Ophthalmic And Otic Compositions Of Facially Amphiphilic Polymers And Oligomers And Uses Thereof

Abstract

The present invention discloses ophthalmic and otic compositions of facially amphiphilic antimicrobial polymers and oligomers and their uses, including their use in methods for treating and preventing ophthalmic infections and otic infections in humans and animals.

1 . An ophthalmic composition, comprising an effective amount of an antimicrobial oligomer of Formula I:
   R 1 —[—X-A 1 -Y—X-A 2 -Y—] m —R 2   (I)   
       or an acceptable salt or solvate thereof, 
       wherein:
 X is NR 8 , —N(R 8 )N(R 8 )—, O, or S; 
 Y is C═O, C═S, O═S═O, or —C(═O)C(═O)—; 
 R 8  is hydrogen or alkyl; 
 A 1  and A 2  are, independently, optionally substituted arylene or optionally substituted heteroarylene, wherein A 1  and A 2  are, independently, optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 A 1  is optionally substituted arylene or optionally substituted heteroarylene and A 2  is a C 3  to C 8  cycloalkyl or —(CH 2 ) q —, wherein q is 1 to 7, wherein A 1  and A 2  are, independently, optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 A 2  is optionally substituted arylene or optionally substituted heteroarylene, and A 1  is a C 3  to C 8  cycloalkyl or —(CH 2 ) q —, wherein q is 1 to 7, wherein A 1  and A 2  are, independently, optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); 
 R 1  is
 (i) hydrogen, a polar (PL) group, or a non-polar (NPL) group, and R 2  is —X-A 1 -Y—R 11 , wherein R 11  is hydrogen, a polar (PL) group, or a non-polar (NPL) group; or 
 (ii) R 1  and R 2  are, independently, hydrogen, a polar (PL) group, or a non-polar (NPL) group; or 
 (iii) R 1  and R 2  together are a single bond; 
 
 NPL is a nonpolar group independently selected from —B(OR 4 ) 2  and —(NR 3′ ) q1NPL —U NPL —(CH 2 ) pNPL —(NR 3″ ) q2NPL —R 4′ , wherein: 
 R 3 , R 3′ , and R 3″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 R 4  and R 4′  are, independently, selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl, any of which is optionally substituted with one or more alkyl or halo groups; 
 U NPL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 3 , —C(═O)—, —C(═O)—N═N—NR 3 —, —C(═O)—NR 3 —N═N—, —N═N—NR 3 —, —C(═N—N(R 3 ) 2 )—, —C(═NR 3 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 3 O—, —R 3 S—, —S—C═N—, and —C(═O)—NR 3 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 the —(CH 2 ) pNPL — alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated; 
 pNPL is 0 to 8; 
 q1NPL and q2NPL are, independently, 0, 1, or 2; 
 PL is a polar group selected from halo, hydroxyethoxymethyl, methoxyethoxymethyl, polyoxyethylene, and —(NR 5′ ) q1pL —U PL —(CH 2 ) pPL —(NR 5″ ) q2PL —V, wherein: 
 R 5 , R 5′ , and R 5″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 U PL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 5 , —C(═O)—, —C(═O)—N═N—NR 5 —, —C(═O)—NR 5 —N═N—, —N═N—NR 5 —, —C(═N—N(R 5 ) 2 )—, —C(═NR 5 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 50 —, —R 5 S—, —S—C═N—, and —C(═O)—NR 5 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 V is selected from nitro, cyano, amino, hydroxy, alkoxy, alkylthio, alkylamino, dialkylamino, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , diazamino, amidino, guanidino, guanyl, semicarbazone, aryl, heterocycle, and heteroaryl, any of which is optionally substituted with one or more of amino, halo, cyano, nitro, hydroxy, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , amidino, guanidino, guanyl, aminosulfonyl, aminoalkoxy, aminoalkythio, lower acylamino, or benzyloxycarbonyl; 
 the —(CH 2 ) pPL — alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated; 
 pPL is 0 to 8; 
 q1PL and q2PL are, independently, 0, 1, or 2; and 
 m is 1 to about 20; 
 
       and an ophthalmically acceptable excipient. 
     
