Structural and energetic quantum chemical investigations into how the bioactive thiazolidinedione and rhodanine scaffolds interact with cytosine to form part of DNA

Abstract

The interaction within biologically active complex configurations composed of thiazolidinedione-cytosine (TC) and rhodanine-cytosine (RC) have been fully investigated using B3LYP and M062X methods in conjunction with various basis sets, including 6-311++G(d,p), 6-311++G(2d,2p), 6-311++G(df,pd) and AUG-cc-pVDZ. Dispersion corrections to interaction energies using M06-2X-GD3 and double hybrid density functionals (B2PLYP-GD2, B2PLYP-GD3 and mPW2PLYP-GD2) have also been taken into account. The results showed that the interaction energies, including long range dispersion corrections obtained using double hybrid density functionals, are about 1–2.5 kcal/mol higher than uncorrected ones. Various combinations of all possible sites around the monomers which could lead to formation of stable complex configurations were considered, and then six double hydrogen bonded interactions which are formed in a cyclic pattern were further investigated for both complex configurations between cytosine-thiazolidinedione and cytosine-rhodanine. The intermolecular hydrogen bonds which are involved in forming of cyclic interaction patterns are of NH⋯O(N) and CH⋯O(N) types.The TCS′2S1 and RCS′2S1 complex configurations were found to have the largest interaction energies within all the complex configurations studied for cytosine-thiazolidinedione and cytosine-rhodanine respectively at all computational levels used for the calculation of interaction energies. These two most stable complex configurations formed between the S1 site of the cytosine monomer and the S′2 site of the thiazolidinedione or rhodanine.The BSSE-corrected interaction energy for six cyclic double hydrogen bonded complex configurations, calculated at M062X/6-311++G(df,pd) level range from −11.26 to −16.22 kcal/mol for TC complexes and −11.04 to −15.59 kcal/mol for RC complexes.The stability order within thiazolidinedione-cytosine (TC) complexes is TCS′2S1 > TCS′1S1 > TCS′2S2 > TCS′1S2 > TCS′3S2 > TCS′3S1 in all levels studied. The same trend was observed for the stability order of rhodanine-cytosine (RC) complexes.The NBO results reveal that the charge transfer occurred from cytosine to thiazolidinedione or rhodanine within complex configurations which are formed at S′1S1, S′1S2, S′2S1 and S′2S2 sites, whereas in the case of complex configurations of cytosine with thiazolidinedione or rhodanine at S′3S1 and S′3S2 sites this order was reversed.The atom in molecule theory (AIM) and natural bond orbital analysis (NBO) were used to understand the nature of the interactions within the complex configurations studied. This showed good consistency with the interaction energies. In addition, good correlations between geometrical parameters, interaction energies, topological AIM data and NBO results were obtained. Based on AIM and NBO results, it is concluded that the H-bond interactions are electrostatic and partially covalent. Finally, the relationship between interaction energies and vibrational frequency changes at involved H-bonds was analyzed.