An ab initioand AIM investigation into the hydration of 2-thioxanthine

Abstract

BackgroundHydration 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.ResultsHydrogen-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...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.Conclusion2TX can interact with water by five different H-bonding regimes, N-H...O, O-H...N, O-H...O, O-H...S and C-H...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...O and O-H...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.

Intermolecular interactions in mixtures of 1-n-butyl-3-methylimidazolium acetate and water: Insights from IR, Raman, NMR spectroscopy and quantum chemistry calculations

“…When water is added to BmimAc, they decrease with a larger extent for the C (2,4,5) -H, indicating an increase of the electron density. This behavior of the 1 H and 13 C chemical shifts of the ring atoms correlates well with the blue shift of the corresponding vibrational modes [41,80,81,[83][84][85][86][87][88][89][90]. The blue shift of the ν(C (2,4,5) -H) as a function of decreasing X BmimAc as well as the decrease of the corresponding 1 H and 13 C chemical shift is compatible with the physical picture that the interactions between the acetate anion and the Bmim + are gradually weakened because of the concomitant increasing predominance of the interactions between water molecules and the COO − moiety of the Ac − over both those between water molecules and between water and the Bmim + .…”

Zinc finger oxidation of Fpg/Nei DNA glycosylases by 2-thioxanthine: biochemical and X-ray structural characterization

“…Considering the polar character of 2TX (associated with a strong negative electrostatic potential around the thione function, ( 42 )), the positively charged surface of the Zn-coordination sphere (defined by the basic residues R247 and K182) is clearly favorable to the approach and to the electrostatic interaction of 2TX to its binding site. The stabilization of the interaction relies next on the π-orbital stacking between the imidazole ring of 2TX and the indole ring of W179 reinforced by the H-bond between the N(9)H of 2TX and the carbonyl of W179 (Figure 2f ).…”