2-Deoxy glycosides are important components of many oligosaccharides with antibiotic and anti-cancer activity, but their synthesis can be very challenging. Phenanthrolines and substituted pyridines promote stereoselective glycosylation of 1-bromo sugars via a double S2 mechanism. Pyridine reacting with α-bromo, 2-deoxyglucose was chosen to model this reaction. The first step involves displacement of bromide by pyridine which can be rate limiting because bromide ion is poorly solvated in the non-polar solvents used for these reactions. We examined a series of small molecules to bind bromide and stabilize this transition state. Geometry optimization and vibrational frequencies were calculated using M06-2X/6-31+G(d,p) and SMD implicit solvation for diethyl ether. More accurate energies were obtained with M06-2X/aug-cc-pVTZ and implicit solvation. Urea, thiourea, guanidine and cyanoguanidine bind bromide more strongly than alkylamines, (NHCHCH)NH. Compared to the uncatalyzed reaction, urea, thiourea and cyanoguanidine lower the free energy of the transition state by 3 kcal/mol while guanidine lowers the barrier by 2 kcal/mol.

A lot of effort has been made in developing vaccine and therapeutic agents against the SARS-CoV-2, concentrating on the Spike protein that binds angiotensin-converting enzyme 2 on human cells. Nowadays, some researches study the role of the -linked glycans as potential targets for vaccines and new agents. Due to the flexibility and diversity of the -linked glycans, in this work, we focus on the -Acetylglucosamine moiety, which is the precursor of nearly all eukaryotic glycans. We performed molecular dynamics simulations to study the effects of the -Acetylglucosamine on the stability of the spike glycoprotein in SARS-CoV-2. After a 100 ns of simulation on the spike proteins without and with the -Acetylglucosamine molecules, we found that the presence of -Acetylglucosamine increases the local stability in their vicinity; even though their effect on the full structure is negligible. Thus; it can be inferred that the -Acetylglucosamine moieties can potentially affect the interaction of the S protein with the ACE2 receptor. We also found that the S1 domain is more flexible than the S2 domain. We propose which of the experimentally observed glycans found on the spike may be more functional than the others. Detailed understanding of glycans is key for the development of new therapeutic strategies.

In our DFT investigations, pristine BNNS as well as trivalent and pentavalent atoms doped BNNS have been taken into consideration for Favipiravir (FPV) drug carriers for the treatment of COVID-19. Among the nanosheets, In doped BNNS (BN(In)NS) interacts with FPV by favorable adsorption energies about -2.44 and -2.38 eV in gas and water media respectively. The charge transfer analysis also predicted that a significant amount of charge about 0.202e and 0.27e are transferred to BN(In)NS in gas and water media respectively. HOMO and LUMO energies are greatly affected by the adsorption of FPV on BN(In)NS and energy gap drastically reduced by about 38.80 % and 64.07 % in gas and water media respectively. Similar results are found from the global indices and work function analysis. Therefore, it is clearly seen that dopant In atom greatly modified the BNNS and enhanced the adsorption behavior along with sensitivity, reactivity, polarity towards the FPV.

The role of repurposed or modified antiviral drugs has become more significant during the current global pandemic of SARS Covid-19. In the present study, four structurally analogous impurity molecules of antiviral drug Favipiravir are selected for preliminary computational investigation for assessing the structure-activity relationship. The optimized geometry and the electronic structures of the compounds are computed using Density Functional Theory as a precursor to evaluating their physical, chemical and spectral properties. The frontier orbitals analysis is performed to obtain global reactivity parameters namely, the chemical potential, absolute electronegativity, global softness, global hardness, electrophilicity, etc. The natural Bond Orbital (NBO) analysis and Mulliken analysis provided an understanding of the charge-transfer interactions of molecules. The possibilities of intermolecular interactions of the drug systems with the receptors are also visualized using the electrostatic potential maps (MEP) derived from the DFT computations. The physiochemical properties are assessed computationally using SwissADME webtool to correlate the structural aspects of the compounds with their biological responses. Useful parameters namely flexibility, lipophilicity, size, polarity, solubility and saturation were also computed to evaluate the therapeutic activity or drug-likeness.

