Toward the Understanding of the Metabolism of Levodopa I. DFT Investigation of the Equilibrium Geometries, Acid-Base Properties and Levodopa-Water Complexes

Levodopa (LD) is used to increase dopamine level for treating Parkinson’s disease. The major metabolism of LD to produce dopamine is decarboxylation. In order to understand the metabolism of LD; the electronic structure of levodopa was investigated at the Density Functional DFT/B3LYP level of theory using the 6-311+G** basis set, in the gas phase and in solution. LD is not planar, with the amino acid side chain acting as a free rotator around several single bonds. The potential energy surface is broad and flat. Full geometry optimization enabled locating and identifying the global minimum on this Potential energy surface (PES). All possible protonation/deprotonation forms of LD were examined and analyzed. Protonation/deprotonation is local in nature, i.e., is not transmitted through the molecular framework. The isogyric protonation/deprotonation reactions seem to involve two subsequent steps: First, deprotonation, then rearrangement to form H-bonded structures, which is the origin of the extra stability of the deprotonated forms. Natural bond orbital (NBO) analysis of LD and its deprotonated forms reveals detailed information of bonding characteristics and interactions across the molecular framework. The effect of deprotonation on the donor-acceptor interaction across the molecular framework and within the two subsystems has also been examined. Attempts to mimic the complex formation of LD with water have been performed

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

<span style="font-size:11.0pt;mso-bidi-font-size: 10.0pt;font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; letter-spacing:-.1pt;mso-ansi-language:EN-GB;mso-fareast-language:EN-US; mso-bidi-language:AR-SA" lang="EN-GB">Intermolecular interaction in the benzene-Ar_n and benzene dimer van der Waals complexes: DFT analysis of the charge distribution and electric response properties</span>

19-27The performance of the DFT/B-97-D and <span style="font-family:Symbol;mso-ascii-font-family: " times="" new="" roman";mso-hansi-font-family:"times="" roman";letter-spacing:-.1pt;="" mso-char-type:symbol;mso-symbol-font-family:symbol"="" lang="EN-GB">wB97-D methods to reproduce the isotropic non-bonded interaction and the electric response properties in the benzene–argon and the π-π interaction in the benzene dimer have been studied. The PES for the interaction of benzene and argon with all possible Arn-benzene (n = 1, 2) conformations has been explored. Results indicate that the <span style="font-family: Symbol;mso-ascii-font-family:" times="" new="" roman";mso-hansi-font-family:"times="" roman";="" letter-spacing:-.1pt;mso-char-type:symbol;mso-symbol-font-family:symbol"="" lang="EN-GB">wB97-XD method is capable of reproducing well positions and depths for the studied benzene-Ar and benzene-benzene clusters to a high degree of accuracy and compare well with the experimental and best benchmark calculations. Satisfactory results have also been obtained for the benzene-X (X = He, Ne and Kr) clusters. The features of the charge density distributions of the studied benzene-Ar van der Waal complexes have been analyzed by calculating the dipole and higher multipole moments and the static polarizibility, its anistropic part and the interaction polarizibility. Trends and relationships to the dispersion interaction energy are suggested. Natural bond orbital analyses of the benzene-Arn vdw complexes show clearly that all carbon valence orbitals are over-populated by about 21% at the expense of the hydrogen atoms valence orbitals. These data also indicate that argon behaves as electron donor in the Ar-benzene vdw complex, and hence, the slight positive charge on argon is at on the expense of its valence (non-bonding) p-orbitals. </span

Eclipsed Acetaldehyde as a Precursor for Producing Vinyl Alcohol

Abstract: The MP2 and DFT/B3LYP methods at 6-311++G(d,p) and aug-cc-pdz basis sets have been used to probe the origin of relative stability preference for eclipsed acetaldehyde over its bisected counterpart. A relative energy stability range of 1.02 to 1.20 kcal/mol, in favor of the eclipsed conformer, was found and discussed. An NBO study at these chemistry levels complemented these findings and assigned the eclipsed acetaldehyde preference mainly to the vicinal antiperiplanar hyperconjugative interactions. The tautomeric interconversion between the more stable eclipsed acetaldehyde and vinyl alcohol has been achieved through a four-membered ring transition state (TS). The obtained barrier heights and relative stabilities of eclipsed acetaldehyde and the two conformers of vinyl alchol at these model chemistries have been estimated and discussed