Synthesis, characterization, and in silico analysis against SARS CoV-2 of novel benzimidazolium salts

In acute conditions, vaccines are very important, although they provide antibodies for fighting against COVID-19 for a certain period. It is necessary to produce an anti-viral agent for a usual healing process against SARS CoV-2 which is responsible the pandemic we are living in. Many drugs with benzimidazole main scaffold are still used in a wide variety of treatment procedures. In this case, substituted benzimidazole structures could be good candidates for fighting against COVID-19. Theoretical calculation methods could be a key tool for overcome the difficulties of individual analyzing of each new structure. In this study, new benzimidazole structures were synthesized and characterized for in silico evaluation as anti-viral agent. The molecules were optimized and analyzed for reactivity with Koopmans Theorem. Also, molecular docking simulations were performed for SARS coronavirus main peptidase (PDB ID: 2GTB), COVID-19 main protease (PDB ID: 5R82), and papain-like protease of SARS CoV-2 (PDB ID: 6W9C) crystals.

Orbital-based Descriptions of Electron Configurations, Ionization, Excitation, and Bonding

This chapter deals with quantitative aspects of molecular orbital (MO) theory: Construction of an orbital diagram, bonding and antibonding overlap, Koopmans’ theorem, orbital energies versus total energies, an explanation of the unintuitive ground state electron configurations seen for some neutral transition metals, and a discussion of orbital energy gaps versus electronic excitations and other observable energy gaps. Localized MOs show the chemical bonds expected from the Lewis structure more readily than the canonical orbitals obtained from solving the SCF equations. It is shown that the delocalization of localized, not the canonical, MOs shows whether a system is delocalized. Algorithms by which to obtain localized MOs are sketched.

Understanding the Chemical Reactivity of Dihydroxyfumaric Acid and its Derivatives through Conceptual DFT

The chemical reactivity descriptors have been calculated through Molecular Electron Density Theory encompassing Conceptual DFT. The validity of �Koopmans� theorem in DFT� (KID) has been assessed by a comparison between the global descriptors (electronegativity, total hardness, and global electrophilicity) calculated through vertical energy values and those arising from the HOMO and LUMO values. These results suggest that the KID procedure is valid and may be used, in conjunction with the B3LYP/3-611G(d, p) level of theory in further studies of related compounds in the aqueous medium. The active sites for nucleophilic and electrophilic attacks have been identified and verified using the local reactivity descriptors: the dual descriptor, the electrophilic and nucleophilic Parr functions, the local reactivity difference index Rk and MEP maps. Obtained results suggest that the antioxidant/antiradical power of investigated compounds may be explained by the highest ambiphilic activation of the oxygen atoms of the hydroxyl groups in the ene-diol moiety.

Orbital Energies and Nuclear Forces in DFT: Interpretation and Validation

The bonding and antibonding character of individual Molecular Orbitals has been previously shown to be related to their orbital energy derivatives with respect to nuclear coordinates, known as Dynamical Orbital Forces. Albeit usually derived from Koopmans' theorem, in this work we show a more general derivation from conceptual DFT, which justifies application in a broader context. The consistency of the approach is validated numerically for valence orbitals in Kohn-Sham DFT. Then, we illustrate its usefulness by showcasing applications in aromatic and antiaromatic systems and in excited state chemistry. Overall, Dynamical Orbital Forces can be used to interpret the results of routine ab initio calculations, be it wavefunction or density based, in terms of forces and occupations.