Competition between cyclization and unusual Norrish type I and type II nitro-acyl migration pathways in the photouncaging of 1-acyl-7-nitroindoline revealed by computations.

Pierpaolo Morgante, Charitha Guruge, Yannick P Ouedraogo, Nasri Nesnas, Roberto Peverati

Scientific reports 2021 Jan 14

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The 7-nitroindolinyl family of caging chromophores has received much attention in the past two decades. However, its uncaging mechanism is still not clearly understood. In this study, we performed state-of-the-art density functional theory calculations to unravel the photo-uncaging mechanism in its entirety, and we compared the probabilities of all plausible pathways. We found competition between a classical cyclization and an acyl migration pathway, and here we explain the electronic and steric reasons behind such competition. The migration mechanism possesses the characteristics of a combined Norrish type I and a 1,6-nitro-acyl variation of a Norrish type II mechanism, which is reported here for the first time. We also found negligible energetic differences in the uncaging mechanisms of the 4-methoxy-5,7-dinitroindolinyl (MDNI) cages and their mononitro analogues (MNI). We traced the experimentally observed improved quantum yields of MDNI to a higher population of the reactants in the triplet surface. This fact is supported by a more favorable intersystem crossing due to the availability of a higher number of triplet excited states with the correct symmetry in MDNI than in MNI. Our findings may pave the way for improved cage designs that possess higher quantum yields and a more efficient agonist release.

Citation

Pierpaolo Morgante, Charitha Guruge, Yannick P Ouedraogo, Nasri Nesnas, Roberto Peverati. Competition between cyclization and unusual Norrish type I and type II nitro-acyl migration pathways in the photouncaging of 1-acyl-7-nitroindoline revealed by computations. Scientific reports. 2021 Jan 14;11(1):1396