The trimeric spike (S) glycoprotein is the trojan horse and the stronghold of the severe acute respiratory syndrome coronaviruses. Although several structures of the S-protein have been solved, a complete understanding of all its functions is still lacking. Our multi-approach study, based on the combination of structural experimental data and quantum-chemical DFT calculations, led to identify a sequestration site for sodium, potassium and chloride ions within the central cavity of both the SARS-CoV-1 and SARS-CoV-2 spike proteins. The same region was found as strictly conserved, even among the sequences of the bat-respective coronaviruses. Due to the prominent role of the main three electrolytes at many levels, and their possible implication in the molecular mechanisms of COVID-19 disease, our study can take the lead in important discoveries related to the SARS-CoV-2 biology, as well as in the design of novel effective therapeutic strategies.

Today, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently caused a severe outbreak worldwide. There are still several challenges in COVID-19 diagnoses, such as limited reagents, equipment, and long turnaround times. In this research, we propose to design molecularly imprinted polymers as a novel approach for the rapid and accurate detection of SARS-CoV-2. For this purpose, we investigated molecular interactions between the target spike protein, receptor-binding domain of the virus, and the common functional monomers used in molecular imprinting by a plethora of computational analyses; sequence analysis, molecular docking, and molecular dynamics (MD) simulations. Our results demonstrated that AMPS and IA monomers gave promising results on the SARS-CoV-2 specific TEIYQAGST sequence for further analysis. Therefore, we propose an epitope approach-based synthesis route for specific recognition of SARS-CoV-2 by using AMPS and IA as functional monomers and the peptide fragment of the TEIYQAGST sequence as a template molecule.

The π-complex theory developed by Michael J. S. Dewar in 1949 has had its most profound impact as part of the Dewar-Chatt-Duncanson model, a seminal and foundational contribution to the field of organometallic chemistry. Over time it has demonstrated its utility in systems far from those originally envisaged, including σ-coordinated metal-complexes. This latter application is notable due to Dewar's original skepticism that his π-complex theory could be extended to σ-bonds. Separately it has previously been demonstrated that a one-electron wave function. can be shown to satisfy an exact one-electron Schrödinger equation describing the motion of the single electron in the average field of the remaining electrons. To celebrate the centenary of his birth this paper seeks to demonstrate that σ-coordinated metal-complexes present a perfect system to exemplify both the utility of the one-electron wave function and the power of the π-complex theory.

The reactions of Ni with propionaldehyde in the gas phase have been systematically investigated using density functional theory at the B3LYP/def2-TZVP level. The decomposition reaction mechanism has been identified. Our calculations indicated that Ni can assist decomposition of propionaldehyde to form NiCO and CH through two types of reaction channel: C-C bond activation and C-H bond activation. In addition, charge decomposition analysis (CDA) was carried out to obtain a deeper understanding for orbital interaction of the initial complex. The bonding properties of the species involved were discussed by means of diverse analysis methods including electron localization function (ELF) and atoms in molecules (AIM).

Accurate chemical shifts for the atoms in molecular mechanics (MD) trajectories can be obtained from quantum mechanical (QM) calculations that depend solely on the coordinates of the atoms in the localized regions surrounding atoms of interest. If these coordinates are correct and the sample size is adequate, the ensemble average of these chemical shifts should be equal to the chemical shifts obtained from NMR spectroscopy. If this is not the case, the coordinates must be incorrect. We have utilized this fact to quantify the errors associated with the backbone atoms in MD simulations of proteins. A library of regional conformers containing 169,499 members was constructed from 6 model proteins. The chemical shifts associated with the backbone atoms in each of these conformers was obtained from QM calculations using density functional theory at the B3LYP level with a 6-311+G(2d,p) basis set. Chemical shifts were assigned to each backbone atom in each MD simulation frame using a template matching approach. The ensemble average of these chemical shifts was compared to chemical shifts from NMR spectroscopy. A large systematic error was identified that affected the H atoms of the peptide bonds involved in hydrogen bonding with water molecules or peptide backbone atoms. This error was highly sensitive to changes in electrostatic parameters. Smaller errors affecting the C and N atoms were also detected. We believe these errors could be useful as metrics for comparing the force-fields and parameter sets used in MD simulation because they are directly tied to errors in atomic coordinates.

