Study on factors affecting quantum yield for the design of improved ortho-nitrobenzyl photoremovable protecting groups

Abstract

Abstract The use of photoremovable protecting groups (PPGs) for the protection and deprotection of biologically active substances has become instrumental in elucidating functional mechanisms in cells. However, the development of chromophores responsive to visible and near-infrared (NIR) light often results in reduced quantum yields (Φu) of uncaging reactions. Because a high quantum yield is essential for practical PPGs, it is imperative to understand the factors influencing it and devise strategies to enhance it. In this study, we systematically investigated nitrobiphenyl scaffolds featuring amino substituents as electron donors, potentially serving as visible and NIR excitable chromophores. Among the synthesized structures, PPGs incorporating carbazole and phenothiazine units as amino substituents exhibited the highest Φu values of 0.2 and 0.1, respectively, rendering them promising candidates for physiological studies. Conversely, diphenylamine substituents yielded considerably lower Φu values. Photophysical properties and quantum chemical calculations provided insights into the nature of the lowest excited states and their impact on Φu, highlighting the significance of achieving the balance between local n–π* excitation and charge-transfer excitation for manipulating the uncaging quantum yield in ortho-nitrobenzyl derivatives.