New Guanidinium and Aminoguanidinim Salts of 2-Hydroxypyridine-3-carboxylic acid: Preparation and spectral, structural, thermal, ADMET, biological, and molecular docking studies

The reaction of guanidine carbonate and aminoguanidine bicarbonate with 2-hydroxypyridine-3-carboxylic acid in various mole ratios (1:1, 1:2, and 2:1) resulted in the formation of the salts [GunH][C6H4NO3]square H2O (1), [GunH][C12H9N2O6] square H2O (2), [GunH](2)[C6H3NO3]square H2O (3), [AmguH][C6H4NO3]square H2O (4), [AmguH][C12H9N2O6] (5), and [AmguH](2)[C6H3NO3]square H2O (6) [where GunH(+) - guanidinium (+1) and AmguH(+) - aminoguanidinium (+1) salts]. Elemental analysis, FT-IR, H-1 NMR, and TG-DTA studies were used to identify and characterize the synthesized simple salts. All compounds were polycrystalline in nature, except (1), which was obtained as single crystal. Single-crystal X-ray diffraction studies confirmed the structure of (1), which crystallizes in a monoclinic system with the P2(1)/n space group, with molecular formula C7H12N4O4. FT- IR spectra of the aminoguanidinium salts reveal N-N stretching frequencies in the range of 989-914 cm(-1), indicating the presence of aminoguanidinium moiety. The NH2 protons of the guanidinium/aminoguanidinium moiety are assigned to the 7-7.5 delta signals in the H-1 NMR signals for the simple salts (1)-(6). The thermal reactivity and stability of the as-prepared salts were investigated in air using simultaneous TG-DTA analysis. Except for compounds (5) and (6), the TG-DTA of all the salts showed dehydration followed by continuous decomposition to produce gaseous products. All the salts underwent endothermic decomposition followed by exothermic combustion in the temperatures range from 120 to 450 degrees C. Furthermore, the salts have appreciable druglikeness characters according to Lipinski's regulations, as predicted by the in silico ADMET properties. Molecular docking studies of salts also revealed good binding affinity toward 3MIW, 4WM8, and 5IBV proteins. Among the six salts prepared, the diguanidinium salts showed good anticancer activity against human lung adenocarcinoma and human breast adenocarcinoma cell lines. The disk diffusion method was adopted to investigate the antibacterial activities of compounds (1)-(6) in vitro against two bacterial strains. All the salts displayed potential antibacterial activity against Escherichia coli and Staphylococcus aureus. (c) 2022 Elsevier B.V. All rights reserved.