Hydrogen Bonding Promoted Tautomerism between Azo and Hydrazone Forms in Calcon with Multistimuli Responsiveness and Biocompatibility.

Realization of multistimuli responsiveness in one molecule remains a challenge due to the difficulty in understanding and control of comprehensive interplay between the external stimuli and the subtle conformation changes. The coexistence of dynamic bonding interactions, hydroxyl group, and the azo chromophore in calcon causes the multistimuli responsiveness to external stimuli including temperature, pH variation, and light irradiation. Density functional theory (DFT), time-dependent DFT (TDDFT), and various molecular dynamics (MD) simulations are employed to systematically investigate the azo-hydrazone tautomerism and E-to- Z isomerization. The inter/intramolecular hydrogen bonding interactions promote the azo-hydrazone tautomerism at different pH conditions. The strong n → π* absorption in the visible light region gives an advantage of calcon without the harm to living cells from UV light. The facial tautomerism renders the calcon temperature sensitivity, which could be triggered at body temperature (311 K) with distinct color change from red to blue. It is also found that in pH = 6.8 both azo and hydrazone isomers have no cytotoxicity on the human lung cells (A549 and H1299) and hepatic epithelial cell of rat (FL83B). The visible-light absorption, pH, and temperature sensitiveness and biocompatibility render calcon potential candidates for biomedical applications.