A molecular electron density theory study to understand the strain promoted [3+2] cycloaddition reaction of benzyl azide and cyclooctyne

62-71The strain promoted [3+2] cycloaddition reaction of benzyl azide with cyclooctyne has been studied within the molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. This reaction takes place through a one-step mechanism with activation free energy of 27.1 kcal mol-1 in gas phase and 30.2 kcal mol-1 in acetonitrile. The activation enthalpies are 13.8 and 16.5 kcal mol-1, respectively in gas phase and acetonitrile. Topological analysis of the electron localization function (ELF) of the reagents shows zwitter-ionic type character of this reaction. The calculated activation free energy is lowered by 5.0 kcal mol-1 in gas phase and 4.2 kcal mol-1 in acetonitrile relative to the analogues reaction with acetylene. The corresponding activation enthalpy is lowered by 6.4 kcal mol-1 in gas phase and 5.9 kcal mol-1 in acetonitrile. A comparative bonding evolution theory (BET) analysis of the two reactions reveals lower energy requirements for the depopulation of the alkyne framework and the formation of pseudoradical centers along the reaction path of the cyclooctyne reaction. Topological analysis of the ELF and the Quantum Theory of Atoms in Molecules (QTAIM) parameters reveal early transition states with no covalent bonding interactions between the reacting nuclei, which is consistent with the forming bond distances greater than 2 Å in each case

A molecular electron density theory study to understand the strain promoted[3+2] cycloaddition reaction of benzyl azide and cyclooctyne

The strain promoted [3+2] cycloaddition reaction of benzyl azide with cyclooctyne has been studied within the molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. This reaction takes place through a one-step mechanism with activation free energy of 27.1 kcal mol-1 in gas phase and 30.2 kcal mol-1 in acetonitrile. The activation enthalpies are 13.8 and 16.5 kcal mol-1, respectively in gas phase and acetonitrile. Topological analysis of the electron localization function (ELF) of the reagents shows zwitter-ionic type character of this reaction. The calculated activation free energy is lowered by 5.0 kcal mol-1 in gas phase and 4.2 kcal mol-1 in acetonitrile relative to the analogues reaction with acetylene. The corresponding activation enthalpy is lowered by 6.4 kcal mol-1 in gas phase and 5.9 kcal mol-1 in acetonitrile. A comparative bonding evolution theory (BET) analysis of the two reactions reveals lower energy requirements for the depopulation of the alkyne framework and the formation of pseudoradical centers along the reaction path of the cyclooctyne reaction. Topological analysis of the ELF and the Quantum Theory of Atoms in Molecules (QTAIM) parameters reveal early transition states with no covalent bonding interactions between the reacting nuclei, which is consistent with the forming bond distances greater than 2 Å in each case

Unveiling the reactions of triethylphosphite and its diethylamino substituted derivatives to carbon tetrachloride with a molecular electron density theory perspective

127-135A molecular electron density theory study is presented herein for the reactions of triethylphosphite (TEP) and its diethylamino substituted derivatives (DEAP and MEAP) to carbon tetrachloride (CCl4). Analysis of the Electron localization function (ELF) has allowed characterizing the electronic structure of the reagents and the conceptual density functional theory (CDFT) study predicted the polar character of the reactions with the electronic flux from TEP, DEAP and MEAP to CCl4. Analysis of the relative energies along the potential energy surfaces has indicated energetically favoured attack on the chlorine atom of CCl4 relative to that on the carbon atom and the reactions became energetically more facile due to introduction of the electron donating diethylamino substituent. This allowed formulating the heterolytic mechanism of the reactions in which the quick exchange of CCl3- with the chlorine atom takes place for TEP, while the exchange is sloweddown in DEAP and MEAP due to mesomeric stabilization of the phosphonium ion. The ELF and Atoms in molecules (AIM) studies indicated early transition states (TSs) with no new covalent bond formation, and the non-covalent interactions at the interatomic bonding regions of the TSs are analysed from the Independent Gradient Model (IGM) analysis based on the Hirshfield partition of electron density

Insights into solvation effects, spectroscopic, Hirshfeld surface Analysis, reactivity analysis and anti-Covid-19 ability of doxylamine succinate: Experimental, DFT, MD and docking simulations

In the present work, the experimental and theoretical reports on electronic and vibrational features of doxylamine succinate (DXS) are presented. The vibrational spectra were documented and wavenumbers were obtained theoretically assigned by means of potential energy distribution. In DXS, N-H…O and C-H…O intermolecular hydrogen bonding contacts are associated with O…H/H…O interactions. Solvation free energy (SFE) for DXS in water, methanol and DMSO, are −10.67, −10.95 and −10.61 eV/mol respectively. Interpretation of electrostatic potential, electron localization function (ELF), localized orbital locator (LOL) as well as atoms-in-molecules (AIM) analysis is also performed. Presence of non-covalent interactions is evident from the non-covalent interaction (NCI) isosurface. Molecular docking and simulations were used to determine the binding energy of DXS in order to investigate its potential activity against the SARS-CoV-2 protease

