Environmentally friendly and efficient TBHP-mediated catalytic reaction for the synthesis of substituted benzimidazole-2-ones: In-silico approach to pharmaceutical applications.

A novel method was used to synthesize benzimidazole-2-ones from the corresponding benzimidazolium salts. These salts were subsequently reacted with potassium tertiary butoxide (KOtBu), followed by oxidation using tertiary butyl hydrogen peroxide (TBHP) at room temperature in tetrahydrofuran (THF) to obtain the desired products in 1 h with excellent yields. After optimizing the reaction conditions, the study focused on preparing benzimidazole-2-ones with diverse substituents at N1 and N3 positions, including benzyl, 2',4',6'-trimethyl benzyl groups, and long-chain aliphatic substituents (hexyl, octyl, decyl, and dodecyl). The compounds were characterized by 1H and 13C NMR spectra, of which compound 2a is supported by single crystal XRD. Benzimidazole-2-one compounds exhibited promising anti-inflammatory and anti-cancer properties. The inhibition of mitochondrial Heat Shock Protein 60 (HSP60) of title compounds was also explored. Computational simulations were employed to assess anti-cancer properties of 19 benzimidazole-2-one derivatives (potential drugs). In-silico docking studies demonstrated promising binding interactions with HSP60, and these results were supported by molecular dynamics simulations. Notably, molecules 2b and 2d exhibited high affinity for HSP60 protein, highlighting their potential efficacy. The developed ligands were viable for the treatment of hepatocellular carcinoma (HCC). The findings provide valuable initial evidence supporting the efficacy of benzimidazole-2-ones as HSP60 inhibitors and lay the foundation for subsequent studies, including in-vitro assays.

Synthesis of bis-1,3-(benz)azoles catalyzed by palladium-PEPPSI complex-based catalysts and the study of photophysical properties.

Many biologically potent molecules have been identified to consist of benzo [b]azoles skeleton that are regarded to be the most important drug targets. Specifically, bis-benzo azoles have been the privileged conjugated structures due to their broad applications in environmental catalysis, and synthesis of various polymers, advanced materials, ligands, and natural products. Considering the significant features, different approaches have been attempted to synthesize such molecules via C-H activations by utilizing the transition metal complexes. In this study, we have developed facile and efficient Pd-based N-heterocyclic carbene (NHC) complexes, i.e., Pd-PEPPSI (Palladium-Pyridine Enhanced Pre-catalyst Preparation Stabilization and Initiation) catalysts that could successfully activate C-H bond and construct C-C bond between two 1,3-(benz)azoles via intermolecular oxidative homo-coupling reaction. The prepared Pd NHC catalysts were characterized by NMR and XPS. Pd NHCs concern about the special electronic and steric factors as the strong σ-donating and poor π-accepting properties of these nuclei renders great diversity in the field of transition metal catalysis as ancillary ligands and catalysts. Key factors of this methodology include low catalyst load, good substrate scope (even with sterically hindered substituted components), but no necessity of any extraneous ligands/oxidants and working at ambient reaction conditions with good to excellent yields of the products. Further, the targeted bis azole molecules have been characterized by single-crystal X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and cyclic voltammetric (CV) studies. The fluorescence and absorption spectra of a few of the synthesized compounds revealed that the electron-donating groups present on N-substituent dictate the absorption and emission bands.