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The intramolecular [3 + 2] cycloaddition (IM32CA) reactions of azides and diazoalkanes leading to fused tricyclic 1,2,3-triazolines and 1-pyrazolines have been studied at the MPWB1K/6-311G(d,p) computational level within the molecular electron density theory (MEDT). The IM32CA reactions of azides are classified as zw- type following non-concerted one-step mechanism with earlier N1-C5 bond formation implied from the bonding evolution theory (BET) study with the Gibbs free activation energies between 26.3–30.0 kcal mol−1 at 298 K in benzene while that of the diazoalkanes are classified as pmr- type with the earlier C3-C5 bond formation and Gibbs free activation energies between 24.7–29.1 kcal mol−1 at 298 K in n-pentane. The influence of substituent effects on these IM32CA reactions is studied. Azide reactions with minimal global electron density transfer (GEDT) are classified as the null electron density flux (NEDF) while that of the diazoalkanes are classified as forward electron density flux (FEDF). QTAIM analysis and ELF study allow revealing the non-covalent interactions at the TSs. [ABSTRACT FROM AUTHOR]

This study introduces the novel Tryptanthrin-malononitrile Knoevenagel adduct (2CTMA) compound as a potential means to enhance the energy efficiency of building window panes, accompanied by a design approach involving the incorporation of a 2CTMA layer between glass plates. The design allows infrared (IR) radiation to pass through while maintaining visible light transmission. The 2CTMA demonstrates strong UV absorption while only absorbing 60% of visible light to that in the UV region, with minimal IR absorption, as confirmed through DFT analysis. Scanning electron microscopic (SEM) and atomic force microscopic (AFM) imaging reveal a uniform film morphology characterised by elongated rod-like structures. X-ray diffraction pattern affirms crystallinity, consistent with SEM observations, while FTIR and Raman spectroscopy confirm the structural integrity and chemical composition of 2CTMA. Remarkably, thermal analysis demonstrates exceptional thermal stability. The proposed design aligns with the United Nations Sustainable Development Goals, offering promising prospects for reducing energy consumption, curbing carbon emissions, and contributing to global warming mitigation and sustainable development. [ABSTRACT FROM AUTHOR]

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]

Context: The controlled slow evaporation process conducted at room temperature has produced a novel hybrid material denoted as (2-hydroxyethyl) trimethylammonium dihydrogen phosphate [2-HDETDHP] (C5H14NO+, H2PO4−), synthesized through the solution growth method. X-ray crystallography analysis reveals a triclinic structure with a filling rate of P and a Z value of 2. This hybrid material displays noteworthy absorption characteristics in the middle and far ultraviolet regions. UV-visible spectroscopy further establishes its transparency in the visible and near-visible ultraviolet domains. FT-IR spectroscopy examines various vibration modes, elucidating their relationships with the functional groups within the structure. Two- and three-dimensional fingerprint maps, coupled with three-dimensional crystal structures through Hirshfeld Surface Analysis, unveil the dominance of O•••H and H•••H interactions in the structure, comprising 49.40% and 50.40%, respectively. Fingerprint plots derived from the Hirshfeld surface assess the percentages of hydrogen bonding interactions, with 80.6% attributed to a fragment patch. The experiment of antimicrobial efficacy of a synthesized product, conducted in triplicate, demonstrated the synthesized product's potential antimicrobial activity. Methods: Hirshfeld surfaces are employed to investigate intermolecular hydrogen bonding, specifically within single phosphate groups. The molecular structure of 2-HDETDHP was refined using single-crystal X-ray analysis, while its optical characteristics were examined through UV-visible spectroscopy. FT-IR spectroscopy is employed for the assignment of molecular vibrations of functional groups in the affined structure. Quantum calculations were executed with the GAUSSIAN 09 software package at B3LYP/6-311G level of theory, to optimize the molecular geometries. The antimicrobial efficacy of a synthesized product was evaluated using the disc diffusion method against antibiotic-resistant Candida albicans, Candida tropicalis, Aspergillus niger, Staphylococcus aureus, and Escherichia coli. Microorganisms were cultured on nutrient agar, and inhibition zones were measured after incubation, with streptomycin and amphotericin as positive controls. [ABSTRACT FROM AUTHOR]

The [3 + 2] cycloaddition (32CA) reactions of a series of pyridinium bis(methoxycarbonyl)methylides (PMYs) and pyridinium dicyanomethylides (PCYs) with cyclooctyne to generate indolizines have been studied within the Molecular Electron Density Theory (MEDT). Interestingly, the electronic structure of these azomethine ylides (AYs) revealed from the topological analysis of the electron localization function (ELF) differs considerably from that of the simplest AY and accordingly, the molecular reactivity is changed. Consequently, the corresponding 32CA reactions of PCYs and PMYs require refluxing toluene conditions to overcome the high activation barrier contrary to the unappreciable energy cost demanded by the simplest AY. This is explained by the analysis of conceptual DFT indices characterizing the ambiphilic character of the PMYs and PCYs classified as strong electrophiles and strong nucleophiles within the standard reactivity scales. The 32CA reactions of PCYs are more facile relative to the PMYs in agreement with the experimental outcome. These polar 32CA reactions show the global electron density transfer (GEDT) higher than 0.2 e and proceed through one-step mechanism with highly asynchronous TSs in which the new covalent bond formation has not been started. Herein, we report the first MEDT study to comprehend the reactivity of pyridinium methylides towards 32CA reactions leading to indolizines. [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]