     
         2 . The composition of  claim 1 , wherein the oligomer has Formula IIa:
   R 1 —X-A 1 -X—Y-A 2 -Y—X-A 1 -X—R 2   (IIa)   
       or an acceptable salt or solvate thereof, 
       wherein:
 X is NR 8 , O, S, or —N(R 8 )N(R 8 )—; 
 Y is C═O, C═S, or O═S═O; 
 R 8  is hydrogen or alkyl; 
 A 1  and A 2  are, independently, optionally substituted arylene or optionally substituted heteroarylene, wherein A 1  and A 2  are, independently, optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); 
 R 1  is a polar group (PL) or a non-polar group (NPL); 
 R 2  is R 1 ; 
 NPL is a nonpolar group —(NR 3′ ) q1NPL —U NPL —(CH 2 ) pNPL —(NR 3″ ) q2NPL —R 4′ , wherein: 
 R 3 , R 3′ , and R 3″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 R 4  and R 4′  are, independently, selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl, any of which is optionally substituted with one or more alkyl or halo groups; 
 U NPL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 3 , —C(═O)—, —C(═O)—N═N—NR 3 —, —C(═O)—NR 3 —N═N—, —N═N—NR 3 —, —C(═N—N(R 3 ) 2 )—, —C(═NR 3 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 3 O—, —R 3 S—, —S—C═N—, and —C(═O)—NR 3 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 the —(CH 2 ) pNPL — alkylene chain is optionally substituted with one or more alkyl, amino or hydroxy groups, or is unsaturated; 
 pNPL is 0 to 8; 
 q1NPL and q2NPL are, independently, 0, 1, or 2; 
 PL is a polar group selected from halo, hydroxyethoxymethyl, methoxyethoxymethyl, polyoxyethylene, and —(NR 5′ ) q1PL —U PL —(CH 2 ) pPL —NR 5′ ) q2PL —V, wherein: 
 R 5 , R 5′ , and R 5″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 U PL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 5 , —C(═O)—, —C(═O)—N═N—NR 5 —, —C(═O)—NR 5 —N═N—, —N═N—NR 5 —, —C(═N—N(R 5 ) 2 )-5—C(═NR 5 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 50 —, —R 5 S—, —S—C═N—, and —C(═O)—NR 5 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 V is selected from nitro, cyano, amino, hydroxy, alkoxy, alkylthio, alkylamino, dialkylamino, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , diazamino, amidino, guanidino, guanyl, semicarbazone, aryl, heterocycle, and heteroaryl, any of which is optionally substituted with one or more of amino, halo, cyano, nitro, hydroxy, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , amidino, guanidino, guanyl, aminosulfonyl, aminoalkoxy, aminoalkythio, lower acylamino, or benzyloxycarbonyl; 
 the —(CH 2 ) pPL — alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated; 
 pPL is 0 to 8; and 
 q1PL and q2PL are, independently, 0, 1, or 2. 
 
     
     
         3 . An ophthalmic composition, comprising an effective amount of an antimicrobial oligomer of Formula II:
   R 1 —[—X-A 1 -X—Y-A2-Y—] m —R 2   (II)   
       or an acceptable salt or solvate thereof, 
       wherein:
 X is NR 8 , O, S, —N(R 8 )N(R 8 )—, —N(R 8 )—(N═N)—, —(N═N)—N(R 8 )—, —C(R 7 R 7′ )NR 8 —, —C(R 7 R 7′ )O—, or —C(R 7 R 7′ )S—; 
 Y is C═O, C═S, O═S═O, —C(═O)C(═O)—, C(R 6 R 6′ )C═O, or C(R 6 R 6′ )C═S; 
 R 8  is hydrogen or alkyl; 
 R 7  and R 7′  are, independently, hydrogen or alkyl, or R 7  and R 7′  together are —(CH 2 ) p —, wherein p is 4 to 8; 
 R 6  and R 6′  are, independently, hydrogen or alkyl, or R 6  and R 6′  together are (CH 2 ) 2 NR 12 (CH 2 ) 2 , wherein R 12  is hydrogen, —C(═N)CH 3  or C(═NH)—NH 2 ; 
 A 1  and A 2  are, independently, optionally substituted arylene or optionally substituted heteroarylene, wherein A 1  and A 2  are, independently, optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); 
 R 1  is
 (i) hydrogen, a polar group (PL), or a non-polar group (NPL), and R 2  is —X-A 1 -X—R 1 , wherein A 1  is as defined above and is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (ii) hydrogen, a polar group (PL), or a non-polar group (NPL), and R 2  is —X-A′-X—R 1 , wherein A′ is aryl or heteroaryl and is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); 
 (iii) —Y-A 2 -Y—R 2 , and R 2  is hydrogen, a polar group (PL), or a non-polar group (NPL); or 
 (iv) —Y-A′ and R 2  is —X-A′, wherein A′ is aryl or heteroaryl and is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (v) R 1  and R 2  are, independently, a polar group (PL) or a non-polar group (NPL); or 
 (vi) R 1  and R 2  together form a single bond; 
 
