Water-soluble polymeric dyes having pendant chromophores

1. A water-soluble light harvesting multichromophore comprising:

a polymeric backbone comprising non-conjugated repeat units derived from amino acids, peptoid monomers, a protected carbonate monomer or a cyclic carbonate monomer; and

a plurality of pendant donor chromophore groups each independently linked to a non-conjugated repeat unit of the polymeric backbone.

2. The multichromophore according to claim 1 , wherein:

the pendant donor chromophore groups are each substituted with a water soluble group;

the pendant donor chromophore groups are configured in energy-transferring proximity to each other; and/or

the pendant donor chromophore groups are selected from a fused tricyclic aryl or heteroaryl group and a BODIPY group.

3. The multichromophore according to claim 1 , wherein the pendant donor chromophore groups are BODIPY groups described by the formula:

wherein:

R 1 -R 7 are each independently selected from H, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, water solubilizing group (WSG) and -L 1 -Z 1 , or

optionally any one or more pairs of substituents selected from R 6 and R 7 , R 2 and R 3 , R 5 and R 6 , R 3 and R 4 , R 4 and R 1 and R 5 and R 1 , together form a divalent radical and are cyclically linked and together with the carbon atoms to which they are bound provide a 5- or 6-membered fused heterocycle, carbocycle, aryl or heteroaryl ring, which ring may be unsubstituted or further substituted with a substituent independently selected from alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, water solubilizing group (WSG) and -L 1 -Z 1 ;

L 1 is a linker;

Z 1 is a non-conjugated repeat unit of the polymeric backbone; and

Y 1 and Y 2 are independently selected from F, OH, H, cyano, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkoxy, substituted alkoxy, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl and WSG;

wherein one of Y 1 , Y 2 and R 1 -R 7 is linked to a non-conjugated repeat unit of the polymeric backbone.

4. The multichromophore according to claim 3 , wherein the pendant donor chromophore groups are described by the following structure:

wherein:

* is a point of linkage to a non-conjugated repeat unit of the polymeric backbone;

Y 1 and Y 2 are each alkynyl substituted with a WSG.

5. The multichromophore according to claim 4 , wherein the pendant donor chromophore groups are described by the following structure:

wherein:

R 11 is L 1 -Z 1 (a linked non-conjugated repeat unit of the polymeric backbone);

each R 9 is an optional substituent selected from halogen, hydroxyl, cyano, nitro, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, heteroaryl and substituted heteroaryl; and t is 0-4.

6. The multichromophore according to claim 1 , wherein the pendant donor chromophore groups are substituted with one or more water solubilizing groups (WSGs) independently selected from the following formula:

wherein:

T 5 is an optional linker;

each T 6 is an linker;

R 11 and R are independently H, alkyl or substituted alkyl; and

each s is an integer from 1 to 50.

7. The multichromophore according to claim 1 , comprising a segment of the formula:

wherein:

the polymeric backbone of non-conjugated repeat units comprises SM 1 and SM 2 co-monomers that are each independently a saturated non-conjugated co-monomer;

each D 1 is independently a pendant donor chromophore linked to SM 1 ;

each Z 1 is independently a chemoselective tag linked to SM 2 ;

x is 75 mol % or more; and

y is 25 mol % or less.

8. The multichromophore according to claim 7 , wherein SM 1 and SM 2 are co-monomers derived from amino acids, peptoid monomers, a protected carbonate monomer or a cyclic carbonate monomer.

9. The multichromophore according to claim 8 , wherein the multichromophore is of the formula:

wherein:

each D 1 is independently a pendant donor chromophore group;

each Z 1 is independently a chemoselective tag;

each L 1 and L 2 are independently a linker;

p 1 and q 1 are independently 0 or 1 wherein p 1 +q 1 ≤1;

p 2 and q 2 are independently 0 or 1 wherein p 1 +q 1 ≤1;

x is 75 mol % or more;

y is 25 mol % or less; and

G 1 and G 2 are each independently selected from a terminal group, a polymer segment, a donor chromophore group, an acceptor fluorophore group, a linker and a linked specific binding member.

10. The multichromophore of claim 9 , wherein p 1 , p 2 , q 1 and q 2 are each 0 and the multichromophore is of the formula:

wherein:

each D 1 is independently a pendant donor chromophore group;

each Z 1 is independently a chemoselective tag;

L 1 and L 2 are each independently a linker;

x is 75 mol % or more;

y is 25 mol % or less; and

G 1 and G 2 are each independently selected from a terminal group, a polymer segment, a donor chromophore group, an acceptor fluorophore group, a linker and a linked specific binding member.

