Methods for preparing crosslinkable zwitterionic polymer membranes and uses thereof

Abstract

A method for making a thin film composite membrane is disclosed, the method including: providing a copolymer comprising (i) a plurality of zwitterionic repeat units and (ii) a plurality of hydrophobic repeat units, each hydrophobic repeat unit comprising an alkene; providing a plurality of crosslinking units, each crosslinking unit comprising a first terminal thiol moiety and a second terminal thiol moiety; providing an initiator; providing a solvent; mixing the copolymer, the plurality of crosslinking units, the initiator, and the solvent to thereby form a mixture; coating the mixture onto a support membrane; evaporating the solvent; and activating the initiator to thereby form a thin film composite membrane comprising a crosslinked zwitterionic copolymer, wherein the weight ratio of copolymer:initiator:plurality of crosslinking units is from about 10:1:1 to about 200:1:1.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority to U.S. Provisional Patent Application No. 63 / 434,679, filed December 22, 2022. [Background technology]

[0002] Membrane filtration is an important and promising method for water purification, reclamation, and reuse. Membranes with various pore sizes can be used for a wide range of purposes, from simple removal of disease-causing microorganisms to desalination by reverse osmosis (RO). Membranes also serve as an efficient, simple, and scalable separation method in various industries, such as the food, beverage, dairy, and bio / pharmaceutical industries. RO membranes are designed for the removal of small neutral molecules from water sources such as brackish water, seawater, groundwater, industrial wastewater, and agricultural wastewater, as well as for the desalination of these water sources. Nanofiltration (NF) membranes are designed for the softening and removal of small neutral molecules from water sources such as industrial wastewater, agricultural wastewater, brackish water, seawater, and groundwater.

[0003] All of the aforementioned membrane processes are often severely affected by fouling, defined as a degradation of membrane performance due to the adsorption and accumulation of feed components on the membrane surface. Significant reductions in membrane permeability and changes in membrane selectivity are common. Fouling management is a significant component of the costs associated with membrane systems, requiring increased energy use, downtime, maintenance and regular cleaning involving chemical use, and more complex processes. Summary of the Invention [Means for solving the problem]

[0004] One aspect of the present invention is a scalable fabrication process for crosslinkable zwitterionic copolymer (XZC) thin film composite (TFC) membranes. Unlike previous approaches to fabricating XZC membranes, a membrane crosslinker is included in the copolymer / solvent casting solution, allowing for immediate membrane crosslinking.

[0005] First, a copolymer composed of a hydrophobic crosslinkable monomer and one (or more) zwitterionic monomer(s) is synthesized. The copolymer and crosslinker are then dissolved in a solvent and coated onto a support membrane to produce a thin film composite (TFC) membrane. After the solvent is evaporated, the membrane is immediately post-treated to crosslink the membrane. The crosslinking reaction reduces the pore size of the selective layer and also imparts stability (e.g., solvent stability and thermal stability) to the membrane selective layer.

[0006] Provided herein are methods for fabricating thin film composite membranes with tunable size-based selectivity for small organic molecules and selectivity between dissolved ions.

[0007] In one aspect, a method for manufacturing a thin film composite membrane is disclosed, the method comprising: providing a copolymer comprising: (i) a plurality of zwitterionic repeat units; and (ii) a plurality of hydrophobic repeat units, each hydrophobic repeat unit comprising an alkene; providing a plurality of cross-linking units, each cross-linking unit comprising a first terminal thiol moiety and a second terminal thiol moiety; Providing an initiator; Providing a solvent; mixing the copolymer, the plurality of crosslinking units, the initiator, and the solvent, thereby forming a mixture; coating the mixture onto a support membrane; evaporating the solvent; activating the initiator, thereby forming a thin film composite membrane comprising the crosslinked zwitterionic copolymer; The weight ratio of copolymer:initiator:multiple crosslinking units is from about 10:1:1 to about 200:1:1. [Brief explanation of the drawings]

[0008] [Figure 1A]Schematic of molecular self-assembly to generate a bicontinuous network of zwitterionic domains (indicated by positively and negatively charged groups) and bridging hydrophobic domains (striped circles). Water and small solutes can pass through the zwitterionic channel, while larger solutes are retained. [Figure 1B] FIG. 1 shows the synthesis scheme of crosslinkable random zwitterionic copolymer (ZAC) and its crosslinking reaction via thiol-ene click chemistry. [Figure 1C] FIG. 1 is a schematic diagram of related UV-assisted crosslinking. DETAILED DESCRIPTION OF THE INVENTION

[0009] Current RO and NF membranes generally feature a polyamide selective layer. These membranes allow water to pass through much faster than certain salt ions (e.g., monovalent ions in the case of RO and divalent ions in the case of NF) when a transmembrane pressure drop is applied to the feed side of the membrane, enabling the removal of salt ions. Polyamide membranes have several important technical limitations, including (1) membrane fouling, defined as the undesirable adsorption of feed components onto the membrane surface, and (2) chlorine sensitivity, defined as the loss or change in performance resulting from treatment with chlorine (e.g., sodium hypochlorite, calcium hypochlorite). Membrane fouling reduces membrane permeability, necessitating expensive chemical treatment of the membrane and leading to operational shutdowns. Chlorine sensitivity prevents easy management of biofouling (microbial growth on the membrane surface) by exposing the membrane to aqueous solutions of chlorine (hypochlorite). This may necessitate the use of alternative / expensive biocides or complex pretreatment processes instead of directly treating the feed solution with inexpensive chlorine (hypochlorite). Cellulose acetate is another polymer selective layer used in the fabrication of RO membranes. Cellulose acetate RO membranes have drawbacks such as membrane fouling, low water permeability, and pH sensitivity, which requires operation within a narrow pH range. Polyethersulfone is another polymer selective layer used to fabricate NF membranes. Polyethersulfone NF membranes have drawbacks such as a high tendency to foul and low water flux.

[0010] Disclosed herein are methods for making thin film composite (TFC) membranes for use with a particular family of copolymers, called crosslinkable zwitterionic copolymers, which contain at least two types of repeat units. (1) Crosslinkable Monomers. A typical crosslinkable moiety is a C=C double bond, which can be polymerized when exposed to a free-radical photoinitiator, including photoinitiators activated by ultraviolet (UV) light. It may also be possible to do this using thermal methods (i.e., using an initiator activated at elevated temperature) or via a redox reaction. The crosslinkable moiety may not be a C=C double bond and instead can be polymerized by exposure to UV light in the absence of a radical initiator. (2) Zwitterionic monomers, which serve to impart water permeability and fouling resistance to the membrane selective layer.

[0011] Some copolymers within this family are described in PCT Application No. PCT / US21 / 32793, "CROSS-LINKABLE ZWITTERIONIC POLYMERS AND THEIR USE IN MEMBRANE FILTERS" (published as WO2021 / 232018), which is incorporated herein by reference.

