Functional diphenylsulfone macromers with grafted polymeric sidechains plus copolymers and articles prepared therefrom

Abstract

Functional diphenylsulfone macromers with grafted polymeric sidechains, copolymers 5 having repeat units derived from the functional diphenylsulfone macromers with grafted polymeric sidechains, and porous polymeric articles containing these copolymers are provided. The grafted polymeric sidechains contain repeat units derived from 2-oxazoline compounds. The porous polymeric article is typically a membrane that can be either a flat sheet or a hollow fiber. The porous polymeric articles can be used to separate mixtures of biomaterials having different average 0 sizes based on the average pore size of the porous polymeric articles. For example, biomaterials such as bacteria, proteins, viruses, and cells can be separated based on size.

Description

[0001] FUNCTIONAL DIPHENYLSULFONE MACROMERS WITH GRAFTED POLYMERIC

[0002] SIDECHAINS PLUS COPOLYMERS AND ARTICLES PREPARED THEREFROM

[0003] Background

[0004] Separation devices having a porous polymeric substrate have been used in a wide range of different industrial, pharmaceutical, and medical applications. Some of these separation devices function by separating a mixture of materials based on the average size of the materials in the mixture. These separation devices typically retain materials of a certain size such as those having a diameter larger than the diameter of the pores in the polymeric substrate while allowing passage of other materials having a diameter smaller than the diameter of the pores in the polymeric substrate.

[0005] Membranes formed from poly ether sulfone (PES) have been used for separating biological materials such as proteins, viruses, and cells based on size. The pore size of PES membranes can be tuned during membrane casting to suit a particular filtration need. Additionally, hydrophilic homopolymers such as, for example, poly(vinyl pyrrolidone) (PVP), poly(oxazoline) (POx), and polyethylene glycol) (PEG) can be added to the membrane casting solution to render the membrane hydrophilic and therefore somewhat resistant to biofouling. However, membranes cast with these hydrophilic homopolymers frequently are not uniformly hydrophilic and remain susceptible to fouling when contaminated compositions are passed through them. Additionally, because these hydrophilic homopolymers are typically water soluble, a fraction of them can be extracted from the membrane during use. Therefore, users typically perform a pre-flush of the membrane to lower the extractable content to a suitable level before filtering the compositions of interest.

[0006] Summary

[0007] Functional diphenylsulfone macromers with grafted polymeric sidechains, copolymers having repeat units derived from the functional diphenylsulfone macromers with grafted polymeric sidechains, and porous polymeric articles containing these copolymers are provided. The grafted polymeric sidechains contain repeat units derived from 2-oxazoline compounds and are usually polymeric. The porous polymeric article is typically a membrane that can be either a flat sheet or a hollow fiber. The porous polymeric articles can be used, for example, to separate mixtures of biomaterials having different average sizes based on the average pore size of the porous polymeric articles. For example, biomaterials such as proteins, viruses, and cells can be separated based on size.

[0008] In a first aspect, a compound of Formula (I) is provided.

[0009] Each R1is independently a leaving group or a nucleophilic group. Each R2is independently a grafted polymeric sidechain comprising a plurality of repeat units of formula -N(C(=O)-R3)-CH2-CH2-. Group R3is an alkyl, alkenyl, aryl, or combination thereof. The variables p and q are each an integer in a range of 0 to 4 with the sum of p + q being an integer equal to at least 1. The compounds of Formula (I) can be referred to as macromers.

[0010] In a second aspect, a copolymer is provided. The copolymer comprises a plurality of repeat units joined by -O- groups. The plurality of repeat units includes (a) a first repeat unit of Formula (II) and (b) a second repeat unit of Formula (III).

[0011] Each R2is independently a grafted polymeric sidechain comprising a plurality of repeat units of formula -N(C(=O)-R3)-CH2-CH2-. The variables p and q are each equal to 0, 1 or 2 with the sum of p + q being an integer equal to at least 1. Group R3is an alkyl, alkenyl, aryl, or combination thereof. Each asterisk (*) is an attachment site to an -O- group that joins repeat units.

[0012] In many embodiments of the second aspect, the first repeat unit of Formula (II) is of Formula (II-A) and / or Formula (II-B)

[0013] (II-A) (II-B) and the second repeat unit of Formula (III) is of Formula (III -A).

[0014] (III-A)

[0015] Each asterisk (*) is an attachment site to an -O- group that joins repeat units.

[0016] In a third aspect, a porous polymeric article is provided that comprises the copolymer described above in the second aspect. In most embodiments, the porous polymeric article is a membrane.

[0017] In a fourth aspect, a method of separating biomaterials based on size is provided. The method includes providing a porous polymeric article as described above in the third aspect and passing an aqueous mixture of biomaterials through the porous polymeric article, wherein the mixture of biomaterials comprises a plurality of bio materials having different average sizes. The method further includes separating the mixture of biomaterials based on their average sizes, wherein a first biomaterial that is smaller than a second biomaterial permeates through the porous polymeric article at a faster rate.

[0018] As used herein, the terms “a”, “an”, “the”, and “at least one” are used interchangeably.

[0019] The term “and / or” means either or both. For example, “A and / or B” means A alone, B alone, or both A and B.

[0020] The term “alkyl” refers to a monovalent group that is a radical of an alkane. The alkyl group can have 1 to 32 carbon atoms, 1 to 20 carbon atoms, 1 to 12 carbon atoms, 1 to 10 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms. The alkyl can be linear, branched, cyclic, or a combination thereof. A linear alkyl has at least one carbon atom while a cyclic or branched alkyl has at least 3 carbon atoms.

[0021] The term “(hetero)alkyl” refers to an alkyl, heteroalkyl, or both.

[0022] The term “heteroalkyl” refers to an alkyl having one or more of the catenated carbon atoms replaced by a heteroatom such as oxygen (-O-), sulfur (-S-), and nitrogen (e.g., -NRb- where Rbis hydrogen or an alkyl). If there is more than one heteroatom, they are separated by at least one carbon atom.

[0023] The term “alkylene” refers to a divalent group that is a radical of an alkane. The alkylene group can have 1 to 32 carbon atoms, 1 to 20 carbon atoms, 1 to 12 carbon atoms, 1 to 10 carbon atoms, 1 to 6 carbon atoms, or 1 to 4 carbon atoms. The alkylene can be linear, branched, cyclic, or a combination thereof. A linear alkylene has at least one carbon atom while a cyclic or branched alkylene has at least 3 carbon atoms.

[0024] The term “(hetero)alkylene” refers to an alkylene or heteroalkylene. The term “heteroalkylene” refers to an alkylene having one or more of the catenated carbon atoms replaced by a heteroatom such as oxygen (-O-), sulfur (-S-), and nitrogen (e.g., -NRb- where Rbis hydrogen or an alkyl). If there is more than one heteroatom, they are separated by at least one carbon atom.

[0025] The term “alkenyl” refers to a monovalent group that is a radical of an alkene, which is a hydrocarbon compound having at least one carbon-carbon double bond. In some embodiments, the alkenyl has a single carbon-carbon double bond. In some more specific embodiments, the alkenyl has an ethylenically unsaturated group (the carbon-carbon double bond is between the last two carbon atoms in a chain). The alkenyl can be linear, branched, cyclic or a combination thereof. The alkenyl often has at least 2, at least 3, at least 4, or at least 5 carbon atoms and can have up to 32 carbon atoms, up to 24 carbon atoms, up to 20 carbon atoms, up to 12 carbon atoms, up to 10 carbon atoms, or up to 5 carbon atoms.

[0026] The term “acyl” refers to a monovalent group of formula -C(=O)-Rawhere Rais an alkyl group as defined above.

[0027] The term “aryl” refers to a monovalent group that is a radical of an aromatic carbocyclic compound. The aryl group has at least one aromatic carbocyclic ring and can have 1 to 3 optional rings that are connected to or fused to the aromatic carbocyclic ring. The additional rings can be aromatic, aliphatic, or a combination thereof. The aryl group usually has 5 to 20 carbon atoms or 6 to 10 carbon atoms.

[0028] The term “(hetero)aryl” refers to an aryl, heteroaryl, or both.

[0029] The term “heteroaryl” refers to a monovalent group that is a radical of an aromatic heterocyclic compound. The heteroaryl has at least one aromatic heterocyclic ring and can have optional rings that are connected or fused to the aromatic heterocyclic ring. The additional rings can be aromatic, aliphatic, or a combination thereof. The heteroaryl typically has 5 to 20, 5 to 12, or 5 to 10 ring atoms with at least one ring atom being a heteroatom such as oxygen, sulfur, or nitrogen.

[0030] The term “leaving group” refers to a group that can depart from a compound with a pair of electrons such as, for example, -F, -Cl, -Br, -I, CF3SO3-, and -SO2-C6H4-CH3.

[0031] The term “nucleophilic group” refers to a group that has an electron-rich atom that can donate a pair of electrons to form a covalent bond. As used herein, the nucleophilic group is often hydroxy (-OH) or -O-Si(Rc)3 where Rcis an alkyl or aryl.

[0032] The term “macromer” is used to refer to a reactive compound having a polymeric group. More particularly, as used herein, the term macromer refers to a functional diphenylsulfone compound having (1) at least two functional groups that are leaving groups or nucleophilic groups and (2) a covalently attached (grafted) polymeric sidechain that is derived from ethylenically unsaturated monomers. The number of functional groups is typically two. The term “monomer” is used herein to refer to a reactive compound that does not have a polymeric group. The monomer is typically a compound at least two functional groups that are leaving groups or nucleophilic groups. The number of functional groups is usually equal to two.

[0033] The terms “polymer” and “polymeric material” are used interchangeably and refer to materials formed by reacting one or more monomers. The terms include homopolymers, copolymers, terpolymers, or the like. Likewise, the terms “polymerize” and “polymerizing” refer to the process of making a polymeric material that can be a homopolymer, copolymer, terpolymer, or the like. The term “copolymer” is used herein to refer to a polymer and polymeric materials derived from more than one type of monomer and / or macromer.

[0034] The terms “casting solution" and “polymer dope” are used interchangeably to refer to the composition used to form a porous membrane.

[0035] The term “membrane” refers to a porous article that is formed from a polymeric composition. The membrane can be in the form of a flat sheet or a hollow fiber. The membranes described herein are typically prepared using a phase separation process.

[0036] For any stated range, the endpoints are considered part of the range.

[0037] Brief Description of the Drawings

[0038] FIG.1 illustrates a perspective view of a partial cross-section of a portion of an exemplary hollow fiber membrane.

[0039] FIG. 2 illustrates a cross-section view of an exemplary hollow fiber membrane.

[0040] FIG. 3 is a scanning electron micrograph of a cross section of an exemplary hollow fiber membrane of Example HFM-1.

[0041] FIG. 4 is a scanning electron micrograph of a lumen wall of an exemplary hollow fiber membrane of Example HFM-1.

[0042] FIG. 5 is a scanning electron micrograph of an outside wall of an exemplary hollow fiber membrane of Example HFM-1.

[0043] Detailed Description

[0044] Functional diphenylsulfone macromers having grafted polymeric sidechains derived from a 2-oxazoline compound, copolymers having repeat units derived from the functional diphenylsulfone macromers with grafted polymeric sidechains, and porous polymeric articles containing the copolymers are provided. The porous polymeric article, which is typically a membrane that can be either a flat sheet or a hollow fiber, can be used to separate mixtures of materials such as biomaterials having different average sizes. Further, the porous articles have chemical functionalities that can provide one or more desirable characteristics such as water wettability, resistance to fouling by proteins and other hydrophobic components of the fluids that are treated, ion exchange capabilities, absorption of certain fluid components, and / or the ability to adjust the effective pore size during use in response to changes in an environmental characteristic such as pH of the treated fluid.

[0045] Advantageously, because the copolymers include macromeric units having covalently attached polymeric sidechains that are hydrophilic, the amount of pre-flushing that needs to be done to remove extractable hydrophilic polymers from a porous polymeric article prepared from these copolymers can be substantially reduced. Additionally, the grafted polymeric sidechains of the copolymer result in the formation of membranes with uniform hydrophilic surfaces. Consequently, these membranes tend to have greater resistance to fouling than those formed using hydrophilic homopolymers. Additionally, the copolymers with grafted polymeric sidechains are typically amphiphilic but not water soluble. Because these copolymers are typically not water soluble, they are typically less extractable than the previously used hydrophilic homopolymers.

[0046] Functional diphenylsulfone macromers with grafted polymeric sidechains

[0047] Functional diphenylsulfone macromers are provided with grafted polymeric sidechains derived from a 2-oxazoline compound. These macromers with grafted polymeric sidechains typically have at least two functional groups that can react with other monomers to form a copolymer. The functional groups can be either leaving groups or nucleophilic groups.

[0048] The functional diphenylsulfone macromers are of Formula (I).

[0049] Each R1is independently a functional group that is either a leaving group or a nucleophilic group. Each R2is independently a grafted polymeric sidechain comprising a plurality of repeat units of formula -N(C(=O)-R3)-CH2-CH2-. Group R3is an alkyl, alkenyl, aryl, or combination thereof. The variables p and q are each an integer in a range of 0 to 4 with the sum of p + q being an integer equal to at least 1. In most embodiments, p and q are each in a range of 0 to 2 or 0 to 1.

[0050] Each group R1is independently a leaving group or a nucleophilic group. Suitable leaving groups include, for example, -F, -Cl, -Br, -I, -SO3-CF3-, and -SO2-C6H4-CH3. Suitable nucleophilic groups include, for example, -OH or -O-Si(R6)3 where each R6group is an alkyl such as those having 1 to 4 carbon atoms. If R1is a hydroxy group, it is typically protected during the formation of the R2grafted polymeric sidechains. For example, the hydroxy group can be protected as a -O-Si(R6)3 group. If desired, the nucleophilic group -O-Si(R6)3 can be converted to a -OH group after formation of the compound of Formula (I) having the grafted polymeric sidechains. It is the group R1that is reactive (i.e., functional) when a polymeric material (i.e., copolymer) is formed that includes repeat units derived from the macromer of Formula (I).

