Construction of copolymer libraries

Abstract

A multi-dimensional copolymer array of a plurality of copolymers, polymerized from at least two independently variable sets of monomers, wherein the polymerization is characterized by: (a) selecting a first homologously varying series of monomers with non-varying polymerizable functional groups; (b) selecting at least one additional homologously varying series of different monomers having non-varying polymerizable functional groups that are reactive with the polymerizable functional groups of the first series of monomers to form copolymers; and (c) separately reacting a plurality of monomers from the first monomer series with a plurality of monomers from each of the additional monomer series to form the plurality of copolymers; wherein the homologous variations of the monomer series are selected to determine the effect of independently varying at least two different structural features of the copolymer on at least one end-use property of the copolymer. Methods for determining the effect of independently varying at least two different structural features of a copolymer and at least one end-use property of the copolymer are also disclosed, in which at least one end-use property of each copolymer of the plurality of copolymers is measured and the variations in each end-use property measured for each of the copolymers is compared as a function of the homologous variation within the monomer series from which the copolymers were polymerized to determine any relationship between the homologous variations and the end-use property variations among the copolymers. The method is useful for identifying members of a plurality of copolymers having useful properties for specific end-uses.

What is claimed is:  
     
         1 . A multidimensional copolymer array, comprising a plurality of copolymers polymerized from at least two independently variable sets of monomers, wherein said polymerization is characterized by: 
 (a) selecting a first homologously varying series of monomers with non-varying polymerizable functional groups;    (b) selecting at least one additional homologously varying series of different monomers having non-varying polymerizable functional groups that are reactive with the polymerizable functional groups of said first series of monomers to form copolymers; and    (c) separately reacting a plurality of monomers from said first monomer series with a plurality of monomers from each of said additional monomer series to form said plurality of copolymers;    wherein said homologous variations of said monomer series are selected to determine the effect of independently varying at least two different structural features of said copolymer on at least one end-use property of said copolymer.    
     
     
         2 . The copolymer array of  claim 1 , wherein said polymerization reaction is a free-radical process.  
     
     
         3 . The copolymer array of  claim 2 , wherein said free-radical process is an ionic polymerization.  
     
     
         4 . The copolymer array of  claim 1 , wherein said separate reactions are performed in parallel.  
     
     
         5 . The copolymer array of  claim 1 , wherein said separate reactions are performed in solution.  
     
     
         6 . The copolymer array of  claim 1 , wherein said separate reactions are performed in bulk.  
     
     
         7 . The copolymer array of  claim 1 , wherein said separate reactions are performed in the presence of a catalyst.  
     
     
         8 . The copolymer array of  claim 1 , wherein said separate reactions are performed in the absence of a catalyst.  
     
     
         9 . The copolymer array of  claim 1 , wherein said copolymers are further modified by chemical reactions or cross-linking.  
     
     
         10 . A multi-dimensional condensation-type copolymer array, comprising a plurality of copolymers polymerized from at least two independently variable sets of monomers, wherein said polymerization is characterized by: 
 (a) selecting a first homologously varying series of monomers with non-varying polymerizable functional groups;    (b) selecting at least one additional homologously varying series of different monomers having non-varying polymerizable functional groups that are reactive with the polymerizable functional groups of said first series of monomers to condense to form copolymers; and    (c) separately reacting a plurality of monomers from said first monomer series with a plurality of monomers from each of said additional monomer series to form said plurality of condensation-type copolymers;    wherein said homologous variations of said monomer series are selected to determine the effect of independently varying at least two different structural features of said copolymer on at least one end-use property of said copolymer.    
     
     
         11 . The copolymer array of  claim 10 , wherein said condensation-type reaction is an interfacial process.  
     
     
         12 . The copolymer array of  claim 10 , wherein said condensation-type reaction is a suspension process.  
     
     
         13 . The copolymer array of  claim 10 , wherein said separate reactions are performed in parallel.  
     
     
         14 . The copolymer array of  claim 10 , wherein said separate reactions are performed in solution.  
     
     
         15 . The copolymer array of  claim 10 , wherein said separate reactions are performed in bulk.  
     
     
         16 . The copolymer array of  claim 10 , wherein said separate reactions are performed in the presence of a catalyst.  
     
     
         17 . The copolymer array of  claim 10 , wherein said separate reactions are performed in the absence of a catalyst.  
     
