Search

The regioselective synthesis of a potent antiviral sugar nucleoside isoxazole analogue in the [3+2] cycloaddition (32CA) reaction of acetonitrile- -N-oxide (ANO) and acetyl-protected 5-ethynyl-2’-deoxyuridine (EDU) has been studied at the MPWB1K/6-311G(d,p) level within perspective of the molecular electron density theory (MEDT). From an electron localization function (ELF) analysis, ANO is classified as a zwitterionic species devoid of any pseudoradical or carbenoid centre. The ortho regioisomer is energetically preferred over the meta one by the activation enthalpy of 21.7–24.3 kJ mol-1, suggesting complete regioselectivity in agreement with the experiment. The activation enthalpy increases from 53.9 kJ mol-1 in the gas phase to 71.5 kJ mol-1 in water, suggesting more facile reaction in low polar solvents. The minimal global electron density transfer (GEDT) at the TSs suggests non-polar character and the formation of new covalent bonds has not been started at the located TSs, showing non-covalent intermolecular interactions from an atoms-in- -molecules (AIM) study and in the independent gradient model (IGM) isosurfaces. The AIM analysis shows more accumulation of electron density at the C–C interacting region relative to the C–O one, and earlier C–C bond formation is predicted from a bonding evolution theory (BET) study.

[3+2] cycloaddition reaction of C-(pyridin-3-yl)-N-phenylnitrone and 2-propen-1-ol yields stereochemically defined potent antinociceptive isoxazolidine derivative. Computational quantum calculations (CQC) are performed for this synthesis to predict the polar character, mechanism and selectivity within the framework of molecular electron density theory (MEDT). Topological analysis of the electron localization function (ELF) classifies the nitrone as a zwitter-ionic(zw-) type three atom component (TAC) showing absence of any pseudoradical or carbenoid centre. Four reaction channels corresponding to the possible regio- and stereoselective pathways are studied at DFT/ /B3LYP/6-311G(d,p) level of theory. The reaction follows one-step mechanism with asynchronous transition states and the computed activation energies agree well with experimental data. The reaction can be differentiated into nine ELF topological phases, with faster C–C bond formation. Global electron density theory (GEDT) at the favoured transition state and conceptual density functional theory (CDFT) indices at the ground state of the reagents indicate non-polar character. Non-covalent interactions are predicted by atoms-in-molecules (AIM) analysis and non-covalent interaction (NCI) plots at the transition states.

Using first principles, the electrical response of carbon nanocones (NC) to the drug benzamide (BZE) was investigated using density functional theory (DFT). The adsorption energies of BZE at the nanocone's bottom (Complex I), side (Complex II), and top (Complex III) are −88.35 kcal/mol, −45.46 kcal/mol and −48.73 kcal/mol. The two other adsorptions, Complexes II and III are physisorption, however, the high value of Eads in the case of Complex I with the drop in bond lengths suggests that Complex I adsorption is chemisorption. The electrical conductivity has risen as a result of the considerable decrease in the nanocone energy gap (from 0.63 eV to 0.61 eV, 0.61 eV and 0.60 eV) caused by the adsorption of BZE. It suggests that the nanocones would be a good fit for the electronic sensors and an appropriate choice for BZE detection. Additionally, the BZE adsorption influences the nanocone's workfunction, which is reduced by approximately 45.19%, 2.8% and 2.05% for complexes I to III. This suggests that the nanocone could be a workfunction-based sensor for the detection of BZE. The increase in binding affinity in complexes reveals that the nanocones will act as a drug delivery carrier. Theoretically, anticipated Raman spectra of BZE and complexes show SERS activity and inactive normal Raman modes are active in the Raman spectrum of complexes. Compounds II and III exhibit weak noncovalent interactions (NCI) and due to the presence of covalent bonding interaction in compound I, significant changes in other bonding and nonbonding electron densities are observed compared to compounds II and III. Adsorption of benzamide on a carbon nanocone Benzamide gives maximum adsorption energy when it is at the bottom of the nanocone Increase in binding affinity in complexes reveals that the nanocones will act as a drug delivery carrier [ABSTRACT FROM AUTHOR]