[0012] The present invention enables scalable fabrication of TFC membranes using crosslinkable zwitterionic copolymers. These membranes can exhibit high salt retention, high small molecule rejection, high protein rejection, tunable pore size, fouling resistance, and chlorine resistance. These membranes can perform a variety of salt separations, including but not limited to desalination, water softening, and selective ion separation. These membranes can also perform a variety of small molecule / macromolecular separations in water sources such as industrial wastewater, brackish water, seawater, groundwater, and aqueous feedstocks produced in various bioprocessing applications. The described membranes typically have effective pore sizes of less than about 3 nm, preferably less than about 2 nm, and more preferably less than about 1 nm.

[0013] To fabricate a TFC membrane using the present invention, one or more crosslinkable zwitterionic copolymers are mixed and dissolved with a solvent and at least one additional small molecule / polymer (referred to herein as an initiator). An initiator is described as a type of small molecule or polymer that initiates a chemical reaction leading to crosslinking of the crosslinkable groups of the crosslinkable zwitterionic copolymer. The initiator may be included in an amount of about 0-20 grams per gram of copolymer, preferably about 0-1 gram per gram of copolymer, and more preferably about 0-0.1 grams per gram of copolymer. One or more additional small molecules / polymers, referred to herein as accelerators or crosslinking units, can also be included. The accelerators / crosslinking units are described as small molecules / polymers that also participate in the crosslinking reaction and provide enhanced reaction rate, conversion, or other improvements. The accelerators / crosslinking units may be included in an amount of about 0-20 grams per gram of copolymer, preferably about 0-1 gram per gram of copolymer, and more preferably about 0-0.1 grams per gram of copolymer.

[0014] In one embodiment, 2-hydroxy-2-methylpropiophenone is used as the initiator. Other examples of initiators include: (1) photoinitiators, i.e., initiators that generate radicals upon exposure to UV light. Examples include, but are not limited to, benzoin ethers, benzil ketals, α-dialkoxy-acetophenones, α-hydroxy-alkyl-phenones, α-amino-alkyl-phenones, acyl-phosphine oxides, benzophenones (with or without an amine synergist), and thioxanthones (with or without an amine synergist). (2) redox initiators, i.e., initiators that generate radicals through a reduction / oxidation (i.e., "redox") reaction, with or without additional chemical reagents. Examples of redox initiators include, but are not limited to, hydrogen peroxide, alkyl peroxides, acyl peroxides, persulfates, disulfides, and dibenzoyl peroxide (used with or without a tertiary amine synergist). (3) thermal initiators, i.e., initiators that generate radicals at elevated temperatures. These include, but are not limited to, benzoyl peroxide, 1,1'-azobis(cyclohexanecarbonitrile), azobisisobutyronitrile, and di-tert-butyl nitroxide. In one embodiment, 1,6-hexanedithiol is used as an accelerator or multiple crosslinking units. Other examples include alkyldithiols, benzenedithiols, ethylene glycol dithiols, biphenyldithiols, multi-arm thiols (e.g., tetra(ethylene glycol)dithiol), monothiols, and thiol-containing polymers / copolymers (e.g., poly(ethylene glycol)dithiol).

[0015] Disclosed herein is the preparation of a TFC membrane by coating a solution of a copolymer, an initiator, a solvent, and optionally an accelerator / multiple crosslinking units onto a porous support by methods well known in the membrane industry (e.g., doctor blade coating, spray coating). Through a chemical reaction involving the copolymer, the initiator, and optionally the accelerator / multiple crosslinking units, the crosslinkable groups on the copolymer chains are activated, forming additional bonds between them. In one embodiment, this is done by activating the initiator with some external exposure (e.g., UV light, elevated temperature) immediately after coating, i.e., before a significant amount of solvent has been lost. In one embodiment, this is done by first removing the solvent by methods well known in the membrane industry (e.g., evaporation or the use of a coagulation bath) to solidify the copolymer selective layer. In this embodiment, the initiator and accelerator are not substantially removed with the solvent, but remain dissolved in / in contact with the solid copolymer selective layer. In this embodiment, immediately after removing the selective layer, the copolymer selective layer is crosslinked by some external exposure (e.g., UV light, elevated temperature). For example, the solvent can be removed by evaporative drying in an oven, followed by crosslinking with UV light immediately after the oven drying step.

[0016] The present invention enables the scalable fabrication of thin film composite (TFC) membranes comprising at least two layers: a porous support with large pores that provide mechanical integrity, and a thin (preferably <10 μm, more preferably <3 μm, and even more preferably <1 μm) layer of crosslinked copolymer that serves as the membrane's "selective layer." In this particular embodiment, the copolymer layer must comprise a continuous, dense layer of copolymer (i.e., not regular "through-holes" that provide pathways for water permeation, excluding unintended, incidental defects that may arise during processing, even if undesirable). In other words, water should permeate the copolymer rather than the copolymer's pores / holes as the primary transport mechanism. Upon deposition, the zwitterionic and ionic / ionizable groups are expected to form clusters through Coulombic interactions. These clusters function as ionic nanochannels that allow water permeation. The copolymer is intentionally crosslinked as described above.

[0017] In one aspect, a method for manufacturing a thin film composite membrane is disclosed, the method comprising: providing a copolymer comprising: (i) a plurality of zwitterionic repeat units; and (ii) a plurality of hydrophobic repeat units, each hydrophobic repeat unit comprising an alkene; providing a plurality of cross-linking units, each cross-linking unit comprising a first terminal thiol moiety and a second terminal thiol moiety; Providing an initiator; Providing a solvent; mixing the copolymer, the plurality of crosslinking units, the initiator, and the solvent, thereby forming a mixture; coating the mixture onto a support membrane; evaporating the solvent; activating the initiator, thereby forming a thin film composite membrane comprising the crosslinked zwitterionic copolymer; The weight ratio of copolymer:initiator:multiple crosslinking units is from about 10:1:1 to about 200:1:1.

[0018] In certain embodiments, the solvent is methanol, acetonitrile, isopropanol, hexane, or any combination thereof. In certain embodiments, the activation is carried out at room temperature.

[0019] In certain embodiments, the initiator is a photoinitiator, a redox initiator, a thermal initiator, or any combination thereof. In certain embodiments, the initiator is a benzoin ether, a benzil ketal, an α-dialkoxyacetophenone, an α-hydroxyalkylphenone, an α-aminoalkylphenone, an acylphosphine oxide, a benzophenone (with or without an amine synergist), a thioxanthone (with or without an amine synergist), a hydrogen peroxide, an alkyl peroxide, an acyl peroxide, a persulfate, a disulfide, a dibenzoyl peroxide (with or without a tertiary amine synergist), a benzoyl peroxide, 1,1'-azobis(cyclohexanecarbonitrile), azobisisobutyronitrile, di-tert-butyl nitroxide, or a combination thereof. In certain embodiments, the initiator is 2,2-dimethoxy-2-phenylacetophenone (DPMA) or 2-hydroxy-2-methylpropiophenone.