     
         18 . The copolymer array of  claim 10 , wherein said polymerizable functional groups of said first monomer series are amine or hydroxyl groups and said polymerizable functional groups of said additional series of monomers are selected from the group consisting of carboxylic acids, esters, anhydrides and isocyanates.  
     
     
         19 . The copolymer array of  claim 18 , wherein said additional series of monomers comprise second and third monomer series, said second monomer series is selected from the group consisting of carboxylic acids, esters, anhydrides and isocyanates, and said third monomer series comprises a plurality of alkylene oxides selected from the group consisting of ethylene oxide, propylene oxide, isopropylene oxide, butylene oxide, isobutylene oxide and random and block polymers and copolymers thereof.  
     
     
         20 . The copolymer array of  claim 18 , wherein said polymerizable functional groups of said first monomer series are hydroxyl groups and said additional monomer series comprise a monomer series with polymerizable carboxylic acid groups.  
     
     
         21 . The copolymer array of  claim 20 , wherein said first monomer series comprises a plurality of different diphenol compounds, each having the general structure:  
       
         
           
           
               
               
           
         
       
       wherein R 1  is selected from the group consisting of —CH═CH—, (—CH 2 —) a , and —CHN(L 1 L 2 ), in which a has a value from zero to eight, inclusive, and L 1  and L 2  are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, provided that L 1  and L 2  are not both hydrogen; b independently has a value between zero and eight, inclusive; and R 2  is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms.  
     
     
         22 . The copolymer array of  claim 20 , wherein said first monomer series comprises a plurality of different aromatic-aliphatic dihydroxy compounds, each having the general structure:  
       
         
           
           
               
               
           
         
       
       wherein R 3  is selected from the group consisting of —CH═CH—, (—CH 2 —) a , and —CHN(L 1 L 2 ), in which a has a value from zero to eight, inclusive, and L 1  and L 2  are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, provided that L 1  and L 2  are not both hydrogen; R 5  and R 6  are each independently selected from the group consisting of hydrogen and straight or branched alkyl groups having up to 18 carbon atoms, R 4  is (—CH 2 —) b , wherein b independently has a value between zero and eight, inclusive; and R 2  is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms.  
     
     
         23 . The copolymer array of  claim 20 , wherein said monomer series with polymerizable carboxylic acid groups comprises a plurality of different dicarboxylic acid compounds, each having the general structure:  
       
         
           
           
               
               
           
         
       
       wherein R is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms.  
     
     
         24 . The copolymer array of  claim 21 , wherein for one or more of said monomers of said first monomer series, at least one of R 2 , L 1  or L 2  contain at least one ether linkage.  
     
     
         25 . The copolymer array of  claim 22 , wherein for one or more of said monomers of said first monomer series, at least one of R 2 , R 5 , R 6 , L 1  or L 2  contain at least one ether linkage.  
     
     
         26 . The copolymer array of  claim 23 , wherein for one or more of said monomers of said dicarboxylic acid monomer series, R contains at least one ether linkage.  
     
     
         27 . The copolymer array of  claim 10 , wherein said copolymers are further modified by chemical reactions or cross-linking.  
     
     
         28 . A method for determining the effect of independently varying at least two different structural features of a copolymer on at least one end-use property of said copolymer, comprising: 
 (a) measuring at least one end-use property of each copolymer of said copolymer array of  claim 1;  and    (b) comparing the variations in each end-use property measured for each of said copolymers as a function of the homologous variation within said monomer series from which said copolymers were polymerized to determine any relationship between said homologous variations and said end-use property variations among said copolymers;    thereby identifying specific members of said plurality of copolymers having useful properties for specific end-uses.    
     
     
         29 . The method of  claim 28 , wherein said polymerization reaction is a free-radical process.  
     
     
         30 . The method of  claim 29 , wherein said free-radical process is an ionic polymerization.  
     
     
         31 . The method of  claim 28 , wherein said separate reactions are performed in parallel.  
     
     
         32 . The method of  claim 28 , wherein said separate reactions are performed in solution.  
     
     
         33 . The method of  claim 28 , wherein said separate reactions are performed in bulk.  
     
     
         34 . The method of  claim 28 , wherein said separate reactions are performed in the presence of a catalyst.  
     
     
         35 . The method of  claim 28 , wherein said separate reactions are performed in the absence of a catalyst.  
     
     
         36 . The method of  claim 28 , wherein said copolymers are further modified by chemical reactions or cross-linking.  
     
     
         37 . The method of  claim 28 , wherein said end-use properties are measured by ELISA, SAM, chromatographic methods, DSC, TGA, DMA, TMA, microscopic techniques or processing methods.  
     