The study of interaction and adsorption of drug molecules on the active surface of noble metal nanocluster is of particular interest due to effective change in the properties of the drug molecules. Surface-enhanced Raman scattering (SERS) theoretical calculations were performed to investigate the adsorption properties of pretomanid (PTD) on pyramidal Ag 2 0 / Au 2 0 / Cu 2 0 metal clusters. The charge transfer process from the M 2 0 pyramids is revealed by MEP and electronic analysis. The frequencies of PTD are enhanced in the PTD–metal complexes due to the noticeable SERS effect, and the binding energies were calculated to be −36.2 kcal/mol, −46.3 kcal/mol and −43.6 kcal/mol with Ag, Au and Cu structures, respectively. For the PTD–metal clusters, there is an entire potential rearrangement due to adsorption process which is due to charge transfer and adsorptions as chemisorption. The polarizability variations are predicted in the order PTD–Au > PTD–Cu > PTD–Ag which contribute the SERS enhancement due to adsorption. Changes in thermodynamic parameters reveal that adsorption is exothermic and at the same time spontaneous with ordered interactions due to the negative values. There is a redshift for the ultraviolet–visible (UV–vis) absorption of PTD–metal complexes with a lowering intensity in comparison with that of PTD, more likely indicating a chemisorption process. SERS enhancement factors are remarkable due to adsorption of conformationally flexible PTD on metal clusters. The noncovalent interactions between PTD and the metal pyramids were also determined. The study provided key information on designing a molecular structure with a good pharmacological profile by calculating bioactivity and drug similarity parameters for bioactive drug molecules. Adsorption of pretomanid on pyramidal metal clusters Chemisorption due to charge transfer interaction between metal clusters and pretomanid Cluster would be a wise choice for creating sensors for detectors of drugs [ABSTRACT FROM AUTHOR]

Important biological compounds, namely, methyl 3-amino-4-(4-bromophenyl)thiophene-2-carboxylate (BPTC) and methyl 3-amino-4-(4-chlorophenyl)thiophene-2-carboxylate (CPTC), were characterized using complementary techniques of Fourier transform infrared (FT-IR), Raman spectroscopy. Nuclear magnetic resonance spectroscopy (NMR) confirmed the structural features, while Ultra Violet–Visible Spectroscopy was used to investigate the electronic properties of both compounds. The quantum chemical calculations for both compounds were performed using the DFT/B3LYP functional with the 6-311++G(d,p) basis set. This study computes electrostatic potential observation, electron localization function (ELF) assessment, and atoms-in-molecules (AIM) analysis. In the present investigation, the global hardness, chemical softness, electrophilicity, nucleophilicity indices, and dipole moment of both compounds were calculated. In addition, a molecular docking analysis was conducted to determine the binding potential of target molecules with protein tyrosine phosphatase. A 200-ns molecular dynamics (MDs) simulation had been performed to assess the compound's binding stability. [ABSTRACT FROM AUTHOR]

The influence of ethylene substitution and the tether length between the two reacting counterparts on the selectivity and reactivity of the intramolecular [3 + 2] cycloaddition (IM32CA) reactions of cyclic nitrones leading to tricyclic isoxazolidines have been studied within the Molecular Electron Density theory at the MPWB1K/6‐311G(d,p) computational level. These zw‐type IM32CA reactions follow one‐step mechanism, and the activation barrier decreases with the introduction of electron withdrawing (EW) substituent at the alkene moiety in both the intramolecular and intermolecular versions. The IM32CA reactions involving unsubstituted alkene have non‐polar character with minimal electron density flux classified as null electron density flux type, while that involving the EW nitro substituted ethylene is more facile with a strong electron density flux from the nitrone to the ethylene moiety, classified as forward electron density flux type. The increase in the polar character of the IM32CA reaction decreases the activation Gibbs free energies associated with these intramolecular processes, while the highly polar IM32CA reactions are disfavored with respect to the intermolecular ones. Interestingly, the preferred regioselectivity observed in low polar IM32CA reactions having three methylene units between the nitrone and ethylene frameworks is reversed to that in nitrones separated with four methylene units, in conformity with the experimental outcome. Finally, electron localization function and quantum theory of atoms‐in‐molecules studies reveal that, in general, these IM32CA reactions involve early transition state structures in which the formation of new C‐C and C‐O single bonds have not yet started. [ABSTRACT FROM AUTHOR]