Polymerizable near-IR dyes
The present invention is directed, in certain embodiments, to polymerizable near-IR dyes and polymers comprising said dyes as monomeric residues. In other embodiments, the present invention also relates to methods for the preparation of polymerizable near-IR dyes, and to the use of polymerizable near-IR dyes in the preparation of fluorescent polymers.
1. A polymerizable near-IR dye having a structure according to formula (I):
or a tautomer, salt, hydrate, or solvate thereof,
wherein:
Z 1 is absent, O, NR Z1 , or S;
R Z1 is H, optionally substituted C 1 -C 10 alkyl, or optionally substituted C 2 -C 10 heteroalkyl;
X 1 is absent, optionally substituted C 6 -C 10 arylene, or optionally substituted C 1 -C 10 heteroarylene;
Z 2 is absent, NR X1 , O, S, NR X2 C(O), OC(O), SC(O), C(O)O, C(O)NR X3 , C(S)O, or C(O)S;
Z 3 is absent or H;
R X1 , R X2 , and R X3 are each independently H, optionally substituted C 1 -C 10 alkyl, or optionally substituted C 1 -C 10 heteroalkyl;
L 1 is absent, optionally substituted C 1 -C 30 alkylene, or optionally substituted C 1 -C 30 heteroalkylene;
Q 1 is NR Z3 C(O)C(R Q1 )CH 2 , OC(O)C(R Q1 )CH 2 , or SC(O)C(R Q1 )CH 2 ;
R Z3 is H, optionally substituted C 1 -C 10 alkyl, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted C 1 -C 10 heteroalkyl, or optionally substituted C 1 -C 10 cycloheteroalkyl;
R Q1 is H, Me, Et, or n-Pr;
each of Y 1 and Y 4 , independently, is absent or optionally substituted C 1 -C 4 alkylene or optionally substituted C 2 -C 4 heteroalkylene;
each of Y 2 and Y 3 , independently, is absent or, together with the carbon atoms to which each is attached, form optionally substituted C 6 -C 10 aryl or optionally substituted C 2 -C 10 heteroaryl;
Y 5 is absent or N or CR 7 ;
R 7 is H, optionally substituted C 1 -C 10 alkyl, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted C 1 -C 10 heteroalkyl, or optionally substituted C 1 -C 10 cycloheteroalkyl;
each of W 1 and W 2 , independently, is NR 2 , S, O, Se, or CR 3 R 4 ;
R 2 , R 3 , and R 4 are independently H, optionally substituted C 1 -C 30 alkyl, optionally substituted C 1 -C 30 heteroalkyl, or -L 2 -Q 2 ;
L 2 is optionally substituted C 1 -C 30 alkylene or optionally substituted C 1 -C 30 heteroalkylene;
Q 2 is H, C(R Q1 )CH 2 , C 6 H 4 CHCH 2 , NR Z3 C(O)C(R Q1 )CH 2 , OC(O)C(R Q1 )CH 2 , or SC(O)C(R Q1 )CH 2 ;
each of R 5 and R 6 , independently, is -L 3 -Q 3 , optionally substituted C 1 -C 30 alkyl, or optionally substituted C 6 -C 10 aryl;
L 3 is optionally substituted C 1 -C 30 alkylene or optionally substituted C 1 -C 30 heteroalkylene;
Q 3 is H, C(R Q1 )CH 2 , C 6 H 4 CHCH 2 , NR Z3 C(O)C(R Q1 )CH 2 , OC(O)C(R Q1 )CH 2 , or SC(O)C(R Q1 )CH 2 ; and
each k is independently 0 or 1.
2. The polymerizable near-IR dye of claim 1 wherein Z 1 is O.
3. The polymerizable near-IR dye of claim 1 , wherein the polymerizable near-IR dye has a structure according to formula (IA):
or a tautomer, salt, hydrate, or solvate thereof,
wherein
each R 3 is H, optionally substituted C 1 -C 30 alkyl, or optionally substituted C 1 -C 30 heteroalkyl; and
each R 4 is H, optionally substituted C 1 -C 30 alkyl, or optionally substituted C 1 -C 30 heteroalkyl.
