Library of pH responsive polymers and nanoprobes thereof
The present disclosure relates to polymers which contain a hydrophobic and hydrophilic segment which is sensitive to pH. In some aspects, the polymers form a micelle which is sensitive to pH and results in a change in fluorescence based upon the particular pH. In some aspects, the disclosure also provides methods of using the polymers for the imaging of cellular or extracellular environment or delivering a drug.
1. A polymer of the formula:
wherein:
R 1 is an alkyl (C≤12) ;
n is an integer from 10-200;
R 2 and R 2 ′ are each independently methyl;
R 3 is a group of the formula:
wherein:
n x is 1-3;
X 1 is a hydrogen or an alkyl (C≤12) ;
X 2 and X 3 are each hydrogen;
X 4 is pentyl, n-propyl, or ethyl and X 5 is pentyl or n-propyl; or X 4 and X 5 are taken together and are alkanediyl (C≤9) or substituted alkanediyl (C≤9) ;
x is an integer from 30 to 150;
R 4 is a group of the formula:
wherein:
n z is 1-10;
Y 1 , Y 2 , and Y 3 are each independently selected from hydrogen, alkyl (C≤12) , cycloalkyl (C≤12) , substituted alkyl (C≤12) , or substituted cycloalkyl (C≤12) ; and
Y 4 is a dye with the following structure:
y is an integer from 1 to 6; and
R 5 is hydrogen, halo, hydroxy, alkyl (C≤12) , or substituted alkyl (C≤12) .
2. The polymer of claim 1 , wherein R 1 is methyl.
3. The polymer of claim 1 , wherein R 4 is:
4. The polymer of claim 1 , wherein X 1 or Y 1 is alkyl (C≤12) .
5. The polymer of claim 4 , wherein X 1 is methyl.
6. The polymer of claim 4 , wherein Y 1 is methyl.
7. The polymer of claim 1 , wherein the polymer is
8. The polymer of claim 1 , wherein the polymer is
wherein Y 4 is the dye with the following structure:
9. The polymer of claim 1 , wherein the polymer is:
wherein: x is an integer from 30 to 150, y is an integer from 1 to 2; and Y 4 is the dye with the following structure:
10. A composition comprising a micelle formed from a plurality of polymers according to claim 1 .
11. The composition of claim 10 , wherein the micelle has a pH transition point and an emission spectra, wherein the micelle dissociates at a pH below the pH transition point; and wherein Y 4 is a dye with the following structure:
12. The polymer of claim 1 , where n x is an integer from 1-2.
13. The polymer of claim 1 , where n x is 1.