     
         38 . The method of  claim 28 , wherein the end-use property that is measured is a mechanical property, a viscoelastic property, a morphological property, an electrical property, an optical property, solute or gas permeability, surface tension or a thermal property.  
     
     
         39 . The method of  claim 28 , wherein the end-use property that is measured is antibacterial activity, blood compatibility, tissue compatibility, drug release characteristics, biological interactions with living organisms, hydrolytic degradation or protein adsorption characteristics.  
     
     
         40 . The method of  claim 28 , wherein the end-use property that is measured is polymer processability, radiation stability, sterilizability, adhesive properties, hydrophobic characteristics or stability to specific reaction conditions.  
     
     
         41 . A method for determining the effect of independently varying at least two different structural features of a condensation-type copolymer on at least one end-use property of said copolymer, comprising: 
 (a) measuring at least one end-use property of each copolymer of said copolymer array of claim  10 ; and    (b) comparing the variations in each end-use property measured for each of said copolymers as a function of the homologous variation within said monomer series from which said copolymers were polymerized to determine any relationship between said homologous variations and said end-use property variations among said copolymers;    thereby identifying specific members of said plurality of copolymers having useful properties for specific end-uses.    
     
     
         42 . The method of  claim 41 , wherein said condensation-type copolymers are prepared by an interfacial process.  
     
     
         43 . The method of  claim 41 , wherein said condensation-type copolymers are prepared by a suspension process.  
     
     
         44 . The method of  claim 41 , wherein said condensation-type copolymers are synthesized in parallel.  
     
     
         45 . The method of  claim 41 , wherein said condensation-type copolymers are polymerized in solution.  
     
     
         46 . The method of  claim 41 , wherein said condensation-type copolymers are polymerized in bulk.  
     
     
         47 . The method of  claim 41 , wherein said condensation-type copolymers are polymerized in the presence of a catalyst.  
     
     
         48 . The method of  claim 41 , wherein said condensation-type copolymers are polymerized in the absence of a catalyst.  
     
     
         49 . The method of  claim 41 , wherein said polymerizable functional groups of said first monomer series are amine or hydroxyl groups and said polymerizable functional groups of said additional series of monomers are selected from the group consisting of carboxylic acids, esters, anhydrides and isocyanates.  
     
     
         50 . The method of  claim 49 , wherein said additional series of monomers comprise second and third monomer series, said second monomer series is selected from the group consisting of carboxylic acids, esters, anhydrides and isocyanates, and said third monomer series comprises a plurality of alkylene oxides selected from the group consisting of ethylene oxide, propylene oxide, isopropylene oxide, butylene oxide, isobutylene oxide and random and block polymers and copolymers thereof.  
     
     
         51 . The method of  claim 49 , wherein said polymerizable functional groups of said first monomer series are hydroxyl groups and said additional monomer series comprise a monomer series with polymerizable carboxylic acid groups.  
     
     
         52 . The method of  claim 51 , wherein said first monomer series comprises a plurality of different diphenol compounds, each having the general structure:  
       
         
           
           
               
               
           
         
       
       wherein R 1  is selected from the group consisting of —CH═CH—, (—CH 2 —) a , and —CHN(L 1 L 2 ), in which a has a value from zero to eight, inclusive, and L 1  and L 2  are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, provided that L 1  and L 2  are not both hydrogen; b independently has a value between zero and eight, inclusive; and R 2  is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms.  
     
     
         53 . The method of  claim 51 , wherein said first monomer series comprises a plurality of different aromatic-aliphatic dihydroxy compounds, each having the general structure:  
       
         
           
           
               
               
           
         
       
       wherein R 3  is selected from the group consisting of —CH═CH—, (—CH 2 —) a , and —CHN(L1L 2 ), in which a has a value from zero to eight, inclusive, and L 1  and L 2  are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, provided that L 1  and L 2  are not both hydrogen; R 5  and R 6  are each independently selected from the group consisting of hydrogen and straight or branched alkyl groups having up to 18 carbon atoms, R 4  is (—CH 2 —) b , wherein b independently has a value between zero and eight, inclusive; and R 2  is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms.  
     
     
         54 . The method of  claim 51 , wherein said monomer series with polymerizable carboxylic acid groups comprises a plurality of different dicarboxylic acid compounds, each having the general structure:  
       
         
           
           
               
               
           
         
       
       wherein R is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms.  
     