11. The multichromophore according to claim 10 , comprising a segment of the formula:

wherein:

each D 1 is independently a pendant donor chromophore group;

each Z 1 is independently a chemoselective tag;

each L 1 and L 2 are independently a linker;

n and p are each independently an integer from 1 to 20 wherein n+p≥2; and

m is 1 or 2.

12. The multichromophore according to claim 11 , wherein the multichromophore comprises q segments of copolymer and is of the formula:

wherein:

each (n) q and each (p) q is independently an integer from 1 to 20, wherein for each of the q segments (n)q+(p) q ≥3; and

q is an integer from 1 to 100.

13. The multichromophore according to claim 12 , wherein the polymeric backbone comprises one or more amino acid sequences selected from the following:

XYXX

XXYXX

XXXYXXX

XXXYXXXX

XXXXYXXX

XXXXYXXXX

XXXXXYXXXXX

XXXXXXYXXXXXX

XXXXXXXYXXXXXXX

XXXXXXXXYXXXXXXXX

XXXXXXXXXYXXXXXXXXX

Y(X) n Y

XY(X) n YX

XXY(X) n YXX

XXXY(X) n YXXX

XXXXY(X) n YXXXX

XXXXXY(X) n YXXXXX

wherein:

each X is a lysine or ornithine residue covalently N-linked to a pendant donor chromophore group; and

each Y is a cysteine residue or a protected cysteine residue.

14. A polymeric tandem dye comprising:

a light harvesting multichromophore comprising:

a polymeric backbone comprising non-conjugated repeat units derived from amino acids, peptoid monomers, a protected carbonate monomer or a cyclic carbonate monomer; and

a plurality of pendant donor chromophore groups each independently linked to a non-conjugated repeat unit of the polymeric backbone; and

an acceptor fluorophore linked to a non-conjugated repeat unit of the polymeric backbone and configured in energy-receiving proximity to at least one pendant donor chromophore group of the light harvesting multichromophore.

15. The polymeric tandem dye according to claim 14 , wherein the polymeric backbone comprises one or more amino acid sequences selected from the following:

XYXX

XXYXX

XXXYXXX

XXXYXXXX

XXXXYXXX

XXXXYXXXX

XXXXXYXXXXX

XXXXXXYXXXXXX

XXXXXXXYXXXXXXX

XXXXXXXXYXXXXXXXX

XXXXXXXXXYXXXXXXXXX

Y(X) n Y

XY(X) n YX

XXY(X) n YXX

XXXY(X) n YXXX

XXXXY(X) n YXXXX

XXXXXY(X) n YXXXXX

wherein:

each X is a lysine or ornithine residue covalently N-linked to a pendant donor chromophore group; and

each Y is a cysteine residue covalently linked to a pendant acceptor fluorophore group.

16. The polymeric tandem dye according to claim 14 , wherein the acceptor fluorophore is selected from a cyanine dye, a rhodamine dye, a xanthene dye, a coumarin dye, a polymethine, a pyrene, a dipyrromethene borondifluoride, a napthalimide, a thiazine dye and an acridine dye.

17. A labelled specific binding member, comprising:

a polymeric tandem dye comprising:

a light harvesting multichromophore comprising:

a polymeric backbone comprising non-conjugated repeat units derived from amino acids, peptoid monomers, a protected carbonate monomer or a cyclic carbonate monomer; and

a plurality of pendant donor chromophore groups each independently linked to a non-conjugated repeat unit of the polymeric backbone; and

an acceptor fluorophore linked to a non-conjugated repeat unit of the polymeric backbone and configured in energy-receiving proximity to at least one pendant donor chromophore group of the light harvesting multichromophore; and

a specific binding member linked to the polymeric tandem dye.

18. The labelled specific binding member according to claim 17 , wherein the specific binding member is an antibody.

19. The labelled specific binding member according to claim 17 , wherein the specific binding member is an antibody fragment or binding derivative thereof.

20. The labelled specific binding member according to claim 18 , wherein the antibody fragment or binding derivative thereof is selected from the group consisting of a Fab fragment, a F(ab′) 2 fragment, a scFv, a diabody and a triabody.