[0020] In certain embodiments, the crosslinking unit is an alkyldithiol, benzenedithiol, ethylene glycol dithiol, biphenyldithiol, a multi-arm thiol (e.g., tetra(ethylene glycol)dithiol), a monothiol, or a thiol-containing polymer or copolymer (e.g., poly(ethylene glycol)dithiol). In certain embodiments, the crosslinking unit is 1,6-hexanedithiol (HDT).

[0021] In certain embodiments, the solvent is a mixture of methanol and acetonitrile. In certain embodiments, the methanol and acetonitrile are present at about 4 to about 6 w / v% in a ratio (v / v) of about 1.5:1 to about 3:1. In certain embodiments, the methanol and acetonitrile are present at about 4.4 to about 4.6 w / v% in a ratio (v / v) of about 1.5:1. In certain embodiments, the methanol and acetonitrile are present at about 5 w / v% in a ratio (v / v) of about 3:1.

[0022] In certain embodiments, the weight ratio of copolymer:initiator:multiple crosslinking units is about 10:1:1 to about 100:1:1. In certain embodiments, the weight ratio of copolymer:initiator:multiple crosslinking units is about 100:1:1 to about 200:1:1. In certain embodiments, the weight ratio of copolymer:initiator:multiple crosslinking units is about 10:1:1.

[0023] In certain embodiments, the amount of initiator is from 0.01 grams to about 20 grams per gram of copolymer. In certain embodiments, the amount of initiator is from about 0.1 grams to about 1 gram per gram of copolymer. In certain embodiments, the amount of initiator is from 0.01 grams to about 0.1 grams per gram of copolymer.

[0024] In certain embodiments, the amount of the crosslinking units is from 0.01 grams to about 20 grams per gram of copolymer. In certain embodiments, the amount of the crosslinking units is from about 0.1 grams to about 1 gram per gram of copolymer. In certain embodiments, the amount of the crosslinking units is from 0.01 grams to about 0.1 grams per gram of copolymer.

[0025] In certain embodiments, the support membrane comprises UE50, Trisep, or a combination thereof. In certain embodiments, the mixture is coated onto the support membrane using a wire-wound rod.

[0026] In certain embodiments, the solvent is evaporated by heating at about 50-100° C. In certain embodiments, the solvent is evaporated by heating at about 80° C.

[0027] In certain embodiments, the initiator is activated by UV light, or elevated temperature, or a combination thereof. In certain embodiments, the initiator is activated by irradiation with UV light.

[0028] In certain embodiments, irradiation is performed for about 10 seconds to about 150 seconds. In certain embodiments, irradiation is performed for about 30 seconds. In certain embodiments, irradiation is performed for about 60 seconds. In certain embodiments, irradiation is performed for about 90 seconds. In certain embodiments, irradiation is performed for about 120 seconds.

[0029] In certain embodiments, the thin film composite membrane comprises at least two layers: a porous support layer and a layer of crosslinked zwitterionic copolymer. In certain embodiments, the layer of crosslinked zwitterionic copolymer has a thickness of about 0.1 μm to about 10 μm. In certain embodiments, the layer of crosslinked zwitterionic copolymer has a thickness of about 1 μm to about 10 μm.

[0030] definition Unless otherwise defined herein, scientific and technical terms used in this application shall have the meanings commonly understood by one of ordinary skill in the art. Generally, the nomenclature used in connection with, and techniques of, chemistry, cell and tissue culture, molecular biology, cell and cancer biology, neurobiology, neurochemistry, virology, immunology, microbiology, pharmacology, genetics, and protein and nucleic acid chemistry described herein are those well known and commonly used in the art.

[0031] The methods and techniques of the present disclosure are generally carried out according to conventional methods well known in the art and described in various general and more specific references cited and discussed throughout the specification, unless otherwise indicated. See, for example, "Principles of Neural Science," McGraw-Hill Medical, New York, NY (2000); Motulsky, "Intuitive Biostatistics," Oxford University Press, Inc. (1995); Lodish et al., "Molecular Cell Biology, 4th ed.", W.H. Freeman & Co., New York (2000); Griffiths et al., "Introduction to Genetic Analysis, 7th ed.", W.H. Freeman & Co., NY (1999); and Gilbert et al., "Developmental Biology, 6th ed.", Sinauer Associates, Inc., Sunderland, MA (2000).

[0032] Chemical terms used herein, unless otherwise defined herein, are used in accordance with conventional usage in the art, as exemplified in "The McGraw-Hill Dictionary of Chemical Terms," ​​Parker S., Ed., McGraw-Hill, San Francisco, CA (1985).

[0033] As used herein, the term "any" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes cases where the event or circumstance occurs and cases where it does not occur. For example, "optionally substituted alkyl" refers to cases where alkyl can be substituted, as well as cases where alkyl is not substituted.

[0034] It will be understood that one skilled in the art can select substituents and substitution patterns for the compounds of the present invention to provide chemically stable compounds that can be easily synthesized from readily available starting materials by techniques known in the art and those described below. When a substituent is itself substituted with multiple groups, it will be understood that such multiple groups can be present on the same carbon or on different carbons, so long as a stable structure results.

[0035] As used herein, the term "optionally substituted" refers to the replacement of one to six hydrogen radicals in a given structure with the radical of a specified substituent, including, but not limited to, hydroxyl, hydroxyalkyl, alkoxy, halogen, alkyl, nitro, silyl, acyl, acyloxy, aryl, cycloalkyl, heterocyclyl, amino, aminoalkyl, cyano, haloalkyl, haloalkoxy, -OCO-CH-O-alkyl, -OP(O)(O-alkyl), or -CH-OP(O)(O-alkyl). Preferably, "optionally substituted" refers to the replacement of one to four hydrogen radicals in a given structure with the above substituents. More preferably, one to three hydrogen radicals are replaced with the above substituents. It is understood that the substituents may be further substituted.

[0036] Articles such as "a," "an," and "the" can mean one or more unless indicated to the contrary or otherwise clear from the context. A claim or description including "or" between one or more members of a group is deemed to be satisfied when one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process, unless indicated to the contrary or otherwise clear from the context. The invention includes embodiments in which exactly one member of a group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one or all of the group members are present in, employed in, or otherwise relevant to a given product or process.

