1H and 13C NMR) and DFT/TD-DFT calculations of potential analgesic drug 2-[2-(dimethylamino)ethyl]-6-methoxy-4-(pyridin-2-yl)-1(2 H)-phthalazinone]]>

摘要

AbstractThe theoretical molecular geometry and the IR, UV,1H and13C NMR spectroscopic properties of 2-[2-(dimethylamino)ethyl]-6-methoxy-4-(pyridin-2-yl)-1(2H)-phthalazinone with the previously demonstratedin?vivoanalgesic activity were characterized. The conformational analysis, performed using the molecular mechanics method with the General AMBER Force Field (GAFF) and the Density Functional Theory (DFT) approach with the B3LYP hybrid functional and the 6–31?+?g(d) basis sets, allowed to determine the most stable rotamer. The theoretical molecular geometry of this conformer was then calculated at the B3LYP/6–311++g(d,p) level of theory, and its phthalazinone core was compared with the experimental geometry of 1(2H)-phthalazinone. The calculated vibrational frequencies and the potential energy distribution enabled to assign the theoretical vibrational modes to the experimental FT-IR bands. The UV spectrum calculated with the Time-Dependent Density Functional Theory (TD-DFT) method in methanol identified the main electronic transitions and their character.1H and13C NMR chemical shifts simulated by the Gauge-Independent Atomic Orbital (GIAO) method in chloroform confirmed the previous assignment of the experimental resonance signals. The stability of the molecule was considered taking into account the hyperconjugation and electron density delocalization effects evaluated by the Natural Bond Orbital (NBO) method. The calculated spatial distribution of molecular electrostatic potential made possible to estimate the regions with nucleophilic and electrophilic properties. The results of the potentiodynamic polarization measurements were also indicated the corrosion inhibition activity of the title compound on 100Cr6 bearing steel in 1?mol?dm?3HCl solution.Graphical abstractDisplay OmittedHighlights?A conformational analysis followed by full geometry optimization were performed.?The experimental and calculated IR, UV,1H and13C NMR spectra are very consistent.?Stabilization results from the hyperconjugative interactions of σ, σ* and π* NBOs.?Electrostatic potential isosurface identifies nucleophilic and electrophilic sites.?The title compound exhibits the corrosion inhibition effect in HCl environment.