Computational study of khellin excited states and photobinding to DNA

Abstract

A theoretical investigation of the formation and spectroscopic properties of the furan and pyrone monoadducts between the photosensitizer khellin and DNA base thymine is reported. The thermal reaction pathways involve very high barriers, whereas the excited state surfaces display low barriers in regions leading to the ground state TS structures and potential wells at the ground state TS geometries. Computed UV absorption spectra are interpreted with the support of molecular orbital calculations, and the role of solvent effects on the spectra is discussed. The red-shift in the khellin spectra upon intercalation in DNA is excellently reproduced by the computational methodology, as is the solvent induced spectral shift. The data also provides an explanation to why khellin predominantly forms furan monoadducts in DNA, as opposed to the closely related psoralen compounds.

A Theoretical Rationale why Furan‐side Monoadduct is More Favorable Toward Diadduct Formation in 8‐Methoxypsoralen and Thymine Complexes

“…The relevant reaction mechanisms remain still unclear up to now. As part of the ongoing studies , the photoreaction of undoubtedly physical models between 8‐MOP and thymine bases on the lowest lying triplet state is herein explored to illuminate what dynamic processes occur for mono‐ and diadducts formation and to answer unambiguously why the furan‐side monoadduct is more possible to form the final diadduct than the pyrone‐side one. The present work aims to contribute toward further knowledge on the photobinding mechanism of psoralens, and stimulate to further experimental studies.…”