 NPL is a nonpolar group independently selected from —B(OR 4 ) 2  and —(NR 3′ ) q1NPL —U NPL —(CH 2 ) pNPL —(NR 3″ ) q2NPL —R 4′ , wherein: 
 R 3 , R 3′ , and R 3″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 R 4  and R 4′  are, independently, selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl, any of which is optionally substituted with one or more alkyl or halo groups; 
 U NPL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 3 , —C(═O)—, —C(═O)—N═N—NR 3 —, —C(═O)—NR 3 —N═N—, —N═N—NR 3 —, —C(═N—N(R 3 ) 2 )—, —C(═NR 3 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 3 O—, —R 3 S—, —S—C═N—, and —C(═O)—NR 3 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 the —(CH 2 ) pNPL — alkylene chain is optionally substituted with one or more alkyl, amino or hydroxy groups, or is unsaturated; 
 pNPL is 0 to 8; 
 q1NPL and q2NPL are, independently, 0, 1, or 2; 
 PL is a polar group selected from halo, hydroxyethoxymethyl, methoxyethoxymethyl, polyoxyethylene, and —(NR 5′ ) q1pL —U PL —(CH 2 ) pPL —(NR 5′ ) q2PL —V, wherein: 
 R 5 , R 5′ , and R 5″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 U PL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 5 , —C(═O)—, —C(═O)—N═N—NR 5 —, —C(═O)—NR 5 —N═N—, —N═N—NR 5 —, —C(═N—N(R 5 ) 2 )—, —C(═NR 5 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 50 —, —R 5 S—, —S—C═N—, and —C(═O)—NR 5 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 V is selected from nitro, cyano, amino, hydroxy, alkoxy, alkylthio, alkylamino, dialkylamino, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , diazamino, amidino, guanidino, guanyl, semicarbazone, aryl, heterocycle, and heteroaryl, any of which is optionally substituted with one or more of amino, halo, cyano, nitro, hydroxy, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , amidino, guanidino, guanyl, aminosulfonyl, aminoalkoxy, aminoalkythio, lower acylamino, or benzyloxycarbonyl; 
 the —(CH 2 ) pPL — alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated; 
 pPL is 0 to 8; 
 q1PL and q2PL are, independently, 0, 1, or 2; and 
 m is 1 to about 20, 
 and an ophthalmically acceptable excipient. 
 
     
     
         4 . An ophthalmic composition, comprising an effective amount of an antimicrobial oligomer of Formula IV:
   R 1 —[—X-A 1 -X-Z-Y-A 2 -Y-Z] m —R 2   (IV)   
       or an acceptable salt or solvate thereof, 
       wherein:
 X is NR 8 , —NR 8 NR 8 —, C═O, or O; 
 Y is NR 8 , —NR 8 NR 8 —, C═O, S, or O; 
 R 8  is hydrogen or alkyl; 
 Z is C═O, C═S, O═S═O, —NR 8 NR 8 —, or —C(═O)C(═O)—; 
 A 1  and A 2  are, independently, optionally substituted arylene or optionally substituted heteroarylene, wherein A 1  and A 2  are, independently, optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); 
 R 1  is
 (i) hydrogen, a polar group (PL), or a non-polar group (NPL), and R 2  is —X-A 1 -X—R 1 , wherein A 1  is as defined above and is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (ii) hydrogen, a polar group (PL), or a non-polar group (NPL), and R 2  is —X-A 1 -X-Z-Y-A 2 -Y—R 1 , wherein A 1  and A 2  are as defined above, and each of which is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (iii) hydrogen, a polar group (PL), or a non-polar group (NPL), and R 2  is —X-A′-X—R 1 , wherein A′ is aryl or heteroaryl and is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (iv) hydrogen, a polar group (PL), or a non-polar group (NPL), and R 2  is —X-A 1 -X-Z-Y-A′-Y—R 1 , wherein A 1  is as defined above, A′ is aryl or heteroaryl, and each of A 1  and A′ is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (v) -Z-Y-A′ and R 2  is hydrogen, a polar group (PL), or a non-polar group (NPL), wherein A′ is aryl or heteroaryl and is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (vi) -Z-Y-A′, and R 2  is —X-A″, wherein A′ and A″ are, independently, aryl or heteroaryl, and each of A′ and A″ is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (vii) R 1  and R 2  are, independently, a polar group (PL) or a non-polar group (NPL); or 
 
