On the Unusual Stability of Succinimidyl Esters in pNIPAm-AAc Microgels

In this contribution, we describe the effects of amide coupling reactions on the physical properties of thermoresponsive hydrogel microparticles (microgels). These microgels, when treated via aqueous carbodiimide/sulfo-succinimide coupling protocols, displayed a dramatic modulation of the microgel phase transition thermodynamics. UV spectrophotometry was used to determine that this modulation was due to remarkably stable hydrogel conjugates of sulfo-NHS that resisted degradation under standard hydrolysis protocols. These intermediates result in a shift of the phase transition, along with a large increase in equilibrium microgel swelling degree, due to an increase in chain-chain Coulombic repulsion. Only aggressive hydrolysis protocols resulted in the recovery of the native microgel phase transition, suggesting that an unusually stable succinimidyl ester is formed in the microgel during coupling.