Ribose Alters the Photochemical Properties of the Nucleobase in Thionated Nucleosides

Substitution of exocyclic oxygen with sulfur was shown to substantially influence the properties of RNA/DNA bases, which are crucial for prebiotic chemistry and photodynamic therapies. Upon UV irradiation, thionucleobases were shown to efficiently populate triplet excited states and can be involved in characteristic photochemistry or generation of singlet oxygen. Here, we show that the photochemistry of a thionucleobase can be considerably modified in a nucleoside, that is, by the presence of ribose. Our transient absorption spectroscopy experiments demonstrate that thiocytosine exhibits 5 times longer excited-state lifetime and different excited-state absorption features than thiocytidine. On the basis of accurate quantum chemical simulations, we assign these differences to the dominant population of a shorter-lived triplet n pi* state in the nucleoside and longer-lived triplet pi pi* states in the nucleobase. This explains the distinctive photoanomerziation of thiocytidine and indicates that the nucleoside will be a less efficient phototherapeutic agent with regard to singlet oxygen generation.

Automated summary

The substitution of oxygen with sulfur in RNA/DNA bases influences their properties significantly. Thionucleobases can efficiently enter triplet excited states upon UV irradiation, leading to characteristic photochemistry or singlet oxygen generation. The presence of ribose in nucleosides modifies the photochemistry of thionucleobases, with thiocytosine showing a longer excited-state lifetime and different absorption features compared to thiocytidine.