Chemistry

The reaction of imidazole-5-carbohydrazide 1 with hydrazonyl halides 2a,b gave the corresponding hydrazide–hydrazone derivatives 3a,b. Afterwards, 3-methyl-5-(4-methyl-2-aryl-1H-imidazol-5-yl)-4-(2-phenylhydrazineylidene)-4H-pyrazole 4a,b was affordably produced by cyclizing the latter compounds 3a,b in EtOH with Et₃N at reflux temperature. The corresponding piperidinyl, morpholinyl, and piperazinyl derivatives 5a–f were produced by a nucleophilic substitution reaction of 3a,b with piperidine, morpholine, and 1-methylpiperazine in EtOH at reflux temperature. The condensation reaction of carbohydrazide 1 with either 3-acetyl-2H-chromen-2-one or 1-(benzofuran-2-yl)ethan-1-one in EtOH with AcOH at reflux temperature yielded the corresponding hydrazones 6 and 7, respectively, in excellent yields. Twelve compounds were evaluated for their antibacterial properties and to ascertain their minimum inhibitory concentrations utilizing well diffusion methods. All compounds showed differing levels of antibacterial efficacy depending on the microbial species. Compounds 4b and 5c had the most favorable results, with inhibition zones of 2.7 cm against the Gram-positive bacterium S. aureus, with a minimum inhibitory concentration (MIC) of 50 µg/mL. Compounds 4b and 5c, demonstrating the highest activity, were subjected to molecular docking investigations to evaluate their inhibitory effects on the enzyme L-glutamine: D-fructose-6-phosphate amidotransferase [GlcN-6-P] of 2VF5. The molecular docking results revealed that both 4b and 5c exhibited a minimum binding energy of −8.7 kcal/mol, whereas the natural ligand GLP displayed a binding energy of −6.2 kcal/mol, indicating a substantial affinity for the active site; thus, they may be considered potent inhibitors of GlcN-6-P synthase.

We have theoretically examined the intermolecular interactions in the cationic states of π-stacked dimers of 4nπ antiaromatic molecules. The ground state of face-to-face π-dimer models, consisting of cyclobutadienes (CBDs), was analyzed as a function of the stacking distance (d) for their monocationic and dicationic states using multi-reference second-order perturbation theory. Multi-configurational wavefunction analysis in a diabatic representation was employed to understand the electronic structures of the dimer models in terms of the monomer electron configurations. It is found that the monocationic dimer exhibits a local minimum at about d = 2.4 Å in the ground state, where each monomer is represented by a superposition between neutral triplet and cationic doublet electron configurations. Crossing of the ground and excited states occurs through changing d, which is due to the small energy gap between the highest occupied and lowest unoccupied molecular orbitals of antiaromatic molecules.

The presence of a so-called ‘inert pair effect’ in the chemistry of the 6p elements has been recognised for almost a century. Following a brief historical overview and a summary of the explanations that have been advanced to account for this effect, a more quantitative study of its prevalence and importance in the chemistry of these elements is presented based on an analysis of data in the recently published Chemdex database. These data clearly reveal a preponderance of lower valent compounds for the elements thallium, lead and bismuth and demonstrate that the various compound types exhibiting lower or higher valances are in accord with the published explanations.