Interplay between Conjugation and Size-Driven Delocalization Leads to Characteristic Properties of Substituted Thymines

Abstract

Substituted thymines, where oxygen is replaced by sulfur or selenium, affect a variety of functions in biological systems and are prospective phototherapeutic agents. In this study, we show that an interplay between two types of delocalization, one due to conjugation and the other owing to the varying size of the substituted atom, leads to distinct absorption spectra and electrophilic sites in substituted thymines. This result is supported by ab initio quantum chemical calculations and a simple particle-in-a-box model. The model explains the unexpected variation in the absorption of 2-thiothymine and 4-thiothymine and makes an unanticipated prediction about the nature of the LUMO in 2-selenothymine that is confirmed by quantum chemical calculations. Here, delocalization due to the large size of selenium dominates that due to conjugation; in essence, a 2-center delocalization exerts a greater influence on molecular properties than a 4-center delocalization. The study highlights that the widely used concept of delocalization may be affected not only by the long-established idea of double bond conjugation but also delocalization owing to the size of atoms.

On the population of triplet states of 2-seleno-thymine

“…The low oscillator strength identifies it as a dark state. It is interesting to note that our results agree nicely with those reported by Pirillo et al 22 at the M062X/6-31+G* level of theory, whereas those obtained by Manae and Hazra 46 with MS-CASPT2(14,10)/ cc-pVTZ (IPEA = 0.25 a.u.) are overestimated by about 0.2 eV, probably due to the different IPEA shift and basis set employed.…”

Photochemical and Photodynamical Properties of Sulfur‐Substituted Nucleic Acid Bases,

“…According to these authors, both types of delocalization compete with each other, with the first type of delocalization dominating in 2-thiothymine. In 4-thiothymine, both types of delocalization work together instead, which lead to larger redshift of its lowestenergy absorption band (104). Similar arguments based on the molecular orbitals involved in the electronic transitions have been presented to explain the redshift of the absorption spectra in the thiouracil derivatives (105).…”

“…The experimentally measured large redshift in absorption, the ultrafast and efficient population of the triplet state, and the high yield of singlet oxygen generation reported for the 4‐thiouracil and 4‐thiothymine derivatives have also stimulated several static and dynamics simulations . According to these calculations, excitation of 4‐thiouracil or 4‐thiothymine derivatives with UVA radiation populates the S 2 (π S π*) state directly, while the S 1 (n S π*) state is shown to exhibit negligible oscillator strength in the Franck–Condon region.…”

“…Thus, the greater redshift in 4‐thiothymine was attributed to the LUMO being localized along the weaker thiocarbonyl bond, whereas the LUMO is localized along the higher energy carbonyl bond in 2‐thiothymine . Manae and Hazra added that the reason behind the localization of the LUMO over the oxygen or the sulfur atom depending on the site of thionation is due to an interplay between two types of electronic delocalization. One type of delocalization was identified as conjugation of the C4=X bond with the C5=C6 bond of the thymine chromophore (where X=O or S).…”

“…One type of delocalization was identified as conjugation of the C4=X bond with the C5=C6 bond of the thymine chromophore (where X=O or S). The second delocalization is due to the size of the X atom, which decreases the energy of the C=S bond relative to that of the C=O bond . According to these authors, both types of delocalization compete with each other, with the first type of delocalization dominating in 2‐thiothymine.…”