Molecules with high nitrogen content are of interest for their potential as high-energy materials. However, many molecules with 100% nitrogen content are unstable and dissociate with low barriers, which limits practical applications. In the present study, cyclic hexamers of the basic unit NCN (70% nitrogen by mass) are studied to determine the structural features and bonding characteristics that lead to more stable molecules. Double- and triple-bonded NCN units are compared to determine which form of NCN contributes the greater stability. Theoretical calculations using density functional theory and couple-cluster theory are carried out on a series of NC molecules to determine trends in stability. Energetic and structural trends, as well as differences between DFT and coupled-cluster theory, are calculated and discussed.

Adsorptions of histidine on the functionalized (10,0) single-walled carbon nanotube (SWNT) and graphene were investigated using density function theory methods, M05-2x and DFT-D. The results show that the binding of the histidine ring to the functionalized SWNT is weaker than that to the pristine SWNT for both singlet and triplet complexes, regardless of the electron-donating (-OH, -NH) or electron-withdrawing (-COOH) character and their attached sites. The present decreased binding is opposite to the well-known enhanced binding in the substituted benzene dimers. Since the atoms of the histidine are distant from the substituent atoms by over 6Å, there would be no interaction between histidine and the substituent as in the case of the substituted benzene systems. The decreased binding can be mainly driven by the aromaticity of the functionalized SWNT. The nucleus-independent chemical shift (NICS) index analysis for the functionalized SWNTs in deed shows that local aromaticity of SWNT is decreased because of the electron redistribution induced by functional groups, and the stacking between the histidine ring and -SWNT is therefore decreased as compared to the pristine SWNT. However, the above trend does not remain for the binding between the histidine and graphene. The binding of the histidine to the functionalized graphene with -OH and -NH is just slightly weaker than that to the pristine graphene, while its binding to COOH-SWNT becomes a little bit stronger.

The Wigner high electron correlation regime is characterized in the literature by an electron-interaction energy much greater than the kinetic energy. Via the 'quantal Newtonian' first law, we discover that for a nonuniform electron density system in this regime, there is a 'quantal compression' of the kinetic energy density. The explanation of this compression provides a fundamental understanding for why the kinetic energy is a smaller fraction of the total energy relative to the same ratio in the low correlation regime. We also discover by application of quantal density functional theory, that the contribution of electron correlations to the kinetic energy - the correlation-kinetic effects - and to the total energy is very significant. We propose that in addition to a high electron-interaction energy, the Wigner regime must thus also be characterized by a high correlation-kinetic energy.

Accurate and efficient treatment of electrostatics is a crucial step in computational analyses of biomolecular structures and dynamics. In this study, we have explored a second-order finite-difference numerical method to solve the widely used Poisson-Boltzmann equation for electrostatic analyses of realistic bio-molecules. The so-called immersed interface method was first validated and found to be consistent with the classical weighted harmonic averaging method for a diversified set of test biomolecules. The numerical accuracy and convergence behaviors of the new method were next analyzed in its computation of numerical reaction field grid potentials, energies, and atomic solvation forces. Overall similar convergence behaviors were observed as those by the classical method. Interestingly, the new method was found to deliver more accurate and better-converged grid potentials than the classical method on or nearby the molecular surface, though the numerical advantage of the new method is reduced when grid potentials are extrapolated to the molecular surface. Our exploratory study indicates the need for further improving interpolation/extrapolation schemes in addition to the developments of higher-order numerical methods that have attracted most attention in the field.

