Molecular Structure, Spectroscopic, Frontier Molecular Orbital Analysis, Molecular Docking Studies, and In Vitro DNA-Binding Studies of Osmium(II)-Cymene Complexes with Aryl Phosphine and Aryl Phosphonium Assemblies.

X-ray crystallography, spectroscopy, computational methods, molecular docking studies, and in vitro DNA-binding studies have been useful in the investigations of intermolecular and intramolecular interactions of osmium-cymene oxalato complexes with aryl phosphine and aryl phosphonium groups in both primary and secondary coordination spheres, respectively. Molecular structures of the novel complexes PPh4[Os(η6-p-cymene)Br(κ2-O,O'-C2O4)] (1) and [Os(η6-p-cymene) (κ2-O,O'-C2O4)PPh3] (2) were resolved by single-crystal X-ray diffraction (XRD). Primary and secondary coordination sphere contacts were investigated using Hirshfeld surface analysis which was supported by molecular docking (MD) studies. The MD data obtained predicted significant differences in binding energy across three receptors for the two osmium complexes. An in vitro DNA-binding study was accomplished using UV-Vis spectroscopy which showed that both 1 and 2 bond with DNA through an intercalation approach. The optimized molecular geometry, frontier molecular orbital (EHOMO and ELUMO) energies, global electrophilicity index (ω), chemical hardness (η), chemical potential (µ), and the energy band gap (EHOMO-ELUMO) were calculated utilizing density functional theory (DFT) methods. Computed structural parameters (bond lengths and angles) support the experimental single-crystal XRD data.

Prophylactic and Therapeutic Potential Zinc Metallodrugs Drug Discovery: Identification of SARS-CoV-2 Replication and Spike/ACE2 Inhibitors.

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) variants with novel spike protein mutations has been shown to be influencing the epidemiological and clinical aspects of the COVID-19 pandemic. OBJECTIVE: Due to studies showing various dietary benefits of zinc as a viral replication inhibitor as well as an immunity enhancer, organometallic complexes incorporating zinc ions can be ideal antiviral candidates due to their structural variation and diverse stereochemistry. METHODS: In silico studies were conducted for the virtual screening of zinc complexes with SARSCoV- 2 and host proteins to explore their effect on viral entry and replication activity. Molegro Virtual Docker along with AutoDock was used for the identification of potential SARS-CoV-2 inhibitor complexes from the Cambridge Structural Database (CSD). Molecular dynamics (MD), density functional theory (DFT), chemical absorption, distribution, metabolism, excretion, and toxicity properties (ADMET) were used to support the findings from virtual screening. RESULTS: In correlation with SARS-CoV-2 RNA-dependent RNA polymerase and spike receptorbinding domain bound with ACE2 docking results, the compound (bis(3,5-dimethyl-1H-pyrazole)- bis(2-furoato)-zinc(ii)) (CSD code ECOZAA) occurs to be a potential metal complex SARS-CoV-2 receptor inhibitor. The compound ECOZAA was observed (in silico binding affinity = - 179.29kcal/mol) to behave better than the clinically approved drug Remdesivir (in silico binding affinity = -62.69kcal/mol) against SARS-CoV-2 RNA-dependent RNA polymerase. The large HOMO- LUMO gap for the ECOZAA compound is an indication of the low chemical reactivity as well as the great kinetic stability of the compound. CONCLUSION: Thus, this study highlights the potential use of zinc metal complexes as SARS-CoV-2 viral entry and replication inhibitors.

Synthesis, in silico docking studies, and antiplasmodial activity of hybrid molecules bearing 7-substituted 4-aminoquinoline moiety and cinnamic acid derivatives.

This paper reports a series of nine hybrid compounds of 7-substituted 4-aminoquinoline and cinnamic acid as antiplasmodial agents. 1 H NMR and 13 C NMR spectroscopic analysis and mass spectrometry studies were used to confirm the structures. The synthesized compounds were moderately active, with IC50 values ranging from 1.8 to 16 µM against the Pf3D7 chloroquine-sensitive strain in vitro. Compound C11 was shown to be the most potent in this investigation, with an IC50 value of 1.8 µM. Molecular docking studies revealed that compounds C14 and C17, with binding energies (ΔG0) of -7.19 and -7.72 kcal/mol and inhibition constants (Ki ) of 5.36 and 2.20 µM, respectively, were the best inhibitor candidates. The results of the Frontier molecular orbitals revealed that compounds possessed a small HOMO-LUMO energy gap. The HOMO-LUMO energy distributions indicated that the cinnamic acid regions favored the LUMO distribution, while the quinoline regions favored the HOMO energy. The investigation of absorption, distribution, metabolism, excretion, and toxicity based on in silico ADME tools predicted that the compounds have a good drug-like character.