[0051] In the macromer of Formula (I), a first aromatic ring can have p groups of formula R2while a second aromatic ring can have q groups of formula R2. The variable p and q are each an integer in a range of 0 to 2 with the sum of p + q being equal to at least 1. Thus, the number of R2groups in the macromer of Formula (I) is equal to 1 , 2, 3 , or 4. In many embodiments, there is a single R2group per macromer (p + q is equal to 1) or a single R2group on each aromatic ring (p + q is equal to 2).

[0052] Each R2is independently a grafted polymeric sidechain comprising a plurality of repeat units of formula -N(C(=O)-R3)-CH2-CH2-. Group R3is an alkyl, alkenyl, aryl, or a combination thereof. While R2includes a plurality of groups of formula -N(C(=O)-R3)-CH2-CH2-, not all these groups need to have the same R3group. That is, R2can contain a first repeat group of formula -N(C(=O)-R3A)-CH2-CH2- and a second repeat group of formula -N(C(=O)-R3B)-CH2-CH2- with R3Aand R3Bbeing different R3groups. These first and second repeat groups can be arranged randomly or in blocks. Thus, the grafted polymeric sidechains can be homopolymers or random copolymers.

[0053] In addition to the plurality of repeat units of formula -N(C(=O)-R3)-CH2-CH2-, the grafted sidechain optionally can include repeat units of formula -NH-CH2-CH2-. These groups can result, for example, from hydrolysis of some of the groups of formula -N(C(=O)-R3)-CH2-CH2-. Thus, group R2can contain n repeat units of formula -N(C(=O)-R3)-CH2-CH2- and m repeat units of formula -NH-CH2-CH2-. Typically, the value of n is in a range of 0 to 2 percent of the sum of m + n (i.e., m n + m) is in a range of 0 to 0.02). Stated differently, the amount of the group -N(C(=O)-R3)-CH2-CH2- is in a range of 98 to 100 weight percent and the group -NH-CH2-CH2- is in a range of 0 to 2 weight percent based on the total weight of repeat groups in the grafted sidechain. These repeat units are typically arranged randomly but, for ease of discussion can be written as -[N(C(=O)-R3)-CH2-CH2]„-[NH-CH2-CH2]m-.

[0054] In many embodiments, the sum of n + m is in a range of 3 to 1000. This sum can be at least 3, at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, at least 100, at least 200, at least 300, at least 400, or at least 500 and up to 1000, up to 900, up to 800, up to 700, up to 600, up to 500, up to 400, up to 300, up to 200, up to 100, up to 90, up to 80, up to 70, up to 60, up to 50, up to 40, up to 30, or up to 20. For example, the sum can be in a range of 3 to 500, 3 to 100, 5 to 100, or 5 to 50.

[0055] Group R3is an alkyl, alkenyl, aryl, or combination thereof. The alkyl often has 1 to 10 carbon atoms such as at least 1, at least 2, at least 3, or at least 4 and up to 10, up to 8, up to 6, or up to 4 carbon atoms. Example alkenyl groups typically have 2 to 10 carbon atoms such as at least 2, at least 3, at least 4 and up to 10, up to 8, up to 6, or up to 4. Example alkenyl groups include, but are not limited to, -C(CH3)=CH2. The aryl group is often phenyl. Combination groups include, for example, an alkyl substituted with a phenyl group, an alkenyl substituted with a phenyl group, a phenyl substituted with an alkyl group, or a phenyl substituted with an alkenyl.

[0056] Oxazoline compounds that are commercially available include, for example, 2-ethyl oxazoline, 2- isopropyl oxazoline, 2-isopropenyl oxazoline, 2-phenyl oxazoline, and 2-butyl oxazoline where R3is respectively, ethyl, isopropyl, isopropenyl, phenyl, and butyl.

[0057] The repeat units in R2of formula -[N(C(=O)-R3)-CH2-CH2]n-[NH-CH2-CH2]m- can be attached to a phenyl group in the functional diphenylsulfone macromer of Formula (I) by any suitable group R4. In many embodiments, group R4is an alkylene, alkylene-C(=O)-, alkylene- ary lene-C(=O)-, alkylene-arylene-alkylene, or alkylene-arylene-alkylene-C(=O)-, wherein the attachment site of R4to the adjacent group of formula -N(C(=O)-R3)-CH2-CH2- in R2is a primary carbon atom, a secondary carbon atom, or a -C(=O)- group. An alkylene group in R4can have any suitable number of carbon atoms but typically has 1 to 10 carbon atoms. The number of carbon atoms can be at least 1, at least 2, at least 3, or at least 4 and up to 10, up to 8, up to 6, or up to 4 carbon atoms. An arylene group in R4can have 6 to 10 carbon atoms but is often phenylene. Example alkylene groups include -CH2- and -CH(CH3)- and example alkylene-C(=O)- groups include -CH2-C(=O)-. Example alkylene-arylene-C(=O)- include -CH2-phenylene-C(=O)-, example alkylene-arylene-alkylene groups include -CEE-phenylene-CEE-, and example alkylene- arylene-alkylene-C(=O)- groups include -CH2-phenylene-CH2-C(=O)-.

[0058] Further, the polymeric sidechain R2can be terminated with any suitable end group Q. The end group is typically a group resulting from a reaction of the growing polymeric chain with a quenching agent. Thus, the grafted sidechain is often of formula -R4-[N(C(=O)-R3)-CH2-CH2]n- [NH-CH2-CH2]m-Q.

[0059] In some embodiments, the monomer of Formula (I) is of Formulas (I-A) or (I-B).

[0060] (I-A) (I-B)

[0061] In these embodiments, p and q in Formula (I) is either 0 or 1 with the sum (p + q) being 1 or 2. The groups R1and R2are the same as described above for Formula (I). There can be a mixture of macromers of Formula (I-A) and (I-B)

[0062] Any suitable method can be used to form the macromers of Formula (I) such as those of Formula (I-A) and (I-B). In some embodiments, the suitable macromers and isomers thereof can be formed using a method such as that described in Reaction Scheme A. Reaction Scheme A

[0063] (4) (7)

[0064] In this reaction scheme, a pre-assembled diphenylsulfone with two leaving groups (L) (compound (1)) can be reacted sequentially in tetrahydrofuran with butyl lithium, dimethylformamide, and sodium borohydride to form a mixture of compounds (2) and (3). Compound (2) and / or compound (3) can then be reacted with phosphorous bromide in the presence of a solvent such as dichloromethane. In practice, compounds (2) and (3) are often separated from each other using column chromatography prior to treatment with phosphorous bromide. For ease of description of the reaction scheme, the reaction with phosphorous bromide is shown only for compound (2). The brominated compound (4) can then be reacted to graft a sidechain to the diphenylsulfone compound. Compound (4) is first reacted with the ethyl oxazoline compound having an R3group (compound (5)) and then with a quenching agent (compound (6)) as shown in the reaction above. The terminal group Q is derived from the quenching agent. The grafted group in Reaction Scheme A is of formula -CH2-[N(C(=O)-R3)-CH2-CH2]n-Q. Alternatively, the sidechain is of formula -CH2-[N(C(=O)-R3)-CH2-CH2]n-[NH-CH2-CH2]m-Q if a small amount of hydrolysis occurs. Group R3as well as variables n and m are described above. In compound (7), group R4is -CH2- but other R4groups can be used as described above.

[0065] The quenching agent (6) in Reaction Scheme A typically has a nucleophilic group that reacts with an end of the growing polymeric chain. Any known quenching agent can be used. Suitable quenching agents include, but are not limited, to compounds such as water, alcohols (e.g., methanol, ethanol, or isopropanol), sodium phenoxide, pyridine, 4-dimethylaminopyridine, sodium thiophenolate, lithium 4-tert-butylphenoxide, and the like. The resulting sidechains are shown in Table A below for these quenching agents. Some quenching agents that can be used may result in a mixture of compound (7) materials with different Q groups or even result in attachment of multiple functionalized diphenylsulfone compounds together. Such quenching agents include, for example, aminobenzoxazole and imidazole. Further, the products produced by the same quenching agent can depend on the composition of group R3as shown in Table A using tertbutanol as the quenching agent. If R3is ethyl and if tert-butanol is used as the quenching agent, a single product is obtained; however, if R3is phenyl and if tert-butanol is used as the quenching agent, a mixture of products is obtained. Typically, it is desirable to select a quenching agent that produces a single product.

[0066] Table A: Structure of Compound (7) with different Q groups

[0067] In some embodiments, the terminal group Q is of formula -X-R5where X is -O-, -S-, or -NH- and R5is hydrogen, an alkyl, an alkyl substituted with an acyl or hydroxy, an alkenyl, an aryl, or aryl substituted with an alkyl. In other embodiments, the terminal group Q is a cationic (hetero)aryl that is optionally substituted with an alkyl or amino group.

[0068] The functional diphenylsulfone macromers of Formula (I) typically have a weight average molecular weight (Mw) ranging from 380 to 50,000 Daltons. The Mw is often at least 380, at least 400, at least 500, at least 1000, at least 1500, at least 2000, at least 2500, at least 3000, at least 4000, at least 5000, at least 10,000, or at least 20,000 Daltons and up to 50,000, up to 45,000, up to 40,000, up to 30,000, up to 25,000, up to 20,000, up to 15,000, up to 10,000, or up to 5,000

[0069] Daltons. For example, the range can be from 380 to 20,000, 500 to 10,000, 1000 to 10,000, 2500 to 10,000, 2000 to 10,000, 2000 to 5000, or 2500 to 5000 Daltons. The weight average molecular weight of the compounds of Formula (I) can be determined by Nuclear Magnetic Resonance (NMR) spectroscopy as described in the Examples below.

[0070] Copolymers having repeat units derived from functional diphenylsulfone macromers with grafted polymeric sidechains

[0071] The difunctional diphenylsulfone macromers with grafted polymeric sidechains of Formula (I) can be used to form copolymers. For ease of discussion, this copolymer is herein referred to as “POLY-1”. POLY-1 is an amphiphilic graft copolymer.

[0072] POLY - 1 is typically formed by reacting a first macromer of Formula (I) having grafted polymeric sidechains of formula R2 with a second monomer of Formula ( having two functional groups R7that are either nucleophilic groups or leaving groups. R1, R2, plus the variables p and q are the same as defined above. The reaction product is typically a copolymer (POLY-1) with repeat units connected via a -O- group. In many embodiments, the first macromer of Formula (I) is of Formula (I- A) and / or (I-B).

[0073] (I-A) (I-B)

[0074] The repeat units of POLY-1 include first repeat units of Formula (II) derived from macromers of Formula (I) and second repeat units of Formula (III) derived from monomers of Formula (IV).

[0075] Copolymer POLY-1 contains a plurality of repeat units joined by -O- groups. Each asterisk (*) is an attachment site to an -O- group that joins repeat units. In many embodiments, POLY-1 has first repeat units of Formula (II- A) and / or (II-B).

[0076] (II-A) (II-B)

[0077] If R1in the first macromer of Formula (I) is a leaving group, then at least some of the second monomer of Formula (IV) has two hydroxy nucleophilic groups as shown in Formula (IVA-1) or two group of formula -O-Si(Rc)3 where each Rcis an alkyl or aryl as shown in Formula (IV-A-2).

[0078] (IV-A-1) (IV-A-2)

[0079] In most embodiments, the second monomer with nucleophilic groups is of Formula (IV-A-1).

[0080] If R1in the first macromer of Formula (I) is a nucleophilic group, however, then at least some of the second monomer of Formula (IV) has two leaving groups as shown in Formula (IV- B).

[0081] (IV-B)

[0082] The two leaving groups are typically -F, -Cl, -Br, -I, CF3SO3-, and -SO2-C6H4-CH3

[0083] In many embodiments, the molar ratio of the first macromer of Formula (I) to the second monomer of Formula (IV) is less than 1. To provide a copolymer with molar ratios less than 1, a mixture of second monomers of Formula (IV) are used with some of the second monomers having R7nucleophilic groups and other second monomers having R7leaving groups. Thus, the second monomer is often a mixture of monomers of Formula (IV-A-1) and / or Formula (IV-A-2) plus monomers of Formula (IV-B). In many embodiments, the second monomer is a mixture of monomers of Formula (IV-A-1) and Formula (IV-B). The first macromer and second monomers are combined such that the total moles of nucleophilic groups are equal to or approximately equal to the moles of leaving groups.

[0084] In many embodiments, the second monomer is of Formula (IV-C), Formula (IV-D), or a mixture thereof.

[0085] The monomer of Formula (IV-C) is within the scope of Formula (IV-A-1) above while the monomer of Formula (IV-D) is within the scope of Formula (IV-B) above. In many embodiments, L is -Cl or -F.

[0086] In some embodiments, each R2comprises a group of formula -R4-[N(C(=O)-R3)-CH2- CH2]n-[NH-CH2-CH2]m-Q where n is an integer equal to at least 1 and m is an integer equal to at least 0. The variables p and q are each equal to 0, 1 or 2 with the sum of p + q being an integer in a range of 1 to 4. Group R4is an alkylene, alkylene-C(=O)-, alkylene-arylene-C(=O)-, alkylene- ary lene-alkylene, or alkylene-arylene-alkylene-C(=O)-, wherein the attachment site of R4to the adjacent group of formula -N(C(=O)-R3)-CH2-CH2- in R2is a primary carbon atom, a secondary carbon atom, or a -C(=O)- group. Group Q is derived from reaction of the growing polymeric chain with a quenching agent, which is typically a nucleophile.

[0087] The copolymer often has first repeat unit of Formula (II- A) and / or Formula (II-B)

[0088] (II-A) (II-B) and second repeat unit of Formula (III- A).

[0089] (III-A)

[0090] Each asterisk (*) is an attachment site to an -O- group that joins repeat units. Such a copolymer is formed from a macromer of Formula (I-A) and / or (I-B)

[0091] (I-A) (I-B) and a second monomer of Formula (IV-C) and / or (IV-D).

[0092] (IV-C) (IV-D)

[0093] A mixture of (IV-C) and (IV-D) is often used. The groups R1, R2, and L are defined above.