Retinoic acids and other vitamin A analogs contain a trimethylcyclohexenyl ring in conjugation with a polyene chain joined at carbon-6 (C6) and carbon-7 (C7). A MP2-SCS/cc-pVDZ// B3LYP/6-31G(d) 2-D potential energy surface was computed for all- retinoic acid, which had 6 minima (3 enantiomeric pairs). The global minima were distorted enantiomers ( = 53°) with half-chair conformations of the ring. Distorted enantiomers ( = 55°) with inverted half-chair ring conformations were 1.7 kJ/mol above the global minima. The enantiomers ( = 164°) were 11.3 kJ/mol above the global minima. Steric energies were computed by the method of Guo and Karplus to identify key structural elements in retinoic acids which determines their conformation. Small molecule crystal structures in the CCDC database with trimethylcyclohexenyl ring and exocyclic double bonds have ring-chain geometries near to one of the 6 energy minima of retinoic acids, except for retinaldehyde iminium cations.

We have performed full configuration interaction computations of the ground states of the molecules Be, BeH, Li, LiH, B, and BH and verified that the core electrons constitute "separated electron pairs." These separated pairs of core electrons have nontrivial structure; the core pair does not simply occupy a single spatial orbital. Our method of establishing the presence of separated electron pairs is direct and conclusive. We do not fit a separated pair model; we work with the wavefunctions of interest directly. To establish that a given group of spin-orbitals contains a quasi-separated pair, we verify by direct computation that the quantum state of the electrons that occupy those spin-orbitals is nearly a pure 2-electron state.

The constitutional isomers and tautomers of oxadiazolones, as well as their mono- and disulfur analogues, were calculated at the B3LYP/aug-cc-pVDZ level. Four groups of 30 molecules each were considered: oxadiazolone, oxadiazolthione, thiadiazolone, and thiadiazolthione isomers. The compounds were categorized into six groups according to permutations of three heteroatoms in the five-membered ring. Additionally, each of the constitutional isomer was considered to have five tautomers conserving stable five-membered ring: two NH tautomers, two rotameric OH (or SH) forms and one CH tautomer. It appeared that the largest difference between oxadiazolone O and S analogues is produced by the kind of chalcogen atom in the ring, which is strained when the O atom is in the ring while much less strained when the S-atom, of much larger van der Waals radius, is built into the ring. The external chalcogen is only modifying the general energetic factors. The comparison of energetics of analogous groups of molecules with thiadiazole and oxadiazole rings is done in details as well as differences resulting from different external chalcogen atoms are discussed as well. The presence of water surrounding was mimicked with the IEF-PCM implicit water model which did not change general isomer relative stability picture, but for some special cases indicated an extra stability of the forms with external OH or SH groups. The aromaticity monitored by the structural HOMA aromaticity index shows that the systems are not additionally stabilized by pi-electron delocalization. The fair linear correlation between the aromaticity indices of oxadiazolones and oxadiazolthiones shows that the pi-electron system in the studied systems is not sensitive to change of the external chalcogen group.

A variety of method and basis set combinations has been evaluated for monooxorhenium(V) complexes with N, O, P, S, Cl, and Se donor atoms. The geometries and energies obtained are compared to both high-level computations and literature structures. These calculations show that the PBE0 method outperforms the B3LYP method with respect to both structure and energetics. The combination of 6-31G** basis set on the nonmetal atoms and LANL2TZ effective core potential on the rhenium center gives reliable equilibrium structures with minimal computational resources for both model and literature compounds. Single-point energy calculations at the PBE0/LANL2TZ,6-311+G* level of theory are recommended for energetics.

The physical explanation for the hydrophobic effect has been the subject of disagreement. Physical organic chemists tend to use a explanation related to pressure, while many biochemists prefer an explanation that involves decreased entropy of the aqueous solvent. We present DFT calculations at the B3LYP/6-31G(d,p) and X3LYP/6-31G(d,p) levels on the solvation of three noble gases (Ne, Ar, and Kr) in clusters of 50 waters. Vibrational analyses show no substantial decreases in the vibrational entropies of the waters in any of the three clusters. The observed positive free energies of transfer from the gas phase or from nonpolar solvents to water appear to be due to the work needed to make a suitable hole in the aqueous solvent. We distinguish between hydrophobic solvations (explicitly studied here) and the hydrophobic effect that occurs when a solute (or transition state) can decrease its volume through conformational change (which is not possible for the noble gases).

