Development of Biological-Event Manipulators Triggered by Light-Activated Compounds

Abstract

Photoresponsive molecular tools have become powerful platforms for manipulating biological functions with high spatiotemporal precision. In this review, we highlight recent advances in the development of light-activated compounds that interact with key signaling molecules and microenvironments. Inspired by various chemical reactions triggered by light-matter interactions, this review covers three representative systems: photoactivatable peroxynitrite (ONOO⁻) generators, visible-light-driven nitric oxide (NO) releasers, and optochemical oxygen (O₂) scavengers. ONOO⁻, a reactive nitrogen species formed from NO and superoxide (O₂⁻), plays a critical role in protein nitration and cellular oxidative stress. By designing molecules that generate both NO and O₂⁻ upon light exposure, efficient ONOO⁻ release was achieved and used to induce nitration reactions. For NO manipulation, the authors developed a class of photoresponsive releasers that utilize photoinduced electron transfer (PeT) to enable blue-to-red light-triggered NO release. These photoresponsive releasers allowed optical control of vasodilation both ex vivo and in vivo, which forms the basis of a minimally invasive approach to modulate blood flow. In addition, a light-responsive O₂ scavenger was developed to induce localized hypoxia in cell cultures. The light-responsive O₂ scavenger enabled optical regulation of the hypoxia-responsive pathway and activation of the transient receptor potential ankyrin 1 (TRPA1) calcium channel, which underscores the utility of this approach. Together, these studies illustrate how rational molecular design, combined with precise photochemical control, can create innovative systems for probing and directing biological events. These technologies are valuable as both a basic research tool and for potential future therapeutic applications.