 (viii) R 1  and R 2  together form a single bond; 
 NPL is a nonpolar group independently selected from —B(OR 4 ) 2  and —(NR 3′ ) q1NPL —U NPL —(CH 2 ) pNPL —(NR 3″ ) q2NPL —R 4′ , wherein: 
 R 3 , R 3′ , and R 3″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 R 4  and R 4′  are, independently, selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl, any of which is optionally substituted with one or more alkyl or halo groups; 
 U NPL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 3 , —C(═O)—, —C(═O)—N═N—NR 3 —, —C(═O)—NR 3 —N═N—, —N═N—NR 3 —, —C(═N—N(R 3 ) 2 )—, —C(═NR 3 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 3 O—, —R 3 S—, —S—C═N—, and —C(═O)—NR 3 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 the —(CH 2 ) pNPL — alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated; 
 pNPL is 0 to 8; 
 q1NPL and q2NPL are, independently, 0, 1, or 2; 
 PL is a polar group selected from halo, hydroxyethoxymethyl, methoxyethoxymethyl, polyoxyethylene, and —(NR 5′ ) q1pL —U PL —(CH 2 ) pPL —(NR 5′ ) q2PL —V, wherein: 
 R 5 , R 5′ , and R 5″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 U PL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 5 , —C(═O)—, —C(═O)—N═N—NR 5 —, —C(═O)—NR 5 —N═N—, —N═N—NR 5 —, —C(═N—N(R 5 ) 2 )—, —C(═NR 5 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 50 —, —R 5 S—, —S—C═N—, and —C(═O)—NR 5 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 V is selected from nitro, cyano, amino, hydroxy, alkoxy, alkylthio, alkylamino, dialkylamino, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , diazamino, amidino, guanidino, guanyl, semicarbazone, aryl, heterocycle, and heteroaryl, any of which is optionally substituted with one or more of amino, halo, cyano, nitro, hydroxy, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , amidino, guanidino, guanyl, aminosulfonyl, aminoalkoxy, aminoalkythio, lower acylamino, or benzyloxycarbonyl; 
 the —(CH 2 ) pPL — alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated; 
 pPL is 0 to 8; 
 q1PL and q2PL are, independently, 0, 1, or 2; and 
 m is 1 to about 20; 
 
       and an ophthalmically acceptable excipient. 
     
