I want to do this reaction but as far as learned from literature, NHS ester-amine reaction is done in a phosphate buffer solution between pH 8 to 9. However, lipoic acid modified polymer precipitates in water. So, it can be a problem to make the reaction in water. On the other hand, this reaction needs unprotonated amine groups which means i should keep pH around 8. Any experience?
I think that if you can find a solvent in which both lipoic acid NHS ester and polyamine free base are soluble, the reaction will occur.
Not exactly dealing with your reaction but gives various approaches to reactions of polymers with smaller organic molecules at specific pH values "similar to yours". If the attached reference helps a little bit, I'll be pleased.
https://www.lifetechnologies.com/ps/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/amine-reactive-crosslinker-chemistry.html
My group examined just simple lipoic acid amide couplings, of course this is a simplified system as ours was not polymer bound (Bioorganic Chemistry 40(1):1-5 · December 2011). Anyway, I would go for DMF, buffered with DIPEA or triethylamine (2-3 equivalents) and add the amine of choice. We found that we didn't have to go via the NHS ester, but used a microwave and EDCI, PyBrOP, or acid chloride was the way to go. I don't think we tried mixed anhydride but that may be a good option as well.
cheer
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