[0037] As used herein, the term "alkyl" refers to a C1-C 10 Straight chain alkyl group or C1-C 10 "Alkyl" refers to saturated aliphatic groups, including, but not limited to, branched-chain alkyl groups. Preferably, an "alkyl" group refers to a C1-C6 straight-chain alkyl group or a C1-C6 branched-chain alkyl group. Most preferably, an "alkyl" group refers to a C1-C4 straight-chain alkyl group or a C1-C4 branched-chain alkyl group. Examples of "alkyl" include, but are not limited to, methyl, ethyl, 1-propyl, 2-propyl, n-butyl, sec-butyl, tert-butyl, 1-pentyl, 2-pentyl, 3-pentyl, neo-pentyl, 1-hexyl, 2-hexyl, 3-hexyl, 1-heptyl, 2-heptyl, 3-heptyl, 4-heptyl, 1-octyl, 2-octyl, 3-octyl, or 4-octyl, and the like. An "alkyl" group may be optionally substituted.

[0038] The term "acyl" is art-recognized and refers to a group represented by the general formula hydrocarbylC(O)-, preferably alkylC(O)-.

[0039] The term "acylamino" is art-recognized and refers to an amino group substituted with an acyl group and may be represented, for example, by the formula hydrocarbylC(O)NH-.

[0040] The term "acyloxy" is art-recognized and refers to a group represented by the general formula hydrocarbylC(O)O-, preferably alkylC(O)O-.

[0041] The term "alkoxy" refers to an alkyl group having an oxygen attached thereto. Representative alkoxy groups include methoxy, ethoxy, propoxy, tert-butoxy, and the like.

[0042] The term "alkoxyalkyl" refers to an alkyl group substituted with an alkoxy group and may be represented by the general formula alkyl-O-alkyl.

[0043] The term "alkyl" refers to saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl-substituted cycloalkyl groups, and cycloalkyl-substituted alkyl groups. In preferred embodiments, a straight-chain or branched-chain alkyl has 30 or fewer carbon atoms in its backbone (e.g., C for straight chain). 1~30 , C for branched chains 3~30 ), more preferably having 20 or fewer carbon atoms.

[0044] Furthermore, the term "alkyl," as used throughout the specification, examples, and claims, is intended to include both unsubstituted and substituted alkyl groups, the latter of which refers to alkyl moieties having substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone, including haloalkyl groups (such as trifluoromethyl and 2,2,2-trifluoroethyl).

[0045] "C x~y " or "C x ~C y The term "C alkyl," when used in conjunction with a chemical moiety such as acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy, is meant to include groups containing x to y carbons in the chain. C alkyl indicates a hydrogen when the group is in a terminal position and a bond when the group is internal. 1~6 An alkyl group contains, for example, 1 to 6 carbon atoms in the chain.

[0046] The term "alkylamino," as used herein, refers to an amino group substituted with at least one alkyl group.

[0047] The term "alkylthio," as used herein, refers to a thiol group substituted with an alkyl group and may be represented by the general formula alkylS-.

[0048] The term "amide," as used herein, refers to the group: [ka] In the formula, R 9 and R 10 each independently represents hydrogen or a hydrocarbyl group, or R 9 and R 10 together with the N atom to which they are attached complete a heterocycle having 4 to 8 atoms in the ring structure.

[0049] The terms "amine" and "amino" are art-recognized and refer to both unsubstituted and substituted amines and salts thereof, for example, a moiety that may be represented by: [ka] In the formula, R 9 , R 10 , and R 10 ' each independently represent hydrogen or a hydrocarbyl group, or R 9 and R 10 together with the N atom to which they are attached complete a heterocycle having 4 to 8 atoms in the ring structure.

[0050] The term "aminoalkyl," as used herein, refers to an alkyl group substituted with an amino group.

[0051] The term "aralkyl," as used herein, refers to an alkyl group substituted with an aryl group.

[0052] The term "aryl," as used herein, includes substituted or unsubstituted monocyclic aromatic groups in which each atom of the ring is carbon. Preferably, the ring is a 5- to 7-membered ring, more preferably a 6-membered ring. The term "aryl" also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjacent rings, at least one of which is aromatic; for example, the other cyclic rings may be cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and / or heterocyclyl. Aryl groups include benzene, naphthalene, phenanthrene, phenol, aniline, and the like.

[0053] The term "carbamate" is art-recognized and refers to the group: [ka] In the formula, R 9 and R 10 independently represent hydrogen or a hydrocarbyl group.

[0054] The term "carbocyclylalkyl," as used herein, refers to an alkyl group substituted with a carbocyclic group.

[0055] The term "carbocycle" includes 5- to 7-membered monocyclic rings and 8- to 12-membered bicyclic rings. Each ring in a bicyclic carbocycle can be selected from saturated, unsaturated, and aromatic rings. Carbocycles include bicyclic molecules in which one, two, three, or more atoms are shared between the two rings. The term "fused carbocycle" refers to a bicyclic carbocycle in which each ring shares two adjacent atoms with the other ring. Each ring in a fused carbocycle can be selected from saturated, unsaturated, and aromatic rings. In an exemplary embodiment, an aromatic ring, e.g., phenyl, can be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Valences permitting, any combination of saturated, unsaturated, and aromatic bicyclic rings is included in the definition of carbocycle. Exemplary "carbocycles" include cyclopentane, cyclohexane, bicyclo[2.2.1]heptane, 1,5-cyclooctadiene, 1,2,3,4-tetrahydronaphthalene, bicyclo[4.2.0]oct-3-ene, naphthalene, and adamantane. Exemplary fused carbocycles include decalin, naphthalene, 1,2,3,4-tetrahydronaphthalene, bicyclo[4.2.0]octane, 4,5,6,7-tetrahydro-1H-indene, and bicyclo[4.1.0]hept-3-ene. A "carbocycle" may be substituted at any one or more positions capable of bearing a hydrogen atom.

[0056] The term "carbocyclylalkyl," as used herein, refers to an alkyl group substituted with a carbocyclic group.

[0057] The term "carbonate" is art-recognized and refers to an -OCO2- group.

[0058] The term "carboxy," as used herein, refers to a group represented by the formula -CO2H.

[0059] The term "ester" as used herein refers to an ester of -C(O)OR 9 refers to a group, wherein R 9 represents a hydrocarbyl group.

[0060] The term "ether," as used herein, refers to a hydrocarbyl group linked to another hydrocarbyl group via an oxygen. Thus, the ether substituent of a hydrocarbyl group can be hydrocarbyl-O-. Ethers can be symmetrical or asymmetrical. Examples of ethers include, but are not limited to, heterocycle-O-heterocycle and aryl-O-heterocycle. Ethers include "alkoxyalkyl" groups, which can be represented by the general formula alkyl-O-alkyl.

[0061] The terms "halo" and "halogen" as used herein mean halogen and include chloro, fluoro, bromo, and iodo.