     
         55 . The method of  claim 52 , wherein for one or more of said monomers of said first monomer series, at least one of R 2 , L 1  or L 2  contain at least one ether linkage.  
     
     
         56 . The method of  claim 53 , wherein for one or more of said monomers of said first monomer series, at least one of R 2 , R 5 , R 6 , L 1  or L 2  contain at least one ether linkage.  
     
     
         57 . The method of  claim 54 , wherein for one or more of said monomers of said dicarboxylic acid monomer series, R contains at least one ether linkage.  
     
     
         58 . The method of  claim 41 , wherein said copolymers are further modified by chemical reactions or cross-linking.  
     
     
         59 . The method of  claim 41 , wherein said end-use properties are measured by ELISA, SAM, chromatographic methods, DSC, TGA, DMA, TMA, microscopic techniques or processing methods.  
     
     
         60 . The method of  claim 41 , wherein the end-use property that is measured is a mechanical property, a viscoelastic property, a morphological property, an electrical property, an optical property, solute or gas permeability, surface tension or a thermal property.  
     
     
         61 . The method of  claim 41 , wherein the end-use property that is measured is antibacterial activity, blood compatibility, tissue compatibility, drug release characteristics, biological interactions with living organisms, hydrolytic degradation or protein adsorption characteristics.  
     
     
         62 . The method of  claim 41 , wherein the end-use property that is measured is polymer processability, radiation stability, sterilizability, adhesive properties, hydrophobic characteristics or stability to specific reaction conditions.  
     
     
         63 . A polyarylate comprising repeating units having the structure:  
       
         
           
           
               
               
           
         
       
       wherein R is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms; 
 R 1  is selected from the group consisting of —CH═CH—, (—CH 2 —) a , and —CHN(L 1 L 2 ), in which a has a value from zero to eight, inclusive, and L 1  and L 2  are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, provided that L 1  and L 2  are not both hydrogen;  
 b independently has a value between zero and eight, inclusive; and  
 R 2  is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms; and  
 wherein at least one of R, R 2 , and, when R 1  is —CHNL 1 L 2 , L 1  or L 2  contains at least one ether linkage.  
 
     
     
         64 . The polyarylate of  claim 63 , wherein R 1  is —CH 2 —CH 2 —, b is one and at least one of R or R 2  contains at least one ether linkage.  
     
     
         65 . The polyarylate of  claim 64 , wherein R 2  is selected from the group consisting of hydrogen, ethyl, butyl, octyl and benzyl, and R contains at least one ether linkage.  
     
     
         66 . The polyarylate of  claim 65  wherein R is —CH 2 —O—CH 2 — or —CH 2 —O—CH 2 —CH 2 —O—CH 2 —.  
     
     
         67 . The polyarylate of  claim 64 , wherein R is selected from the group consisting of —CH 2 —C(═O)—, —CH 2 —CH 2 —C(═O)—, —CH═CH— and (—CH 2 —) z , wherein z is an integer between two and eight, inclusive.  
     
     
         68 . The polyarylate of  claim 67 , wherein R 2  is 
       —CH 2 —CH 2 —O—CH 2 —CH 2 —O—CH 2 —CH 2 —OH. 
     
     
         69 . A tyrosine-derived diphenol compound having the structure:  
       
         
           
           
               
               
           
         
       
       wherein R 1  is selected from the group consisting of —CH═CH—, (—CH 2 —) a , and —CHN(L 1 L 2 ), in which a has a value from zero to eight, inclusive, and L 1  and L 2  are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, provided that L 1  and L 2  are not both hydrogen; 
 b independently has a value between zero and eight, inclusive; and  
 R 2  is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms; and  
 wherein at least one of R 2  or, when R 1  is —CHNL 1 L 2 , L 1  or L 2  contains at least one ether linkage.  
 
     
     
         70 . The diphenol of  claim 69 , wherein R 1  is —CH 2 —CH 2 —, b is one and R contains at least one ether linkage.  
     
     
         71 . The diphenol of  claim 70 , wherein R 2  is 
       —CH 2 —CH 2 —O—CH 2 —C 2 —O—CH 2 —CH 2 —OH. 
     
     
         72 . The diphenol of  claim 69 , wherein R 2  is selected from the group consisting of hydrogen, ethyl, butyl, octyl and benzyl, and R 1  is —CHNL 1 L 2 , wherein at least one of L 1  or L 2  contains at least one ether linkage.  
     