4. The polymerizable near-IR dye of claim 3 , wherein each R 3 and R 4 is, independently, C 1 -C 5 alkyl optionally substituted with SO 3 H or B(OH) 2 .
5. The polymerizable near-IR dye of claim 1 , wherein the polymerizable near-IR dye has a structure according to formula (IB):
or a tautomer, salt, hydrate, or solvate thereof,
wherein
Y 2 , together with the carbon atoms to which it is attached, form optionally substituted C 6 -C 10 arylene or optionally substituted C 2 -C 10 heteroarylene; and
Y 3 , together with the carbon atoms to which it is attached, form optionally substituted C 6 -C 10 arylene or optionally substituted C 2 -C 10 heteroarylene.
6. The polymerizable near-IR dye of claim 1 , wherein the polymerizable near-IR dye has a structure according to formula (IC):
or a tautomer, salt, hydrate, or solvate thereof,
wherein each of R 8 -R 15 is, independently, H, SO 3 H, B(OH) 2 , optionally substituted amino, optionally substituted C 1 -C 10 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted ester, optionally substituted C 1 -C 10 alkoxy, optionally substituted C 6 -C 10 aryloxy, optionally substituted C 6 -C 10 thioalkyl, optionally substituted C 6 -C 10 thioaryl, optionally substituted C 1 -C 10 heteroalkyl, optionally substituted C 2 -C 10 heteroaryl, optionally substituted C 2 -C 10 heteroalkoxy, optionally substituted C 2 -C 10 heteroaryloxy, nitro, azido, carboxy, hydroxy; or, any two R 8 -R 15 in the ortho position to each other, together with the carbon atoms to which each is attached, form an optionally substituted phenyl ring.
7. The polymerizable near-IR dye of claim 6 , wherein the polymerizable near-IR dye has a structure according to formula (ID):
or a tautomer, salt, hydrate, or solvate thereof.
8. The polymerizable near-IR dye of claim 6 , wherein the polymerizable near-IR dye has a structure according to formula (IE):
or a tautomer, salt, hydrate, or solvate thereof,
wherein:
each of Y 6 , Y 7 , Y 8 , and Y 9 , is, independently, N or CR 16 ; and
R 16 is H, SO 3 H, B(OH) 2 , optionally substituted amino, optionally substituted C 1 -C 10 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted ester, optionally substituted C 1 -C 10 alkoxy, optionally substituted C 6 -C 10 aryloxy, optionally substituted C 6 -C 10 thioalkyl, optionally substituted C 6 -C 10 thioaryl, optionally substituted C 1 -C 10 heteroalkyl, optionally substituted C 2 -C 10 heteroaryl, optionally substituted C 2 -C 10 heteroalkoxy, optionally substituted C 2 -C 10 heteroaryloxy, nitro, azido, carboxy, or hydroxy.
9. The polymerizable near-IR dye of claim 6 , wherein the polymerizable near-IR dye has a structure according to formula (IF):
or a tautomer, salt, hydrate, or solvate thereof,
wherein:
Y 10 is O, S, or NR Z3 ,
Y 6 is N or CR 16 ; and
R 16 is H, SO 3 H, B(OH) 2 , optionally substituted amino, optionally substituted C 1 -C 10 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted ester, optionally substituted C 1 -C 10 alkoxy, optionally substituted C 6 -C 10 aryloxy, optionally substituted C 6 -C 10 thioalkyl, optionally substituted C 6 -C 10 thioaryl, optionally substituted C 1 -C 10 heteroalkyl, optionally substituted C 2 -C 10 heteroaryl, optionally substituted C 2 -C 10 heteroalkoxy, optionally substituted C 2 -C 10 heteroaryloxy, nitro, azido, carboxy, or hydroxy.
