Synthesis of non-symmetric N-benzylbispidinol amides and study of their inhibitory activity against the main protease of the SARS-CoV-2 virus.

Based on the data obtained by molecular modeling of the non-covalent interaction of non-symmetric N-benzylbispidin-9-ol amides with the active site of the main protease 3CLpro of the SARS-CoV-2 virus, a series of compounds was synthesized, and their inhibitory activity against 3CLpro was studied and compared with that of the known inhibitor ML188 (IC50 = 1.56±0.55 µmol L-1). It was found that only compound 1g containing the 1,4-dihydroindeno[1,2-c]pyrazole fragment showed moderate activity (IC50 = 100±5.7µmol L-1) and was characterized by the highest calculated binding energy among the studied bispidine derivatives according to molecular docking data.

Pi-conjugated N-heterocyclic compounds: correlation of computational and electrochemical data.

Electrochemical reduction potentials of a broad selection of nitrogen-containing molecules suitable as bridging (dipodal and tripodal) ligands in coordination and organometallic chemistry are reported and compared with results of semiempirical calculations. Trends of electrode potentials observed experimentally agree with respective calculated data, deviations can be explained by invoking peculiarities of the involved molecular orbitals and ligand-electrode surface interactions.

Fragmentation of 3,7-dialkyl-1,5-diphenyl-3,7-diazabicyclo[3.3. 1]nonan-9-ones under electron ionization.

A series of 3,7-dialkyl-1,5-diphenyl-3,7-diazabicyclo[3.3. 1]nonan-9-ones was prepared, and the details of their fragmentation under electron ionization (EI) were elucidated. The molecular ions of each compound under consideration were quite abundant in their EI spectra. Full-scan spectra exhibited a number of fragment ions which were clearly assigned using MS/MS and accurate mass measurements. The basic fragmentation of 3,7-dialkyl-1,5-diphenylbispidinones was due to the cleavage of C(1)-C(2) bond followed by a hydrogen migration similar to an odd-electron McLafferty rearrangement. Alternatively, the C(1)-C(2) bond cleavage was followed by the elimination of an imine molecule, Alk-N=CH(2). Further fragmentation resulted in ions at m/z 234 and 103, present in the spectra of all the compounds under study. The fragmentation pathways proposed in this paper are based on the substituent shifts, accurate mass measurements and collision-induced dissociation spectra of selected ions. The results of the present work can be useful in selecting the fragment ions suitable for identification and quantitation of bispidinones in biological matrices.