[0062] The terms "hetaralkyl" and "heteroaralkyl," as used herein, refer to an alkyl group substituted with a hetaryl group.

[0063] The terms "heteroaryl" and "hetaryl" include substituted or unsubstituted aromatic monocyclic ring structures, preferably 5- to 7-membered rings, more preferably 5- to 6-membered rings, where the ring structure of such rings contains at least one heteroatom, preferably 1 to 4 heteroatoms, more preferably 1 or 2 heteroatoms. The terms "heteroaryl" and "hetaryl" also include polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjacent rings, at least one of which is heteroaromatic; for example, the other cyclic rings may be cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and / or heterocyclyl. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine, and the like.

[0064] The term "heteroatom," as used herein, means an atom of any element other than carbon or hydrogen. Preferred heteroatoms are nitrogen, oxygen, and sulfur.

[0065] The term "heterocyclylalkyl," as used herein, refers to an alkyl group substituted with a heterocycle group.

[0066] The terms "heterocyclyl," "heterocycle," and "heterocyclic" refer to substituted or unsubstituted non-aromatic ring structures, preferably 3- to 10-membered rings, more preferably 3- to 7-membered rings, whose ring structures contain at least one heteroatom, preferably 1 to 4 heteroatoms, more preferably 1 or 2 heteroatoms. The terms "heterocyclyl" and "heterocyclic" also include polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjacent rings, at least one of which is heterocyclic; for example, the other cyclic rings may be cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and / or heterocyclyl. Heterocyclyl groups include, for example, piperidine, piperazine, pyrrolidine, morpholine, lactones, lactams, and the like.

[0067] The term "hydrocarbyl," as used herein, refers to a group bonded through a carbon atom that has no =0 or =S substituents, typically has at least one carbon-hydrogen bond and a primary carbon backbone, but may optionally contain heteroatoms. Thus, groups such as methyl, ethoxyethyl, 2-pyridyl, and even trifluoromethyl are considered hydrocarbyl for purposes of this application, while substituents such as acetyl (which has an =0 substituent on the linking carbon) and ethoxy (which is linked through an oxygen rather than a carbon) are not. Hydrocarbyl groups include, but are not limited to, aryl, heteroaryl, carbocycle, heterocycle, alkyl, alkenyl, alkynyl, and combinations thereof.

[0068] The term "hydroxyalkyl," as used herein, refers to an alkyl group substituted with a hydroxy group.

[0069] The term "lower," when used in conjunction with chemical moieties such as acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy, is meant to include groups having 10 or fewer, preferably 6 or fewer atoms in the substituent. "Lower alkyl," for example, refers to an alkyl group containing 10 or fewer, preferably 6 or fewer, carbon atoms. In certain embodiments, an acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy substituent as defined herein is a lower acyl, lower acyloxy, lower alkyl, lower alkenyl, lower alkynyl, or lower alkoxy, respectively, regardless of whether they are used alone or in combination with other substituents (such as when used in the descriptions hydroxyalkyl and aralkyl (where, for example, atoms in aryl groups are not counted when counting the number of carbon atoms in an alkyl substituent)).

[0070] The terms "polycyclyl," "polycycle," and "polycyclic" refer to two or more rings (e.g., cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl, and / or heterocyclyl) in which two or more atoms are common to two adjacent rings, e.g., the rings are "fused rings." Each ring of a polycycle can be substituted or unsubstituted. In certain embodiments, each ring of a polycycle contains 3 to 10 atoms, preferably 5 to 7 atoms.

[0071] The term "sulfate" is art-recognized and refers to the group -OSO3H, or a pharmaceutically acceptable salt thereof.

[0072] The term “sulfonamide” is art-recognized and refers to a group represented by the general formula: [ka] In the formula, R 9 and R 10 independently represent hydrogen or hydrocarbyl.

[0073] The term "sulfoxide" is art-recognized and refers to the group --S(O)--.

[0074] The term "sulfonate" is art-recognized and refers to the group SO3H, or a pharmaceutically acceptable salt thereof.

[0075] The term "sulfone" is art-recognized and refers to the group -S(O)2-.

[0076] The term "substituted" refers to moieties having substituents replacing a hydrogen on one or more backbone carbons. It is understood that "substituted" or "substituted with" includes the implicit proviso that such substitution is subject to the permissible valences of the substituted atom and substituent, and that the substitution results in a stable compound (e.g., one that does not spontaneously undergo transformation by rearrangement, cyclization, elimination, etc.). As used herein, the term "substituted" is intended to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this invention, heteroatoms (such as nitrogen) can have hydrogen substituents and / or any permissible substituents described herein that satisfy the valences of the heteroatoms. Substituents can include any of the substituents described herein, such as halogen, hydroxyl, carbonyl (such as carboxyl, alkoxycarbonyl, formyl, or acyl), thiocarbonyl (such as thioester, thioacetate, or thioformate), alkoxyl, phosphoryl, phosphate, phosphonate, phosphinate, amino, amido, amidine, imine, cyano, nitro, azido, sulfhydryl, alkylthio, sulfate, sulfonate, sulfamoyl, sulfonamido, sulfonyl, heterocyclyl, aralkyl, or an aromatic or heteroaromatic moiety. Those skilled in the art will understand that the moieties substituted on the hydrocarbon chain can themselves be substituted, if appropriate.

[0077] The term "thioalkyl," as used herein, refers to an alkyl group substituted with a thiol group.

[0078] The term "thioester" as used herein refers to a group selected from the group consisting of -C(O)SR 9 or -SC(O)R 9 In the formula, R 9 represents a hydrocarbyl.

[0079] The term "thioether" as used herein is equivalent to an ether, where the oxygen is replaced by a sulfur.

[0080] The term "urea" is art-recognized and may be represented by the general formula: [ka] In the formula, R 9 and R 10 independently represent hydrogen or hydrocarbyl.

[0081] The term "modulate," as used herein, includes inhibiting or suppressing a function or activity (such as cell proliferation), as well as enhancing a function or activity.

[0082] The phrase "pharmaceutically acceptable" is art-recognized. In certain embodiments, this term includes compositions, excipients, adjuvants, polymers, and other materials and / or dosage forms that are suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio, within the scope of sound medical judgment.

[0083] "Salt" is used herein to refer to an acid addition salt or a base addition salt.

[0084] Many of the compounds useful in the methods and compositions of the present disclosure have at least one stereocenter in their structure. This stereocenter may exist in the R or S configuration, and the R and S designations are used in accordance with the conventions set forth in Pure Appl. Chem. (1976), 45, 11-30. The present disclosure contemplates all stereoisomeric forms, including enantiomeric and diastereomeric forms of the compounds, salts, prodrugs, or mixtures thereof, including all possible mixtures of stereoisomers. See, e.g., WO 01 / 062726.