10. The polymerizable near-IR dye of claim 6 , wherein the polymerizable near-IR dye has a structure according to formula (IG):
or a tautomer, salt, hydrate, or solvate thereof,
wherein:
Y 10 is O, S, or NR Z3 ,
Y 6 is N or CR 16 ; and
R 16 is H, SO 3 H, B(OH) 2 , optionally substituted amino, optionally substituted C 1 -C 10 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted ester, optionally substituted C 1 -C 10 alkoxy, optionally substituted C 6 -C 10 aryloxy, optionally substituted C 6 -C 10 thioalkyl, optionally substituted C 6 -C 10 thioaryl, optionally substituted C 1 -C 10 heteroalkyl, optionally substituted C 2 -C 10 heteroaryl, optionally substituted C 2 -C 10 heteroalkoxy, optionally substituted C 2 -C 10 heteroaryloxy, nitro, azido, carboxy, or hydroxy.
11. The polymerizable near-IR dye of claim 1 , wherein the polymerizable near-IR dye is:
12. A polymer having a structure according to formula (II):
or a tautomer, salt, hydrate, or solvate thereof,
the polymer comprising a polymerizable near-IR dye and a monomer;
wherein:
Z 1 is absent, O, NR Z1 , or S;
R Z1 is H, optionally substituted C 1 -C 10 alkyl, or optionally substituted C 2 -C 10 heteroalkyl;
X 1 is absent, optionally substituted C 6 -C 10 arylene, or optionally substituted C 1 -C 10 heteroarylene;
Z 2 is absent, NR X1 , O, S, NR X2 C(O), OC(O), SC(O), C(O)O, C(O)NR X3 , C(S)O, or C(O)S;
Z 3 is absent or H;
R X1 , R X2 , and R X3 are each independently H, optionally substituted C 1 -C 10 alkyl, or optionally substituted C 1 -C 10 heteroalkyl;
L 1 is absent, optionally substituted C 1 -C 30 alkylene, or optionally substituted C 1 -C 30 heteroalkylene;
Q 1 is NR Z3 C(O)C(R Q1 )CH 2 , OC(O)C(R Q1 )CH 2 , or SC(O)C(R Q1 )CH 2 ;
R Z3 is H, optionally substituted C 1 -C 10 alkyl, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted C 1 -C 10 heteroalkyl, or optionally substituted C 1 -C 10 cycloheteroalkyl;
R Q1 is H, Me, Et, or n-Pr;
each of Y 1 and Y 4 , independently, is absent or optionally substituted C 1 -C 4 alkylene or optionally substituted C 2 -C 4 heteroalkylene;
each of Y 2 and Y 3 , independently, is absent or, together with the carbon atoms to which each is attached, form optionally substituted C 6 -C 10 aryl or optionally substituted C 2 -C 10 heteroaryl;
Y 5 is absent or N or CR 7 ;
R 7 is H, optionally substituted C 1 -C 10 alkyl, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted C 1 -C 10 heteroalkyl, or optionally substituted C 1 -C 10 cycloheteroalkyl;
each of W 1 and W 2 , independently, is NR 2 , S, O, Se, or CR 3 R 4 ;
R 2 , R 3 , and R 4 are independently H, optionally substituted C 1 -C 30 alkyl, optionally substituted C 1 -C 30 heteroalkyl, or -L 2 -Q 2 ;
L 2 is optionally substituted C 1 -C 30 alkylene or optionally substituted C 1 -C 30 heteroalkylene;
Q 2 is H, C(R Q1 )CH 2 , C 6 H 4 CHCH 2 , NR Z3 C(O)C(R Q1 )CH 2 , OC(O)C(R Q1 )CH 2 , or SC(O)C(R Q1 )CH 2 ;
each of R 5 and R 6 , independently, is -L 3 -Q 3 , optionally substituted C 1 -C 30 alkyl, or optionally substituted C 6 -C 10 aryl;
L 3 is optionally substituted C 1 -C 30 alkylene or optionally substituted C 1 -C 30 heteroalkylene;
Q 3 is H, C(R Q1 )CH 2 , C 6 H 4 CHCH 2 , NR Z3 C(O)C(R Q1 )CH 2 , OC(O)C(R Q1 )CH 2 , or SC(O)C(R Q1 )CH 2 ; and
each k is independently 0 or 1;
wherein, the group Q 1 is linked to a group J, and
J is at least one monomer comprising HEMA (hydroxyethyl methacrylate), DMA (N,N-Dimethylacrylamide), HPA (Hydroxypropyl acrylate), methyl methacrylate, acrylamide, PEGMA (polyethyleneglycol methacrylate), methacrylic acid, hydroxyethyl acrylate, N-vinyl pyrrolidone, methacryloylaminopropyl trimethylammonium chloride, diallyl dimethyl ammonium chloride, vinyl benzyl trimethyl ammonium chloride, or sodium sulfopropyl methacrylate.
