Dykun O. Structure and physico-chemical properties of gossypol Schiff bases and hydrazones

The thesis is devoted to investigation of the structure and radical scavenging properties of gossypol Schiff bases and the hydrazones. Seven gossypol Schiff bases and two hydrazones were synthesized (three of which are new compounds). The structures and tautomeric equilibria of synthesized gossypol imine derivatives were studied by NMR, FT-IR, UV-Vis spectroscopy and quantum chemistry methods. Complete assignment of all signals (13C NMR) and bands in vibrational and electronic absorption spectra were established using DFT and TD-DFT calculations. Free radical scavenging activity of synthesized compounds was evaluated by total stoichiometries, EC50, VCEAC and TEAC assays using the free DPPH (2,2’-diphenyl-1-picrylhydrazyl) radical and ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)) radical cation in ethanol. The rate constants for the reaction of gossypol imine derivatives with DPPH in the slow step were obtained. The most reactive O-H groups of the studied compounds were established using quantum chemical calculations. It was shown that all the studied compounds are effective radical scavenging agents toward DPPH radical and ABTS radical cation. Investigation of the reactivity of gossypol Schiff bases toward DPPH in the presence of chloride acid were carried out. The existence of correlation between chemical shifts of protons of N-H groups and reaction rate constants was shown. This allows predicting the reactivity of gossypol Schiff bases toward free radicals. It was found that gosypol imine derivatives inhibit cell proliferation and have cytostatic activity.