[0094] POLY-1 can include additional optional repeat units in addition to those of Formulas (II) and (III). These optional repeat units include the following third repeat units of Formula (V-A), Formula (V-B), Formula (V-C), Formula (V-D), Formula (V-E), or a combination thereof.

[0095] (V-E) wherein an asterisk (*) is the attachment site to an -0- group that joins repeat units. In many embodiments these repeat units are derived from monomers such as, for example, those of Formula (VI-A) to (VI-E) respectively or isomers thereof. In these formulas, the group R8is either a nucleophilic group or a leaving group as described above. In many embodiments, R8is hydroxy.

[0096] (VI-A)

[0097] While any amount of the first macromer of Formula (I) can be used to form POLY-1, the amount typically needs to be controlled if the resulting copolymer POLY-1 is used to prepare a membrane such as those described below. For example, if the membrane is prepared using a phase separation process, the amount of first macromer of Formula (I) needs to be controlled so that POLY-1 is amphiphilic but not water soluble. If the amount of the first macromer of Formula (I) is too low, a membrane formed from the copolymer tends not to have sufficient antifouling characteristics and biomaterials such as proteins can undesirably stick to its surface. Increasing the amount of the first macromer of Formula (I) used to form the graft copolymer POLY-1 tends to increase the amount of POLY- 1 on the membrane surface during solvent induced phase separation (SIPS) casting and tends to provide the desired membrane surface properties (e.g., water wettability and fouling resistance) at lower concentrations of POLY-1 in the casting solution. If the content of the first macromer of Formula (I) is too great, however, POLY-1 may be water soluble. Water solubility of POLY-1 is generally undesirable because this can lead to loss of the copolymer into the precipitation bath during membrane casting and / or to higher water extractability of the graft copolymer from the finished membrane. Thus, it is often desirable to prepare POLY-1 with the maximum amount of the macromer of Formula (I) that can be incorporated while minimizing water solubility. This maximum amount depends on the hydrophilicity of the grafted polymeric sidechains, which in turn depends on the composition of the grafted polymeric sidechains.

[0098] The amphiphilic grafted copolymer POLY-1 is often prepared from a polymerizable composition that contains 10 to 60 weight percent of a first macromer of Formula (I) based on a total weight of the polymerizable material (i.e., macromers and monomers). The amount of the first macromer is often at least 10, at least 15, at least 20, at least 25, or at least 30 weight percent and up to 60, up to 55, up to 50, up to 45, up to 40, up to 35, or up to 30 weight percent based on the total weight of polymerizable composition. In some embodiments, the amount of the first macromer of Formula (I) ranges from 10 to 55, 10 to 50, 10 to 45, 10 to 40, 10 to 30, 15 to 60, 15 to 55, 15 to 50, 15 to 45, 15 to 40, 20 to 60, 20 to 55, 20 to 50, 20 to 45, 20 to 40, 20 to 35, or 20 to 30 weight percent based on the total weight of polymerizable composition.

[0099] In addition to the macromer of Formula (I), the polymerizable composition used to form POLY-1 can contain 40 to 90 weight percent of a second monomer of Formula (IV). The amount of the monomer of Formula (IV) can be at least 40, at least 45, at least 50, at least 55, at least 60, at least 65, or at least 70 and up to 90, up to 85, up to 80, up to 75, up to 70, up to 65, or up to 60 weight percent based on a total weight of polymerizable composition. In some embodiments, the amount of the second monomer of Formula (IV) ranges from 45 to 90, 50 to 90, 55 to 90, 60 to 90, 70 to 90, 40 to 85, 45 to 85, 50 to 85, 55 to 85, 60 to 85, 40 to 80, 45 to 80, 50 to 80, 55 to 80, 60 to 80, 65 to 80, or 70 to 80 weight percent based on the total weight of polymerizable composition.

[0100] In addition to the macromer of Formula (I) and the monomer of Formula (IV), the polymerizable composition used to form POLY-1 can optionally contain 0 to 50 weight percent of a third monomer of Formula (V-A), (V-B), (V-C), (V-D), (V-E), or a mixture thereof. The amount of this third monomer, if present, can be at least 1, at least 2, at least at least 5, at least 10, or at least 15 and up to 50, up to 40, up to 30, up to 25, up to 20, up to 15, up to 10, or up to 5 weight percent based on the total weight of polymerizable composition.

[0101] POLY-1 typically has a weight average molecular weight (Mw) ranging from 10,000 to 250,000 Daltons. The weight average molecular weight is typically at least 10,000, at least 15,000, at least 20,000 at least 25,000, at least 30,000, at least 35,000, at least 40,000, at least 45,000, at least 50,000, at least 75,000, or at least 100,000 Daltons and up to 250,000, up to 225,000, up to 200,000, up to 175,000, up to 150,000, up to 125,000, up to 100,000, up to 80,000, up to 60,000, up to 50,000, up to 40,000, up to 35,000, or up to 30,000 Daltons. In some embodiments, the range is from 20,000 to 200,000, 25,000 to 100,000, from 25,000 to 80,000, from 25,000 to 60,000, from 25,000 to 50,000, or from 25,000 to 40,000 Daltons. The weight average molecular weight can be determined by gel permeation chromatography (GPC) as described in the Examples below.

[0102] Porous polymeric articles

[0103] Porous polymeric articles are provided that contain an amphiphilic grafted copolymer POLY-1 having repeat units derived from the functional diphenylsulfone macromers with grafted polymeric sidechains as described above. Although the porous polymeric article can be in any form, it typically is a membrane. The membrane can be, for example, in the form of a flat sheet or a hollow fiber. The membranes are typically formed by a phase separation process.

[0104] In many embodiments, the phase separation process used to form the membrane is a solvent induced phase separation (SIPS) process and the resulting membrane can be referred to as a “SIPS membrane”. SIPS membranes are sometime referred to by other names such as, for example, “DIPS membranes” formed by diffusion induced phase separation, “NIPS membranes” formed by non-solvent induced phase separation, or as “phase inversion membranes”. These processes are all referred to herein as SIPS processes and the products as SIPS membranes.

[0105] In a SIPS process, the polymeric material is combined with other solution components such as a suitable solvent for the polymeric material to prepare a substantially homogeneous solution that is referred to interchangeably as a “casting solution” or as a “polymer dope”. The casting solution is formed into either a flat sheet using a coating process or a hollow tube using a spinning process. The flat sheet or hollow fiber is then immersed in a “quench solution” containing a non-solvent for the polymeric material. Exchange of the solvent in the casting solution with the non-solvent in the quench solution results in phase separation of the polymer solution yielding a solid, porous flat sheet or hollow fiber. In some embodiments, the flat sheet or hollow fiber can be exposed to a humid atmosphere or steam prior to immersion into the quench solution to begin the phase separation process.

[0106] The casting solution used to form the SIPS membrane typically includes a mixture of polymeric materials and a water-miscible organic solvent. The mixture of polymeric materials includes POLY-1 as described above having grafted polymeric sidechains, a second polymer POLY-2 that is typically an aromatic polyether sulfone lacking grafted polymeric sidechains, and an optional third polymer POLY-3 that is typically a hydrophilic pore former. In addition to the polymeric materials, the casting solution also contains a water-miscible solvent that can dissolve POLY-1, POLY-2, and optional POLY-3. Still further, the casting solution can optionally contain water.

[0107] The casting solution contains POLY-1, which is the copolymer described above that comprises (1) repeat units of Formula (II) that is a diphenylsulfone with at least one grafted polymeric sidechain R2as well as (2) repeat units of Formula (III) that is a diphenylsulfone without grafted polymeric sidechains. The casting solution typically contains 1 to 20 weight percent of POLY-1 based on a total weight of the casting solution. The amount can be at least 1, at least 1.5, at least 2, at least 2.5, at least 3, at least 4, or at least 5 weight percent and up to 20, up to 18, up to 15, up to 12, up to 10, up to 8, or up to 5 weight percent based on the total weight of the casting solution. For example, the amount of POLY-1 can be in a range of 1.5 to 20, 1.5 to 15, 2 to 20, 2 to 15, 2 to 10, or 2 to 5 weight percent based on the total weight of the casting solution. The various repeat units are connected to each other by -O- linkages.

[0108] In addition to POLY-1, the casting solution includes a second polymer that can be referred to as POLY-2. POLY-2 is an aromatic polyether sulfone having repeat units of Formula (III) wherein an asterisk (*) is the attachment site to an -O- group that joins two repeat units. This second polymer can be a homopolymer or copolymer. If POLY-2 is a copolymer, it is free of repeat units of Formula (II) and is made from a polymerizable mixture that is free of the macromer of Formula (I). POLY-2 lacks the grafted polymeric sidechains that are included in POLY-1.

[0109] In some embodiments of POLY-2, the repeat units of Formula (III) are combined with one or more optional repeat units of Formula (V-A), Formula (V-B), Formula (V-C), Formula (V-D), Formula (V-E), or a combination thereof as described above as optional repeat units that can be included in POLY-1. These optional repeat units typically are no greater than 50 mole percent of all the repeat units in POLY-2. That is, they can be present in an amount of 0 to 50 mole percent based on all the repeat units included in POLY-2. For example, these optional repeat units can be up to 50, up to 45, up to 40, up to 35, up to 30, up to 25, up to 20, up to 15, up to 10, or up to 5 mole percent of all the repeat units in POLY-2.

[0110] POLY-2 typically has a weight average molecular weight (Mw) in a range of 30,000 to 150,000 Daltons (30 to 150 kDa). For example, Mw is often at least 30, at least 40, at least 50, at least 60, or at least 70 and up to 150, up to 140, up to 130, up to 120, up to 100, up to 90, up to 80, up to 70, up to 60, or up to 50 kDa. The range can be, for example, from 30 to 120, 50 to 120, or 60 to 100 kDa. The weight average molecular weight can be determined by gel permeation chromatography (GPC) as described in the Examples below. The amount of POLY-2 in the casting solution is typically in a range of 10 to 40 weight percent based on the total weight of the casting solution. The amount can be at least 10, at least 12, at least 15, or at least 20 weight percent and up to 40, up to 35, up to 30, up to 25, up to 20, or up to 15 weight percent based on the total weight of the casting solution. For example, the amount of POLY-2 can be in a range of 10 to 35, 10 to 30, 10 to 25, 12 to 40, 12 to 35, 12 to 30, 12 to 25, 15 to 40, 15 to 35, 15 to 30, 15 to 25, 20 to 40, 20 to 35, or 20 to 30 weight percent based on the total weight of the casting solution. The amount of POLY-2 in the casting solution can impact the pore size of the resulting membrane formed from the casting solution. For example, an increase in the amount of POLY-2 tends to decrease the average pore size of the membrane. Varying the amount of POLY -2 can be used to alter the size of materials that can permeate though the membrane and / or the speed of permeation through the membrane.

[0111] An optional third polymeric material, which is referred to as POLY-3, is often included in the casting solution in addition to POLY-1 and POLY-2. This third polymer is typically selected to be a hydrophilic polymer that has greater water solubility than either POLY-1 or POLY-2. When phase separation occurs in the process of making the membrane, the third polymer (POLY- 3) typically does not undergo phase separation. That is, POLY-3 remains in solution unlike both POLY-1 and POLY-2. Suitable POLY-3 hydrophilic polymers include, for example, poly(2- vinylpyrrolidone), polyethylene glycol, polyvinyl alcohol, polyglycol monoester, carboxylmethylcellulose, a polysorbitate such as polyoxyethylene sorbitan monooleate, carboxymethylcellulose polyacrylic acid, polyacrylamide, poly(oxazoline) a copolymer thereof, or a blend thereof. In many embodiments, POLY-3 is a polyethylene glycol or a polymeric mixture that includes polyethylene glycol.

[0112] POLY-3 can have any desired molecular weight and may comprise a mixture of polymers of multiple molecular weights. In some embodiments the amount of one or more components of POLY-3 in the membrane is desired to be low to reduce its extractability. In such cases the weight average molecular weight of that component of POLY-3 is often less than 1000 Daltons. For example, the weight average molecular weight may be up to 750 Daltons such as in a range of 100 to 750, 100 to 500, 100 to 400, 200 to 750, 200 to 500, or 200 to 400 Daltons. In other embodiments the amount of one or more components of POLY-3 in the membrane is desired to be high to impart greater fouling resistance or to tune the porosity of the membrane. In such cases the weight average molecular weight of that component of POLY-3 is often greater than 1000 Daltons. For example, the weight average molecular weight of that component of POLY-3 can be up to 750,000 Daltons such as in a range of 1,100 to 750,000 Daltons, 1,100 to 500,000 Daltons, 1,100 to 400,000 Daltons, 2,000 to 500,000 Daltons, or 20,000 to 50,000 Daltons. The weight average molecular weight can be determined by gel permeation chromatography (GPC) as described in the Examples below. The amount of POLY-3 in the casting solution is typically in a range of 0 to 65 weight percent based on a total weight of the casting solution. The amount can be at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, or at least 40 weight percent and up to 65, up to 60, up to 55, up to 50, up to 45, up to 40, or up to 35 weight percent based on the total weight of the casting solution. For example, the amount can be in a range of 1 to 65, 1 to 60, 5 to 60, 10 to 60, 10 to 50, 10 to 40, 10 to 30, 20 to 60, 20 to 50, 20 to 40, 30 to 30 to 60, 30 to 50, or 30 to 40 weight percent based on the total weight of the casting solution.

[0113] In addition to POLY-1, POLY-2, and POLY-3, the casting solution can include a water- miscible organic solvent. Water-miscible organic solvents that can be used include, for example, glycol, glycerol, butyrolactone, s-caprolactam, \ -mcth Ipy rrolidone, dimethyl sulfoxide, dimethyl acetoamide, dimethyl formamide, and combinations thereof. In some embodiments, the water- miscible organic solvent includes \ -mcth Ipy rrolidone because it usually is a good solvent for both POLY-1 and POLY-2.