The intramolecular [3 + 2] cycloaddition (32CA) reactions of allenic nitrones have been studied within the molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. These zwitter-ionic type 32CA reactions show high activation free energies between 22.2 and 34.9 kcal mol−1 in ethanol consistent with their predicted non-polar character and follow one-step mechanism with highly asynchronous transition states. Interestingly, when the nitrone and the allene moieties are separated by two methylene units, the [3 + 2] addition is energetically feasible along the C5-C6 terminal double bond of the allene, while the presence of four methylene units change the cyclization selectivity towards the internal C4-C5 double bond of the allene. This is in complete agreement with the experimental outcomes. The molecular mechanism study in terms of bonding evolution theory (BET) shows varied electron density changes along these two reaction paths. Finally, the topological analysis of AIM (atoms-in-molecules) reveals the presence of non-covalent interactions at the interatomic bonding regions of the transition states, which agrees well with the electron localization function analysis and the forming C–C and C-O bond distances. [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]

The [3+2] cycloaddition (32CA) reaction between cyclic azomethine ylide (generated from N-phenacylquinolinium bromide) and N-arylmaleimide, leading to pyrrolo[1,2-a]quinolone, has been investigated using the Molecular Electron Density Theory at the B3LYP/6-311++G(d,p) computational level with D3 correction. This study focuses on the zwitter-ionic type 32CA reaction, highlighting its polar character with the electronic flux from the azomethine ylide to the alkene. The reaction proceeds with complete endo-stereoselectivity, and the activation parameters show minimal variations in different solvents, consistent with experimental observations. The activation energy is associated with the depopulation of the N2–C1 and C4–C5 bonding regions, formation of non-bonding electron density at N2 nitrogen and creation of pseudoradical centers at C3, C4 and C5. These findings suggest that the formation of new covalent bonds does not occur at the transition states, in line with the presence of non-covalent interactions at the interatomic bonding regions, as revealed by the topological analysis of the Quantum Theory of Atoms-in-Molecules. [ABSTRACT FROM AUTHOR]

The [3 + 2] cycloaddition (32CA) reactions of N-methyl-C-(2-furyl) nitrone with maleimide derivatives have been studied in gas phase, ethanol and acetonitrile within the Molecular Electron Density Theory (MEDT) framework at the B3LYP-D3/6-31G(d) level. Topological analysis allows classifying the nitrone as a zwitterionic (zw-) three-atom component (TAC) associated with high energy barrier. Interestingly, the global electron density transfer (GEDT) between 0.10 and 0.13 e predicts low polar character of forward electron density transfer (FEDF) type with the electronic flux from the nitrone to the maleimides, resulting in decreased activation parameters relative to that of the nitrone cycloadditions with simple alkenes. These 32CA reactions follow a one-step mechanism under kinetic control with highly asynchronous bond formation, and no new covalent bonds are formed at the TSs. The predicted exo-selectivity agrees well with the experimental findings. Inclusion of solvent effects increases the activation energy, in particular along the endo pathway. The activation enthalpies are between 5.58 and 7.68 kcal/mol in gas phase and between 6.61 and 11.10 kcal/mol in ethanol and acetonitrile. Also, the influence of temperature was investigated at 289.15 K, 298.15 K and 393.15 K. Non-covalent interactions (NCIs) were identified at the interactions regions of the TSs from the topological analysis of the AIM (atoms-in-molecules) and characterized using Independent Gradient Model (IGM) analysis. [ABSTRACT FROM AUTHOR]

The [3+2] cycloaddition reactions of formonitrile oxide and benzonitrile oxide with a tricyclic strained alkene bearing norbornene and cyclohexene double bonds have been studied from the molecular electron density theory perspective at the MPWB1K/6-311G(d,p) computational level. Electron localization function shows the absence of pseudoradical and carbenoid centers, classifying formonitrile and benzonitrile oxides as zwitterionic three-atom components, consistent with the high activation free energies of 26.0 and 28.5 kcal·mol–1, respectively, in their cycloaddition reaction with the strained alkene in CH2Cl2. These reactions follow a one-step mechanism under kinetic control and present total site selectivity, as the addition of formonitrile and benzonitrile oxides to the norbornene double bond is energetically preferred by 4.9 and 8.0 kcal·mol–1, respectively, over the cyclohexene double bond in agreement with the experiments, and complete exo-stereoselective control is predicted. The minimal global electron density transfer predicts nonpolar character, while the electron localization function topological analysis implies that the activation energy is related only to the formation of non-bonding electron density at N2 nitrogen and pseudoradical center at C3 atom of the nitrile oxides. The total electron densities less than 0.1 e and positive Laplacian of electron density at the forming C–C and C–O bond critical points of the early transition states indicate noncovalent interactions which were characterized by visualization of the AIM-RDG isosurfaces. [ABSTRACT FROM AUTHOR]

