An ab initio and AIM investigation into the hydration of 2-thioxanthine

Background: Hydration is a universal phenomenon in nature. The interactions between biomolecules and water of hydration play a pivotal role in molecular biology. 2-Thioxanthine (2TX), a thio-modified nucleic acid base, is of significant interest as a DNA inhibitor yet its interactions with hydration water have not been investigated either computationally or experimentally. Here in, we reported an ab initio study of the hydration of 2TX, revealing water can form seven hydrated complexes. Results: Hydrogen-bond (H-bond) interactions in 1: 1 complexes of 2TX with water are studied at the MP2/6-311G(d, p) and B3LYP/6-311G(d, p) levels. Seven 2TX center dot center dot center dot H2O hydrogen bonded complexes have been theoretically identified and reported for the first time. The proton affinities (PAs) of the O, S, and N atoms and deprotonantion enthalpies (DPEs) of different N-H bonds in 2TX are calculated, factors surrounding why the seven complexes have different hydrogen bond energies are discussed. The theoretical infrared and NMR spectra of hydrated 2TX complexes are reported to probe the characteristics of the proposed H-bonds. An improper blue-shifting H-bond with a shortened C-H bond was found in one case. NBO and AIM analysis were carried out to explain the formation of improper blue-shifting H-bonds, and the H-bonding characteristics are discussed. Conclusion: 2TX can interact with water by five different H-bonding regimes, N-H center dot center dot center dot O, O-H center dot center dot center dot N, O-H center dot center dot center dot O, O-H center dot center dot center dot S and C-H center dot center dot center dot O, all of which are medium strength hydrogen bonds. The most stable H-bond complex has a closed structure with two hydrogen bonds (N(7)-H center dot center dot center dot O and O-H center dot center dot center dot O), whereas the least stable one has an open structure with one H-bond. The interaction energies of the studied complexes are correlated to the PA and DPE involved in H-bond formation. After formation of H-bonds, the calculated IR and NMR spectra of the 2TX-water complexes change greatly, which serves to identify the hydration of 2TX.