[0114] Any suitable amount of the water-miscible organic solvent can be included in the casting solution. The amount can be, for example, in a range of 20 to 70 weight percent based on a total weight of the casting solution. The amount can be at least 20, at least 25, at least 30, at least 35, at least 40, or at least 45 weight percent and up to 70, up to 65, up to 60, up to 55, up to 50, up to 45, or up to 40 weight percent based on the total weight of the casting solution. For example, the amount can be in a range of 20 to 65, 20 to 60, 20 to 55, 20 to 50, 20 to 45, 20 to 40, 25 to 65, 25 to 60, 25 to 55, 25 to 50, 25 to 45, 25 to 40, 30 to 60, 30 to 55, 30 to 50, 30 to 45, or 30 to 40 weight percent based on the total weight of the casting solution.

[0115] The casting solution can optionally include water. For example, the casting solution can contain 0 to 10 weight percent water. If present, the amount can be at least 1, at least 2, at least 3, at least 4, or at least 5 and up to 10, up to 8, up to 6, up to 5, or up to 4 weight percent based on the total weight of the casting solution. The amount can be, for example, in a range of 1 to 8, 1 to 6, 1 to 5, 2 to 10, 2 to 8, 2 to 6, 2 to 5, 3 to 10, 3 to 8, 3 to 6, or 3 to 5 weight percent based on the total weight of the casting solution.

[0116] In some embodiments, the casting solution contains 1 to 20 weight percent POLY-1, 10 to 40 weight percent POLY-2, 0 to 65 weight percent POLY-3, 20 to 70 weight percent water- miscible organic solvent, and 0 to 10 weight percent water based on a total weight of the casting solution. In some examples, the casting solution contains 1.5 to 15 weight percent POLY-1, 12 to 30 weight percent POLY-2, 20 to 50 weight percent POLY-3, 25 to 55 weight percent water- miscible organic solvent, and 2 to 6 weight percent water. In other examples, the casting solution contains 2 to 10 weight percent POLY-1, 15 to 25 weight percent POLY-2, 30 to 40 weight percent POLY-3, 30 to 40 weight percent water-miscible organic solvent, and 3 to 5 weight percent water. In most embodiments, the casting solution is transparent and macroscopically homogeneous.

[0117] The membrane that is formed from the casting solution can be either in the form of a sheet or a hollow fiber membrane. Both types of membranes can be formed from the casting solution. After casting either a sheet or hollow fiber, the sheet or the hollow fiber is immersed in a quenching bath that results in the precipitation of the membrane. If desired, the membrane can optionally be transferred to a second bath such as a water bath to extract additional materials from the membrane.

[0118] In many embodiments, the precipitation bath includes water and optionally can further include water-miscible organic solvents such as those listed above for use in the casting solution. For example, the precipitation bath often contains 50 to 100 weight percent water and 0 to 50 weight percent of a water-miscible organic solvent. In some embodiments, the precipitation bath includes 55 to 100 weight percent water and 0 to 45 weight percent water-miscible organic solvent or 60 to 100 weight percent water and 0 to 40 weight percent water-miscible organic solvent. The water-miscible solvent is often selected to be \ -mcth lpyrrolidonc.

[0119] While any suitable method can be used to form a membrane sheet, the casting solution is often heated to an elevated temperature such as, for example, in a range of 40 to 80 degrees Celsius. The casting solution can be coated onto a support that is also heated in a range of 40 to 80 degrees Celsius. The film can be prepared as a coating using, for example, a notch bar with a suitable gap height, such as in a range of 25.4 to 508 micrometers. The notch bar is often heated in a range of 40 to 80 degrees Celsius before spreading the casting solution out on the surface of the support. Immediately after forming a film of the casting solution on the support, the coated support is typically immersed into the precipitation bath that is often heated in a range of 40 to 80 degrees Celsius. If desired, the membrane optionally can be further extracted in a second bath that contains water. The membrane can be dried in an oven after formation. The temperature of the oven can be, for example, in a range of 40 to 80 degrees Celsius.

[0120] In some embodiments, the membrane is in the form of a sheet. The sheet typically has a thickness in a range of 30 to 250 micrometers. For example, the thickness can be at least 30, at least 40, at least 50, at least 60, at least 80, or at least 100 and up to 250, up to 225, up to 200, up to 175, up to 150, up to 125, up to 120, up to 110, or up to 100 micrometers. The range can be, for example, from 30 to 200, 30 to 150, 50 to 150, 50 to 125, 50 to 1110, or 50 to 100 micrometers.

[0121] In many embodiments, the membrane is in the form of a hollow fiber. The hollow fiber can be formed by extruding the casting solution through a coaxial spinneret die. This coaxial spinneret die typically has an annular gap as well as a central inner channel that is arranged coaxially to the annular gap. The annular gap is separated from the central inner channel by a needle. The casting solution is introduced into the annular gap while a bore liquid is introduced into the inner chamber. The bore liquid stabilizes the lumen of the hollow fiber membrane as it is formed.

[0122] The spinneret die is selected depending on the desired dimensions of the hollow fiber membranes. While any suitable spinneret die can be used, the outer diameter of the annulus is often in a range of 300 to 1000 micrometers. The annulus outer diameter can be, for example, at least 300, at least 400, at least 500 and up to 1000, up to 800, or up to 600 micrometers. The inner diameter of the annulus, which is also the outer diameter of the needle, is often in a range of 190 to 980 micrometers. The annulus inner diameter can be, for example, at least 190, at least 200, at least 300, or at least 500 and up to 980, up to 900, up to 800, up to 600, or up to 500 micrometers. The inner diameter of the needle is often in a range of 40 to 830 micrometers. The needle inner diameter can be, for example, at least 40, at least 50, at least 75, at least 100, at least 150, at last 200 at least 250, at least 300, at least 350, at least 400 and up to 830, up to 800, up to 750, up to 700, up to 650, up to 600, up to 550, or up to 500 micrometers.

[0123] One exemplary spinneret die has an annulus outer diameter of 1000 micrometers, a needle outer diameter of 980 micrometers, an annular gap of 10 micrometers, a needle inner diameter of 830 micrometers, and a needle thickness of 75 micrometers. Another exemplary spinneret die has an annulus outer diameter of 500 micrometers, a needle outer diameter of 300 micrometers, an annular gap of 100 micrometers, a needle inner diameter of 150 micrometers, and a needle thickness of 75 micrometers. Yet another exemplary spinneret die has an annulus outer diameter of 410 micrometers, a needle outer diameter of 300 micrometers, an annular gap of 55 micrometers, a needle inner diameter of 150 micrometers, and a needle thickness of 75 micrometers. Still another exemplary spinneret die has an annulus outer diameter of 300 micrometers, a needle outer diameter of 190 micrometers, an annular gap of 55 micrometers, a needle inner diameter of 40 micrometers, and a needle thickness of 75 micrometers.

[0124] The bore liquid composition typically includes a water-miscible organic solvent, water, and optionally a hydrophilic polymer such as those listed above for POLY-3. Any suitable water- miscible organic solvent can be used such as those described above for use in the casting solution. In some embodiments, the water-miscible organic solvent used in the bore liquid includes N- methylpyrrolidone and any optional hydrophilic polymer used in the bore liquid includes polyethylene glycol.

[0125] The amount of the water-miscible organic solvent in the bore liquid composition is often in a range of 30 to 95 weight percent based on a total weight of the bore liquid. The amount can be at least 30, at least 35, at least 40, at least 45, or at least 50 weight percent and up to 95, up to 90, up to 85, up to 80, up to 75, up to 70, up to 65, up to 60, up to 55, or up to 50 weight percent. For example, the amount can be in a range of 30 to 90, 30 to 80, 30 to 75, 30 to 70, 30 to 60, 30 to 50, 40 to 90, 40 to 80, 40 to 75, 40 to 70, 40 to 60, or 40 to 50 weight percent. The amount of water in the bore liquid composition is often in a range of 1 to 55 weight percent based on a total weight of the bore liquid. The amount can be at least 1.5, at least 2, at least 2.5, at least 3, at least 4, at least 5, at least 10 weight percent and up to 55, up to 50, up to 45, up to 40, up to 35, up to 30, up to 25, up to 20, up to 15, or up to 10 weight percent. For example, the amount can be in a range of 1 to 50, 1 to 40, 1 to 30, 1 to 20, 1 to 15, 1 to 10, 2 to 50, 2 to 40, 2 to 30, 2 to 20, 2 to 15, 2 to 10, 5 to 50, 5 to 40, 5 to 30, 5 to 20, or 5 to 15 weight percent.

[0126] The amount of the optional hydrophilic polymer in the bore liquid composition is often in a range of 0 to 60 weight percent based on the total weight of the bore liquid. The amount can be 0, at least 1, at least 5, at 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40 weight percent and up to 60, up to 55, up to 50, up to 45, up to 40, up to 35, or up to 30 weight percent. For example, the amount can be in a range of 0 to 50, 10 to 60, 10 to 55, 10 to 50, 10 to 45, 10 to 40, 20 to 60, 20 to 55, 20 to 50, 20 to 45, 20 to 40, 30 to 60, 30 to 55, 30 to 50, 30 to 45, 40 to 60, or 40 to 50 weight percent.

[0127] Overall, the bore liquid composition contains 30 to 95 weight percent water-miscible organic solvent, 1 to 55 weight percent water, and 0 to 60 weight percent of the optional hydrophilic polymer. In some examples, the bore liquid composition contains 35 to 80 weight percent water-miscible organic solvent, 2 to 40 weight percent water, and 20 to 55 weight percent hydrophilic polymer. In other examples, the bore liquid composition contains 35 to 75 weight percent water-miscible organic solvent, 2 to 20 weight percent water, and 30 to 55 weight percent hydrophilic polymer. In still other examples, the bore liquid composition contains 40 to 50 weight percent water-miscible organic solvent, 5 to 15 weight percent water, and 40 to 50 weight percent hydrophilic polymer. Typically, the bore liquid is transparent and macroscopically homogenous.

[0128] As noted above, the bore liquid is introduced into the inner chamber while the casting solution is introduced into the annular gap of the coaxial spinneret die. In some embodiments, the casting solution is passed through a fdter to remove any particulate materials prior to introduction into the annular gap. Both fluid streams are often heated prior to introduction into the die. For example, both fluid streams can be heated in a range of 30 to 80 degrees Celsius. The flow rate of the bore liquid and the flow rate of the casting solution each usually can be independently controlled.

[0129] After leaving the coaxial spinneret die and before entering the precipitation bath, the extruded product optionally passes through a climate-controlled zone with defined climatic conditions. The climate-controlled zone is often in the form of an encapsulated chamber. The extruded product often has a retention time no greater than 10 seconds within the climate- controlled zone having a relative humidity of 20 to 95 percent and a temperature of 25 to 75 degrees C. The relative humidity is often at least 40, at least 50, at least 55, at least 60, at least 65, at least 70, or at least 75 percent and up to 90, up to 85, up to 80, up to 75, or up to 70 percent. The temperature is often at least 25, at least 30, at least 35, at least 40, at least 45, or at least 50 degrees Celsius and up to 90, up to 85, up to 80, or up to 75 degrees Celsius. For example, the climate-controlled zone contains air with a relative humidity of 75 to 90% and a temperature of 30 to 50 °C, a relative humidity of 60 to 75% and a temperature of 50 to 70°C, or a relative humidity of 75 to 90% and a temperature of 50 to 70°C.

[0130] The retention time within the climate-controlled zone is often at least 0.5, at least 1, at least 2, or at least 3 and up to 10, up to 8, up to 6, or up to 5 seconds. To establish stable conditions in the climate-controlled zone, the air often flows through the climate-controlled zone with a velocity of less than 0.5 m / s and preferably with a velocity in the range from 0.15 to 0.35 m / s.

[0131] As the extruded product is directed through the climate-controlled zone set to the climatic conditions, pre-coagulation may occur on the outside of the extruded product by absorption of water vapor acting as the non-solvent, before entering the precipitation bath.

[0132] After passing through the climate-controlled zone, the extruded product is directed into the precipitation bath that is in a range of 50 to 80 degrees Celsius to complete the formation of the hollow fiber membrane structure. The composition of the precipitation bath can be the same as described above for prepare membranes in the form of sheets. In the precipitation bath, the membrane structure is formed by precipitation (e.g., coagulation) and then stabilized. Extraction of the water-miscible solvents and the hydrophilic polymer occurs at the same time. That is, water, the water-miscible organic solvent, and the optional hydrophilic POLY-3 can be extracted. The pores of the membrane are formed within the precipitation bath due to the phase separation and extraction processes that occur.

[0133] After formation and extraction within the precipitation bath, the hollow fiber membrane can be processed using conventional methods. For example, the hollow fiber membrane optionally can be further treated by pouring deionized water through the lumen and extracted in water at an elevated temperature such as, for example, 70 to 100 degrees Celsius for several hours.

[0134] After drying either at room temperature or elevated temperatures, the hollow fiber membrane can be wound onto a coil or formed directly into bundles with a suitable fiber count and length. Before production of the bundles, supplementary threads in the form of multifilament yams can be added to the hollow fiber membranes to ensure a spacing of the hollow fiber membranes relative to one another for better flow around the individual hollow fiber membranes in the bundle.

[0135] The membrane typically contains 1 to 50 weight percent POLY-1 based on a total weight of the membrane. For example, the membrane can contain at least 1, at least 2, at least 3, at least 5, at least 10, at least 15, at least 20, or at least 25 and up to 50, up to 45, up to 40, up to 35, up to 30, up to 25, or up to 20 weight percent POLY-1. The amount can be in a range of 2 to 50, 2 to 40, 3 to 30, 5 to 30, 5 to 25 or 5 to 20 weight percent based on a total weight of the membrane. In addition to POLY-1, the membrane typically contains 50 to 99 weight percent POLY-2 based on a total weight of the membrane. The amount of POLY-2 can be at least 50, at least 55, at least 60, at least 65, at least 70, at least 75, or at least 80 and up to 99, up to 98, up to 97, up to 95, up to 90, up to 85, up to 80, up to 75 based on a total weight of the membrane. The amount of POLY-2 can be in a range of 50 to 98, 60 to 98, 70 to 97, 70 to 95, 75 to 95, or 80 to 95 based on a total weight of the membrane.