The importance of impurity-related detection and certification in drug manufacture is highlighted in this study, which presents theoretical structural and spectral properties of clomipramine (CPA) and methotrimeprazine HCl (MPH) as well as their adsorption on graphene and fullerene. Investigating adsorption may reveal details about their reactivity, electronic and structural properties. The molecule's frontier molecular orbitals (FMOs) energies and energy gaps were calculated. Three-dimensional visualization of the electrostatic potential diagrams was mapped. Docking was used to find the binding with the receptors. Enhancement for different wave numbers is seen in the graphene/fullerene complex-molecules assembly. Non-covalent interactions (NCI) can be characterized using topological analysis and the respective isosurfaces. In the CPA-graphene cluster, the graphene system shows strong repulsive non-covalent interactions (red portions). Two small green portions of the isosurface between CPA and graphene frameworks indicate weak non-covalent interactions. [ABSTRACT FROM AUTHOR]

The Grignard reagent promoted [3+2] cycloaddition (32CA) reaction of mesitonitrile oxide (MNO) with Baylis–Hilman adduct (BHA) has been studied within the Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311G(d,p) computational level. Topological analysis of the Electron Localization Function (ELF) allows classifying MNO as a zwitterionic three-atom-component (TAC), participating in zw-type 32CA reactions. In spite of the strong nucleophilic character of MNO, the low electrophilic character of BHA and the BHA:Mg(II) complex make the corresponding 32CA reactions to have a very low polar character, respectively. The reaction presents total ortho regioselectivity to afford 2-isoxazolines, while the diastereoselectivity is reversed in the Mg(II)-promoted 32CA reaction relative to that in the absence of the Mg(II) cation, in complete agreement with the experiments. The preferred transition state structure (TS) associated with the Mg(II)-promoted process shows complexation of the magnesium atom with the oxygens of MNO and BHA (hydroxyl oxygen), with the corresponding critical points (CPs) showing non-covalent interactions (NCIs) in the AIM-RDG isosurfaces. This MEDT study provides a complete comprehension of the role of the Grignard reagent in the zw-type 32CA reactions of nitrile oxides with Baylis–Hilman adduct; although formation of the BHA:Mg(II) complex slightly accelerates the 32CA reaction to decrease the activation Gibbs free energy by 3.1 kcal mol−1, the more remarkable role of the Mg(II) cation is the change of the diastereoselectivity of these 32CA reactions involving a chiral ethylene. [ABSTRACT FROM AUTHOR]

Using metal substrates that are nanoscale in size, surface-enhanced Raman scattering (SERS) is a technique for enhancing the Raman signal of biomolecules. Numerous industries including sensing materials, adsorption and medical devices, use nanomaterials like nanocages and nanoclusters. To discover a possible novel sensor platform involving a small metal cluster and a curved rigid substrate, we used density functional theoretical (DFT) simulations to explore the adsorption of glycoluril (GLC), a prospective drug intermediate, on a pure magnesium oxide cage (Mg12O12). This well defined cage was used as (i) an exact probable structure that could be used as well as (ii) a general model for MgO nanostructures. We also investigated the mono Al-doped Mg12O12 nanocage version Mg11AlO12. All computations were performed at the M06-2X level of theory. The GLC binds to the Mg12O12 nanocage by way of strong donor–acceptor interactions. The adsorption is releasing − 45.80 kcal mol−1 of energy. Due to Al doping, the energy gap of GLC-Mg11AlO12 (1.91 eV) is reduced from that of GLC-Mg12O12 (4.28 eV) and hence there is an increase in electrical conductivity of GLC-Mg11AlO12. The electronic change in the nanocage's conductivity can be transformed into an electrical signal which can be used to detect the presence of the drug analyte. In addition, when a GLC molecule is present, the work function of the nanocage is also reduced. The MgO nanocage, we conclude, is a work function type as well as a possible electronic sensor for GLC drug detection. GLC desorption from the Mg11AlO12 surface recovers more quickly in comparison with Mg12O12 recovery time. The AIM and NCIs assessed in this study were performed to help analyze the electronic structures of the complexes. Our findings pave the possibility for Mg11AlO12 nanostructures to be used in drug recognition. [ABSTRACT FROM AUTHOR]