13. The polymer claim 12 , wherein the polymer has a structure according to formula (IIA):
or a tautomer, salt, hydrate, or solvate thereof,
wherein
each R 3 is H, optionally substituted C 1 -C 30 alkyl, or optionally substituted C 1 -C 30 heteroalkyl; and
each R 4 is H, optionally substituted C 1 -C 30 alkyl, or optionally substituted C 1 -C 30 heteroalkyl.
14. The polymer of claim 12 , wherein the polymer has a structure according to formula (IIB):
or a tautomer, salt, hydrate, or solvate thereof,
wherein
Y 2 , together with the carbon atoms to which it is attached, form optionally substituted C 6 -C 10 arylene or optionally substituted C 2 -C 10 heteroarylene; and
Y 3 , together with the carbon atoms to which it is attached, form optionally substituted C 6 -C 10 arylene or optionally substituted C 2 -C 10 heteroarylene.
15. The polymer of claim 12 , wherein the polymerizable near-IR dye has a structure according to formula (IID):
or a tautomer, salt, hydrate, or solvate thereof,
wherein each of R 1 , R 9 , R 12 , and R 13 is, independently, H, SO 3 H, B(OH) 2 , optionally substituted amino, optionally substituted C 1 -C 10 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted ester, optionally substituted C 1 -C 10 alkoxy, optionally substituted C 6 -C 10 aryloxy, optionally substituted C 6 -C 10 thioalkyl, optionally substituted C 6 -C 10 thioaryl, optionally substituted C 1 -C 10 heteroalkyl, optionally substituted C 2 -C 10 heteroaryl, optionally substituted C 2 -C 10 heteroalkoxy, optionally substituted C 2 -C 10 heteroaryloxy, nitro, azido, carboxy, hydroxy; or, R 8 and R 9 or R 12 and R 13 are, independently, together with the carbon atoms to which each is attached, form an optionally substituted phenyl ring.
16. The polymer of claim 15 , wherein the polymer has a structure according to formula (IIE):
or a tautomer, salt, hydrate, or solvate thereof,
wherein:
each of Y 6 , Y 7 , Y 8 , and Y 9 is, independently, N or CR 16 ; and
R 16 is H, SO 3 H, B(OH) 2 , optionally substituted amino, optionally substituted C 1 -C 10 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted ester, optionally substituted C 1 -C 10 alkoxy, optionally substituted C 6 -C 10 aryloxy, optionally substituted C 6 -C 10 thioalkyl, optionally substituted C 6 -C 10 thioaryl, optionally substituted C 1 -C 10 heteroalkyl, optionally substituted C 2 -C 10 heteroaryl, optionally substituted C 2 -C 10 heteroalkoxy, optionally substituted C 2 -C 10 heteroaryloxy, nitro, azido, carboxy, or hydroxy.
17. The polymer of claim 16 , wherein the polymer has a structure according to formula (IIF):
or a tautomer, salt, hydrate, or solvate thereof,
wherein:
Y 6 is CR 16 ;
Y 10 is O, S, or NR Z3 ; and
R 16 is H.
