Synthesis, Crystal Structure, Hirshfeld Surface and Docking Studies of 2‐(methacryloyloxy)ethyl‐6‐amino‐5‐cyano‐2‐methyl‐4‐(thiophen‐2‐yl)‐4H‐pyran‐3‐carboxylate

Crystalline organic compound,2‐(methacryloyloxy)ethyl‐6‐amino‐5‐cyano‐2‐methyl‐4‐(thiophen‐2‐yl)‐4H‐pyran‐3‐carboxylate (ACMP) was synthesized by one‐pot three components reaction. The title compound is characterized by spectral techniques and single‐crystal XRD. 2D and 3D Hirshfeld surface analysies were studied to understand the intermolecular contacts. The study revealed that H...H, O−H...N, and N−H...O are the most significant contributor towards crystal packing with a percentage contribution of 45.1, 13.2 and 16.8 %, respectively. Further, to get more insight into the electronic properties of the molecular structure of ACMP compound, chemical stability and reactivity have been well explored by the frontier molecular orbital (FMO) approach. Despite, the molecular docking study was employed to predict the binding affinity between the ACMP and COVID‐19 Mpro and spike protease. The analysis showed that the several interactions including H‐bond, pi‐alkyl and pi‐pi interactions with the active sites of amino acid residues of 6LU7 and 2AJF. [ FROM AUTHOR]

Synthesis, crystal structure, DFT and molecular docking studies of N-acetyl-2,4-[diaryl-3-azabicyclo[3.3.1]nonan-9-yl]-9-spiro-4'-acetyl-2'-(acetylamino)-4',9-dihydro-[1',3',4']-thiadiazoles: A potential SARS-nCoV-2 Mpro (COVID-19) inhibitor.

In this paper, we describe the synthesis and crystal structure analysis of N-acetyl-2,4-[diphenyl-3-azabicyclo[3.3.1]nonan-9-yl]-9-spiro-4'-acetyl-2'-(acetylamino)-4',9-dihydro-[1',3',4']-thiadiazole (3a) and N-acetyl- 2,4-[bis(p-methoxyphenyl)-3-azabicyclo[3.3.1]nonan-9-yl]-9-spiro-4'-acetyl-2'-(acetylamino)-4',9-dihydro-[1',3',4']-thiadiazole (3b). The title compounds 3a and 3b are characterized by 1D NMR and single crystal x-ray diffraction analysis. Non-covalent interactions in a molecule were identified by Hirshfeld surface (dnorm contacts and 2D fingerprint plot) analysis. In addition, the existence of chalcogen bond (S•••O bond) in the molecular structures (3a and 3b) are described by NCI-RDG and QTAIM analysis. NBO analysis is employed to describe the orbital interactions and electron transfer between sulfur and oxygen atoms. Molecular docking is carried out for compounds 3a and 3b with COVID-19 viral protein SARS-nCoV-2 Mpro (PDB ID: 6LU7).

Synthesis, Crystal structure, Hirshfeld surface, DFT and Docking studies of 4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)(phenyl)methyl]-5-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one

In the present work, 4-[(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)(phenyl)methyl]-5-methyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (BPZ) was synthesized by one pot multicomponent reaction of ethylacetoacetate, phenylhydrazine and benzaldehyde in the presence of Ce-MCM-48 catalyst. The title compound was characterized by FT-IR, 1H NMR, and 13C NMR spectral studies and single crystal XRD technique. The intermolecular contacts of the title compound were studied by Hirshfeld surface (dnorm surfaces and 2D fingerprint plots) analysis whereas an intra-molecular hydrogen bonding interaction was examined through NCI-RDG plot. The geometry of the molecular structure was optimized by using the density functional theory (DFT) at B3LYP/6-311g(d,p) level. Molecular electrostatic potential (MEP), natural bond orbital (NBO) analysis, nonlinear optical properties (NLO) and global chemical reactivity parameters (GCRP) were described through computational method. Further, the molecular docking study was done for title compound with COVID-19 caused protein structure (6LU7, nCoV-SARS-2 Mpro). The study revealed that the significant conventional hydrogen bonding and other interactions were observed between active amino acid residue of nCoV-SARS-2 Mpro and BPZ ligand.