Structural and electronic investigation of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs): Correlations between spectroscopic and molecular docking features upon salmon sperm DNA

•DHPMs were obtained with a multi-component reaction (MCR).•Spectra for all compounds were recorded and compared with TD-DFT simulations.•The interaction between DHPM and salmon sperm DNA was monitored in the UV region.•DHPMs planarity level can trigger different DNA interaction modes.•The oxidized molecules prefer to stay deep inside the minor groove of DNA. A set of 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) was prepared via a “one-pot” three-component Biginelli reaction using different aldehydes, ethyl acetoacetate, urea, and catalyzed by iron chloride hexahydrate. Subsequently, these compounds were submitted to chemical oxidation with nitric acid in order to obtain their respective oxidized forms. Density functional theory (DFT) was applied to investigate the structural, electronic, and bonding characteristics of these compounds. This study results show that in the DHPMs (1-3), the six-membered ring adopts a pseudo-boat conformation, and the heights of the C4 and N1 atoms from the boat plane depend on the type of the substituent on the aryl ring. Experimental electronic spectra for all compounds were recorded and compared with simulations obtained by time-dependent-DFT (TD-DFT). The interaction between those DHPMs and salmon sperm DNA was monitored spectrophotometrically in the UV region, binding constants (Kb) were estimated, and docking studies were performed using the PatchDock® server. Considering the differences in overall planarity and spectral signature of the compounds studied, we concluded that the reduced DHPMs are prone to achieve partial intercalation of their structures between the DNA nitrogen base pairs while the oxidized ones prefer to stay deep inside of the minor groove of this biomolecule.