Schiff bases encompassing a 1,2,3-triazole motif were synthesized using an efficient multi-step synthesis. The formations of targeted Schiff base ligands were confirmed by different spectroscopic techniques (FT-IR, ¹H NMR, ¹³C NMR, and CHN analysis). The spectral data analysis revealed that the newly designed hydrazones exist as a mixture of trans-E and cis-E diastereomers. Densityfunctional theory calculations (DFT) for the Schiff bases showed that the trans-trans form has the lowest energy structure with maximum stability compared to the other possible geometrical isomers that could be present due to the orientation of the amidic NH–C=O group. The energy differences between the trans-trans on one side and syn-syn and syn-trans isomers on the other side were 9.26 and 5.56 kcal/mol, respectively. A quantitative structure-activity relationship investigation was also performed in terms of density functional theory. The binding affinities of the newly synthesized bases are, maybe, attributed to the presence of hydrogen bonds together with many hydrophobic interactions between the ligands and the active amino acid residue of the receptor. The superposition of the inhibitor N3 and an example ligand into the binding pocket of 7BQY is also presented. Further interesting comparative docking analyses were performed. Quantitative structure-activity relationship calculations are presented, illustrating possible inhibitory activity. Further computer-aided cytotoxicity analysis by Drug2Way and PASS online software was carried out for Schiff base ligands against various cancer cell lines. Overall, the results of this study suggest that these Schiff base derivatives may be considered for further investigation as possible therapeutic agents for COVID-19.

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to the lack of effective targeted medications, often resulting in the recurrence of metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival in breast cancer patients. Pyranopyrazole and pyrazolone are privileged options for the development of anticancer agents. Inspired by this proven scientific fact, we report here the synthesis of two new series of suggested anticancer molecules incorporating both heterocycles together with their characterization by IR, ¹H NMR, ¹³C NMR, ¹³C NMR-DEPT, and X-ray diffraction methods. An attempt to get the pyranopyrazole-gold complexes was conducted but unexpectedly yielded benzylidene-2,4-dihydro-3H-pyrazol-3-one instead. This unexpected result was confirmed by X-ray crystallographic analysis. All newly synthesized compounds were assessed for their anti-proliferative activity against two different human breast cancer cells, and the obtained results were compared with the reference drug Staurosporine. The target compounds revealed variable cytotoxicity with IC₅₀ at a low micromolar range with superior selectivity indices. Target enzyme EGFR-TK and CDK-9 assays showed that compounds 22 and 23 effectively inhibited both biological targets with IC₅₀ values of 0.143 and 0.121 µM, respectively. Molecular docking experiments and molecular dynamics simulation were also conducted to further rationalize the in vitro obtained results. Communicated by Ramaswamy H. Sarma

The highly contagious nature of Covid‐19 attracted us to this challenging area of research, mainly because the disease is spreading very fast and until now, no effective method of a safe treatment or a vaccine is developed. A library of novel 1,2,3‐triazoles based 1,2,4‐triazole, 1,3,4‐oxadiazole and/or 1,3,4‐thiadiazole scaffolds were designed and successfully synthesized. Different spectroscopic tools efficiently characterized all the newly synthesized hybrid molecules. An interesting finding is that some of the newly designed compounds revealed two isomeric forms. The ratio is affected by the size of the attached group as well as the type of the heteroatom forming the side ring attached to the central 1,2,3‐triazole ring. The experimental spectroscopic data is in agreement with the DFT calculations at B3LYP 6‐31G (d,p) with regard to the geometrical conformation of the prepared compounds. The DFT results revealed that the stability of one isomeric form over the other in the range of 0.057–0.161 Kcal mol ⁻¹ . A docking study was performed using PyRx and AutoDockVina to investigate the activity of the prepared 1,2,3‐triazoles as antiviral agents. Bond affinity scores of the 1,2,3‐triazole derivatives were detected in the range of −6.0 to −8.8 kcal/mol showing binding to the active sites of the 6LU7 protease and hence could be anticipated to inhibit the activity of the enzyme. Verification of the docking results was performed using the M ^pro alignment of coronaviruses substrate‐binding pockets of COVID‐19 against the ligands. As per these results, it can be proposed that the title hybrid molecules are acceptable candidates against COVID‐19 for possible medicinal agents.

Zirconium tetrachloride reacted with C₂H₄(Ph₂PNSiMe₃)₂-1,2 1 under C–H activation to give the NCN chelate complex ZrCl₃{κ³-N,C,N′-C₂H₃(Ph₂PNSiMe₃)₂}, while the reaction with C₅H₃N(Ph₂PNSiMe₃)₂-2,6 gave an N-donor adduct. Cp*TiCl₃ reacts with trimethylsilyliminophosphines under dehalosilylation in all cases. In contrast to 1, the potentially C–N chelating benzylphosphinimine (4-Bu^tC₆H₄CH₂)Ph₂PNSiMe₃ undergoes dehalosilylation with TiCl₄ in preference to C–H activation, while prolonged reflux with ZrCl₄ affords the salt [4-Bu^tC₆H₄CH₂P(Ph)₂NHSiMe₃]₂[Zr₂Cl₁₀]. The molecular structures of the latter, ZrCl₃{C₂H₃(Ph₂PNSiMe₃)₂}, C₅H₃N(Ph₂PNTiCl₂Cp*)₂-2,6, and TiCl₂Cp*{NPPh₂CH₂C₆H₄Bu^t-4} have been determined by X-ray diffraction.