     
         73 . The diphenol of  claim 72 , wherein at least one of L 1  or L 2  is 
       —CH 2 —CH 2 —O—CH 2 —CH 2 —O—CH 2 —CH 2 —OH. 
     
     
         74 . A poly(amide ester) comprising repeating units having the structure:  
       
         
           
           
               
               
           
         
       
       wherein R 3  is selected from the group consisting of —CH═CH—, (—CH 2 —) a , and —CHN(L 1 L 2 ), in which a has a value from zero to two, inclusive, and L 1  and L 2  are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, provided that L 1  and L 2  are not both hydrogen; 
 R 5  and R 6  are each independently selected from the group consisting of hydrogen and straight or branched alkyl groups having up to 18 carbon atoms;  
 R 4  is (—CH 2 —) b , wherein b independently has a value between zero and eight, inclusive;  
 R 2  is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms; and  
 R is selected from the group consisting of saturated and unsaturated, substituted and unsubstituted alkyl, aryl and alkylaryl groups containing up to 18 carbon atoms; and  
 wherein at least one of R, R 2 , R 5 , R 6  and, when R 3  is —CHNL 1 L 2 , L 1  or L 2 , contains at least one ether linkage.  
 
     
     
         75 . The poly(amide ester) of  claim 74 , wherein R 3  is (—CH 2 —) a  and a is zero, b is one, one of R 5  or R 6  is hydrogen, the other of R 5  or R 6  is a methyl group, and at least one of R or R 2  contains at least one ether linkage.  
     
     
         76 . The poly(amide ester) of  claim 75 , wherein R 2  is selected from the 
       group consisting of hydrogen, ethyl, butyl, octyl and benzyl, and R contains at least one ether linkage.  
     
     
         77 . The poly(amide ester) of  claim 76 , wherein R is 
       —CH 2 —O—CH 2 — or —CH 2 —O—CH 2 —CH 2 —O—CH 2 —. 
     
     
         78 . The poly(amide ester) of  claim 75 , wherein R is selected from the group consisting of —CH 2 —C(═O)—, —CH 2 —CH 2 —C(═O)—, —CH═CH— and (—CH 2 —) z , wherein z is an integer between two and eight, inclusive.  
     
     
         79 . The poly(amide ester) of  claim 78 , wherein R 2  is 
       —CH 2 —CH 2 —O—CH 2 —CH 2 —O—CH 2 —CH 2 —OH. 
     
     
         80 . An aliphatic-aromatic dihydroxy monomer having the structure:  
       
         
           
           
               
               
           
         
       
       wherein R 3  is selected from the group consisting of —CH═CH—, (—CH 2 —) a , and —CHN(L 1 L 2 ), in which a has a value from zero to two, inclusive, and L 1  and L 2  are independently selected from the group consisting of hydrogen and straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms, provided that L 1  and L 2  are not both hydrogen; 
 R 5  and R 6  are each independently selected from the group consisting of hydrogen and straight or branched alkyl groups having up to 18 carbon atoms;  
 R 4  is (—CH 2 —) b , wherein b independently has a value between zero and eight, inclusive; and  
 R 2  is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms; and  
 wherein at least one of R 2 , R 5 , R 6  and, when R 3  is —CHNL 1 L 2 , L 1  or L 2 , contains at least one ether linkage.  
 
     
     
         81 . The dihydroxy compound of claim  80 , wherein R 3  is (—CH 2 —) a  and a is zero, b is one, one of R 5  or R 6  is hydrogen, the other of R 5  or R 6  is a methyl group, and R 2  contains at least one ether linkage.  
     
     
         82 . The dihydroxy compound of claim  81 , wherein R 2  is 
       —CH 2 —CH 2 —O—CH 2 —CH 2 —O—CH 2 —CH 2 —OH. 
     
     
         83 . The dihydroxy compound of claim  80 , wherein R 2  is selected from the group consisting of hydrogen, ethyl, butyl, octyl and benzyl, and at least one of R 3 ,R 5  or R 6  contains at least one ether linkage.  
     
     
         84 . The dihydroxy compound of claim  83 , wherein one of R 5  or R 6  is hydrogen, the other of R 5  or R 6  is a methyl group, and R 3  is —CHNL 1 L 2 , wherein at least one of L 1  or L 2  contains at least one ether linkage.  
     
     
         85 . The dihydroxy compound of claim  83 , wherein R 3  is (—CH 2 —) a  and a is zero, and at least one of R 5  or R 6  contains at least one ether linkage.