[0136] The membrane may optionally contain POLY-3, the water-miscible organic solvent, and / or water. The amount of POLY-3 is typically in a range of 0 to 20 weight percent based on the total weight of the membrane. For example, the amount of POLY-3 can be at least 0.1, at least 0.5, or at least 1, at least 2, at least 3, or at least 5 and up to 20, up to 15, up to 10, up to 8, or up to 5 weight percent. The amount of water-miscible organic solvent is typically in a range of 0 to 1 weight percent based on the total weight of the membrane. For example, the amount of the water- miscible organic solvent can be at least 0.05, at least 0.1, at least 0.2, at least 0.3, or at least 0.5 and up to 1, up to 0.8, up to 0.6, up to 0.5, up to 0.3, or up to 0.1 weight percent.

[0137] FIG. 1 illustrates a perspective view of a partial cross-section of a portion of an exemplary hollow fiber membrane 12. Hollow fiber membrane 12 may have a continuous hollow lumen 16 that extends from one end to the other end of the fiber. An outer surface 18 facing outwards forms an outer side of the fiber and an inner surface 20 facing towards the hollow lumen 16 define a fiber portion 26 having a wall thickness 28. The fiber portion 26 is typically porous and contains a polymeric blend comprising a mixture of POLY- 1 and POLY-2.

[0138] The hollow fiber membranes formed are typically an integrally asymmetric, permeable hollow fiber membrane. As used herein, the term “asymmetric” means that the average pore size varies throughout the wall thickness 28. The term “integrally” means that the pore size changes gradually in size over the wall thickness 28 of the fiber portion 26.

[0139] The wall thickness 28 of the fiber portion 26, measured between the outer surface 18 and the inner surface 20 of the fiber 26 portion of the hollow fiber membrane 12, can be in the range of from 10 to 400 micrometers or 20 to 300 micrometers. The fiber portion 26 is formed from the casting solution. The wall thickness can be at least 10, at least 20, at least 30, at least 40, at least 50, at least 60, at least 80, or at least 100 micrometers and up to 400, up to 350, up to 300, up to 275, up to 250, up to 225, up to 200, up to 175, up to 150, up to 125, up to 100, up to 80, or up to 60, or up to 50 micrometers. In some hollow fiber membranes, the wall thickness is in a range of 30 to 200, 30 to 100, 40 to 150, 40 to 100, 40 to 80, or 40 to 60 micrometers.

[0140] Similarly, to achieve a desirable flow and / or pressure drop through the lumen of the hollow fiber membranes, the inside diameter of the hollow fiber membranes, which corresponds to the diameter of the inner wall 20 in FIG. 1, is often in the range of from 50 to 800 micrometers. This diameter can be at least 50, at least 60, at least 80, at least 100, at least 150, at least 200, at least 250, or at least 300 micrometers and up to 800, up to 700, up to 600, up to 500, up to 400, up to 300, or up to 200 micrometers. In some hollow fiber membranes, the inside diameter is in a range of 50 to 700, 50 to 600, 100 to 500, 100 to 400, 100 to 300, or 100 to 200 micrometers.

[0141] Wall thicknesses and diameters (i.e., inner or lumen diameter, and outer diameter) of the membranes can be determined using scanning or transmission electron micrographs (SEM or TEM, respectively), for example with a magnification up to 20,000 times. In some embodiments, the hollow fiber membrane can have tortuous structures extending from the inner surface toward to the outer surface.

[0142] FIG. 2 illustrates a cross-section view of an exemplary hollow fiber membrane 112. Hollow fiber membrane 112 may have a continuous hollow lumen 116, which extends from one end to the other end of the fiber; an outer surface 118 facing outwards, which forms an outer side of the fiber; an inner surface 120 facing towards the hollow lumen 116, which defines the limits of the continuous hollow lumen 116. The fiber portion 126 of the membrane has a cross sectional thickness 128 that begins at the inner surface 120 and extends to the outer surface 118. The pore size progressively changes across the cross-sectional thickness 128. Although the pore size can either progressively increase or decrease across the cross-section zone 128, the pore size often progressively decreases. Across the cross-section zone, for example, the pore size (diameter) often varies in a range from 10 to 100 nanometers but there can be pores having a larger diameter such as up to 500, up to 1000, up to 5000, or even up to 10,000 nanometers.

[0143] FIG. 3, FIG. 4, and FIG. 5 are scanning electron micrographs of an exemplary the hollow fiber membrane that was formed in Example HFM-1 as described below. FIG. 3 shows a cross section of the hollow fiber membrane, FIG. 4 shows the lumen wall of the hollow fiber membrane, and FIG. 5 shows the outside wall of the hollow fiber membrane. The hollow fiber membrane is porous across its width, but the size and shape of the pores vary across the diameter of the membrane.

[0144] The membranes described herein, which are typically prepared using POLY-1 and POLY- 2, are advantageous compared to previously known membranes. POLY-1, as described above, is a copolymer that is often prepared by reacting a first macromer of Formula (I) having grafted polymeric sidechains of formula R2. with a second monomer of Formula (IV) having two functional groups R7that are either nucleophilic groups or leaving groups. The reaction product is typically a copolymer with repeat units connected via an -O- group. Thus, the copolymer has a plurality of groups R2, which are grafted poly(oxazoline) sidechains. In contrast, various other patent application publications such as WO 2021 / 1011987 (Jijun Ge et al.) have described preparing a membrane from a mixture of two separate polymeric materials (i.e., a poly (ether sulfone) and a separate poly(oxazoline)). There is not a copolymer as in the current application with a poly(ether sulfone) backbone and grafted poly(oxazoline) sidechains.

[0145] Unlike previously prepared membranes such as those described in WO 2021 / 1011987, the structural features of POLY- 1 can be modified and controlled. For example, both the molecular weight and graft density of the poly(oxazoline) sidechains can be controlled via stoichiometry during synthesis. Thus, the polymeric structure of POLY- 1 can be systematically refined to impart desirable characteristics to the membrane such as a particular porosity, pore size, and / or surface hydrophilicity. With the methodology described herein, POLY-1 is purified by conventional synthetic techniques and provided as a solid for direct incorporation into the membrane casting formulations along with POLY-2 and optionally POLY-3.

[0146] WO 2021 / 1011987 describes randomly crosslinking the poly(oxazoline) at multiple locations to a matrix of poly(ether sulfone) in an uncontrolled manner. Further, the crosslinked networks described in WO 2021 / 1011987 present a cumbersome manufacturing pathway in that a mixture of poly(oxazoline) and poly(ether sulfone) must be coated or cast. Then the coating is irradiated to induce crosslinking of the polymers. Finally, the crosslinked network must be taken up in a suitable solvent for casting into a membrane format. Without the crosslinking, the poly(oxazoline) can be undesirably extracted from the membrane after its formation. A separate crosslinking step in not needed when the membranes are formed from POLY-1 and POLY -2 as described herein.

[0147] Methods of using the porous articles

[0148] The porous articles can be used for separating various composition based on the size of components in the composition. In many embodiments, the porous articles are membranes suitable for separating components of a mixture based on the size of the components. For example, a mixture of biomaterials can be separated based on the size of the various biomaterials in the mixture. The larger biomaterials are typically retained upstream of the membranes and / or pass through (i.e., permeate) the membrane at a slower speed than smaller biomaterials. Thus, the composition exiting the membrane tends to have an enriched concentration of the smaller biomaterials compared to the original mixture of biomaterials.

[0149] Thus, a method of separating components based on size is provided. The method includes providing a porous separation article as described above, which is typically a membrane. The method further includes passing a first composition through the membrane, wherein the first composition of biomaterials comprises a plurality of different biomaterials with different average sizes. The method further includes separating the plurality of different biomaterials based on their different average sizes. A first biomaterial that has a smaller average size than a second biomaterial can typically permeate through the membrane more rapidly than the second biomaterial. Likewise, the second biomaterial that has a larger average size than the first biomaterial will be retained by the membrane and / or will permeate through the membrane more slowly than the first biomaterial. Thus, a second composition exiting the membrane will have a higher concentration of the first biomaterial and a lower concentration of the second component compared to the original first composition of biomaterials.

[0150] The biomaterials that can be separated include, for example, bacteria, viruses, viral particles, proteins, protein fragments, fusion proteins, cells, and the like. Different size biomaterials within the same general category as well as biomaterials within different general categories can be separated based on their different average sizes. The second composition exiting the membrane will have a higher concentration of the smaller biomaterials.

[0151] For example, the membrane can selectively retain viruses or viral particles having a larger average size than other biomaterials in the first composition of biomaterials. Further different size viruses and / or viral particles can be separated from each other with the smaller vimses and / or viral particles permeating though the membrane more quickly. In a specific example, an adeno- associated virus or a portion of an adeno-associated virus can be separated from larger viruses.

[0152] Likewise, different bacteria can be separated based on their average sizes with the smaller bacteria permeating through the membrane more quickly or bacteria can be separated from different types of biomaterials based on average size differences.

[0153] Similarly, proteins or protein fragments can be separated from other biomaterials. In some examples, the proteins or protein fragments are smaller than the other biomaterials can permeate faster though the membrane. The protein or protein fragment can be, for example, a monoclonal antibody, a monoclonal antibody fragment, or a fusion protein.

[0154] In some embodiments, the hollow fiber membrane of the present discourse can be used for multiple extracorporeal blood purification procedures including dialysis, blood oxygenation, and plasmapheresis. Examples

[0155] Unless otherwise noted or readily apparent from the context, all parts, percentages, ratios, etc. in the Examples and the rest of the specification are by weight.

[0156] Table 1: Materials Used in the Examples

[0157] Test Methods

[0158] GPC Method

[0159] Gel permeation chromatography data was obtained using an Agilent 1260 Infinity GPC equipped with isocratic pump, standard degasser, standard autosampler, thermostatted column compartment set to 55 °C, and a refractive index detector using two Agilent PLGel 5 pm Mixed-D 300 x 7.5 mm gel permeation chromatography columns. Gel permeation chromatography samples were prepared at 5 mg / mL in a solution of 20 mM lithium bromide in N-methylpyrrolidone and then passed over a Pall 0.2 micrometer polypropylene syringe filter. The columns were held at 55 °C and the flow rate was 0.8 mL / min. All molecular weight data are reported against Agilent polystyrene standards (Polystyrene calibration kit S-M-10 part # PL2010-0100).

[0160] Measurement of Total Nitrogen (TN) in Aqueous Extract

[0161] Hollow fiber membranes were extracted in water to determine the concentration of nitrogen (“total nitrogen”, or TN) in the aqueous extract. Ten dry fibers approximately 30 inches in length were weighed, then placed in a 40 mL glass vial, to which 25 mL of ultrapure water (obtained from a Milli-Q Gradient A10 lab water purification system, available as catalog number ZMQS6V0T1 from MilliporeSigma, St. Louis, MO) was added. The vial opening was covered with aluminum foil, and the vial was placed in an oven (Thelco Laboratory Oven) set to a temperature of 50 °C.

[0162] After 72 hours, the vial was removed from the oven. The aqueous extract was filtered with a 0.45 micrometers polypropylene syringe fdter (available as Target2 from Fisher Scientific) into a separate 20 mL glass vial. Prior to being used, the syringe filter was flushed with 20 mL of ultrapure water.

[0163] The concentration of total nitrogen (TN) in aqueous extracts was measured on a commercially available Total Organic Carbon Analyzer (available as TOC-L from Shimadzu Scientific Instruments) with a Total Nitrogen Module (available as TNM-L). The TN curve was calibrated over the range from 0 to 20 ppm TN using potassium nitrate, with check standards (6.8 ppm TN by \ -vinvlpy rrolidonc) run before and after the aqueous extract samples tested. TN data are reported as milligrams of TN per gram of fiber (mg / g).

[0164] NMR Spectroscopy Method 1 : Structure Characterization

[0165] Nuclear magnetic resonance spectra were obtained using a Bruker Avance III 300 MHz instrument or a Bruker Avance III 500 MHz equipped with a broadband cryoprobe. Proton (1H) spectra were obtained at a 15° pulse angle and a relaxation delay of 4 seconds.

[0166] NMR Spectroscopy Method 2: Membrane Composition

[0167] To measure the composition of membranes, dry membrane samples were dissolved in N.N-dimcthylformamidc-t / - (< / -DMF). The dissolved sample was then transferred by Pasteur pipette to an NMR sample tube. 1-dimensional NMR spectra were collected on a Bruker Avance 600 MHz spectrometer equipped with an inverse cry oprobe. H NMR spectra were collected using a 15° pulse and 0. Is relaxation delay over 128 scans.13C Carbon NMR spectra were collected over 256 Scans.

[0168] NMR Spectroscopy Method 3 : Aqueous Extract Composition

[0169] To measure the composition of aqueous extract, 4 mL of aqueous extract were transferred to a dried, weighed glass vial. The extract was rehydrated with 600 pL (microliters) of D2O solution. Samples were then transferred to an NMR sample tube using a glass Pasteur pipette. H NMR spectra were collected using a 15° pulse and 0.1s relaxation delay over 128 scans using a Bruker Avance 600 MHz spectrometer equipped with an inverse cryoprobe.

[0170] Water and Isopropanol Drop Wicking Test

[0171] Extracted, dried flat sheet membrane samples were placed on a lightbox. A small drop of water was gently placed on one side of the membrane. If the water drop spontaneously wicked into the film — as evidenced by that spot turning from white and opaque to transparent — the membrane was porous and hydrophilic.

[0172] If the water drop beaded up on the surface, a small drop of IPA was gently placed on the other side of the film. If the IPA spread, but did not wick, that side of the membrane was not porous. If the IPA drop wicked into the film, then the membrane was porous and hydrophobic.

[0173] Scanning Electron Microscopy (SEM)

[0174] Scanning electron microscopy images were obtained using secondary electron imaging (SEI), which is used to image surface morphology of a sample. Analysis was performed on the Hitachi SU8230 field emission scanning electron microscope (HITACHI, Schaumburg, IL). A low accelerating voltage of 2.0 keV, 10 pA current, and working distance of 3.5-4.5 mm were used. To reduce the likelihood of sample charging and allow for improved imaging, samples were sputter coated with a thin gold / palladium conductive coating prior to analysis.

