Red-shifted two-photon-sensitive phenanthridine photocages: synthesis and characterisation

Herein we describe the synthesis and photophysical study of a novel class of phenanthridine-based, one- and two-photon sensitive, photoremovable protecting groups (PPGs) with absorption wavelengths extending beyond 400 nm. Photocages are indispensable tools for the controlled release of biologically active agents and have found widespread utility in neurophysiology and optogenetics. However, the effectiveness of many PPGs is hindered by their limited absorption of visible light. To address this challenge, we developed a small library of 3-dimethyl amino phenanthridine derivatives through a concise five-step synthetic route. Through comprehensive photophysical and photochemical analysis, coupled with DFT/TD-DFT calculations, we elucidated the key components governing their behaviour. This rational design approach facilitated the development of phenanthridine PPGs with enhanced uncaging quantum yield, paving the way for their broader application in controlled drug delivery and molecular manipulation.