Theoretical investigation on hydrogen bond interaction of diketo/keto-enol form uracil and thymine tautomers with intercalators

Abstract

The interaction of diketo and keto-enol form of thymine and uracil tautomers with acridine (Acr), phenazine (Phen), benzo[c]cinnoline (Ben), 1,10-phenanthroline (1,10-Phe), and 4,7-phenenthroline (4,7-Phe) intercalating drug molecules was studied using density functional theory at B3LYP/6-311++G** and M05-2×/6-311++G** levels of theory. From the interaction energy, it is found that keto-enol form tautomers have stronger interaction with intercalators than diketone form tautomers. On complex formation of thymine and uracil tautomers with benzo[c]cinnoline the drug molecules have high interaction energy values of -20.14 (BenT3) and -20.55 (BenU3) kcal mol, while phenazine has the least interaction energy values of -6.52 (PhenT2) and -6.67 (PhenU2) kcal mol. The closed shell intermolecular type interaction between the molecules with minimum elliptical value of 0.018 and 0.019 a.u at both levels of theory has been found from topological analysis. The benzo[c]cinnoline drug molecule with thymine and uracil tautomers has short range intermolecular N-H…N, C-H…O, and O-H...N hydrogen bonds (H-bonds) resulting in higher stability than other drug molecules. The proper hydrogen bonds N-H..N and O-H..N have the frequency shifted toward the lower side (red shifted) with the elongation in their bond length while the improper hydrogen bond C-H...O has the frequency shifted toward the higher side (blue shifted) of the spectral region with the contraction in their bond length. Further, the charge transfer between proton acceptor and donor along with stability of the bond is studied using natural bond orbital (NBO) analysis. Graphical abstract Hydrogen bond interaction of diketo/keto-enol form uracil and thymine tautomers with intercalators.

Phosphine oxides as NMR and IR spectroscopic probes for the estimation of the geometry and energy of PO⋯H–A hydrogen bonds

“…In computational methods, the strength of a hydrogen bonded complex is defined as the energy needed to separate the interacting molecules to an infinite distance. [5][6][7][8][9] Hydrogen bond energy can also be estimated indirectly, using its correlations with experimental and calculated geometric parameters, [10][11][12] as well as electron density properties. [13][14][15] An analysis of electron density distribution can be carried out using quantum theory of atoms in molecules (QTAIM 16 ) or experimental electron density obtained by X-ray crystallographic measurements.…”

Theoretical Researches On Binding Modes and Stability of Hydrogen Bonds Between Uracil and Formic Acid

“…Uracil, a unique nucleic acid base in RNA, can form hydrogen bond with adenine to participate in transcription and translation, and then maintain inheritance, immune and other life activities. Various studies have reported that uracil can bind to water, ketones and other small molecules through hydrogen bonds [11][12][13][14][15][16][17], affecting the structure and properties of uracil. Formic acid, with the least steric hindrance in fatty acids, exists in the muscles, blood and excreta of the human body.…”