[0175] Preparatory Examples

[0176] Sodium Phenoxide

[0177] To a dry 1 L round bottom flask equipped with a mechanical stirrer and short path distillation head with receiving flask was added 50 g phenol (531 mmol, 1.05 equivalents) and 800 g toluene. Approximately 400 g of toluene was distilled off followed by portionwise addition of 20.24 g sodium hydride as a 60 wt.% dispersion in mineral oil (506 mmol, 1 equivalent). After the initial reaction, the reactant solution was heated to 60 °C and stirred overnight. After stirring overnight, about 200 g of toluene was distilled off, the short path distillation head replaced with a Schlenk stopcock adapter, distillation bridge, and a Schlenk receiving vessel. The reactant solution was frozen in liquid nitrogen, the entire apparatus pumped down to > 0.4 mTorr, and the toluene was statically distilled into the receiving flask which was cooled in liquid nitrogen. After the distillation was complete, the apparatus was back-filled with argon, the stopcocks sealed, and the reaction vessel was transferred to a glovebox for storage. The product obtained was 60.24 g sodium phenoxide as a white solid in 98% yield.

[0178] H NMR (300 MHz, ACETONITRILE-^) 5 ppm 6.91 - 6.99 (m, 2 H) 6.37 - 6.45 (m, 2 H) 6.25 (tt, J=7.11, 1.15 Hz, 1 H). Lithium 4-tert-butylphenoxide

[0179] To a 2 L round bottom flask equipped with a stir bar was added 100 g (666 mmol) 4-terL butylphenol and 1100 g toluene. 600 g of toluene was distilled off to give a 14 wt.% solution of 4- tert-butylphenol in toluene. To a dry 250 mL round bottom flask equipped with a mechanical stirrer and nitrogen inlet was added 39.7 g of the 4-terLbutylphenol toluene solution (38 mmol, 1 equivalent) and 40 mL dry THF before cooling in an ice bath. To this solution was added dropwise 22.6 mL 1.6 M n-BuLi in hexanes (36.1 mmol, 0.95 equivalents) to give a 6.5 wt.% solution of 4- t-butylphenoxide.

[0180] 2 -Phenyl-2-oxazolinium tetrafluoroborate

[0181] To a 500 mL round bottom flask equipped with a stir bar was added 133.6 g of 48 wt.% aqueous HBF4(730 mmol HBF4, 2.15 equivalents), and 133.6 g commercially pure methanol. The solution was immersed in an isopropanol bath which was cooled to -35 °C using a recirculating chiller. 50 g of purified 2-phenyl-2-oxazoline (340 mmol, 1 equivalent) was then added dropwise. After full addition of 2-phenyl-2-oxazoline, the suspension was filtered over a glass frit and washed with cold diethyl ether. After drying, 53.17 g of 2-phenyl-2-oxazolinium tetrafluoroborate (67% yield) was obtained as a white powder.

[0182] 'H-NMR (300 MHz, CD3CN) 5 ppm 8.04 (m, 2 H), 7.88-7.96 (m, 1 H), 7.69-7.76 (m, 2 H), 5.18 (t, J = 9.9 Hz, 2 H), 4.28 (t, J = 9.9 Hz, 2 H).

[0183] 4-Fluoro-l-(4-fluorophenyl)sulfonyl-2-methyl-benzene

[0184] °. / I FjcF

[0185] To a 2 L 3-neck round bottom flask equipped with a mechanical stirrer was added 410.09 g of 4-fluorobenzenesulfonyl chloride (2.11 mol, 1 equivalent) and 316.22 g 3 -fluoro toluene (2.87 mol, 1.36 equivalents) under an N2atmosphere. The reaction mixture was heated to 70 °C and 315.18 g A1CL (2.36 mol, 1.12 equivalents) was added portion-wise and the reaction was maintained at 70 °C for 4 hours. The reactant solution was cooled to about 40 °C, and 557 mL of IM HO was added very slowly to maintain an internal temperature below 90 °C. The product was recrystallized thrice from an isopropanol-water mixture to give 348.85 g of 4-fluoro-l- (fluorophenyl)sulfonyl-2-methyl-benzene as a white solid in 61% yield.

[0186] Regiochemistry was determined by 2D NMR. H-NMR 4-fluoro-l-(4- fluorophenyl)sulfonyl-2-methyl-benzene (300 MHz, CD2O2) 5 ppm 8.25 (dd, .7=8.8. 5.9 Hz, 1 H) 7.92 (m, 1 H) 7.88 - 7.90 (m, 1 H) 7.20 - 7.30 (m, 2 H) 7.14 (td, J=8.4, 2.6 Hz, 1 H) 7.01 (dd, .7=9.5, 2.6 Hz, 1 H) 2.46 (s, 3 H). H-NMR 2-fluoro-l-(4-fluorophenyl)sulfonyl-2-methyl-benzene (500 MHz, CD2CI2) 5 ppm 8.01 - 8.07 (m, 2 H) 7.97 (t, J=1.8 Hz, 1 H) 7.21 - 7.28 (m, 2 H) 7.18 (d, .7=8.1 Hz, 1 H) 6.99 (s, 1 H) 6.97 (s, 1 H) 2.42 (s, 3 H).

[0187] 2-(Bromomethyl)-4-fluoro-l -(4-fluorophenv )sulfonyl benzene

[0188] To a 500 mL 3 -neck round bottom flask equipped with a mechanical stirrer was added 49.91 g 4-fhioro-l-(fluorophenyl)sulfonyl-2-methyl-benzene (186.0 mmol, 1 equivalent), 51.22 g NBS (279.1 mmol, 1.50 equivalents), 3.38 g AIBN (20.2 mmol, 0.11 equivalents) and 186 mL chlorobenzene. The reaction mixture was heated to 85-96 °C and maintained in this temperature range for 21 hours. The reaction mixture was cooled to 43 °C and 12.88 g DEP (93.26 mmol, 0.50 equivalents) and 4.93 g DIPEA (38.1 mmol, 0.20 equivalents) were added to the reaction and the temperature was maintained at 50 °C for 2 hours before cooling to room temperature. The solids were filtered and the reaction mixture concentrated under reduced pressure. The product was isolated by recrystallization from isopropanol to give 50.0 g of 2-(bromomethyl)-4-fluoro-l-(4- fluorophenyl) sulfonyl benzene as an off-white solid in 77% yield.

[0189] H NMR (300 MHz, DICHLOROMETH ANE-c / 2) 5 ppm 8.23 (dd, .7=8.8, 5.5 Hz, 1 H) 7.88 - 8.03 (m, 2 H) 7.17 - 7.40 (m, 4 H) 4.87 (s, 2 H).

[0190] (5-Fluoro-2-((4-fluoroDhenyl)sulfonyl)Dhenyl)methanol and sulfonylbis(5-fluoro-2, 1- Dhenyleneldimethanol

[0191] To a dry Parr reactor was added 60.67 g bis(4-fluorophenyl) sulfone (238.7 mmol, 1 equivalent) and 1060.6 g THF and the solution was cooled to -78 °C after which 124 g of a 1.6 M solution of BuLi in hexanes (286 mmol, 1.2 equivalents) was added and the reaction was stirred for 1 horn. After stirring for 1 hour, 22.2 mL DMF (287 mmol, 1.2 equivalents) was added slowly and the reaction was allowed to proceed for a further 45 minutes followed by addition of 30 mL AcOH (524 mmol, 2.2 equivalents). The reaction was warmed to room temperature and diluted with 200 mL each H2O and MeOH and transferred to a 3 L round bottom flask and cooled to 0 °C in an ice bath. 21.73 g NaBH4(574.4 mmol, 2.4 equivalents) was then added portionwise and the reaction allowed to warm to room temperature over 1 hour before cooling once more to 0 °C. The reaction mixture was acidified to pH 5-6 with 2 M HO and extracted with 3 x 350 mL portions EtOAc. The combined extracts were washed with saturated aqueous NaHCO, and brine. The washed extract was dried over MgSOj. filtered over celite, and concentrated under reduced pressure. The products were purified by column chromatography (silica gel, EtOAc / hexanes) to isolate both 25.7 g (5-fluoro-2-((4-fluorophenyl)sulfonyl)phenyl)methanol as a white solid in 38% yield and 13.6 g (sulfonylbis(5-fluoro-2,l-phenylene))dimethanol as a white solid in 18% yield.

[0192] H NMR for (fluoro-2-((4-fluorophenyl)sulfonyl)phenyl)methanol (chloroform-d, 300 MHz) 5 8.15 (dd, 1H, J=8.80, 8.8 Hz), 7.91-7.87 (m, 2H), 7.35 (dd, .7=9.54. 2.57 Hz, 1 H), 7.24- 7.18 (m, 3H), 4.77 (d, .7=6.24 Hz, 2 H), 2.78 (t, J=6.79 Hz, 1 H). Tl NMR for (sulfonylbis(5- fluoro-2,l-phenylene))dimethanol (DMSO-d6, 300 MHz) 5 8.12 (dd, 2H, J=5.9, 8.8 Hz), 7.52 (br d, 1H, .7=2.9 Hz), 7.44 (dt, 2H, J=2.9, 8.4 Hz), 5.62 (t, 2H, J=5.7 Hz), 4.53 (d, 4H, J=5.5 Hz), 3.3- 3.3 (m, 1H).

[0193] 4,4'-Sulfonylbis(3-(bromomethyl)-l -fluorobenzene)

[0194] To a 250 mL two-neck round bottom flask was added 12.13 g (sulfonylbis(5-fluoro-2,l- phenylene))dimethanol (38.6 mmol 1 equivalent) followed by 75 mL DCM. The reactant solution was cooled to 0 °C after which 9.4 mL PBr3(100 mmol, 2.59 equivalents) was added slowly. The ice-bath was removed, and the reaction stirred for 16 hours. The solution was then cooled to 0 °C and saturated aqueous NaHCO, was slowly added until no more gas evolved upon addition. The aqueous phase was extracted with DCM and the combined organic fractions were dried with MgSOj. filtered through a celite plug, and concentrated under reduced pressure. The product was recrystallized twice from isopropanol to give 6.13 g 4,4'-Sulfonylbis(3-(bromomethyl)-l- fluorobenzene) as a white solid in 36% yield.

[0195] Tl NMR (chloroform-d, 300 MHz) 5 8.23-8.18 (m, 2H), 7.32-7.30 (m, 2H), 7.29-7.21 (m, 2H), 4.66 (s, 4H). Polymer Examples (i.e., Macromers)

[0196] Polymer Example 1 (PEI): Polyfethyl oxazoline)-a-2-N-benzyl-4.4'-difluorodiphenylsulfone

[0197] 50mer

[0198] All glassware is silanized for this reaction and dried prior to use. In a glovebox, to a 1 L Schlenk vessel equipped with a stir bar were added 10.5114 g 2-(bromomethyl)-4-fluoro-l-(4- fluorophenyl) sulfonyl benzene (30.3 mmol, 1 equivalent), 150 g 2-ethyl-2-oxazoline (1.51 mol, 50 equivalents), and 240 g acetonitrile. The reaction was maintained at 70 °C until all polymerizable material had been consumed by NMR analysis. The polymerization was terminated by addition of 5.45 mL of water (302 mmol, 10 equivalents). After the chain end had been consumed the reactant solution was concentrated under reduced pressure. The crude was refluxed overnight with methyl tert-butyl ether and decanted. The polymer was dried in a vacuum oven at 80 °C for 48 hours to give 153.22 g of poly(ethyl oxazoline)-a-2-N-benzyl-4,4'-difluorodiphenylsulfone as a white resinous solid in 97% yield.

[0199] T1 NMR (500 MHz, ACETONITRILE-^) 5 ppm 8.27 (m, 1 H) 7.99 (m, 2 H) 7.37 (m, 3

[0200] H, overlap with chlorobenzene) 4.72 (m, 2 H) 6.98 (m, 1 H) 3.41 (br m, 194 H) 2.33 (m, 96 H)

[0201] I.03 (m, 145 H). GPC data PDI = 1.08, Mn = 7377 g / mol, Mw = 7979 g / mol.

[0202] Polymer Example 2 (PE2): Polyfethyl oxazoline)-a-2-N-benzyl-4.4'-difluorodiphenylsulfone 50mer

[0203] All glassware is silanized for this reaction and dried prior to use. In a glovebox, to a 250 mL Schlenk vessel equipped with a stir bar were added 1.38 g 2-phenyl-2-oxazolinium tetrafluoroborate (5.89 mmol, 1.46 equivalents), 20 g 2-ethyl-2-oxazoline (202 mmol, 50 equivalents), and 22.6 g chlorobenzene and then a second 250 mL Schlenk vessel equipped with a stir bar was charged with 1.2215 g 2-(chloromethyl)-4-fluoro-l-(4-fluorophenyl)sulfonyl benzene (4.04 mmol, 1 equivalent) and 1.34 g potassium iodide (8.07 mmol, 2 equivalents) to act as the receiving and reaction vessel. The monomer and solvent were stirred with the 2-phenyl-2- oxazolinium tetrafluoroborate for 1 hour and the vessel was equipped with a distillation bridge connected to the 250 mL Schlenk flask containing the 2-(chloromethyl)-4-fluoro-l-(4- fluorophenyl) sulfonyl benzene and potassium iodide. The monomer and solvent solution was freeze-pump-thawed for 3 cycles before evacuating the entire apparatus and statically distilling the monomer and solvent into the receiving / reaction vessel. After the static distillation had completed, the reactant solution was heated to 70 °C until NMR analysis indicated about 90% conversion. The polymerization was terminated by addition of 1.63 mL methanol (40.4 mmol, 10 equivalents) until the living chain-end signal at 4.90 ppm in CD3CN had disappeared byXH NMR. After the chain end had been consumed, the reactant solution was filtered over a plug of cotton and concentrated. The crude was refluxed overnight with methyl tert-butyl ether and decanted. The polymer was dried in a vacuum oven at 60 °C overnight 19.41 g of poly(ethyl oxazoline)-a-2-N-benzyl-4,4'- difluorodiphenylsulfone as a white resinous solid in 92% yield.