     
         5 . The composition of  claim 4  wherein the oligomer has Formula IVa, Formula IVb, or Formula IVc:
   R 1 —X-A 1 -X-Z-Y-A 2 -Y—R 2   (IVa)     R 1 —X-A 1 -X-Z-Y-A 2 -Y-Z-X-A 1 -X—R 2   (IVb)     R 1 —X-A 1 -X-Z-Y-A 2 -Y-Z-X-A 1 -X-Z-Y-A 2 -Y—R 2   (IVc)   
       or an acceptable salt or solvate thereof, 
       wherein:
 X is NR 8 , —NR 8 NR 8 —, C═O, or O; 
 Y is NR 8 , —NR 8 NR 8 —, C═O, S, or O; 
 R 8  is hydrogen or alkyl; 
 Z is C═O, C═S, O═S═O, —NR 8 NR 8 —, or —C(═O)C(═O)—; 
 A 1  and A 2  are, independently, optionally substituted arylene or optionally substituted heteroarylene, wherein A 1  and A 2  are, independently, optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); 
 R 1  is hydrogen, a polar group (PL), or a non-polar group (NPL); 
 R 2  is R 1 ; 
 NPL is a nonpolar group —(NR 3′ ) q1NPL —U NPL —(CH 2 ) pNPL —(NR 3″ ) q2NPL —R 4′ , wherein: 
 R 3 , R 3′ , and R 3″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 R 4  and R 4′  are, independently, selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl, any of which is optionally substituted with one or more alkyl or halo groups; 
 U NPL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 3 , —C(═O)—, —C(═O)—N═N—NR 3 —, —C(═O)—NR 3 —N═N—, —N═N—NR 3 —, —C(═N—N(R 3 ) 2 )—, —C(═NR 3 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 3 O—, —R 3 S—, —S—C═N—, and —C(═O)—NR 3 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 the —(CH 2 ) pNPL — alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated; 
 pNPL is 0 to 8; 
 q1NPL and q2NPL are, independently, 0, 1, or 2; 
 PL is a polar group selected from halo, hydroxyethoxymethyl, methoxyethoxymethyl, polyoxyethylene, and —(NR 5′ ) q1pL —U PL —(CH 2 ) pPL —(NR 5′ ) q2PL —V, wherein: 
 R 5 , R 5′ , and R 5″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 U PL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 5 , —C(═O)—, —C(═O)—N═N—NR 5 —, —C(═O)—NR 5 —N═N—, —N═N—NR 5 —, —C(═N—N(R 5 ) 2 )—, —C(═NR 5 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 50 —, —R 5 S—, —S—C═N—, and —C(═O)—NR 5 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 V is selected from nitro, cyano, amino, hydroxy, alkoxy, alkylthio, alkylamino, dialkylamino, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , diazamino, amidino, guanidino, guanyl, semicarbazone, aryl, heterocycle, and heteroaryl, any of which is optionally substituted with one or more of amino, halo, cyano, nitro, hydroxy, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , amidino, guanidino, guanyl, aminosulfonyl, aminoalkoxy, aminoalkythio, lower acylamino, or benzyloxycarbonyl; 
 the —(CH 2 ) pPL — alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated; 
 pPL is 0 to 8; and 
 q1PL and q2PL are, independently, 0, 1, or 2. 
 
     
     
         6 . An ophthalmic composition, comprising an effective amount of an antimicrobial oligomer of Formula V:
   R 1 —[-A 1 -W-A 2 -W—] m —R 2   (V)   
       or an acceptable salt or solvate thereof, 
       wherein:
 A 1  and A 2  are, independently, optionally substituted arylene or optionally substituted heteroarylene, wherein: 
 (i) A 1  and A 2  are, independently, optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (ii) one of A 1  or A 2  is as defined above and is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); and the other of A 1  or 
 A 2  is the group —C≡C(CH 2 ) p C≡C—, wherein p is 0 to 8, and the —(CH 2 ) p — alkylene chain is optionally substituted with one or more amino or hydroxyl groups; 
 W is absent, or represents —CH 2 —, —CH 2 —CH 2 —, —CH═CH—, or —C≡C—; 
 R 1  is
 (i) hydrogen, a polar group (PL), or a non-polar group (NPL), and R 2  is -A 1 -R 1 , wherein A 1  is as defined above and is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (ii) hydrogen, a polar group (PL), or a non-polar group (NPL), and R 2  is -A 1 -W-A 2 -R 1 , wherein each of A 1  and A 2  is as defined above and is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (iii) A′-W— and R 2  is -A 1 -W-A′, wherein A′ is aryl or heteroaryl, either of which is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (iv) A′-W— and R 2  is -A′, wherein A′ is aryl or heteroaryl, either of which is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) groups(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (iv) R 1  and R 2  together form a single bond; 
 
