Pyrazolo[3,4-b]hydroquinoline-5-ones: photochemical and DFT computational studies

Abstract

It is crucial to look at the light sensitivity factor in penta/hexahydropyrazolo[3,4-b]quinoline-5-ones because the therapeutic characteristics of these compounds and the corresponding oxidized products differ from one another. For this purpose, a series of penta/hexahydropyrazolo[3,4-b]quinoline-5-one compounds were exposed to UV light (λ ≥ 280 nm) to clarify the effects of various electron-donating/withdrawing substitutions at the N₁- and C₃-positions of the pyrazole ring on the rate of photochemical reactions. Therefore, the hydrogen atom at the N₁-position of the pyrazole ring was replaced by phenyl, para-methoxyphenyl, and para-nitrophenyl groups to elucidate the electronic effect on the rate of their photoreaction. The steric effect was examined by the location of the methyl or phenyl groups on the C₃-atom of the pyrazole ring. The results of this study indicate that based on the proposed “electron-transfer induced photo-oxidation”, besides the effect of the nature of solvent on the progress of the reaction, the electron-donating nature of the N₁-substitution and also the presence of the less-hindered methyl group at the C₃-position affected the shortening of the irradiation time. In addition to the experimental work, and to propose a logic mechanism, all possible positions in the molecule to donate an electron to the electron-accepting solvent were investigated, which was supported by density functional theory (DFT) computation by the B3LYP method with the 6-311++G(d,p) basis set in the conductor-like polarizable continuum model (CPCM), including MEP (molecular electrostatic potential) calculation, natural bond orbital (NBO) analysis, and the calculation of the HOMO–LUMO energy gap (HLG).