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Abstract We report here a method to make a branched and partially ethoxylated polyethyleneimine derivative directly from ethanolamine. The polymerization reaction is catalysed by a pincer complex of Earth-abundant metal, manganese, and produces water as the only byproduct. Industrial processes to produce polyethyleneimines involve the transformation of ethanolamine to a highly toxic chemical, aziridine, by an energy-intensive/waste-generating process followed by the ring-opening polymerization of aziridine. The reported method bypasses the need to produce a highly toxic intermediate and presents advantages over the current state-of-the-art. We propose that the polymerization process follows a hydrogen borrowing pathway that involves (a) dehydrogenation of ethanolamine to form 2-aminoacetaldehyde, (b) dehydrative coupling of 2-aminoacetaldehyde with ethanolamine to form an imine derivative, and (c) subsequent hydrogenation of imine derivative to form alkylated amines.

The sobering reality is that numerous infectious diseases can no longer be effectively treated with antibiotics, necessitating immediate attention and action. Therefore, this study explores a thiadiazol derivative for the purpose of elucidating its antibacterial efficacy against carbapenem-resistant Klebsiella pneumonia and Pseudomonas aeruginosa. Prior to this examination, the compound (DOP) under study was structurally and electronically investigated utilizing density functional theory (DFT) at the ωB97XD/6–311++G (d, p) level of theory. Interestingly, this comprehensive investigation encompassed spectral analyses including FT-IR, and UV-excitation all studied in different solvents including DMSO, water, and methanol. Results of the frontier molecular orbital (FMO) analysis, DOP_gas showcased the lowest energy gap of 3.943 eV, implying heightened reactivity. Substantially, results from the pharmacokinetic studies illuminated facets of distribution, metabolism, and toxicity. Thus, registering the compound to possess incredible drug-like properties suggesting no detriments in terms of treatment. Notwithstanding, resounding results from the molecular docking studies presented DOP exhibited notable binding affinities and formed strong conventional hydrogen bonds with specific residues, indicating robust interactions. Particularly, DOP_6V78 and DOP_4WEJ displayed the highest affinities of -11.0 kcal/mol and 10.1 kcal/mol against Klebsiella pneumonia and Pseudomonas aeruginosa, respectively. These findings underscore the potential therapeutic efficacy of DOP against Carbapenem-resistant strains, suggesting its favorable attributes in comparison to conventional drugs in terms of binding affinity and interaction strength.

Parasitic infections such as lymphatic filariasis (elephantiasis) solely result from the infestation of a slender and thread-like worm. This condition precipitates swelling, often accompanied by skin alterations, potentially leading to substantial disability and disfigurement. Recent advancements in preventive measures for lymphatic filariasis encompass mass drug administration (MDA) involving antifilarial drugs. To that effect, this investigation employs an experimental and theoretical approach, utilizing the DFT/6–311++(2p,2d)/ωB97X-D level of theory, to evaluate the anti-filarial properties of a thiadiazol derivative, designated by the code (PTA). The comparative analysis of the spectroscopic data (FT-IR, UV, and NMR) was observed to be in good agreement. The geometry equilibration, it was observed that attributed to the influence of solvents and their properties, including the dielectric constant and polarity C18-S2 bond exhibited the highest bond length values 1.80208 (Å) in a gaseous environment. In the comparison of energy gaps, PTA_DMSO exhibited the smallest gap at 3.899 eV, while PTA_Water displayed a broader gap at 4.724 eV. PTA_Chloroform and PTA_Gas followed closely with energy gaps of 4.718 and 4.599 eV, respectively. The smaller energy gap observed in PTA_DMSO suggests higher reactivity and lower stability of the compound in this solvent. This finding underscores the potential efficacy of the ligand in DMSO as a promising drug candidate in this particular medium. From the molecular docking analysis shows the hydrogen bonds formed between 3VKL and PTA are four hydrogen bonds with a binding affinity of -4.6 kcal/mol, while with the two standard drugs, dimethylcarbamazine, one hydrogen bond with a binding affinity of -4.30 kcal/mol and albendazole with three hydrogen bonds with a binding affinity of -5.3 kcal/mol. Also, with 4BME protein, three hydrogen bonds with a binding affinity of -4.6 kcal/mol for PTA, one hydrogen bond for diethylcarbamazine with a binding affinity of -4.6 kcal/mol and two hydrogen bonds for albendazole with a binding affinity of -2.9 kcal/mol.

