Synthesis of pyrrolo[3,2,1-hi]indazoles from indole-7-ketoximes

Treatment of the 2,4-dinitrophenyl ethers of some indole-7-ketoximes with base results in a cyclisation reaction to yield pyrrolo[3,2,1-hi]indazoles.     

A hybrid forces Quantum Mechanical Charge Field Molecular Dynamics of Cs+ ion in aqueous ammonia: A solvation lability, “structure breaking” phenomenon and hydrogen bond properties

The dynamics and structure of Cs⁺ solvation in an aqueous ammonia solution have been investigated using the Quantum Mechanical Charge Field Molecular Dynamics (QMCF-MD) simulation method. The system contained 18.6% ammonia in aqueous solution at 298.15 K. The QM region was set to a radius of 7.0 Å to include the first and second solvation shells. The Hartree-Fock (HF) level was applied to calculate the ion-ligand and ligand–ligand interactions in the QM region using the LANL2DZ-ECP basis set for the ion and DZP-Dunning for the ligands. The radial distribution revealed only one solvation shell, indicating a labile solvation structure. The various coordination number of ligands suggests an instant exchange between them. The mean residence times of 1.29 and 0.9 ps were less than in the pure water and liquid ammonia system, indicating higher mobility ligands of the aqueous ammonia system. The preferential factor 0.55 supports the hypothesis that the Cs⁺ ion prefers to be dissolved in water. As the ligands moves further away from the ion, the observed number of hydrogen bonds increases, revealing the “structure-breaking” property of the Cs⁺ ion. The minimum angle ligand-ion-ligand tends to be higher near the ion, confirming this phenomenon.     

Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach

Before entering the cell, the SARS-CoV-2 spike glycoprotein receptor-binding domain (RBD) binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. Hence, this RBD is a critical target for the development of antiviral agents. Recent studies have discovered that SARS-CoV-2 variants with mutations in the RBD have spread globally. The purpose of this in silico study was to determine the potential of a fruit bromelain-derived peptide. DYGAVNEVK. to inhibit the entry of various SARS-CoV-2 variants into human cells by targeting the hACE binding site within the RBD. Molecular docking analysis revealed that DYGAVNEVK interacts with several critical RBD binding residues responsible for the adhesion of the RBD to hACE2. Moreover, 100 ns MD simulations revealed stable interactions between DYGAVNEVK and RBD variants derived from the trajectory of root-mean-square deviation (RMSD), radius of gyration (Rg), and root-mean-square fluctuation (RMSF) analysis, as well as free binding energy calculations. Overall, our computational results indicate that DYGAVNEVK warrants further investigation as a candidate for preventing SARS-CoV-2 due to its interaction with the RBD of SARS-CoV-2 variants.