Functional cellular substrates for localized cell stimulation by small molecules provide an opportunity to control and monitor cell signalling networks chemically in time and space. However, despite improvements in the controlled delivery of bioactive compounds, the precise localization of gaseous biomolecules at the single-cell level remains challenging. Here we target nitric oxide, a crucial signalling molecule with site-specific and concentration-dependent activities, and we report a synthetic strategy for developing spatiotemporally controllable nitric oxide-releasing platforms based on photoactive porous coordination polymers. By organizing molecules with poor reactivity into polymer structures, we observe increased photoreactivity and adjustable release using light irradiation. We embed photoactive polymer crystals in a biocompatible matrix and achieve precisely controlled nitric oxide delivery at the cellular level via localized two-photon laser activation. The biological relevance of the exogenous nitric oxide produced by this strategy is evidenced by an intracellular change in calcium concentration, mediated by nitric oxide-responsive plasma membrane channel proteins.

Carbon monoxide-releasing metal–organic frameworks are developed for investigating gas biology at the single cell level.

The development of nitric oxide (NO) releasing materials has been of significant importance due to their application in cell biology and biomedicine. Besides the macromolecular scaffold dangling NO releasing moiety, porous materials have been used to host such NO releasing molecules. Here we synthesized a series of porous coordination polymers (PCPs), in which N-nitrosamine functional groups as photoactive NO donors were introduced into the framework scaffolds by post-synthetic nitrosation of amine functionalized analogous PCPs. We further demonstrated a controlled release of NO from the PCPs by light irradiation. Though isoreticular frameworks based on octanuclear clusters of titanium or aluminium ions were chosen due to their water-stability, the frameworks showed difference in stability in cell culture media; while aluminium frameworks were less stable in water and physiological media, the titanium analogue was highly stable even under physiological conditions.

The discovery of NO, CO, and H2S as gasotransmitters and their beneficial role in multiple physiological functions opened an era of research devoted to exogenously deliver them as therapeutic agents....