[0204] H NMR (300 MHz, ACETONITRILE-^) 5 ppm 8.25 (br m, 1 H, overlap with solvent) 7.99 (br m, 2 H) 7.38 (br m, 3 H, overlap with solvent) 6.99 (br m, 1 H) 4.73 (br m, 2 H) 3.42 (br m, 200 H) 2.35 (br m, 97 H) 1.05 (br m, 154 H). PDI = 1.26, Mn = 8031 g / mol, Mw = 10083 g / mol.

[0205] Polymer Example 3 (PE3): Poly(ethyl oxazoline)-a-2-N-benzyl-4.4’-difluorodiphenylsulfone 50mer

[0206] All glassware is silanized for this reaction and dried prior to use. In a glovebox, to a 250 mL Schlenk vessel equipped with a stir bar were added 695 mg 2-phenyl-2-oxazolinium tetrafluoroborate (2.96 mmol, 1.46 equivalents), 10 g 2-ethyl-2-oxazoline (101 mmol, 50 equivalents), and 22.6 g chlorobenzene and then a second 250 mL Schlenk vessel equipped with a stir bar was charged with 611 mg 2-(chloromethyl)-4-fluoro-l-(4-fluorophenyl)sulfonyl benzene (2.02 mmol, 1 equivalent) and 670 mg potassium iodide (4.04 mmol, 2 equivalents) to act as the receiving and reaction vessel. The monomer and solvent were stirred with the 2-phenyl-2- oxazolinium tetrafluoroborate for 1 hour and the vessel was equipped with a distillation bridge connected to the 250 mL Schlenk flask containing the 2-(chloromethyl)-4-fluoro-l-(4- fluorophenyl) sulfonyl benzene and potassium iodide. The monomer and solvent solution was freeze-pump-thawed for 3 cycles before evacuating the entire apparatus and statically distilling the monomer and solvent into the receiving / reaction vessel. After the static distillation had completed, the reactant solution was heated to 70 °C until NMR analysis indicated about 90% conversion. The polymerization was terminated by addition of 817 pL (microliters) methanol (20.2 mmol, 10 equivalents) until the living chain-end signal at 4.90 ppm in CD3CN had disappeared by NMR.

[0207] After the chain end had been consumed, the reactant solution was filtered over a plug of cotton and concentrated. The crude was refluxed overnight with methyl tert-butyl ether and decanted. The polymer was dried in a vacuum oven at 60 °C overnight 8.98 g of poly(ethyl oxazoline)-a-2-N- benzyl-4,4’ -difluorodiphenylsulfone as a white resinous solid in 90% yield.

[0208] Tf NMR (300 MHz, ACETONITRILE-^) 5 ppm 8.25 (br m, 1 H) 7.99 (br m, 2 H) 7.38 (br m, 3 H, overlap with solvent) 6.99 (br m, 1 H) 4.73 (br m, 2 H) 3.42 (br m, 217 H) 2.35 (br m, 107 H) 1.05 (br m, 162 H). PDI = 1.60, Mn = 7703 g / mol, Mw = 12319 g / mol.

[0209] Polymer Example 4 (PE4): Poly(ethyl oxazoline)-a-2-N-benzyl-4.4’-difluorodiphenylsulfone 25mer

[0210] All glassware is silanized for this reaction and dried prior to use. In a glovebox, to a 1 L Schlenk vessel equipped with a stir bar were added 15.5988 g 2-(bromomethyl)-4-fluoro-l-(4- fluorophenyl) sulfonyl benzene (33.9 mmol, 1 equivalent), 111.3 g 2-ethyl-2-oxazoline (1.12 mol, 25 equivalents), and 178 g acetonitrile. The reaction was maintained at 70 °C until all monomer had been consumed by NMR analysis. The polymerization was terminated by addition of 5.21 g of sodium phenoxide (44.9 mmol, 1 equivalent). After the chain end had been consumed the reactant solution was acidified to pH ~ 5 using a few mL of concentrate hydrochloric acid, filtered over celite, and concentrated under reduced pressure. The crude was refluxed overnight with methyl tert-butyl ether and decanted. The polymer was dried in a vacuum oven at 60 °C for 24 hours to give 125.31 g of poly(ethyl oxazoline)-a-2-N-benzyl-4,4’-difluorodiphenylsulfone as a white resinous solid in 98% yield.

[0211] H NMR (300 MHz, ACETONITRILE-^) 5 ppm 8.20 (m, 1H) 7.98 (m, 2 H) 7.50 - 6.78 (br overlapping multiplets, 11 H, residual phenol) 4.72 (m, 2 H) 4.12 (m, 2 H) 3.43 (brm, 105 H) 2.35 (m, 57 H) 1.04 (m, 89 H). GPC data PDI = 1.09, Mn = 4105 g / mol, Mw = 4471 g / mol.

[0212] Polymer Example 5 (PE5): Polvtethyl oxazoline)-a-2-N-benzyl-4.4’-difluorodiphenylsulfone- block-poly(phenyl oxazoline)

[0213] All glassware was silanized for this reaction and dried in an oven at 120 °C for at least 30 minutes directly prior to use. To a Schlenk flask equipped with a stir bar in a glovebox was added 3.50 g 2,2'-dibromomethyl-4,4'-difluorodiphenylsulfone (10.1 mmol, 1 equivalent), 10 g 2-ethyl-2- oxazoline (101 mmol, 10 equivalents), and 16 g acetonitrile. The vessel was removed from the glovebox, heated to 70 °C, and the polymerization was allowed to proceed until no monomer remained by NMR analysis. After the monomer was consumed, 7.42 g 2-phenyl-2 -oxazoline (50.4 mmol, 5 equivalents) was added and the reaction was allowed to proceed until no monomer remained by NMR. the reaction was quenched by addition of 9.64 mL t-butanol (50.4 mmol, 5 equivalents) and allowed to proceed until all the living chain end signal at 4.90 ppm in CD3CN had been consumed and then concentrated by rotary evaporation to give a thick yellow resinous syrup. The crude was refluxed with MTBE overnight, the solvent decanted, and the polymer dried in a vacuum oven at 60 °C overnight to give 18.6 g poly(ethyl oxazoline)-a-2-N-benzyl-4,4’- difluorodiphenylsulfone-block-poly(phenyl oxazoline) in 89% yield as a white resinous solid.

[0214] Tl NMR (300 MHz, ACETONITRILE-^) 5 ppm 8.26 (br m, 1 H) 8.13 (br m, 1 H) 7.99 (brm, 2 H) 7.42 (br m, 23 H) 4.71 (br m, 2 H) 3.40 (br m, 51 H) 2.34 (br m, 15 H) 1.04 (br m, 24 H). GPC data PDI = 1.12, Mn = 2925 g / mol, Mw = 3268 g / mol.

[0215] Polymer Example 6 (PE6): Bis-Poly(ethyl oxazoline)-a-2.2’-N-benzyl-4.4’- difluoro diphenylsulfone

[0216] All glassware was silanized for this reaction and dried in an oven at 120 °C for at least 30 minutes directly prior to use. To a Schlenk flask in a glovebox was added a stir bar and 1.7758 g 2,2'- dibromomethyl-4,4'-difluorodiphenylsulfone (4.04 mmol, 1 equivalent), 20 g 2-ethyl-2 -oxazoline (202 mmol, 50 equivalents), and 32 g acetonitrile. The vessel was removed from the glovebox, heated to 70 °C, and the polymerization was allowed to proceed until no monomer remained by NMR analysis. After the monomer was consumed, the reaction was quenched by addition of 1.45 mL water (80.7 mmol, 20 equivalents) and allowed to proceed until all the living chain end signal at 4.90 ppm in CD3CN had been consumed and concentrated by rotary evaporation to give a thick yellow resinous syrup. The crude was refluxed with MTBE overnight, the solvent decanted, and the polymer dried in a vacuum oven at 60 °C overnight to give 19.66 g of bis-poly(ethyl oxazoline)-a-2,2’-N-benzyl-4,4’-difluorodiphenylsulfone in 89% yield as a white resinous solid. T1 NMR (300 MHz, ACETONITRILE-^) 5 ppm 8.32 (br m, 1H) 7.47 (br m, 2H) 7.02 (br m, 1H) 4.47 (br m, 4H) 3.41 (m, 140 H) 2.35 (br m, 70 H) 0.93 - 1.22 (m, 105 H). GPC data PDI = 1.18, Mn = 5526 g / mol, Mw = 6526 g / mol.

[0217] Graft Copolymer Examples

[0218] Graft Copolymer Example 1 (GCE1): Polyfether sulfone)-graft-polv(ethyl oxazoline) 30 wt.%. 1.9 mol% polyfethyl oxazoline) 50mer sidechains

[0219] To a resin ketle was added 180.7631 g 4,4 ’-sulfonyldiphenol (722 mmol, 1 equivalent), 176.6407 g 4,4 ’-difluorodiphenylsulfone (695 mmol, 0.962 equivalents), 239.58 g K2CO3 (1.73 mol, 2.4 equivalents), 288.80 g of a 50 wt.% solution of poly(ethyl oxazoline)-a-2-N-benzyl-4,4’- difluorodiphenylsulfone (27.6 mmol, 0.038 equivalents) from polymer example 1 (PEI), and 577.9 g NMP were added. The resin kettle was equipped with a heating mantle connected to a J-KEM temperature controller affixed with a ! inch stainless-steel thermocouple inserted into the reaction vessel. The resin kettle was also equipped with a stainless-steel mechanical stir shaft equipped with a stainless-steel backed Teflon stir blade and a 4-prong propeller. The resin kettle was also equipped with a ! inch stainless-steel dip tube inserted into the reactant solution to deliver a steady N2 stream. Finally, the resin kettle was equipped with a short path distillation head equipped with a thermocouple and a 500 mL pear shaped flask immersed in a dry ice isopropanol bath.

[0220] 271.1 g of toluene was added to the reactant solution, the entire apparatus was wrapped in glass wool, and heating was commenced to 150 °C to azeotropically distill excess water out of the reactant solution. After the distillation was complete the pot temperature was increased to 165 °C via the temperature controller and the dip tube was placed above the reactant solution and the reaction was maintained at 165 °C for 4 hours before cooling to room temperature. The reactant solution was diluted with 700 g DMF and the polymer was precipitated by pouring into 16 kg of DI water with stirring. The precipitate was filtered and dried under a nitrogen stream for 3 days to give 419.05 g poly(ether sulfone)-graft-poly(ethyl oxazoline) as an off-white solid in 87% yield.

[0221] Tl NMR (300 MHz, DMSO-t / e) 5 ppm 8.00 (d, J=8.80 Hz, 4 H) 7.28 (br d, J=8.44 Hz, 4 H) 3.38 (br s, 9 H, overlap with NMP) 2.29 (br s, 1.68 H, overlap with NMP) 0.95 (br s, 2.66 H). GPC data PDI = 2.61, Mn = 58324 g / mol, Mw = 152351 g / mol.

[0222] Graft Copolymer Example 2 (GCE2): Polytether sulfone)-graft-poly(ethyl oxazoline) 15 wt.%. 0,85 mol% polvtethyl oxazoline) 50mer sidechains

[0223] To a resin kettle was added 50.3007 g 4,4 ’-sulfonyldiphenol (201 mmol, 1 equivalent), 50.5976 g 4,4’-difluorodiphenylsulfone (199 mmol, 0.99 equivalents), 67.36 g K2CO3 (487 mmol, 2.4 equivalents), 18.3700 g of poly(ethyl oxazoline)-a-2-N-benzyl-4,4’-difluorodiphenylsulfone (946 pmol, 0.0084 equivalents) from polymer example 2 (PE2), and 201.3 g NMP were added. The resin kettle was equipped with a heating mantle connected to a J-KEM temperature controller affixed with a ‘A inch stainless-steel thermocouple inserted into the reaction vessel. The resin kettle was also equipped with a stainless-steel mechanical stir shaft equipped with a stainless-steel backed Teflon stir blade and a 4-prong propeller. The resin kettle was also equipped with a 0.25 inch stainless-steel dip tube inserted into the reactant solution to deliver a steady N2stream. Finally, the resin kettle was equipped with a short path distillation head equipped with a thermocouple and a 500 mL pear shaped flask immersed in a dry ice isopropanol bath. 76.7 g of toluene was added to the reactant solution, the entire apparatus was wrapped in glass wool, and heating was commenced to 150 °C to azeotropically distill excess water out of the reactant solution. After the distillation was complete the pot temperature was increased to 165 °C via the temperature controller and the dip tube was placed above the reactant solution and the reaction was maintained at 165 °C for 4 hours before cooling to room temperature. The reactant solution was diluted with 500 g DMF and the polymer was precipitated by pouring into 8 kg of DI water with stirring. The precipitate was filtered and dried in a solvent oven at 130 °C overnight to give 90.29 g poly(ether sulfone) -graft-poly (ethyl oxazoline) as an off-white solid in 84% yield.

[0224] Tl NMR (300 MHz, DMSO-G?6) 5 ppm 8.00 (d, J=8.80 Hz, 4 H) 7.28 (br d, J=8.44 Hz, 4 H) 3.35 (could not integrate, overlap with NMP) 2.29 (could not integrate, overlap with NMP) 0.95 (br s, 0.4 H). GPC data PDI = 4.83, Mn = 81028 g / mol, Mw = 391377 g / mol.