The carbenoid‐type (cb‐type) intramolecular [3+2] cycloaddition (IM32CA) reactions of four fluorinated azomethine ylides (AYs) bearing an ester carbonyl substituent have been studied from the molecular electron density theory (MEDT) perspective. The presence of two fluorine atoms in these species changes the pseudodiradical structure of the simplest AY to that of a carbenoid one, according to the cb‐type molecular reactivity of these IM32CA reactions. These IM32CA reactions present low activation energies, lesser than 3.0 kcal ⋅ mol−1, and a strongly exothermic character, more than −34.0 kcal ⋅ mol−1, showing a complete chemo‐ and regioselectivity. The presence of the electron‐withdrawing −CN group at the aryl ester framework increases the global electron density transfer (GEDT) at the transition state structure (TS), which fluxes from the nucleophilic AY moiety to the electrophilic carbonyl ester, diminishing the activation energy by 2 kcal ⋅ mol−1 relative to that of the phenyl substituent. Electron Localization Function and Atom‐in‐Molecules topological analyses of the most favorable TSs show the early character of these cb‐type IM32CA reactions. The present MEDT study makes it possible to establish that the carbenoid structure of these fluorinated AYs together with their supernucleophilic character are responsible for the high reactivity and selectivities shown by these three‐atom‐components participating in cb‐type 32CA reactions towards carbonyl compounds. [ABSTRACT FROM AUTHOR]

The zwitterionic (zw-) type intramolecular [3 + 2] cycloaddition (IM32CA) reactions of C,N-disubstituted nitrones bearing acyclic and cyclic alkene functionalities have been studied from the molecular electron density theory (MEDT) perspective. The nitrones under study were classified as zwitterionic species from the topological analysis of the electron localization function (ELF). These IM32CA reactions show non-polar character and follow a non-concerted one step mechanism with activation free energies of 22.8--35.2 kcal mol-1 in toluene. When the N-butenyl system is attached to the nitrogen atom of the nitrone, the IM32CA reaction presents total regioselectivity with the terminal alkene carbon involved in C--C bond formation in complete agreement with the experimental findings. Interestingly, the activation free energy shows a sharp increase of 6.1 kcal mol-1 on dimethyl substitution of the terminal carbon owing to the considerable increase in the non-covalent strongly repulsive interaction revealed by the reduced density gradient scatter map of the NCI plot. This agrees well with the experiments showing no reaction of the corresponding nitrone. For the nitrones with a cyclic alkene functionality, the activation energies are decreased by 5.1--6.2 kcal mol-1 compared to the acyclic one, due to the relatively lower energy cost demanded for the similar bonding changes along the reaction path. [ABSTRACT FROM AUTHOR]

The intramolecular [3+2] cycloaddition (32CA) reactions of azido alkynes leading to spirocyclic, tricyclic, and bicyclic triazolooxazines has been studied within the molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) level. The electron localization function (ELF) characterizes the azido alkynes as zwitterionic species. Analysis of the conceptual DFT indices allows classifying the azide moiety as the electrophilic counterpart and the alkyne as the nucleophilic one. These 32CA reactions are under kinetic control with the activation free energies of 23.4–26.7 kcal mol−1. Along the reaction path, the pseudoradical centre is created initially at C4, consistent with the Parr function analysis; however, the sequence of bond formation is controlled by the energetically feasible formation of the six-membered oxazine ring. The intermolecular interactions at the transition states were characterized from the quantum theory of atoms in molecules (QTAIM) study and the non-covalent interaction (NCI) gradient isosurfaces. [ABSTRACT FROM AUTHOR]

The BF3 Lewis acid (LA) catalyzed [3+2] cycloaddition (32CA) reaction of 1‐pyrroline‐1‐oxide (PNO) with 2,3‐dihydrofuran (DHF) has been studied within the molecular electron density theory (MEDT) at the ωB97X‐D/6‐311G(d,p) computational level. Electron localization function (ELF) characterizes PNO and the corresponding PNO : BF3 complex as zwitterionic species. Conceptual DFT indices allow classifying PNO and DHF as marginal electrophiles and strong nucleophiles, while the PNO : BF3 complex is a strong electrophile. Consequently, while the non‐catalyzed 32CA reaction is non‐polar, the BF3 catalyzed one has a high polar character, revealed by the analysis of the global electron density transfer (GEDT) at the transition state structures. The BF3 catalyzed 32CA reaction, which is classified as of reverse electron density flux (REDF), presents high exo stereoselectivity, and total ortho regioselectivity. The presence of the BF3 catalyst decreases the activation enthalpy of the 32CA reaction in dichloromethane by 7.5 kcal mol−1, as a consequence of the increase of the polar character of the reaction, in complete agreement with the experimentally observed acceleration. [ABSTRACT FROM AUTHOR]