 NPL is a nonpolar group independently selected from —B(OR 4 ) 2  or —(NR 3′ ) q1NPL —U NPL —(CH 2 ) pNPL —(NR 3″ ) q2NPL —R 4 , wherein: 
 R 3 , R 3′ , and R 3″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 R 4  is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl, any of which is optionally substituted with one or more alkyl or halo groups; 
 U NPL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 3 , —(C═O)—, —(C═O)—N═N—NR 3 —, —(C═O)—NR 3 —N═N—, —N═N—NR 3 —, —C(═N—N(R 3 ) 2 )—, —C(═NR 3 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 3 O—, —R 3 S—, —S—C═N— and —(C═O)—NR 3 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 the —(CH 2 ) pNPL — alkylene chain is optionally substituted with one or more alkyl, amino or hydroxyl groups, or the alkylene chain is unsaturated; 
 pNPL is 0 to 8; 
 q1NPL and q2NPL are, independently, 0 to 2; 
 PL is a polar group selected from halo, hydroxyethoxymethyl, methoxyethoxymethyl, polyoxyethylene, and —(NR 5′ ) q1pL —U PL —(CH 2 ) pPL —(NR 5′ ) q2PL —V, wherein: 
 R 5 , R 5′ , and R 5″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 U PL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 5 , —(C═O)—, —(C═O)—N═N—NR 5 —, —(C═O)—NR 5 —N═N—, —N═N—NR 5 —, —C(═N—N(R 5 ) 2 )—, —C(═NR 5 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 50 —, —R 5 S—, —S—C═N—, and —(C═O)—NR 5 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 V is selected from nitro, cyano, amino, hydroxyl, alkoxy, alkylthio, alkylamino, dialkylamino, —NH(CH 2 ) p NH 2 , —N(CH 2 CH 2 NH 2 ) 2 , diazamino, amidino, guanidino, guanyl, semicarbazone, aryl, heterocycle, and heteroaryl, any of which is optionally substituted with one or more of amino, halo, cyano, nitro, hydroxyl, —NH(CH 2 ) p NH 2 , —N(CH 2 CH 2 NH 2 ) 2 , amidino, guanidino, guanyl, aminosulfonyl, aminoalkoxy, aminoalkythio, lower acylamino, or benzyloxycarbonyl; 
 the —(CH 2 ) pPL — alkylene chain is optionally substituted with one or more amino or hydroxyl groups, or the alkylene chain is unsaturated; 
 pPL is 0 to 8; 
 q1PL and q2PL are, independently, 0 to 2; and 
 m is 1 to about 25; 
 and an ophthalmically acceptable excipient. 
 
     
     
         7 . The composition of  claim 6  wherein the oligomer has Formula Va:
   R 1 -A 1 -W-A 2 -W-A1-R 2   (Va)   
       or an acceptable salt or solvate thereof, 
       wherein:
 A 1  and A 2  are, independently, optionally substituted arylene or optionally substituted heteroarylene, wherein:
 (i) A 1  and A 2  are, independently, optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); or 
 (ii) one of A 1  or A 2  is as defined above and is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); and the other of A 1  or A 2  is the group —C≡C(CH 2 ) p C≡C—, wherein p is 0 to 8, and the —(CH 2 ) p — alkylene chain is optionally substituted with one or more amino or hydroxyl groups; 
 
 W is —C≡C—; 
 R 1  is hydrogen, a polar group (PL), a non-polar group (NPL), or —W-A′, wherein A′ is aryl or heteroaryl, either of which is optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); 
 R 2  is R 1 ; 
 NPL is a nonpolar group —(NR 3′ ) q1NPL —U NPL —(CH 2 ) pNPL —(NR 3″ ) q2NPL —R 4 ; 
 R 3 , R 3′ , and R 3″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 R 4  is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl, any of which is optionally substituted with one or more alkyl or halo groups; 
 U NPL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 3 , —(C═O)—, —(C═O)—N═N—NR 3 —, —(C═O)—NR 3 —N═N—, —N═N—NR 3 —, —C(═N—N(R 3 ) 2 )—, —C(═NR 3 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 3 —O—, —R 3 —S—, —S—C═N—, and —(C═O)—NR 3 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 the alkylene chain —(CH 2 ) pNPL — is optionally substituted with one or more alkyl, amino or hydroxyl groups, or the alkylene chain is unsaturated; 
 pNPL is 0 to 8; 
 q1NPL and q2NPL are, independently, 0 to 2; 
 PL is a polar group selected from halo, hydroxyethoxymethyl, methoxyethoxymethyl, polyoxyethylene, and —(NR 5′ ) q1pL —U PL —(CH 2 ) pPL —(NR 5′ ) q2PL —V, wherein: 
 R 5 , R 5′ , and R 5″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 U PL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 5 , —(C═O)—, —(C═O)—N═N—NR 5 —, —(C═O)—NR 5 —N═N—, —N═N—NR 5 —, —C(═N—N(R 5 ) 2 )—, —C(═NR 5 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 50 —, —R 5 S—, —S—C═N—, and —(C═O)—NR 5 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 V is selected from nitro, cyano, amino, hydroxyl, alkoxy, alkylthio, alkylamino, dialkylamino, —NH(CH 2 ) p NH 2 , —N(CH 2 CH 2 NH 2 ) 2 , diazamino, amidino, guanidino, guanyl, semicarbazone, aryl, heterocycle, and heteroaryl, any of which is optionally substituted with one or more of amino, halo, cyano, nitro, hydroxyl, —NH(CH 2 ) p NH 2 , —N(CH 2 CH 2 NH 2 ) 2 , amidino, guanidino, guanyl, aminosulfonyl, aminoalkoxy, aminoalkythio, lower acylamino, or benzyloxycarbonyl; 
 the alkylene chain —(CH 2 ) pPL — is optionally substituted with one or more amino or hydroxyl groups, or the alkylene chain is unsaturated; 
 pPL is 0 to 8; and 
 q1PL and q2PL are, independently, 0 to 2. 
 
