Computational Study of the Kinetics and Mechanisms of Gas-Phase Decomposition of -Diacetamides Using Density Functional Theory.

In this research work, we examined the decomposition mechanisms of -substituted diacetamides. We focused on the substituent effect on the nitrogen lone-pair electron delocalization, with electron-withdrawing and electron donor groups. DFT functionals used the following: B1LYP, B3PW91, CAMB3LYP, LC-BLYP, and X3LYP.

Stochastic Nature and Intramolecular Coupling in Optical Response Profiles: Critical Analysis through Semiclassical Models.

We have studied the nonlinear absorptive and dispersive responses considering a molecular system consisting of two-levels, where aspects of the vibrational internal structure and intramolecular coupling are inserted, in addition to the considerations of interaction with the thermal reservoir. The Born-Oppenheimer electronic energy curve for this molecular model consists of two-intercrossing harmonic oscillator potentials with minima displaced in energy and nuclear coordinate. The results obtained show how these optical responses are sensitive to explicit considerations of both intramolecular coupling and the presence of the solvent through their stochastic interaction.

Interaction of the new inhibitor paxlovid (PF-07321332) and ivermectin with the monomer of the main protease SARS-CoV-2: A volumetric study based on molecular dynamics, elastic networks, classical thermodynamics and SPT.

The COVID-19 pandemic has accelerated the study of drugs, most notably ivermectin and more recently Paxlovid (PF-07321332) which is in phase III clinical trials with experimental data showing covalent binding to the viral protease M. Theoretical developments of catalytic site-directed docking support thermodynamically feasible non-covalent binding to M. Here we show that Paxlovid binds non-covalently at regions other than the catalytic sites with energies stronger than reported and at the same binding site as the ivermectin B1a homologue, all through theoretical methodologies, including blind docking.

Comparative study of SARS-CoV-2 infection in different cell types: Biophysical-computational approach to the role of potential receptors.

Cellular susceptibility to SARS-CoV-2 infection in the respiratory tract has been associated with the ability of the virus to interact with potential receptors on the host membrane. We have modeled viral dynamics by simulating various cellular systems and artificial conditions, including macromolecular crowding, based on experimental and transcriptomic data to infer parameters associated with viral growth and predict cell susceptibility. We have accomplished this based on the type, number and level of expression of the angiotensin-converting enzyme 2 (ACE2), transmembrane serine 2 (TMPRSS2), basigin2 (CD147), FURIN protease, neuropilin 1 (NRP1) or other less studied candidate receptors such as heat shock protein A5 (HSPA5) and angiotensin II receptor type 2 (AGTR2).

Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach.

The SARS-CoV-2 pandemic has accelerated the study of existing drugs. The mixture of homologs called ivermectin (avermectin-B1a [HB1a] + avermectin-B1b [HB1b]) has shown antiviral activity against SARS-CoV-2 in vitro. However, there are few reports on the behavior of each homolog.

Structural deformability induced in proteins of potential interest associated with COVID-19 by binding of homologues present in ivermectin: Comparative study based in elastic networks models.

The COVID-19 pandemic has accelerated the study of the potential of multi-target drugs (MTDs). The mixture of homologues called ivermectin (avermectin-B1a + avermectin-B1b) has been shown to be a MTD with potential antiviral activity against SARS-CoV-2 . However, there are few reports on the effect of each homologue on the flexibility and stiffness of proteins associated with COVID-19, described as ivermectin targets.

Tetradentate metal complexes derived from cephalexin and 2,6-diacetylpyridine bis(hydrazone): Synthesis, characterization and antibacterial activity.

Metal(II) coordination compounds of a hydrazone ligand (HL) derived from the condensation of cephalexin antibiotic with 2,6-diacetylpyridine bis(hydrazone) were synthesized. The hydrazone ligand and mononuclear [ML(H2O)2][PF6] (M(II)=Mn, Co, Ni, Zn) complexes were characterized by several techniques, including elemental and thermal analysis, molar conductance and magnetic susceptibility measurements, electronic, FT-IR, EPR and (1)H NMR spectral studies. The cephalexin 2,6-diacetylpyridine bis(hydrazone) ligand HL behaves as a monoanionic tetradentate NNNO chelating agent.