Density Functional Theory (B3LYP/6-311+G(d, p)) Study of Stability, Tautomerism and Acidity of 2-Thioxanthine in Gas and Aqueous Phases

Abstract

This work is a contribution of theoretical chemistry to the knowledge of 2‑thioxanthine's properties. Its aim first consists in checking the chemistry's results related to the exploitation of semi-empirical methods; it provides theoretical data on the acidity of 2‑thioxanthine tautomers. To do this, the DFT method with the B3LYP functional, associated with the 6‑311+G(d, p) basis set was used. The aqueous phase was modelled with the Polarizable Continuum Model (PCM). The results show that in gas and aqueous phases 2‑thioxanthine can exist as a mixture of four tautomers 2TX(1,3,7), 2TXX(1,3,9), 2TX(1,7,10) and 2TX(1,9,10). The relative stability decreases in the order 2TX(1,3,7)> 2TX(1,3,9)> 2TX(1,9,10)> 2TX(1,7,10). This work establishes that the tautomer 2TX(1,9,10) comes from the 2TX(1,3,7) via the 2TX(1,3,9) one. It demonstrates that the acidity of the most stable tautomer’s nitrogen 2TX(1,3,7), decreases in the order 7> 3> 1 in gas phase and in the order 3> 7>1 in aqueous phase. It provides data to elucidate the mechanisms to understand biological activities of 2‑thioxanthine.