Reversible Solubility Switching of a Polymer Triggered by Visible-Light Responsive Azobenzene Photochromism with Negligible Thermal Relaxation

This study reports the reversible solubility switching of a polymer triggered by non-phototoxic visible light. A photochromic polymerizable azobenzene monomer with four methoxy groups at the ortho-position (mAzoA) was synthesized, exhibiting reversible photoisomerization between trans- and cis-states using green (546 nm) and blue light (436 nm). Free radical copolymerization of hydrophilic dimethylacrylamide (DMAAm) with mAzoA produced a light-responsive random copolymer (P(mAzoA-r-DMAAm)) that shows a reversible photochromic reaction to visible light. Optimizing mAzoA content resulted in P(mAzoA_10.7-r-DMAAm)_{3.0 kDa} exhibiting LCST-type phase separation in PBS (pH 7.4) with trans- and cis-states at 39.2 °C and 32.9 °C, respectively. The bistable temperature range of 6.3 °C covers 37 °C, suitable for mammalian cell culture. Reversible solubility changes were demonstrated under alternating green and blue light at 37 °C. 1H NMR indicated significant retardation of thermal relaxation from cis- to trans-states, preventing undesired thermal mechanical degradation. Madin Darby Canine Kidney (MDCK) cells adhered to the P(mAzoA-r-DMAAm) hydrogel, confirming its non-cytotoxicity and potential for biocompatible interfaces. This principle is useful for developing hydrogels that can reversibly stimulate cells mechanically or chemically in response to visible light.