     
     
         8 . An ophthalmic composition, comprising an effective amount of an antimicrobial random copolymer of Formula VI:
   A-(B) n1 -(D) m1 -H  (VI)   
       or an acceptable salt or solvate thereof, 
       wherein:
 A is the residue of a chain transfer agent; 
 B is —[CH 2 —C(R 11 )(B 11 )]—, wherein B 11  is —X 11 —Y 11 -Z 11 , wherein 
 X 11  is carbonyl (—C(═O)—) or optionally substituted C 1-6  alkylene; or X 11  is absent; 
 Y 11  is O, NH, or optionally substituted C 1-6  alkylene; or Y 11  is absent; 
 Z 11  is -Z 11A -Z 11B , wherein Z 11A  is alkylene, arylene, or heteroarylene, any of which is optionally substituted; or Z 11A  is absent; and Z 11B  is -guanidino, -amidino, —N(R 3 )(R 4 ), or —N + (R 3 )(R 4 )(R 5 ), wherein R 3 , R 4 , and R 5  are, independently, hydrogen, alkyl, aminoalkyl, aryl, heteroaryl, heterocyclic, or aralkyl; or 
 Z 11  is pyridinium 
 
       
         
           
           
               
               
           
         
       
       or phosphonium 
       
         
           
           
               
               
           
         
         wherein R 81 , R 911 , R 921 , and R 931  are, independently, hydrogen or alkyl; 
         R 11  is hydrogen or C 1-4  alkyl; 
         D is —[CH 2 —C(R 21 )(D 21 )]—, wherein D 21  is —X 21 —Y 21 -Z 21 , wherein 
         X 21  is carbonyl (—C(═O)—) or optionally substituted C 1-6  alkylene; or X 21  is absent; 
         Y 21  is O, NH, or optionally substituted C 1-6  alkylene, or Y 21  is absent; 
         Z 21  is alkyl, cycloalkyl, alkoxy, aryl, or aralkyl, any of which is optionally substituted; 
         R 21  is hydrogen or C 1-4  alkyl; 
         m 1 , the mole fraction of D monomer, is about 0.1 to about 0.9; and 
         n 1 , the mole fraction of B monomer, is 1−m 1 ; 
         wherein the copolymer is a random copolymer of B and D monomers, and 
         wherein the copolymer has a degree of polymerization of about 5 to about 50; and 
         an ophthalmically acceptable excipient. 
       
     
     
         9 . An antimicrobial ophthalmic composition, the composition comprising:
 (a) an antimicrobial oligomer of Formula IIa:
   R 1 —X-A 1 -X—Y-A 2 -Y—X-A 1 -X—R 2   (IIa) 
   
