Photochemical mechanism of DEACM uncaging: A combined time-resolved spectroscopic and computational study

The elementary steps of photocleavage in (coumarin-4-yl)methyl photoremovable protecting groups (PPGs) are elucidated by a combined electronic structure and time-resolved visible pump infrared probe (VIS-pump IR-probe) spectroscopic study. We specifically focus on the [7-(diethylamino)coumarin-4-yl]methyl (DEACM) PPG which has found increasing interest in biological applications over recent years. A series of leaving groups (LGs) are investigated, including azide (DEACM-N3), thiocyanate (DEACM-SCN), carbonate (DEACM-Carb), and a DEACM caged thymine nucleobase (DEACM-T) representing a model system for caged DNA. These systems are found to exhibit vastly different photocleavage time scales, ranging from the subpicosecond scale in the case of DEACM-SCN to ∼35 picoseconds in the case of DEACM-N3 and ∼540 picoseconds in the case of DEACM-Carb. In the case of DEACM-SCN, the appearance of the product is biphasic, with a fast (< ps) and a slower (20 ps) population. Conversely, the free azide and carbonate LGs appear with single exponential kinetics. Consistent with these observations, theoretical analysis based on Time-Dependent Density Functional Theory (TDDFT) studies reveals that the bright S1(π-π*) state features a barrier to dissociation that results from nonadiabatic crossings with higher-lying states. The barrier height is a sensitive function of the ligand species and of combined geometric displacements in the RC-X bond stretch coordinate (X = N, S and O, respectively) and the dihedral angle of the leaving group relative to the coumarin scaffold. Two-dimensional potential energy surface scans are carried out for these coordinates, showing that the rotation around the dihedral angle precedes dissociation of the respective leaving group. In contrast to DEACM-N3, DEACM-Carb, and DEACM-T, the DEACM-SCN system exhibits a barrierless path towards dissociation, resulting in an ultrafast photocleavage component in agreement with experiment.