Mixed-ligand complexes of copper(ii) with thienoyltrifluoroacetonate and nitrogen containing ligands: synthesis, structures, antimicrobial activity, cytotoxicity, Hirshfeld surface analysis and DFT studies.

Mixed-ligand complexes of copper(ii) with thienoyltrifluoroacetonate (TTA-H), 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen), and tetramethylethylenediamine (tmen), associated with counter ions such as Cl-, and NO3 - have been synthesized and characterized by molar conductance measurements, elemental analysis, mass spectrometry, IR and UV-Vis spectroscopy, antimicrobial activity, cytotoxicity assay studies, and single-crystal X-ray diffraction. The UV-Vis spectra and crystal structures are consistent with the adoption of square pyramidal geometry for all of the complexes except [Cu(TTA)tmen]NO3 and [Cu(TTA)2tmen] which have square planar and octahedral geometries, respectively. Conductance measurements of the mixed-ligand complexes indicated that they were all non-electrolytes, with the ligands and anions being coordinated to Cu except [Cu(TTA)tmen]NO3 which is a 1 : 1 electrolyte. All of the complexes were moderately active on all the fungi tested (Candida albicans, Aspergillus niger, Penicillium notatum, Rhizopus stolonifer) except [Cu(TTA)bipyCl] which showed increased activity in Candida albicans and Aspergillus niger. All of the compounds tested showed LC50 values greater than 100 with [Cu(TTA)(phen)NO3] being the least toxic of the compounds. Molecular geometries of the complexes were optimized at the PBE1PBE/def2SVP and PBE1PBE/6-311g(d,p) level of theory and the results were compared with the single-crystal X-ray diffraction data. Electronic properties such as HOMO, LUMO, HOMO-LUMO gaps and global reactivity descriptors are reported at the PBE1PBE/6-311g(d,p) level of theory. Hirshfeld surface analysis was carried out to investigate the cooperative non-covalent supramolecular interactions within the various complexes.

In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV.

An outbreak of a cluster of viral pneumonia cases, subsequently identified as coronavirus disease 2019 (COVID-19), due to a novel SARS-CoV-2 necessitates an urgent need for a vaccine to prevent infection or an approved medication for a cure. In our in silico molecular docking study, a total of 173 compounds, including FDA-approved antiviral drugs, with good ADME descriptors, and some other nucleotide analogues were screened. The results show that these compounds demonstrate strong binding affinity for the residues at the active sites of RNA-dependent RNA-polymerase (RdRp) modelled structures and Chymotrypsin-like cysteine protease (3CLpro) of the HCoV proteins. Free energies (ΔG's) of binding for SARS-CoV-2 and SARS-CoV RdRp range from - 5.4 to - 8.8 kcal/mol and - 4.9 to - 8.7 kcal/mol, respectively. Also, SARS-CoV-2 and SARS-CoV 3CLpro gave ΔG values ranging from - 5.1 to - 8.4 kcal/mol and - 5.5 to - 8.6 kcal/mol, respectively. Interesting results are obtained for ivermectin, an antiparasitic agent with broad spectrum activity, which gave the highest binding energy value (- 8.8 kcal/mol) against the 3CLpro of SARS-CoV-2 and RdRps of both SARS-CoV and SARS-CoV-2. The reason for such high binding energy values is probably due to the presence of hydroxy, methoxy and sugar moieties in its structure. The stability of the protein-ligand complexes of polymerase inhibitors considered in this investigation, such as Sofosbuvir, Remdesivir, Tenofovir, Ribavirin, Galidesivir, 5c3, 5h1 and 7a1, show strong to moderate hydrogen bonding and hydrophobic interactions (π-π stacked, π-π T-shaped, π-sigma and π-alkyl). The stability provided from such interactions translate into greater antiviral activity or inhibitory effect of the ligands. Assessment of the average free energies of binding of the FDA approved drugs are highly comparable for conformers of a particular inhibitor, indicating similar modes of binding within the pockets. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13721-021-00299-2.

Investigation of the reactivity indices for the formation of substituted dinitroanilines and correlations to their dockings on α-tubulin of Plasmodium falciparum.

The local and global reactivity descriptors of substituted dinitroaniline analogues were investigated using M06-2X/6-31 + G(d,p) method. It was observed that NH2 (m = 3.53 eV; p = 3.70 eV) substituent conveyed the highest nucleophilic character on the benzene ring system than the other groups under study. For the substrates 4-substituted-1-chloro-2,6-dinitrobenzenes, the condensed to atom electrophilicity ([Formula: see text]) increases in the order COOCH3 > NO2 > F > SO3H > CN > Cl > Br. The para substituted groups with the halogens follow the order of increasing electronegativity, F > Cl > Br. However, the nucleophilicity of the halo substituents of the products increases in the order, F > Br > Cl. Molecular docking simulations using the homology model with the crystallographic structure of zinc-induced bovine tubulin heterodimer (1JFF) as one of the templates reveal that the interactions between the tubulins of Plasmodium falciparum and dinitroaniline analogues are due to H-bonding. In general, the binding interaction is with the following residues: Met137, ARG64, Lys60, Glu183, Val4, His28, Cys171, Tyr224, Asn206, 228, Ile235, and Leu238. The pKas of the residue decrease as the ring activating power of the substituents increases from strongly activating to weakly activating groups. There is no evidence of intra or intermolecular H-bonding between Arg64 and Cys171. Electronegativity (χ) gives a better generic description of the dinitroanilines than any other parameters considered. Short-range hydrophobic interaction contributes to reduced binding affinities of the ligands. Graphical abstractReaction of substituted 2,6-dinitro chlorobenzene with diisopropylamine. Orbital interaction between the substrates and diisopropylamine in the formation of the dinitroanilines.

Ring-whizzing in polyene-PtL2 complexes revisited.

Ring-whizzing was investigated by hybrid DFT methods in a number of polyene-Pt(diphosphinylethane) complexes. The polyenes included cyclopropenium(+), cyclobutadiene, cyclopentadienyl(+), hexafluorobenzene, cycloheptatrienyl(+), cyclooctatetraene, octafluorooctatetraene, 6-radialene, pentalene, phenalenium(+), naphthalene and octafluoronaphthalene. The HOMO of a d(10) ML2 group (with b2 symmetry) interacting with the LUMO of the polyene was used as a model to explain the occurrence of minima and maxima on the potential energy surface.

A terminal, fluxional η4-benzene complex with a thermally accessible triplet state is the primary photoproduct in the intercyclobutadiene haptotropism of (CpCo)phenylenes.

Low-temperature irradiation of linear [3]- and [4]phenylene cyclopentadienylcobalt complexes generates labile, fluxional η(4)-arene complexes, in which the metal resides on the terminal ring. Warming induces a haptotropic shift to the neighboring cyclobutadiene rings, followed by the previously reported intercyclobutadiene migration. NMR scrutiny of the primary photoproduct reveals a thermally accessible 16-electron cobalt η(2)-triplet species, which, according to DFT computations, is responsible for the rapid symmetrization of the molecules along their long axes. Calculations indicate that the entire haptotropic manifold along the phenylene frame is governed by dual-state reactivity of alternating 18-electron singlets and 16-electron triplets.