A combined experimental and theoretical study is presented to predict and analyze the inhibition efficiency and adsorption mechanism of 4-aminobenzoic acid molecule for copper corrosion in molar nitric acid. Experimentally, the investigation has been performed through polarization curves, electrochemical impedance spectroscopy (EIS), scanning electron microscopy, energy-dispersive X-ray spectrometry, and atomic force microscopy studies. Theoretically, the inhibition effect of 4-aminobenzoic acid on copper corrosion is evaluated from the DFT/B3LYP/6-311+G(d,p) calculated frontier molecular orbital (FMO) energies, global and local reactivity descriptors defined within the conceptual density functional theory (CDFT), electrostatic potential (ESP) mapping, and conformational analysis while the mechanism of adsorption onto the copper surface is studied from DFT-based molecular dynamics simulation. We obtained a good correlation between theoretical energy gap and the experimental corrosion inhibition efficiency for copper by amino acids. The experimental and theoretical findings show good agreement in both gas phase and water, establishing 4-aminobenzoic acid as a potent inhibitor of copper corrosion under acidic conditions. [ABSTRACT FROM AUTHOR]

The [3+2] cycloaddition (32CA) reactions of norbornadiene with aryl and alkyl substituted diazomethylphosphonates (SDAPs) have been studied within the molecular electron density theory (MEDT). Electron localization function (ELF) shows the presence of a pseudoradical C3 center at the alkyl SDAPs, classifying them as pseudo(mono)radical species, while the aryl SDAP is classified as a zwitterionic one, owing to the delocalization of the C3 electron density on the C3‐P bond. These 32CA reactions present high activation enthalpies in dichloromethane, between 17.3 and 21.6 kcal mol−1, being strongly exothermic by more than 33.8 kcal mol−1. While these 32CA reactions present a total syn facial selectivity, the endo/exo stereoselectivity depends on the steric hindrance caused by the bulk substituents present in these SDAPs along the approach to norbornadiene. Interestingly the phenyl group provokes a lesser hindrance than that of the small methyl group, justifying the 95 % of exo stereoselectivity experimentally observed. ELF and the AIM (Atoms‐in‐Molecules) analyses account for the bonding changes along these 32CA reactions. The energy cost for the rupture of the norbornadiene C−C and that of the SDAPs N−N double bonds are the major contributors to the activation energies of these non‐polar 32CA reactions. [ABSTRACT FROM AUTHOR]

A molecular electron density theory (MEDT) study is performed for the [3 + 2] cycloaddition (32CA) reactions of benzonitrile oxide (BNO) and diphenyldiazomethane (DPDM) to cyclopentene (CP) and norbornene (NBN) with the objective to analyse the experimentally observed acceleration in NBN reactions relative to the CP ones. The activation enthalpy of the 32CA reaction of NBN with BNO is lowered than that of CP by 2.1–2.9 kcal mol−1 in gas phase, DMSO, acetonitrile and THF, while the corresponding differences are 1.3–1.8 kcal mol−1 with DPDM. The 32CA reactions of DPDM show lower activation parameters compared to that of BNO consistent with the respective pseudo(mono)radical and zwitterionic type characters of DPDM and BNO. The syn diastereofacial approach of NBN is energetically feasible compared to the anti one. The global electron density transfer (GEDT) is identified to anticipate the minimal electron density flux at the TS entity, which is otherwise not accounted by the global electrophilicities of the separated regents. This MEDT study allows comprehending that for these non-polar reactions, the acceleration in NBN cycloadditions compared to the CP ones is due to the relatively lower energy cost demanded for the depopulation and subsequent rupture of C–C double bond of NBN followed by sequential bonding changes along the reaction paths, rather than the "predistorted geometry towards the TSs" as previously proposed in the 32CA reactions of norbornene derivatives. [ABSTRACT FROM AUTHOR]

A molecular electron density theory (MEDT) study for the [3 + 2] cycloaddition (32CA) reaction of indoledione and N‐methyl glycine with (E)‐1‐bromonitrostyrene leading to the spirooxindole‐pyrrolidine adduct is presented. Electron localisation function (ELF) study of the in situ generated azomethine ylide classifies a pseudodiradical electronic structure associated with low activation energies. This 32CA reaction is a polar process with electronic flux from the strongly nucleophilic azomethine ylide to the strongly electrophilic nitrostyrene, confirmed from the global electron density transfer (GEDT) above 0.20 e at the transition states (TSs). Parr function analysis predicts the correct regioselectivity from the two‐centre interactions. The reaction is kinetically controlled with negative free energy of reaction which makes it irreversible. The activation enthalpy of the favoured TS is lowered by 3.4, 6.3 and 9.3 kcal mol−1 in methanol relative to the other feasible reaction paths, consistent with the experimentally observed complete regioselectivity and stereoselectivity. ELF topological characterisation along the reaction path predicts a two‐stage one‐step molecular mechanism, and bond formation is controlled by the nucleophilic character of the azomethine ylide. ELF study, Laplacian of electron density and independent gradient model (IGM) analysis predict non‐covalent interactions at the TSs, where the new C–C bond formation has not been started. [ABSTRACT FROM AUTHOR]

