A new Schiff base, 4-((1E,2E)-3-(furan-2-yl)allylidene)amino)-N-(5-methylisoxazol-3-yl) benzene-sulfonamide (L), was synthesized by thermal condensation of 3-(2-furyl)acrolein and sulfamethoxazole (SMX), and the furan Schiff base (L) was converted to a phenol Schiff base (L’) according to the Diels–Alder [4 + 2] cycloaddition reaction and studied experimentally. The structural and spectroscopic properties of the Schiff base were also corroborated by utilizing density functional theory (DFT) calculations. Furthermore, a series of lanthanide and transition metal complexes of the Schiff base were synthesized from the nitrate salts of Gd, Sm, Nd, and Zn (L1, L2, L3, and L4), respectively. Various spectroscopic studies confirmed the chemical structures of the Schiff-base ligand and its complexes. Based on the spectral studies, a nine-coordinated geometry was assigned to the lanthanide complexes and a six-coordinated geometry to the zinc complex. The elemental analysis data confirmed the suggested structure of the metal complexes, and the TGA studies confirmed the presence of one coordinated water molecule in the lanthanide complexes and one crystalline water molecule in the zinc complex; in addition, the conductivity showed the neutral nature of the complexes. Therefore, it is suggested that the ligand acts as a bidentate through coordinates to each metal atom by the isoxazole nitrogen and oxygen atoms of the sulfur dioxide moiety of the SMX based on FTIR studies. The ligand and its complexes were tested for their anti-inflammatory, anti-hemolytic, and antioxidant activities by various colorimetric methods. These complexes were found to exhibit potential effects of the selected biological activities.

This work employs rigorous absolute binding free energy calculations and QM/MM methods to calculate the total binding energy of two recently crystallized peptidomimetic covalent inhibitors of the SARS-CoV-2 M^protarget.

COVID-19 has caused lockdowns all over the world in early 2020, as a global pandemic. Both theoretical and experimental efforts are seeking to find an effective treatment to suppress the virus. In silico drug design can play a vital role in identifying promising drug candidates against COVID-19. Herein, we focused on the main protease of SARS-CoV-2 that has crucial biological functions in the virus. We performed a ligand-based virtual screening followed by a docking screening for testing approved drugs and bioactive compounds listed in the DrugBank and ChEMBL databases. The top 8 docking results were advanced to all-atom MD simulations to study the relative stability of the protein–ligand interactions. MD simulations support that the catalytic residue, His41, has a neutral side chain with a protonated delta position. An absolute binding energy (ΔG) of −42 kJ mol⁻¹ for the protein–ligand (Mpro-N3) complex has been calculated using the potential-of-mean-force (geometrical) approach. Furthermore, the relative binding energies were computed for the top docking results. Our results suggest several promising approved and bioactive inhibitors of SARS-CoV-2 Mpro as follows: a bioactive compound, ChEMBL275592, which has the best MM/GBSA binding energy; the second-best compound, montelukast, is an approved drug used in the treatment of asthma and allergic rhinitis; the third-best compound, ChEMBL288347, is a bioactive compound. Bromocriptine and saquinavir are other approved drugs that also demonstrate stability in the active site of Mpro, albeit their relative binding energies are low compared to the N3 inhibitor. This study provides useful insights into de novo protein design and novel inhibitor development, which could reduce the cost and time required for the discovery of a potent drug to combat SARS-CoV-2.

This contribution presents a comprehensive computational study on the reactions of secondary ozonide (SOZ) with ammonia and water molecules. The mechanisms were studied in both a vacuum and the aqueous medium. All the molecular geometries were optimized using the B3LYP functional in conjunction with several basis sets. M06-2X, APFD, and ωB97XD functionals with the full basis set were also used. In addition, single-point energy calculations were performed with the G4MP2 and G3MP2 methods. Five different mechanistic pathways were studied for the reaction of SOZ with ammonia and water molecules. The most plausible mechanism for the reaction of SOZ with ammonia yields HC(O)OH, NH₃, and HCHO as products, with ammonia herein acting as a mediator. This pathway is exothermic and exergonic, with an overall barrier height of only 157 kJ mol⁻¹ using the G3MP2 method. All the reaction pathways between SOZ and water molecules are endothermic and endergonic reactions. The most likely reaction pathway for the reaction of SOZ with water involves a water dimer, in which the second water molecule acts as a mediator, with an overall barrier height of only 135 kJ mol⁻¹ using the G3MP2 method. Solvent effects were found to incur a significant reduction in activation energies. When the second H₂O molecule acts as a mediator in the reaction of SOZ with water, the barrier height of the rate-determining step state decreases significantly.