[0225] Graft Copolymer Example 3 (GCE3): Polylether sulfone)-graft-polv(ethyl oxazoline) 5 wt.%, 0.24 mol% polvtethyl oxazoline) 50mer sidechains

[0226] To a resin kettle was added 50.00 g 4,4 ’-sulfonyldiphenol (200 mmol, 1 equivalent), 50.59 g 4,4 ’-difluorodiphenylsulfone (199 mmol, 0.99 equivalents), 66.34 g K2CO3 (480 mmol, 2.4 equivalents), 5.05 g of poly(ethyl oxazoline)-a-2-N-benzyl-4,4’ -difluorodiphenylsulfone (964 pmol, 0.00241 equivalents) from polymer example 3 (PE3), and 200 g NMP were added. The resin kettle was equipped with a heating mantle connected to a J-KEM temperature controller affixed with a 0.25 inch stainless-steel thermocouple inserted into the reaction vessel. The resin kettle was also equipped with a stainless-steel mechanical stir shaft equipped with a stainless-steel backed Teflon stir blade and a 4-prong propeller. The resin kettle was also equipped with a 0.25 inch stainless-steel dip tube inserted into the reactant solution to deliver a steady N2 stream. Finally, the resin kettle was equipped with a short path distillation head equipped with a thermocouple and a 500 mL pear shaped flask immersed in a dry ice isopropanol bath. 75 g of toluene was added to the reactant solution, the entire apparatus was wrapped in glass wool, and heating was commenced to 150 °C to azeotropically distill excess water out of the reactant solution. After the distillation was complete the pot temperature was increased to 165 °C via the temperature controller and the dip tube was placed above the reactant solution and the reaction was maintained at 165 °C for 4 hours before cooling to room temperature. The reactant solution was diluted with 240 g DMF and the polymer was precipitated by pouring into 8 kg of DI water with stirring. The precipitate was filtered and dried in a solvent oven at 130 °C overnight to give 89.82 g poly(ether sulfone)-graft- poly(ethyl oxazoline) as an off-white solid in 92% yield.

[0227] Tl NMR (300 MHz, DMSO-t / e) 5 ppm 8.00 (d, J=8.80 Hz, 4 H) 7.28 (br d, J=8.44 Hz, 4 H) 3.35 (could not integrate, overlap with NMP) 2.29 (could not integrate, overlap with NMP) 0.95 (br s, 0.4 H). GPC data PDI = 5.82, Mn = 37275 g / mol, Mw = 217027 g / mol.

[0228] Graft Copolymer Example 4 (GCE4): Polvtether sulfone)-graft-polv(ethyl oxazoline) 30 wt.%, 3,7 mol% polvtethyl oxazoline) 25mer sidechains

[0229] To a resin kettle was added 125.9471 g 4,4 ’-sulfonyldiphenol (503 mmol, 1 equivalent), 118.8949 g 4,4 ’-difluorodiphenylsulfone (468 mmol, 0.929 equivalents), 166.93 g K2CO3 (1.21 mol, 2.4 equivalents), 201.96 g of a 50 wt.% solution of poly(ethyl oxazoline)-a-2-N-benzyl-4,4’- difluorodiphenylsulfone (35.6 mmol, 0.071 equivalents) from polymer example 4 (PE4), and 402.2 g NMP were added. The resin kettle was equipped with a heating mantle connected to a J-KEM temperature controller affixed with a 0.25 inch stainless-steel thermocouple inserted into the reaction vessel. The resin kettle was also equipped with a stainless-steel mechanical stir shaft equipped with a stainless-steel backed Teflon stir blade and a 4-prong propeller. The resin kettle was also equipped with a 0.25inch stainless-steel dip tube inserted into the reactant solution to deliver a steady N2 stream. Finally, the resin kettle was equipped with a short path distillation head equipped with a thermocouple and a 500 mL pear shaped flask immersed in a dry ice isopropanol bath. 188.9 g of toluene was added to the reactant solution, the entire apparatus was wrapped in glass wool, and heating was commenced to 150 °C to azeotropically distill excess water out of the reactant solution. After the distillation was complete the pot temperature was increased to 165 °C via the temperature controller and the dip tube was placed above the reactant solution and the reaction was maintained at 165 °C for 4 hours before cooling to room temperature. The reactant solution was diluted with 300 g DMF and the polymer was precipitated by pouring into 16 kg of DI water with stirring. The precipitate was filtered and dried under a nitrogen stream for 3 days to give 331.6 g poly(ether sulfone)-graft-poly(ethyl oxazoline) as an off-white solid in 99% yield.

[0230] H NMR (300 MHz, DMSO-t / e) 5 ppm 8.00 (d, J=8.80 Hz, 4 H) 7.28 (br d, J=8.44 Hz, 4 H) 3.35 (m, 6 H, overlap with NMP) 2.29 (m, 2 H, overlap with NMP) 0.95 (br s, 3 H). GPC data PDI = 2.12, Mn = 26585 g / mol, Mw = 56229 g / mol.

[0231] Preparation of Polymer Dope and Sheet Membrane

[0232] Examples MEM-1 to MEM-3 and Comparative Example CMEM-1

[0233] A polymer dope (i.e., casting solution) was prepared with PES, PEG400, NMP, and GCE1 according to the amounts in Table 2. The polymer dope was mixed using a centrifugal mixer (available as SpeedMixer™ from FlackTek) for 15 seconds at 800 rpm, followed by 9.75 minutes at 1200 rpm, then heated in an oven set to 50 °C for 30 minutes to 1 horn, then mixed again at the same settings. The resulting polymer dope was a macroscopically homogenous, viscous liquid.

[0234] The polymer dope was kept in an oven set to 50 °C until right before casting. A glass plate and notch bar were both pre-heated in the same oven and removed immediately prior to each casting. A bead of polymer dope was poured onto the glass plate and was spread into a thin film using a notch bar coater with a gap height of 10 mil (254 micrometers). Immediately after casting, the film was immersed in a precipitation bath comprising 1500 mL of NMP and 2000 mL of water at a temperature of 50 °C. The thin film precipitated within a few seconds, to form a white, opaque membrane, at which point the membrane was transferred to a second water bath for extraction. After sitting in the second water bath overnight, the membrane was placed in an oven set to 50 °C to dry. The membrane was tested using the Water and Isopropanol Drop Wicking Test to determine porosity and hydrophobicity / hydrophilicity.

[0235] Table 2: Composition of Polymer Dopes and Corresponding Membrane Characteristics

[0236] Hollow Fiber Membrane Example 1 (HFM-1): Prepared with 2,5 wt% GCE1

[0237] A polymer dope was prepared with the following composition: 21.7 wt% PES, 2.4 wt% GCE1, 36.5 wt% PEG400, 36.5 wt% NMP, and 3 wt% deionized water. The polymer dope was mixed using a centrifugal mixer (available as SpeedMixer™ from FlackTek) for 15 seconds at 800 rpm, followed by 9.75 minutes at 1200 rpm. The polymer dope was transferred to a hopper, heated to 50 °C, and allowed to degas overnight. The resulting polymer dope was transparent and macroscopically homogeneous.

[0238] A gear pump (Model H-9000, available from Zenith Pumps, 1710 Airport Road, P.O. Box 5020, Monroe, NC 28111-5020) was used to pump the polymer dope from the hopper to a spinneret die with an inner channel for a bore liquid and an annular gap for the polymer dope, separated by a needle. The flow path was heated to 50 °C and included a 15 micrometer in-line filter. The spinneret die had an annular gap of 410 micrometers, a needle outer diameter of 300 micrometers, and a needle inner diameter of 150 micrometers. The spinneret die was fixed at a height of 26.5 cm above an aqueous precipitation bath and was heated to 50 °C. The bore liquid consisted of 45 wt% PEG400, 45 wt% NMP, and 10 wt% deionized water.

[0239] The extruded polymer dope fell through a climate-controlled zone with an air temperature of 54 °C and a relative humidity of 89%. Air was blown through the climate-controlled zone to achieve a steam mass flow rate of 1.5 kg / h. The extruded polymer dope then entered an aqueous precipitation bath heated to 50 °C, thereby vitrifying the pore structure of the hollow fiber membrane. The hollow fiber membrane was collected at a line speed of 135 ft / min and wound on a drum.

[0240] The resulting hollow fiber membrane bundle was flushed down the lumen volume with approximately 4 L of deionized water, then extracted in water heated to 90 °C for 1 horn, and finally dried at room temperature overnight. The hollow fiber membrane had an inner diameter of 200 micrometers and an average wall thickness of 63 micrometers.

[0241] The hollow fiber membrane was analyzed using NMR spectroscopy and the membrane comprised 91.01 wt% PES, 7.83 wt% GCE1, 1.04 wt% PEG400, and 0.126 wt% NMP. The hollow fiber membrane was extracted and the total nitrogen (TN) in the aqueous extract was 0.1358 mg / g. The aqueous extract was analyzed with NMR spectroscopy and no poly(ethyl oxazoline) was detected.

[0242] Scanning electron micrographs of the hollow fiber membrane are shown in FIG. 3, FIG. 4, and FIG. 5.

[0243] Comparative Hollow Fiber Membrane Example 1 (CHFM-1): Prepared with PEtOx ho mopolymer A polymer dope was prepared as in HFM-1, but with the following composition: 25.5 wt%

[0244] PES, 9 wt% poly(2-ethyl-2 -oxazoline) (available under the trade name Aquazol® 50 from Polymer Chemistry Innovations, 4231 S. Fremont Ave., Tucson, AZ 85714-1628), 30.3 wt% polyethylene glycol) with a molecular weight of 200 g / mol (PEG200, available from J.T. Baker, 100 Matsonford Road, Suite 200 Radnor, PA 19087), 33.2 wt% NMP, and 2 wt% deionized water. The polymer dope was transferred to a hopper, heated to 50 °C, and allowed to degas overnight. The resulting polymer dope was transparent and macroscopically homogeneous.

[0245] A gear pump was used to was pump the polymer dope from the hopper to a spinneret die with an inner channel for a bore liquid and an annular gap for the polymer dope, separated by a needle. The flow path was heated to 50 °C and included a 15 micrometers in-line filter. The spinneret die had an annular gap of 410 micrometers, a needle outer diameter of 300 micrometers, and a needle inner diameter of 150 micrometers. The spinneret die was fixed at a height of 27 cm above an aqueous precipitation bath and was heated to 50 °C. The bore liquid consisted of 50 wt% PEG200, 45 wt% NMP, and 5 wt% deionized water. The extruded polymer dope fell through a climate-controlled zone with an air temperature of 52 °C and a relative humidity of 90%. The extruded polymer dope then entered an aqueous precipitation bath heated to 50 °C, thereby vitrifying the pore structure of the hollow fiber membrane. The hollow fiber membrane was collected at a line speed of 146 ft / min and wound on a drum. The resulting hollow fiber membrane bundle was extracted in water heated to 90 °C for 1 hour, then dried at room temperature overnight. The hollow fiber membrane had an inner diameter of 202 micrometers and an average wall thickness of 64 micrometers. The hollow fiber membranes were extracted and the total nitrogen (TN) in the aqueous extract was 0.3699 mg / g. Table 3 : Total Nitrogen in Aqueous Extract

Claims

What is claimed is:wherein each R1is independently a leaving group or a nucleophilic group; each R2is independently a grafted polymeric sidechain comprising a plurality of repeat units of formula -N(C(=O)-R3)-CH2-CH2-;R3is an alkyl, alkenyl, aryl, or combination thereof; p is an integer in a range of 0 to 4; q is an integer in a range of 0 to 4; and p + q is an integer equal to at least 1.

2. The macromer of Formula (I) that is of Formula (I-A), Formula (I-B),(I-A) (I-B) or a mixture thereof.

3. The macromer of claim 1 or 2, wherein each R1is a leaving group selected from -F, -Cl, - Br, -I, CF3SO3-, and -SO2-C6H4-CH3, or a nucleophilic group selected from -OH and -OSi(R6)3 where each R6is an alkyl.

4. The macromer of any one of claims 1 to 3, wherein group R2comprises n repeat units of formula -N(C(=O)-R3)-CH2-CH2- and optionally further comprises m repeat units of formula -NH-CH2-CH2-, wherein n is an integer equal to at least 3 and m is an integer equal to at least 0 and wherein a m (n + m) is in a range of 0 to 0.02.

5. The macromer of claim 4, where n + m is in a range of 3 to 1000.

6. The macromer of any one of claims 1 to 5, wherein the plurality of repeat units of formula-N(C(=O)-R3)-CH2-CH2- comprise a first repeat unit of formula -N(C(=O)-R3A)-CH2-CH2- and a second repeat unit of formula -N(C(=O)-R3B)-CH2-CH2- with R3Aand R3Bbeing different R3groups.

7. A copolymer comprising a plurality of repeat units joined by -O- groups, wherein the plurality of repeat units comprises: a) first repeat units of Formula (II)wherein each R2is a grafted polymeric sidechain comprising a plurality of repeat units of formula -N(C(=O)-R3)-CH2-CH2-;R3is an alkyl, alkenyl, aryl, or combination thereof; p is an integer in a range of 0 to 4; q is an integer in a range of 0 to 4; p + q is an integer equal to at least 1; and b) second repeat units of Formula (III)wherein an asterisk (*) is the attachment site to an -O- group that joins repeat units.The copolymer of claim 7, wherein the first repeat units of Formula (II) are(II-A) (II-B) of Formula (II-A) or Formula (II-B).

9. The copolymer of claim 7 or 8, wherein the plurality of repeat units further comprises a third repeat unit that is different than the first repeat unit and the second repeat unit, wherein thethird repeat unit is of Formula (V-A), Formula (V-B), Formula (V-C), Formula (V-D), Formula (VI), or a combination thereof(V-E) wherein an asterisk (*) is the attachment site to an -O- group that joins repeat units.

10. The copolymer of any one of claim 7 to 9, wherein the copolymer comprises 10 to 60 weight percent of the first repeat unit of Formula (II).

11. The copolymer of any one of claim 7 to 10, wherein the weight average molecular weight is in a range of 10,000 to 250,000 grams / mole.

12. A porous polymeric article comprising a first copolymer of any one of claims 7 to 11.

13. The porous polymeric article of claim 12, wherein the porous polymeric article is a membrane comprising 1 to 50 weight percent of the first copolymer and 50 to 99 weight percent of a second polymer that is an aromatic poly ether sulfone having repeat units of Formula (III)(Ill) wherein an asterisk (*) is the attachment site to an -O- group that joins two repeat units.

14. The porous polymeric article of claim 13, wherein the membrane is a hollow fiber membrane.

15. A method of separating biomaterials based on size differences, the method comprising: providing a porous polymeric article of any one of claims 12 to 14; passing an aqueous mixture of biomaterials through the porous polymeric material, wherein the mixture of biomaterials comprises biomaterials having different average sizes; and separating the mixture of biomaterials based on their average sizes, wherein a first biomaterial that is smaller than a second biomaterial permeates through the porous polymeric article at a faster rate.

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