Photophysics and Photosensitizing Mechanism of Thiothymines Investigated Using Multi-Reference Quantum Chemistry

Abstract

Thymine, a DNA nucleobase, when photoexcited, relaxes to the ground state on an ultrafast timescale. In contrast, when one or both oxygen atoms in thymine are replaced with sulphur (yielding three different thiothymines), the molecule on photoexcitation populates its triplet excited state with near unity yield. Thiothymines also exhibit a redshift in their absorption spectrum compared to thymine, and in their triplet state, are able to photosensitize ground state oxygen to singlet oxygen. These photoproperties make thiothymines potential drugs to be used in photodynamic therapy. Three major questions are addressed in this work, all of which focus on understanding how position of substitution affect these photoproperties. Wavefunction-based multi-reference electronic structure methods, specifically, complete active space self-consistent field (CASSCF) and its extensions have been used. First, we explain the absorption spectra, where, substitution at the 4th position (4- thiothymine) exhibits a significantly higher redshift as compared to thionation at the 2nd position (2-thiothymine). We find that this unexpected trend can be attributed to an interplay between two types of delocalization in thymine: one due to conjugation with a double bond and the other owing to the size of the atom substituted. This work demonstrates that studying substitutions in isolation can be misleading, and the intrinsic features of the parent molecule need to be considered. Also, this study shows that the well-established idea of delocalization is not just affected by conjugation with another pi system, but is also influenced by the size of atoms. Second, we look at how position of substitution affects triplet lifetimes since 4- thiothymine was found to have a longer triplet lifetime than 2-thiothymine. This dif- ference arises from the decay dynamics of 2-thiothymine being distinct from that of 4-thiothymine and 2,4-dithiothymine. The findings regarding absorption spectra and triplet lifetimes of thiothymines were extended to another molecule, xanthine, to evaluate their generality. This molecule highlights the generality of absorption properties amongst thiobases, while suggesting prudence in making predictions about excited state properties, especially when excited state structures vary significantly from ground state structures. Finally, we have investigated the mechanism of photosensitization, and calculated the rates of photosensitization of oxygen by thiothymines. Recently, a method built on certain classical approximations was proposed. In our work, we have employed a time-dependent variant of Fermi’s Golden rule, where the treatment is purely quantum mechanical. We believe this is the first instance where this rate expression has been used for bimolecular nonradiative energy transfer.