The in silico and in vitro antifungal activities of a series of bis(cycloalkylsulfenyl)-1,3,4-thiadiazole derivatives were evaluated against Candida albicans (C. albicans) and Aspergillus niger (A. niger). Crystallographic analysis of 1,6-bis(2-cyclopentylsulfenyl-1,3,4-thiadiazole-5-sulfenyl)hexane (C5C6TD) in the monoclinic P21/n space group revealed coplanar 1,3,4-thiadiazole-2-sulfenyl rings and a hexamethylene spacer, with twist-envelope cyclopentyl conformations. In vitro MTT assays confirmed all derivatives were non-toxic to RAW 264.7 macrophages at the tested concentration range of 3.125-100 mu g mL-1. In silico ADMET and ProTox-III predictions showed that carbon spacer length influenced pharmacokinetics and toxicity; six-carbon spacers were predicted to be class VI toxic, whereas four-carbon spacers were class IV. All derivatives demonstrated prominent in vitro antifungal efficacy, with minimum inhibitory concentrations (MICs) between 8 and 64 mu g mL-1. Compound C5C6TD specifically exhibited MICs of 62.5 and 31.25 mu g mL-1 against C. albicans and A. niger, respectively. Furthermore, computational docking analysis indicated robust binding pocket interactions with target proteins, showing excellent binding energies of -10.67 kcal mol-1 for lanosterol 14-alpha demethylase (PDB: 5V5Z) and -10.32 kcal mol-1 for glucose oxidase (PDB: 1GAL). These findings highlight the therapeutic potential of these thiadiazoles as safe, active antifungal agents.
Coal remains an important component of China's energy mix, and the goals of carbon peaking and carbon neutrality have increased the need for research on clean coal combustion. Based on density functional theory, we use a sulfur-containing armchair-edge model of coal char to investigate the adsorption, migration, and rearrangement of atomic and molecular oxygen, followed by SO2 formation and release. Following the chemisorption of two oxygen atoms, SO2 formation and release proceed through three transition states with barriers of 378.12, 149.84, and 367.65 kJ/mol, respectively. For molecular oxygen, physisorption is followed by chemisorption and two subsequent transition states associated with SO2 formation and release, with barriers of 238.32 and 345.59 kJ/mol, respectively. Bond order analysis and transition state theory are used to examine the proposed pathways. Rate constants are also calculated at different temperatures. The reported kinetic trends suggest that atomic oxygen increases the rate constant of the rate-limiting step and thereby facilitates SO2 release from the sulfur-containing coal char model.
This study reports the synthesis of a novel pyrazoline-based thiophene-benzothiazole hybrid and the evaluation of its antioxidant activity. The target compound was obtained via a 3+2 cycloaddition approach starting from chalcones synthesized by the Claisen-Schmidt condensation of 4-(methylthio) benzaldehyde and 2-acetyl-5-bromothiophene, followed by cyclization with 2-hydrazinobenzothiazole. The structure of the synthesized pyrazoline derivative was confirmed using FT-IR, 1H NMR, 13C NMR, and DEPT-135 spectroscopic techniques. Antioxidant activity was assessed using the phosphomolybdenum assay and compared with ascorbic acid as a reference standard. The compound exhibited measurable antioxidant activity, with an IC50 of 121.65 & micro;g/mL compared with 66.55 & micro;g/mL for ascorbic acid, indicating lower antioxidant potency than the reference standard. Molecular docking against the EphB4 receptor tyrosine kinase (PDB ID: 3ZEW) was used as an exploratory assessment of a potential cancer-related interaction and was interpreted independently of the antioxidant response. DFT calculations at the B3LYP/6-311G(d,p) level provided complementary insight into the structural and electronic properties of the compound, without assigning the calculated electronic descriptors as direct mechanistic evidence of its antioxidant activity. Overall, the results provide preliminary insights into the structural and electronic features of the compound and its potential antioxidant behavior.