[0085] Furthermore, certain compounds containing alkenyl groups can exist as Z (Zusammen) or E (Entgegen) isomers. In each case, the present disclosure includes both mixtures and separate individual isomers.

[0086] Some compounds may also exist in tautomeric forms, and such forms, although not explicitly shown in the formulae given herein, are intended to be included within the scope of the present disclosure.

[0087] "Solvate" refers to a form of a compound associated with a solvent or water, usually by solvolysis (also called a "hydrate"). This physical association involves hydrogen bonding. Conventional solvents include water, ethanol, acetic acid, and the like. The compounds of the present invention may be prepared, for example, in crystalline form and may also be solvated or hydrated. Suitable solvates include pharmaceutically acceptable solvates, such as hydrates, and further include both stoichiometric and non-stoichiometric solvates. In certain instances, a solvate can be isolated, for example, when one or more solvent molecules are incorporated into the crystal lattice of the crystalline solid. "Solvate" encompasses both solution-phase and isolatable solvates. Representative solvates include hydrates, ethanolates, and methanolates.

[0088] As used herein, the term "isotopic variant" refers to a compound that contains an unusual proportion of isotopes at one or more of the atoms that constitute that compound. For example, an "isotopic variant" of a compound may contain, for example, deuterium ( 2 H or D), carbon-13 ( 13 C), nitrogen-15( 15 In compounds where such isotopic substitutions have been made, the following atoms, if present, may be changed so that, for example, any hydrogen 2 Either carbon may be H / D 13 C or any nitrogen 15It will be understood that the presence and location of such atoms may be determined within the skill of the art. Similarly, the present invention may include the preparation of isotopic variants using radioactive isotopes, for example, when the resulting compounds may be used in drug and / or substrate tissue distribution studies. The radioactive isotope tritium, i.e., 3 H, and carbon-14, i.e., 14 C is particularly useful for this purpose due to its ease of incorporation and simple means of detection. 11 C. 18 F, 15 O and 13 Compounds substituted with positron emitting isotopes, such as N, can be prepared and would be useful in positron emission tomography (PET) studies to examine substrate receptor occupancy. All isotopic variants of the compounds provided herein, whether radioactive or not, are intended to be encompassed within the scope of the present invention.

[0089] It is also understood that compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or in the arrangement of their atoms in space are termed "isomers." Isomers that differ in the arrangement of their atoms in space are termed "stereoisomers."

[0090] Stereoisomers that are not mirror images of one another are called "diastereomers," while stereoisomers that are non-superimposable mirror images of each other are called "enantiomers." When a compound has an asymmetric center, for example, if it is bonded to four different groups, a pair of enantiomers is possible. Enantiomers can be characterized by the absolute configuration of their asymmetric center and described by the Cahn and Prelog R- and S-sequencing rules or by the way the molecule rotates the plane of polarized light, designated as dextrorotatory or levorotatory (i.e., as (+)- or (-)-isomers, respectively). Chiral compounds can exist as individual enantiomers or as mixtures thereof. A mixture containing equal proportions of enantiomers is called a "racemic mixture."

[0091] "Tautomers" refer to interchangeable forms of a particular compound structure, differing in the substitution of hydrogen atoms and electrons. Thus, two structures can be in equilibrium through the transfer of electrons and atoms (usually H). For example, enols and ketones are tautomers because they rapidly interconvert upon treatment with either acid or base. Another example of a tautomer is the acid and nitro forms of phenylnitromethane, which are similarly formed by treatment with acid or base. Tautomeric forms can be relevant to achieving optimal chemical reactivity and biological activity of a compound of interest.

[0092] As used herein, a pure enantiomer compound is substantially free of other enantiomers or stereoisomers of the compound (i.e., in enantiomeric excess). In other words, the "S" form of a compound is substantially free of the "R" form of the compound and is thus in enantiomeric excess of the "R" form. The terms "enantiomerically pure" or "pure enantiomer" mean that a compound contains greater than 95%, greater than 96%, greater than 97%, greater than 98%, greater than 98.5%, greater than 99%, greater than 99.2%, greater than 99.5%, greater than 99.6%, greater than 99.7%, greater than 99.8%, or greater than 99.9% by weight of an enantiomer. In certain embodiments, the weight is based on the total weight of all enantiomers or stereoisomers of the compound.

[0093] As used herein, unless otherwise specified, the term "enantiomerically pure R compounds" refers to at least about 95% by weight R compounds and up to about 5% by weight S compounds, at least about 99% by weight R compounds and up to about 1% by weight S compounds, or at least about 99.9% by weight R compounds and up to about 0.1% by weight S compounds. In certain embodiments, the weights are based on the total weight of the compounds.

[0094] As used herein, unless otherwise specified, the term "enantiomerically pure S compound" or "S compound" refers to at least about 95% by weight S compound and up to about 5% by weight R compound, at least about 99% by weight S compound and up to about 1% by weight R compound, or at least about 99.9% by weight S compound and up to about 0.1% by weight R compound. In certain embodiments, the weights are based on the total weight of the compound.

[0095] In the compositions provided herein, the enantiomerically pure compound, or its pharmaceutically acceptable salt, solvate, hydrate, or prodrug, can be present together with other active or inactive ingredients. For example, a pharmaceutical composition containing an enantiomerically pure R compound can contain, for example, about 90% excipients and about 10% enantiomerically pure R compound. In certain embodiments, the enantiomerically pure R compound in such a composition can contain, for example, at least about 95% by weight of the R compound and up to about 5% by weight of the S compound, based on the total weight of the compound. For example, a pharmaceutical composition containing an enantiomerically pure S compound can contain, for example, about 90% excipients and about 10% of the enantiomerically pure S compound. In certain embodiments, the enantiomerically pure S compound in such a composition can contain, for example, at least about 95% by weight of the S compound and up to about 5% by weight of the R compound, based on the total weight of the compound. In certain embodiments, the active ingredient can be formulated with little or no excipients or carriers.

[0096] The compounds of the present invention may possess one or more asymmetric centers; therefore, such compounds can be produced as individual (R)- or (S)-stereoisomers or as mixtures thereof.

[0097] Unless otherwise indicated, the description or naming of a particular compound in the specification and claims is intended to include both individual enantiomers and mixtures, racemic or otherwise, thereof. The methods for the determination of stereochemistry and the separation of stereoisomers are well-known in the art.

[0098] Those skilled in the art of organic synthesis will recognize that the maximum number of heteroatoms in a stable and chemically feasible heterocycle (whether aromatic or non-aromatic) is determined by the ring size, degree of unsaturation, and valence of the heteroatoms. Generally, a heterocycle may have from 1 to 4 heteroatoms, so long as the heteroaromatic ring is chemically feasible and stable. [Example]

[0099] In order that the invention described herein may be more fully understood, the following examples are set forth. The examples described in this application are provided to illustrate the compounds, compositions, materials, devices, and methods provided herein, and should not be construed in any way as limiting the scope thereof.