A molecular electron density theory (MEDT) study for the [3+2] cycloaddition (32CA) reaction of 4‐chlorobenzonitrile oxide (CBNO) and β‐aminocinnamonitrile (ACN) has been performed at the MPWB1K/6‐311G(d,p) computational level. This 32CA reaction, characterised as the zwitterionic type (zw‐type), presents an activation enthalpy of 11.8, 14.2 and 16.6 kcal mol−1, in gas phase, benzene and methanol. The formation of 3‐aryl‐5‐(β‐aminostyryl)‐1,2,4‐oxadiazole is predicted as the energetically feasible one following a non‐concerted two‐stage one‐step mechanism. This zw‐type 32CA reaction shows a total chemo and regioselectivity. The global electron density transfer at the most favourable transition state structure (TS), higher than 0.14 e, suggests some polar character. The most energetically favoured TS shows an intramolecular hydrogen bond between the amine −NH2 of ACN and the oxygen of CBNO, which favours this zw‐type 32CA reaction. This behaviour is enhanced with the inclusion of a methanol molecule hydrogen bonded to this oxygen atom. The present MEDT study suggests that the best experimental conditions are to use a non‐polar solvent such as benzene containing catalytic amounts of a protic solvent such as methanol. [ABSTRACT FROM AUTHOR]

The [3 + 2] cycloaddition (32CA) reactions of 1‐pyrroline‐1‐oxide with acetylene and with a series of four symmetrically disubstituted acetylenes (XC ≡ CX, X = CH3, NH2, OH, F), leading to 4,5‐disubstituted bicyclic 4‐isoxazolines, have been studied within molecular electron density theory at the B3LYP‐D3/6‐311++G(d,p) computational level. These 32CA reactions take place through a one‐step mechanism, with activation enthalpies in toluene between 24.4 (X = NH2) and 12.9 (X = F) kcal mol−1. Due to the strong exergonic character of these 32CA reactions, between −12.0 and −47.6 kcal mol−1, they are irreversible. The 32CA reaction of difluoroacetylene, involving fluorine as the most electronegative atom of this series attached to the acetylene carbons, presents the lowest activation enthalpy due to the increase of the polar character of this 32CA reaction, evidenced by the analysis of the global electron density transfer at the corresponding transition state structure. The topological analysis of the electron localization function along the reaction paths of these 32CA reactions allows us to characterize them as the zwitterionic‐type ones. The formation of the new CC and CO single bonds takes place at the end of the reactions through the coupling of pseudoradical centers. [ABSTRACT FROM AUTHOR]

A molecular electron density theory study is presented for [3 + 2] cycloaddition (32CA) reactions of 2,2-dimethyl-1-pyrroline-1-oxide with the nitrile functions to analyse the mechanism and experimentally observed regioselectivity. Electron localisation function (ELF) study predicts zwitter-ionic character of the cyclic nitrone, allowing its participation in zw-type 32CA reactions associated with high energy barrier demanding overcome through appropriate electrophilic–nucleophilic interactions. Analysis of the CDFT indices predict the global electronic flux from the strong nucleophilic nitrone to the electrophilic nitrile functions. These 32CA reactions are endergonic with reactions Gibbs free energies between 5.5 and 39.2 kcal · mol - 1 in toluene. The ortho regiochemical pathway is preferred owing to the higher thermodynamic stability of the 2,3-dihydro-1,2,4-oxadiazole derivatives. The 32CA reaction of the nitrile function with carbomethoxy substituent is more facile relative to that with the phenyl substituent. Bonding evolution theory study predicts one-step mechanism with early TSs for the ortho pathway, while a one-step-two-stage mechanism is predicted for the meta reaction path, in conformity with the ELF and AIM topological studies at the TSs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The [3 + 2] cycloaddition (32CA) reactions of 1-pyrroline-1-oxide with N-vinyl nucleobases leading to bicyclic N,O nucleoside analogues have been studied within the molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. These non-polar zwitterionic type 32CA reactions take place through a one-step mechanism with minimal global electron density transfer (GEDT) at the TSs and the exo/ortho approach mode as the energetically favoured reaction path. The 32CA reactions of N-vinyl nucleobases with thymine and cytosine substituents respectively show the activation enthalpies of 15.2 and 12.5 kcal mol−1 in toluene. The reactions are irreversible due to strong exothermic character of − 35.4–− 26.4 kcal mol−1 in toluene. The bonding evolution theory (BET) study suggests that these 32CA reactions take place through the coupling of pseudoradical centres with earlier C–C bond formation and the formation of new C–C and C–O covalent bonds has not been started in the TSs. Non-covalent interactions (NCI) are predicted at the TSs from the visualization of NCI gradient isosurfaces. [ABSTRACT FROM AUTHOR]