Boronic acids (R-B(OH)) and their boroxine (RBO) dehydration products have emerged as important classes of compounds with a multitude of diverse applications. However, the available heats of formation for these compounds are not always as accurate as would be required for further use. In this study the heats of formation at 298.15 K of R-B(OH) and RBO (R = H, Li, HBe, HB, HC, HN, HO, F, and Cl) have been calculated at the G2, G3[G3B3], and G4 levels of theory and used to determine the enthalpy changes for the dehydration reactions: 3 R-B(OH) → RBO + 3 HO; comparisons are made with other rigorous levels of theory, CBS-Q[CBS-QB3] and W1U, as well as with experimental values wherever possible. Enthalpy changes for the dehydration reactions have also been calculated using second-order Møller-Plesset perturbation theory (MP2) with the Dunning-Woon correlation-consistent aug-cc-pVDZ and aug-cc-pVTZ basis sets, and B3LYP density functional theory with the 6-311++G(2,2) basis set. With the exception of HN-B(OH), the dehydration reactions are consistently predicted to be exothermic. Our results provide a cautionary note for the use of the B3LYP functional in the calculation of structures and energies of boronic acids and boroxines. Where comparisons could be made, the G4 and W1U predictions for the heats of formation of these boron compounds differ significantly.

Using density functional theory, we have studied the effects on structural and electronic consequences (including HOMO-LUMO energy gaps, vertical ionization potentials (IP), and vertical electron affinities (EA)) of the following two factors: (a) - and β-substituents acting as inductive donors (CH), inductive acceptors that are electron-donating through resonance (Br), inductive electron acceptors (CF), and resonance enabled acceptors (NO); and (b) of pyrrole nitrogens with P-atoms. The principal results of the study are: (1) For the bare Ni-porphyrin, the solvents were found not to affect the HOMO-LUMO gaps but to change the IP and EA noticeably. (2) In the series CH → Br → CF → NO the HOMO-LUMO energy gaps, IP, and EA increase for both - and β-substituents. The ruffling distortion of the porphyrin core is retained, and becomes stronger for the two acceptor groups. In general, effects of -substituents on the ruffling distortion of the porphyrin core is more pronounced. (3) Most significantly, complete replacement of pyrrole nitrogens in the NiP with phosphorus atoms produces the species, NiP(P), with the structural and electronic features drastically different from the original NiP. This implies that NiP(P) can possess interesting and unusual novel properties, including aromaticity and reactivity, leading to its various beneficial potential applications. Furthermore, NiP(P) high stability both in the gas phase and different solvents was shown, implying the feasibility of its synthesis.

Reaction and activation energy barriers are calculated for the H abstraction reactions (C(6)H(5)SH + X(•) → C(6)H(5)S + XH, X = H, OH and HO(2)) at the BB1K/GTLarge level of theory. The corresponding reactions with H(2)S and CH(3)SH are also investigated using the G3B3 and CBS-QB3 methods in order to demonstrate the accuracy of BB1K functional in finding activation barriers for hydrogen atom transfer reactions. Arrhenius parameters for the title reactions are fitted in the temperature range of 300 K-2000 K. The calculated reaction enthalpies are in good agreement with their corresponding experimental reaction enthalpies. It is found that H abstraction by OH radicals from the thiophenol molecule proceed in a much slower rate in reference to the analogous phenol molecule. [Formula: see text] of thiophenoxy radical is calculated to be 63.3 kcal/mol. Kinetic parameters presented herein should be useful in describing the decomposition rate of thiophenol; i.e., one of the major aromatic sulfur carriers, at high temperatures.