[0100] material Sulfobetaine methacrylate (SBMA, 95%), 2-methacryloyloxyethyl phosphorylcholine (MPC, 97%), 2,2,2-trifluoroethyl methacrylate (TFEMA), 2,2-dimethoxy-2-phenylacetophenone (DMPA, 99%), N,N,N',N'',N''-pentamethyldiethylenetriamine (PMDETA, 99%), 1,6-hexanedithiol (≥97%, FG), ethyl α-α-bromoisobutyrate (EBIB, 98%), CuBr (99%), sodium sulfate, Acid Blue 45, Brilliant Blue R, Chicago Sky Blue 6B, Direct Red 80, methyl orange, ethyl orange, and activated aluminum oxide (basic, Brockmann I, standard grade) were purchased from Sigma-Aldrich. Allyl methacrylate (AMA, ≥98.0%), methanol (>99.8%), acetonitrile (≥99.5%), isopropyl alcohol (IPA, 99.5%), trifluoroethanol (TFE, ≥99.0%), sodium chloride (ACS certified), ethanol, and riboflavin (98%) were purchased from Fisher Scientific. Vitamin B12 was purchased from MP Biomedicals. Hexane was obtained from VWR. d4-methanol (99.5%) and d6-DMSO (99.5%) were purchased from Cambridge Isotope Laboratories Inc. Ascorbic acid was purchased from GBiosciences. Commercially available nanofiltration membrane NP-30 (permeability: 1.75 LMH / b) was obtained from Sterlitech. Ultrafiltration support membrane UE-50 was obtained from Sterlitech Membranes. Ultrafiltration support membrane PS-35 was obtained from Solecta Membranes.

[0101] Example 1. Polymer synthesis Random copolymers of TFEMA and MPC underwent microphase separation to form networks of disordered bicontinuous domains of approximately 1.3 nm in size (Bengani-Lutz, et al., Self-Assembling Zwitterionic Copolymers as Membrane Selective Layers with Excellent Fouling Resistance: Effect of Zwitterion Chemistry. ACS Applied Materials & Interfaces 9, 20859-20872, (2017)). Copolymers of AMA with the similar zwitterionic monomer sulfobetaine methacrylate (SBMA) also formed very similar morphologies (Lounder, et al., Zwitterionic Ion-Selective Membranes with Tunable Subnanometer Pores and Excellent Fouling Resistance. Chemistry of Materials 33, 4408-4416, (2021)). Thus, upon casting, P(AMA-r-TFEMA-r-MPC) was expected to self-assemble into a similar morphology, resulting in a network of MPC-rich nanodomains, which allowed the permeation of water and solutes small enough to fit into these “nanochannels” held by the hydrophobic TFEMA / AMA-rich domains ( Figure 1A ).

[0102] P(AM-r-SBMA-r-MPC) Copolymers of allyl methacrylate (AMA or AM), sulfobetaine methacrylate (SBMA), and 2-methacryloyloxyethyl phosphorylcholine (MPC) were synthesized by Activators Regenerated by Electron Transfer Atom Transfer Radical Polymerization (ARGET-ATRP). The reaction solution consisted of 60 wt% AMA, 20 wt% SBMA, and 20 wt% MPC.

[0103] P(AM-r-TFEMA-r-MPC) The statistical / random copolymer presented here combines three different monomers: the zwitterionic monomer 2-methacryloyloxyethyl phosphorylcholine (MPC), the highly hydrophobic monomer trifluoroethyl methacrylate (TFEMA), and the hydrophobic monomer allyl methacrylate (AM), which possesses a C-C double bond that can readily undergo thiol-ene click reactions (Figure 1B). The double bonds present in the AMA units can be crosslinked via thiol-ene click reactions in the presence of dithiols (Figure 1B). Thiol-ene "click" chemistry is characterized by extremely high reaction rates, high conversions, and selective yields. These features make it a good choice for post-functionalization of membranes in roll-to-roll systems, where short residence times and high yields are required. The reaction mechanism allows for the reliable incorporation of a wide range of functional groups on timescales tailored to membrane production rates.

[0104] This crosslinking reaction is carried out in a solvent that preferentially partitions into the hydrophobic domains but not into the zwitterionic domains. The solvent also plasticizes the TFEMA / AMA domains, increasing the mobility of the functional groups sufficiently to allow the crosslinking reaction. The crosslinked hydrophobic domains are more rigid, limiting the swelling of the zwitterionic domains when immersed in water. Therefore, the effective pore size of the crosslinked ZAC-based membranes is smaller than that of the non-crosslinked copolymer selective layer in water. The membranes were then exposed to UV light for various periods ranging from 10 to 40 seconds. During UV curing, DMPA acted as a photoinitiator, generating radicals on the 1,6-hexanedithiol, which then reacted with the allylic double bonds of the AM repeat units (Figure 1C).

[0105] Example 2. Bench-scale membrane production TFC membranes were fabricated using the copolymers described above. First, the copolymer and crosslinker were dissolved in a mixture of methanol and acetonitrile (v:v ratio 3:1) at 5.0 w / v% (i.e., 5 g polymer / 95 mL solvent). The crosslinkers were 2,2-dimethoxy-2-phenylacetophenone (DPMA) and 1,6-hexanedithiol (HDT) (copolymer:DMPA:HDT mass ratio 10:1:1). The solution was then passed through a syringe filter and coated onto a support membrane (UE50, Trisep) using a wire-wound rod (Gardo, wire size No. 16). The coated membrane was then transferred to a convection oven at 80 °C to evaporate the solvent. The crosslinker is not expected to evaporate in the oven, thereby being uniformly distributed throughout the dried copolymer selective layer after solvent evaporation. The entire membrane sheet was then irradiated with UV light (365 nm) to initiate the crosslinking reaction.

[0106] Example 3. Pilot-scale membrane production TFC membranes were fabricated using the copolymers described above. First, the copolymer and crosslinker were dissolved in a mixture of methanol and acetonitrile (v:v ratio 1.5:1) at 4.4–4.6 w / v% (i.e., 4.4–4.6 g of polymer per 95 mL of solvent). The crosslinkers were 2,2-dimethoxy-2-phenylacetophenone (DPMA) and 1,6-hexanedithiol (HDT). (Copolymer:DMPA:HDT mass ratios of 100:1:1 and 200:1:1 were investigated.) The resulting solution was then passed through a syringe filter.