18. The polymer of claim 17 , wherein R Q1 is methyl.
19. A polymer comprising a polymerizable near-IR dye and a monomer, said polymer having a repeating unit according to formula (III):
wherein:
each D 1 and D 2 is independently a residue of a polymerizable near-IR dye, wherein said polymerizable near-IR dye has a structure according to formula (I):
or a tautomer, salt, hydrate, or solvate thereof,
wherein:
Z 1 is absent, O, NR Z1 , or S;
R Z1 is H, optionally substituted C 1 -C 10 alkyl, or optionally substituted C 2 -C 10 heteroalkyl;
X 1 is absent, optionally substituted C 6 -C 10 arylene, or optionally substituted C 1 -C 10 heteroarylene;
Z 2 is absent, NR X1 , O, S, NR X2 C(O), OC(O), SC(O), C(O)O, C(O)NR X3 , C(S)O, or C(O)S;
Z 3 is absent or H;
R X1 , R X2 , and R X3 are each independently H, optionally substituted C 1 -C 10 alkyl, or optionally substituted C 1 -C 10 heteroalkyl;
L 1 is absent, optionally substituted C 1 -C 30 alkylene, or optionally substituted C 1 -C 30 heteroalkylene;
Q 1 is NR Z3 C(O)C(R Q1 )CH 2 , OC(O)C(R Q1 )CH 2 , or SC(O)C(R Q1 )CH 2 ;
R Z3 is H, optionally substituted C 1 -C 10 alkyl, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted C 1 -C 10 heteroalkyl, or optionally substituted C 1 -C 10 cycloheteroalkyl;
R Q1 is H, Me, Et, or n-Pr;
each of Y 1 and Y 4 , independently, is absent or optionally substituted C 1 -C 4 alkylene or optionally substituted C 2 -C 4 heteroalkylene;
each of Y 2 and Y 3 , independently, is absent or, together with the carbon atoms to which each is attached, form optionally substituted C 6 -C 10 aryl or optionally substituted C 2 -C 10 heteroaryl;
Y 5 is absent or N or CR 7 ;
R 7 is H, optionally substituted C 1 -C 10 alkyl, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted C 1 -C 10 heteroalkyl, or optionally substituted C 1 -C 10 cycloheteroalkyl;
each of W 1 and W 2 , independently, is NR 2 , S, O, Se, or CR 3 R 4 ;
R 2 , R 3 , and R 4 are independently H, optionally substituted C 1 -C 30 alkyl, optionally substituted C 1 -C 30 heteroalkyl, or -L 2 -Q 2 ;
L 2 is optionally substituted C 1 -C 30 alkylene or optionally substituted C 1 -C 30 heteroalkylene;
Q 2 is H, C(R Q1 )CH 2 , C 6 H 4 CHCH 2 , NR Z3 C(O)C(R Q1 )CH 2 , OC(O)C(R Q1 )CH 2 , or SC(O)C(R Q1 )CH 2 ;
each of R 5 and R 6 , independently, is -L 3 -Q 3 , optionally substituted C 1 -C 30 alkyl, or optionally substituted C 6 -C 10 aryl;
L 3 is optionally substituted C 1 -C 30 alkylene or optionally substituted C 1 -C 30 heteroalkylene;
Q 3 is H, C(R Q1 )CH 2 , C 6 H 4 CHCH 2 , NR Z3 C(O)C(R Q1 )CH 2 , OC(O)C(R Q1 )CH 2 , or SC(O)C(R Q1 )CH 2 ; and
each k is independently 0 or 1;
with the proviso that
each J 1 and J 2 is a residue of HEMA (hydroxyethyl methacrylate), DMA (N,N-Dimethylacrylamide), HPA (Hydroxypropyl acrylate), methyl methacrylate, acrylamide, PEGMA (polyethyleneglycol methacrylate), methacrylic acid, hydroxyethyl acrylate, N-vinyl pyrrolidone, methacryloylaminopropyl trimethylammonium chloride, diallyl dimethyl ammonium chloride, vinyl benzyl trimethyl ammonium chloride, or sodium sulfopropyl methacrylate,
wherein:
D 1 and D 2 can be the same or different;
J 1 and J 2 can be the same or different;
m is an integer from 1 to 100;
n is an integer from 0 to 100;
a is an integer from 0 to 100; and
z is an integer from 0 to 100.
20. The polymer of claim 19 wherein the polymerizable near-IR dye is: