Post-synthesis modification of thermo-responsive hydrogels: Hydrazone crosslinking of α-oxoaldehyde obtained from NIPAm-based polymers

Abstract

Currently, the chemistry of alpha-oxoaldehydes (α-oxo-ALD) is a versatile and useful tool in the field of bioconjugation of peptides and proteins. The combination of smart materials with biomolecules also represents an important opportunity for the development of smart functional materials in a wide range of applications. However, the development of thermosensitive polymeric materials with α-oxo-ALD has not yet been reported. For this reason, the incorporation of these highly reactive functional groups in a thermo-responsive polymer by a successful protocol is reported in this work. Poly-N-isopropylacrylamide (p-NIPAm) functionalized with α-oxo-ALD (p-NIPAm-α-oxo-ALD) was obtained from precursor hydrogels (HGs) based on NIPAm crosslinked with (+)-N,N′-diallyltartramide (DAT). This crosslinker presents vicinal hydroxyl groups which can be cleaved with periodate to yield nanoparticles (10–100 nm range) with pendant α-oxo-ALD groups. Furthermore, the p-NIPAm-α-oxo-ALD product obtained was used to synthesize novel thermo-responsive hydrogels by its reaction with adipic acid dihydrazide (AADH). Then, the formation of hydrazone bonds at different pHs and the effect of thermal transition of p-NIPAm on the gelation were studied. The developed protocol may be fully investigated as a platform to obtain materials for specific applications.