Understanding the geometry and [3+2] cycloadditions of nitrile imine in terms of molecular electron density theory

645-652Nitrile imine has been classified as carbenoid type three atom component (TAC) by coupled cluster single doubles plus perturbative triples (CCSD(T)) calculations. [3+2] cycloaddition (32CA) reactions of nitrile imine with a set of olefins has been studied in this report in terms of Global electron density transfer (GEDT), Bonding evolution theory (BET) and Quantum theory of atoms in molecules (QTAIM) analyses at B3LYP and MPW1K levels. The reactions have been non-polar showing non-covalent interactions and hence GEDT doesn't make the reaction feasible by inducing significant electrophilic-nucleophilic interaction between reactants as occurs in case of polar processes. Mutual penetration of forming bonds to the Van-der Waals' surface has been reproduced in asymmetry indices at the transition states. BET and QTAIM study confirmed initial rupture of olefinic bond, followed by the formation of pseudoradical centres and subsequently the bond-formation processes

Understanding the geometry and [3 + 2] cycloadditions of nitrile imine in terms of molecular electron density theory

Nitrile imine has been classified as carbenoid type three atom component (TAC) by CCSD(T) calculations. [3+2] cycloaddition (32CA) reactions of nitrile imine to a set of olefins is studied in this report in terms of global electron density transfer (GEDT), Bonding evolution theory (BET) and Quantum theory of atoms in molecules (QTAIM) analyses at B3LYP and MPWB1K levels. The reactions are non-polar showing non-covalent interactions and hence GEDT doesn't make the reaction feasible by inducing significant electrophilic-nucleophilic interaction between reactants as occurs in case of polar processes. Mutual penetration of forming bonds to the Van-der Waals' surface was reproduced in asymmetry indices at the transition states. BET and QTAIM study confirmed initial rupture of olefinic bond, followed by the formation of pseudoradical centres and subsequently the bond-formation processes

DFT study for radical capture by mitochondria oxidotoxin protective ionic and non-ionic amphiphilic α-phenyl-N-<i>t</i>-butyl nitrone derivatives

9-20DFT analysis for radical capture by a series of biologically active amphiphilic α-phenyl-N-t-butyl nitrone derivatives has been reported in the present study. A detailed analysis of global and local reactivity descriptors has been presented from both natural and electrostatic based charges. Reactivities of the investigated nitrones for radical capture have been compared by interaction energy calculations derived from a perturbative orbital independent theoretical model. The transition states for radical attacks have been located and the activation barriers for radical capture are calculated. The cis attack is found to be energetically favored in each case. Finally, the hyperfine splitting constants have been computed and compared with the reported experimental findings

1,3-dipolar cycloadditions. Part XX. DFT study of the configuration and conformation of C-aryl-N-phenyl nitrones and their reactivities as 1,3-dipoles to methyl and ethyl crotonates

1444-1452The preferred configurations and conformations of C-aryl-N-phenyl nitrones have been predicted theoretically by detailed comparison of DFT/B3LYP/6-311+G(2d,p) calculated gauge invariant atomic orbital nuclear magnetic shielding tensors and experimentally recorded chemical shift values. The frontier molecular orbital energies, electronic chemical potentials, chemical hardness, chemical softness and global electrophilicity indices of C-aryl-N-phenyl nitrones have been calculated at DFT/B3LYP/ 6-31+G(d,p) level of theory. Condensed Fukui functions and local electrophilicity indices have been computed to characterize the reactive sites and predict the preferred interactions of C-aryl-N-phenyl nitrones to methyl and ethyl crotonates. The softness matching indices have been evaluated to determine the regioselectivity of the cycloaddition reactions. The theoretical predictions were found to be in complete agreement with the experimental results implying that the DFT based reactivity indices correctly predict the regioselectivities of 1,3-dipolar cycloadditions of C-aryl-N-phenyl nitrones to methyl and ethyl crotonates

1,3-Dipolar cycloadditions. Part XXI: Catalytic effects of Lewis acids on 1,3-dipolar cycloaddition of <i style="">C</i>-(4-chlorophenyl)-<i style="">N</i>-phenyl nitrone to benzylidene acetophenone

835-842The normal electron demand reaction of C-chlorophenyl-N-phenyl nitrone with benzylidene acetophenone and the effects of mild Lewis acid catalysts like metal triflates and magnesium bromide on the reaction rate are reported. Frontier molecular orbital energies are calculated to rationalise the regioselectivity of the cycloaddition