The strain‐promoted [3 + 2] cycloaddition (SP‐32CA) reactions of two diazoalkanes with strained dibenzocyclooctyne (DIBO) have been studied within the molecular electron density theory. Analysis of the electron localisation function of diazoalkanes allows characterising their pseudoradical structures. These pmr‐type 32CA reactions, which follow a one‐step mechanism with high asynchronicity and some polar character, have lower activation enthalpies, 11.4 and 15.4 kcal mol−1, than those with acetylene, 19.7 and 23.1 kcal mol−1, in agreement with the experimental outcomes. Analysis of the changes in electron density along the SP‐32CA reaction of phenyldiazomethane with DIBO indicates that the strain favours the depopulation of the C–C triple bond of DIBO, reducing the activation energy. [ABSTRACT FROM AUTHOR]

The mechanism and regioselectivity of [3+2] cycloaddition (32CA) reactions of benzonitrile oxide with ethyl trans-cinnamate, ethyl crotonate and trans-2-penten-1-ol has been studied in gas phase and in acetonitrile, ethyl acetate and tetrahydrofuran using the B3LYP functional in connection with 6-31G(d) basis set. The 32CA reactions followed one-step mechanism with asynchronous TSs. The calculated global electron density transfer (GEDT) at the TSs showed electronic flux from benzonitrile oxide to ethyl trans-cinnamate and ethyl crotonate, while the electronic flux from trans-2-penten-1-ol to benzonitrile oxide was predicted, in complete agreement with the Conceptual Density Functional Theory (CDFT) indices. The regioselectivity is correctly described in coherence with the experiment data. The intermolecular interaction at the TSs was realized through visualization and quantification by means of independent gradient model (IGM) analysis based on promolecular density. [ABSTRACT FROM AUTHOR]

The [3 + 2] cycloaddition (32CA) reaction of phenyl azide 4 with ethynylbenzene 5 in presence of ethyl magnesium bromide (EtMgBr) has been studied within the Molecular Electron Density Theory with the aim to rationalise the high‐yielding direct regioselective synthesis of 1,5‐disubstituted‐1,2,3‐triazoles. Topological analysis of the electron localisation function (ELF) of phenyl azide 4 indicates that it has a zwitterionic structure participating in zw‐type 32CA reactions. Computed activation parameters along the two feasible reaction paths for this 32CA reaction makes the rationalisation of the experimental outcomes possible. Grignard reagent‐mediated processes have a polar character and complete regioselectivity, which is in line with the fast, clean, and high yielding reaction experimentally observed. The reaction follows a one‐step mechanism involving a high asynchronous transition state structure. Topological analysis of the ELF and calculated quantum theory of atoms‐in‐molecule parameters indicate that formation of new C–N single bonds does not begin exactly at the corresponding transition state structure. [ABSTRACT FROM AUTHOR]

The [3+2] cycloaddition (32CA) reaction of benzonitrile oxide to α-methylene cyclopentanone and propionitrile oxide to γ-methyl-α-methylene-γ-butyrolactone, yielding regio- and stereochemically defined spiroisoxazolines, has been studied at the MPWB1K/6-311G(d,p) computational level. These processes proceed by a one-step mechanism through asynchronous transition states. Ortho regioselectivity and anti diastereofacial selectivity are predicted in complete agreement with the experimental outcomes. [ABSTRACT FROM AUTHOR]

[3 + 2] cycloaddition (32CA) reaction of C,N-diaryl nitrone with benzylidene acetone has been studied to analyse the mechanism, selectivity and polar character of this nitrone-enone cycloaddition. Topological analysis of the electron localization function (ELF) shows the absence of pseudoradical and carbenoid centre in the nitrone, which allows its classification as a zwitter-ionic (zw) type three atom component (TAC) and hence participation in zw- type cycloadditions is associated with high activation energy barriers. This 32CA reaction follows a one-step mechanism with asynchronous TSs. Endo/meta product is obtained as the major cycloadduct experimentally, which can be rationalized from its calculated lowest activation energy among the four possible reaction pathways. Global electron density transfer (GEDT) at the TSs predict the non-polar character of this 32CA reaction. Topological analysis of the ELF and QTAIM parameters was performed at the TSs. Finally, non-covalent interaction (NCI) gradient isosurfaces are computed to obtain a visualization of non-covalent interactions at the interatomic bonding regions. The experimental and theoretical aspects of [3+2] cycloaddition reactions of C,N-diaryl nitrone with benzylidene acetone is described. The reaction is meta/endo selective and follows one step mechanism with non-covalent interactions. The C-C and C-O bonds are generated through coupling of pseudoradical centers. [ABSTRACT FROM AUTHOR]

Nitrile 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 nonpolar 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. [ABSTRACT FROM AUTHOR]

