Preferability of Molnupiravir, an Anti-COVID-19 Drug, toward Purine Nucleosides: A Quantum Mechanical Study.

Structural aspects of molnupiravir complexed with the RNA of the SARS-CoV-2 virus have been recently resolved inside the RNA-dependent RNA polymerase (RdRp), demonstrating the interactions of molnupiravir with purine nucleosides. However, the preference of molnupiravir to interact with one purine nucleoside over another has not been clearly investigated. Herein, the complexation of molnupiravir in its active form with guanosine and adenosine was compared, using sundry density functional theory calculations. The plausible tautomeric structures of the molnupiravir drug in complex with guanosine/adenosine were minutely scrutinized. The relative energy findings outlined the favorability of amino-molnupiravir···keto-amino-guanosine and imino-molnupiravir···amino-adenosine optimized complexes. According to the interaction (Eint) and binding (Ebind) energy values, higher preferential base-pairing of molnupiravir with guanosine over the adenosine one was recognized with Eint/Ebind values of -31.16/-21.81 and -13.93/-12.83 kcal/mol, respectively. This could be interpreted by the presence of three and two hydrogen bonds within the former and latter complexes, respectively. Observable changes in the electronic properties and global indices of reactivity of the studied complexes also confirmed the preferential binding within the studied complexes. The findings from the quantum theory of atoms in molecules and the noncovalent interaction index also support the partially covalent nature of the investigated interactions. For both complexes, changes in thermodynamic parameters outlined the spontaneous, exothermic, and nonrandom states of the inspected interactions. Inspecting the solvent effect on the studied interactions outlined more observable amelioration within the water medium compared with the gas one. These results would be a durable ground for the forthcoming studies concerned with the interactions of the molnupiravir drug with purine nucleosides.

Effects of Lewis Basicity and Acidity on σ-Hole Interactions in Carbon-Bearing Complexes: A Comparative Ab Initio Study.

The effects of Lewis basicity and acidity on σ-hole interactions were investigated using two sets of carbon-containing complexes. In Set I, the effect of Lewis basicity was studied by substituting the X3/X atom(s) of the NC-C6H2-X3 and NCX Lewis bases (LB) with F, Cl, Br, or I. In Set II, the W-C-F3 and F-C-X3 (where X and W = F, Cl, Br, and I) molecules were utilized as Lewis acid (LA) centers. Concerning the Lewis basicity effect, higher negative interaction energies (Eint) were observed for the F-C-F3∙∙∙NC-C6H2-X3 complexes compared with the F-C-F3∙∙∙NCX analogs. Moreover, significant Eint was recorded for Set I complexes, along with decreasing the electron-withdrawing power of the X3/X atom(s). Among Set I complexes, the highest negative Eint was ascribed to the F-C-F3∙∙∙NC-C6H2-I3 complex with a value of -1.23 kcal/mol. For Set II complexes, Eint values of F-C-X3 bearing complexes were noted within the -1.05 to -2.08 kcal/mol scope, while they ranged from -0.82 to -1.20 kcal/mol for the W-C-F3 analogs. However, Vs,max quantities exhibited higher values in the case of W-C-F3 molecules compared with F-C-X3; preferable negative Eint were ascribed to the F-C-X3 bearing complexes. These findings were delineated as a consequence of the promoted contributions of the X3 substituents. Dispersion forces (Edisp) were identified as the dominant forces for these interactions. The obtained results provide a foundation for fields such as crystal engineering and supramolecular chemistry studies that focus on understanding the characteristics of carbon-bearing complexes.

R•-hole interactions of group IV-VII radical-containing molecules: A comparative study.

For the first time, the potentiality of the sp2-hybridized group IV-VII radical (R•)-containing molecules to participate in R•-hole interactions was comparatively assessed using •SiF3,•POF2, •SO2F, and •ClO3 models in the trigonal pyramidal geometry. In that spirit, a plethora of quantum mechanical calculations was performed at the MP2/aug-cc-pVTZ level of theory. According to the results, all the investigated R•-containing molecules exhibited potent versatility to engage in R•-hole … Lewis base interactions with significant negative binding energies for the NCH-based complexes. The strength of R•-hole interactions was perceived to obey the •ClO3 … > â€¢SO2F … > â€¢POF2 … > â€¢SiF3 … Lewis base order, outlining an inverse correlation between the binding energy and the atomic size of the R•-hole donor. Benchmarking of the binding energy at the CCSD/CBS(T) computational level was executed for all the explored interactions and addressed an obvious similarity between the MP2 and CCSD energetic findings. QTAIM analysis critically unveiled the closed-shell nature of the explored R•-hole interactions. SAPT-EDA proclaimed the reciprocal contributions of electrostatic and dispersion forces to the total binding energy. These observations demonstrate in better detail the nature of R•-hole interactions, leading to a convincing amelioration for versatile fields relevant to materials science and drug design.