This study is aimed at evaluating the impact of solvation on the structural, spectroscopy (UV, NMR, FT-IR), reactivity, bonding interactions, and the drug potential of Pyridine 4-Carbaldehyde Semi-carbazone (PCS) against the disease (cholera) causing protein in the Gram-negative bacterium; Vibrio cholerae. Notably, the study was carried out using both experimental and theoretical calculations based on density functional theory (DFT) at the GD3B/B3LYP/6–311G++(2D,2P) level of theory along with molecular docking. Results from the UV- spectrum showed very fair absorption levels across the different solvents used, with theoretical peaks at 463 nm, 467 nm, 470 nm and 468 nm for PCS_DMSO, PCS_ETOH, PCS_H2O and PCS_MEOH, respectively. The study reveals discrepancies between experimental and theoretical 1H NMR shifts. However, theoretical 13C NMR shifts show minute differences. RDG analysis reveals steric repulsions in the pyridine ring. Whereas, the investigation of electronic properties reveal that the decreasing order of PCS_DMSO (3.668 eV) > PCS_H2O (3.206 eV) > PCS_MEOH (3.202 eV) > PCS_ETOH (0.312 eV). The results of docking showed that PCS had binding affinities of -5.0 Kcal/mol with protein 7P3R and -5.4 Kcal/mol with protein 1XTC which happen to be much lesser than -10.2 Kcal/mol formed between erythromycin and 7P3R. However, erythromycin formed a non-feasible bonding interactions with 1XTC with biding affinity of 18.0 Kcal/mol. Results of the MD simulation showed that PCS-MEOH had a higher energy value than PCS-DMSO, PCS-ETOH, and PCS-H2, indicating that it can interact with other substances more effectively, disperse more quickly. These results from the various studied objectives, however, suggest Pyridine 4-Carbaldehyde Semi-carbazone to be a lead compound for tackling the incidence, distribution and prevalence of cholera.

The present study is focused on the synthesis, characterization, DFT Studies, and in silico biological evaluation of novel benzenesulfonamides as antidiabetic agents. The compounds were synthesized and characterized experimentally using the NMR, FT-IR and HRMS while the molecular electronic structure properties were investigated using DFT-based theoretical methods at the M06-2X/6–311++G (d, p) level of theory. The results of the calculated vibrational energies were in perfect agreement with those of the experimental frequencies for different functional groups. The natural bond orbital (NBO) analysis was also carried out to study the intramolecular charge transfer interactions and energies of stabilization. Molecular docking simulation showed that the compounds; 3-Methyl-2-(4-methylphenylsulfonamido)-N-(2-oxo-2(piperidin-1-yl) ethyl) pentanamide (MMOPEP), 3-Methyl-N-(2-oxo-2-(piperidin-1-yl)ethyl))-2-(phenylsulfonamido)pentanamide (MOPEPP) and, 3-Methyl-2-(4-nitrophenylsulfonamido)-N-(2-oxo-2-(piperidin-1-yl)ethyl)pentanamide (MNOPEP) fitted tightly to the amino acid residues binding sites of insulin inhibiting protein receptors (7m17) with an average binding affinity of −6.9 kcal/mol, −6.6 kcal/mol, −6.7 kcal/mol respectively, thereby stimulating the release of insulin from functioning pancreatic beta cells which will in turn, lower blood glucose. This study provides a platform for scrutiny and clinical trials of benzenesulfonamide-based drugs as antidiabetic agents.