, and X is halogen, the method according to claim 22.

24. The method according to claim 23, wherein the halogen is bromine, chlorine, fluorine or iodine.

25. The method according to claim 22, wherein the electrophile is a halide, and the halide is allyl bromide, 4-vinylbenzyl chloride, or 2-chloroethyl acrylate.

26. The carboxybetaine monomer is 【Chemical Formula 3】 wherein R is substituted or unsubstituted alkyl, allyl or vinyl, the method according to claim 19.

27. The cation intermediate is 【Chemical Formula 4】 wherein, the method according to claim 26.

28. The method according to claim 19, wherein the base is an alkali hydroxide.

29. The method according to claim 28, wherein the alkali hydroxide is sodium hydroxide.

30. The carboxybetaine monomer is 【Chemical Formula 5】 wherein, the method according to claim 19.

31. A method for preparing a polymer comprising a carboxybetaine monomer, comprising polymerizing a plurality of carboxybetaine monomers obtained by the method according to any one of claims 19 to 30, thereby preparing a polymer.

Images