       or an acceptable salt or solvate thereof, 
       wherein:
 X is NR 8 , O, S, or —N(R 8 )N(R 8 )—; 
 Y is C═O, C═S, or O═S═O; 
 R 8  is hydrogen or alkyl; 
 A 1  and A 2  are, independently, optionally substituted arylene or optionally substituted heteroarylene, wherein A 1  and A 2  are, independently, optionally substituted with one or more polar (PL) group(s), one or more non-polar (NPL) group(s), or a combination of one or more polar (PL) group(s) and one or more non-polar (NPL) group(s); 
 R 1  is a polar group (PL) or a non-polar group (NPL); 
 R 2  is R 1 ; 
 NPL is a nonpolar group independently selected from —B(OR 4 ) 2  and —(NR 3′ ) q1NPL —U NPL —(CH 2 ) pNPL —(NR 3″ ) q2NPL —R 4′ , wherein: 
 R 3 , R 3′ , and R 3″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 R 4  and R 4′  are, independently, selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, and heteroaryl, any of which is optionally substituted with one or more alkyl or halo groups; 
 U NPL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 3 , —C(═O)—, —C(═O)—N═N—NR 3 —, —C(═O)—NR 3 —N═N—, —N═N—NR 3 —, —C(═N—N(R 3 ) 2 )—, —C(═NR 3 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 3 O—, —R 3 S—, —S—C═N—, and —C(═O)—NR 3 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 the —(CH 2 ) pNPL — alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated; 
 pNPL is 0 to 8; 
 q1NPL and q2NPL are, independently, 0, 1, or 2; 
 PL is a polar group selected from halo, hydroxyethoxymethyl, methoxyethoxymethyl, polyoxyethylene, and —(NR 5 ) q1PL —U PL —(CH 2 ) pPL —(NR 5′ ) q2PL —V, wherein: 
 R 5 , R 5′ , and R 5″  are, independently, selected from hydrogen, alkyl, and alkoxy; 
 U PL  is absent or selected from O, S, S(═O), S(═O) 2 , NR 5 , —C(═S)—, —C(═O)—N═N—NR 5 —, —C(═O)—NR 5 —N═N—, —N═N—NR 5 —, —C(═N—N(R 5 ) 2 )—, —C(═NR 5 )—, —C(═O)O—, —C(═O)S—, —C(═S)—, —O—P(═O) 2 O—, —R 50 —, —R 5 S—, —S—C═N—, and —C(═O)—NR 5 —O—, wherein groups with two chemically nonequivalent termini can adopt both possible orientations; 
 V is selected from nitro, cyano, amino, hydroxy, alkoxy, alkylthio, alkylamino, dialkylamino, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , diazamino, amidino, guanidino, guanyl, semicarbazone, aryl, heterocycle and heteroaryl, any of which is optionally substituted with one or more of amino, halo, cyano, nitro, hydroxy, —NH(CH 2 ) p NH 2  wherein p is 1 to 4, —N(CH 2 CH 2 NH 2 ) 2 , amidino, guanidino, guanyl, aminosulfonyl, aminoalkoxy, aminoalkythio, lower acylamino, or benzyloxycarbonyl; 
 the —(CH 2 ) pPL — alkylene chain is optionally substituted with one or more amino or hydroxy groups, or is unsaturated; 
 pPL is 0 to 8; and 
 q1PL and q2PL are, independently, 0, 1, or 2; 
 
       or a pharmaceutically acceptable salt or solvate thereof, in an amount effective for treatment and/or prophylaxis of a microbial infection of an eye of an animal; and
 (b) an ophthalmically acceptable excipient, 
 
       wherein the composition is suitable for administration to one or more tissues of the eye. 
     
     
         10 . A method of treating a microbial infection in an eye of an animal comprising administering to the eye of the animal in need thereof an effective amount of an ophthalmic composition of  claim 1 . 
     
     
         11 . A method for treating a microbial infection in an eye of an animal comprising administering to one or more tissues of the eye an antimicrobial ophthalmic composition comprising an antimicrobial oligomer of Formula I of  claim 1  in an amount effective to treat the infection. 
     
     
         12 . A method for treating a microbial infection in an eye of an animal comprising administering to one or more tissues of the eye an antimicrobial ophthalmic composition comprising an antimicrobial oligomer of Formula II of  claim 3  in an amount effective to treat the infection. 
     
     
         13 . A method for treating a microbial infection in an eye of an animal comprising administering to one or more tissues of the eye an antimicrobial ophthalmic composition comprising an antimicrobial oligomer of Formula IV of  claim 4  in an amount effective to treat the infection. 
     
     
         14 . A method for treating a microbial infection in an eye of an animal comprising administering to one or more tissues of the eye an antimicrobial ophthalmic composition comprising an antimicrobial oligomer of Formula V of  claim 6  in an amount effective to treat the infection. 
     
     
         15 . A method for treating a microbial infection in an eye of an animal comprising administering to one or more tissues of the eye an antimicrobial ophthalmic composition comprising an antimicrobial oligomer of Formula VI of  claim 8  in an amount effective to treat the infection.