[0107] Pilot production was performed using a pilot coater at UMASS Amherst. A support membrane roll (UE50) was operated at a line speed of 6 to 14 feet per minute. The copolymer / crosslinker solution was coated onto the support membrane web using a slot die. After coating, the web was passed through a convection oven at 80°C to evaporate the solvent. The crosslinker was not expected to evaporate in the oven, thereby resulting in a uniform distribution throughout the dry copolymer selective layer after solvent evaporation. The entire membrane sheet was then irradiated with UV light (>240 nm) to initiate the crosslinking reaction.

[0108] Incorporation by Reference All U.S. and PCT patent publications and U.S. patents mentioned herein are incorporated by reference in their entirety as if each individual patent publication or patent was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control.

[0109] Other embodiments Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments described herein. The scope of the embodiments described herein is not intended to be limited to the above description, but rather is as set forth in the appended claims. Those skilled in the art will appreciate that various changes and modifications to this description can be made without departing from the spirit or scope of the invention, as defined in the following claims.

Claims

1. 1. A method for manufacturing a thin film composite membrane, the method comprising: providing a copolymer comprising: (i) a plurality of zwitterionic repeat units; and (ii) a plurality of hydrophobic repeat units, wherein each hydrophobic repeat unit comprises an alkene; providing a plurality of cross-linking units, each cross-linking unit comprising a first terminal thiol moiety and a second terminal thiol moiety; Providing an initiator; providing a solvent; mixing the copolymer, the plurality of crosslinking units, the initiator, and the solvent, thereby forming a mixture; coating the mixture onto a support film; evaporating the solvent; activating the initiator, thereby forming the thin film composite membrane comprising a crosslinked zwitterionic copolymer; The method, wherein the weight ratio of the copolymer:the initiator:the plurality of crosslinking units is from about 10:1:1 to about 200:1:

1.

2. 10. The method of claim 1, wherein the solvent is methanol, acetonitrile, isopropanol, hexane, or any combination thereof.

3. 3. The method of claim 1, wherein the activation is performed at room temperature.

4. The method of any one of claims 1 to 3, wherein the initiator is a photoinitiator, a redox initiator, a thermal initiator, or any combination thereof.

5. 5. The method of any one of claims 1 to 4, wherein the initiator is a benzoin ether, a benzil ketal, an α-dialkoxy-acetophenone, an α-hydroxy-alkyl-phenone, an α-amino-alkyl-phenone, an acyl-phosphine oxide, a benzophenone (with or without an amine synergist), a thioxanthone (with or without an amine synergist), a hydrogen peroxide, an alkyl peroxide, an acyl peroxide, a persulfate, a disulfide, a dibenzoyl peroxide (with or without a tertiary amine synergist), a benzoyl peroxide, 1,1'-azobis(cyclohexanecarbonitrile), azobisisobutyronitrile, di-tert-butyl nitroxide, or a combination thereof.

6. 6. The method of claim 5, wherein the initiator is 2,2-dimethoxy-2-phenylacetophenone (DPMA) or 2-hydroxy-2-methylpropiophenone.

7. 7. The method of any one of claims 1 to 6, wherein the crosslinking unit is an alkyldithiol, benzenedithiol, ethylene glycol dithiol, biphenyldithiol, a multi-arm thiol (e.g., tetra(ethylene glycol)dithiol), a monothiol, or a thiol-containing polymer or copolymer (e.g., poly(ethylene glycol)dithiol).

8. The method of claim 7, wherein the crosslinking unit is 1,6-hexanedithiol (HDT).

9. The method according to any one of claims 1 to 8, wherein the solvent is a mixture of methanol and acetonitrile.

10. 10. The method of claim 9, wherein the methanol and acetonitrile are present at about 4 to about 6 w / v % in a ratio (v / v) of about 1.5:1 to about 3:

1.

11. 11. The method of claim 10, wherein the methanol and acetonitrile are present in a ratio (v / v) of about 1.5:1 at about 4.4 to about 4.6 w / v%.

12. 11. The method of claim 10, wherein the methanol and acetonitrile are present in a ratio (v / v) of about 3:1 at about 5% w / v.

13. 13. The method of any one of claims 1 to 12, wherein the weight ratio of the copolymer:the initiator:the plurality of crosslinking units is from about 10:1:1 to about 100:1:

1.

14. 14. The method of claim 13, wherein the weight ratio of the copolymer:the initiator:the plurality of crosslinking units is from about 100:1:1 to about 200:1:

1.

15. 14. The method of claim 13, wherein the weight ratio of the copolymer:the initiator:the plurality of crosslinking units is about 10:1:

1.

16. 16. The method of any one of claims 1 to 15, wherein the amount of initiator is from 0.01 grams to about 20 grams per gram of copolymer.

17. 17. The method of claim 16, wherein the amount of the initiator is from about 0.1 grams to about 1 gram per gram of the copolymer.

18. 17. The method of claim 16, wherein the amount of the initiator is from 0.01 grams to about 0.1 grams per gram of the copolymer.

19. 19. The method of any one of claims 1 to 18, wherein the amount of the plurality of crosslinking units is from 0.01 grams to about 20 grams per gram of the copolymer.

20. 20. The method of claim 19, wherein the amount of the plurality of crosslinking units is from about 0.1 grams to about 1 gram per gram of the copolymer.

21. 20. The method of claim 19, wherein the amount of the plurality of crosslinking units is from 0.01 grams to about 0.1 grams per gram of the copolymer.

22. The method of any one of claims 1 to 21, wherein the support membrane comprises UE50, Trisep, or a combination thereof.

23. The method of any one of claims 1 to 22, wherein the mixture is coated onto the support film using a wire-wound rod.

24. 24. The method of any one of claims 1 to 23, wherein the solvent is evaporated by heating at about 50-100°C.

25. 25. The method of claim 24, wherein the solvent is evaporated by heating at about 80°C.

26. 26. The method of any one of claims 1 to 25, wherein the initiator is activated by UV light, or elevated temperature, or a combination thereof.

27. 26. The method of any one of claims 1 to 25, wherein the initiator is activated by irradiation with UV light.

28. 28. The method of claim 27, wherein the irradiation is for about 10 seconds to about 150 seconds.

29. 29. The method of claim 28, wherein the irradiation is for about 30 seconds.

30. 29. The method of claim 28, wherein the irradiation is for about 60 seconds.

31. 29. The method of claim 28, wherein the irradiation is for about 90 seconds.

32. 29. The method of claim 28, wherein the irradiation is for about 120 seconds.

33. 33. The method of any one of claims 1 to 32, wherein the thin film composite membrane comprises at least two layers: a porous support layer and a layer of the crosslinked zwitterionic copolymer.

34. 34. The method of claim 33, wherein the layer of crosslinked zwitterionic copolymer has a thickness of about 0.1 μm to about 10 μm.

35. 35. The method of claim 34, wherein the layer of crosslinked zwitterionic copolymer has a thickness of about 1 μm to about 10 μm.

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