Synthesis, conformational analysis and antioxidant activity of semicarbazones with phenol fragments

In the present work, a number of semicarbazones with phenolic fragments were synthe-sized. A conformational analysis of the obtained compounds was carried out, and their antioxidant properties were evaluated. Semicarbazones containing phenolic fragments are of interest as effec-tive antioxidants which are able to neutralize free radicals and prevent oxidative stress, which is associated with a wide range of diseases, including cancer, diabetes, and cardiovascular disease. Semicarbazones with fragments of resorcinol, 2-methoxyphenol, 2,6-di-tert-butylphenol, alkylated pyrocatechol were synthesized. The yields were 72-82%. Semicarbazones of 2,3-dihydroxy-4,6-di-tert-butylbenzaldehyde and 4-hydroxy-3,5-di-tert-butylacetophenone were synthesized for the first time. The IR spectra of the compounds show absorption in the region of 1577-1598 cm-1, corre-sponding to the frequency of C=N stretching vibrations, and signals near 1668-1679 cm-1, corre-sponding to C=O stretching vibrations in semicarbazones. In the 1H NMR spectra, the aldehyde protons of the starting compounds in the downfield region of the spectrum are replaced by a sharp singlet at 7.73-9.31 ppm, which indicates the presence of CH=N fragments. There is also a peak in the 10 ppm region corresponding to one NH proton, and peak per 2 protons at 6 ppm corresponding to NH2 protons. The conformational analysis of the obtained compounds was carried out using quantum chemical calculations using the B3LYP functional and the 6-311+G (d,p) basis set, as well as NOESY two-dimensional NMR correlation spectroscopy. The antioxidant activity of all products was determined in vitro: radical cation scavenging activity was assessed using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) and iron reduction capacity was determined using the PFRAP method (ferricyanide/prussian blue). All the studied substances showed a higher antioxi-dant activity compared to agidol. Semicarbazones with fragments of 2-methoxyphenol and 2,6-di-tert-butylphenol showed the best ability to inhibit radical cations. Semicarbazones with a fragment of resorcinol and alkylated pyrocatechol showed the best iron-reducing activity.