Abstract: The [3+2] cycloaddition (32CA) reactions of C‐phenyl‐N‐methyl nitrone to acyclic olefins bearing electron donating and weak electron withdrawing groups lead to complete ortho regioselectivity. The experimentally observed ortho selectivity can be rationalized from the activation energies of the located transition states at DFT/MPW1PW91/6‐311G(d,p) level of theory. The reaction of this nitrone to ethyl vinyl ether is predicted to be non‐polar by global electron density transfer (GEDT) calculations. Bonding evolution theory (BET) study led to topological characterization of the reaction pathway into different phases and indicated initial rupture of the olefinic double bond followed by the formation of pseudoradical centres and earlier formation of C−C bond. Quantum theory of atoms in molecules (QTAIM) study of electron density was performed for (3,–1) critical points at the region near the forming C−C and C−O bonds and was found to be in complete agreement with the Electron localization function (ELF) topological analysis. Electrostatic potential surface study for the transition states indicated greater mutual penetration distances of C−C forming bond compared to the C−O forming bond. [ABSTRACT FROM AUTHOR]

- tert-butylmethanimine -oxide is a potent spin-trapping probe for biologically important radicals, and this nitrone undergoes complete regioselective cycloadditions to less electron-deficient monosubstituted olefins. In the present study, solvent effects on the cycloaddition of this nitrone to styrene have been theoretically studied in terms of the global properties of the reactants, electrophilic and nucleophilic Parr function analysis and the activation and reaction energies of located transition states and products. Formation energies of optimized radical adducts were computed to determine their stabilities in different solvents. The cycloaddition is predicted to be completely ortho regioselective which is in complete agreement with experiments and involved earlier C-C bond formation owing to the insufficient depopulation of -conjugated carbon atom in styrene and shows varying asymmetry indices in different solvents. Decrease in activation parameters and increase in stability of cycloadducts are predicted with decreasing solvent polarity. Aqueous media destabilize the radical adducts as predicted from the calculated formation energy, enthalpy and free energy of reaction. Hydroxyl as well as methyl radical adducts are predicted to be more stable than superoxide anion radical adducts. These predictions are in complete agreement with the experiments. [ABSTRACT FROM AUTHOR]

DFT studies have been carried out for the cycloaddition reactions of a cyclic nitrone, 1-pyrroline-1-oxide and an acyclic nitrone, C,N-diphenyl nitrone to an unsymmetrically disubstituted dipolarophile, 1-cinnamoyl-1-piperidine. These reactions proved to be opposite to each other with respect to the electron demand character predicted by the electronic chemical potentials, electrophilicities and charge transfer at the transition states. The regio- and stereoselectivities have been predicted from DFT based reactivity indices, interaction energy calculations using a perturbative orbital independent theoretical model and the activation parameters of the located transition states. Two different concepts have been used for the evaluation of interaction energies. The selectivities were found to be in conformity with the experimental findings. The time gaps between the formations of - and - bonds were evaluated from single trajectory simulations. The asynchronicity of bond formation process was analyzed from the wiberg bond indices, atom-atom overlap weighted NAO bond orders and the calculated asymmetry indices of the transition states. DFT study has been carried out for cycloaddition reactions of 1-pyrroline-1-oxide and C, N-diphenyl nitrone to 1-cinnamoyl-1-piperidine in terms of global and local indices, interaction energies, activation parameters and rate constants. Single trajectory calculations suggested a concerted mechanism for these reactions. [ABSTRACT FROM AUTHOR]

1,3-dipolar cycloaddition reactions of an electron deficient C-aryl-N-phenyl nitrone to benzylidene derivatives (with different electrophilicities) have been analyzed by density functional theory calculations. The transition states corresponding to the endo and exo approaches along the feasible regioisomeric reaction channels have been located for each cycloaddition. The reactions follow a concerted mechanism with asynchronous transition states. The asynchronicity along the regiochemical reaction modes depends on the β-carbon electrophilicities of the olefins. The regio and stereochemistries predicted from the calculated activation energy barriers (with solvent and higher basis set corrections) of the located transition states are in conformity with the experimental results. The local electrophilicities, softness matching indices and the interaction energies were then calculated to analyze how well these reactivity parameters can interpret the regioselectivities of such reactions. The electronic populations at the reactive sites computed from electrostatic potential-driven atomic charges provided correct and consistent predictions for each theoretical model contrary to the natural orbital based charges. Cycloadditions of C-(4-nitrophenyl)-N-phenyl nitrone to styrene, ethyl cinnamate and nitrostyrene follow concerted mechanism with asynchronous transition states. DFT calculated activation energies were in complete agreement with the experimental findings. Two-center and four-center interaction studies based on electrostatic potential driven (MK algorithm) charges provided correct regiochemical predictions unlike natural population analysis for these reactions. [ABSTRACT FROM AUTHOR]

Experimental and theoretical studies were carried out to highlight the influence of mild Lewis acid catalysts on the cycloadditions leading to stereochemically defined tetrasubstituted isoxazolidines. Considerable acceleration and increased exo stereoselectivity were observed for lithium triflate and magnesium bromide catalyzed processes. DFT-based reactivity indices reflected the differences in polar character of the catalyzed and uncatalyzed pathways. The regioselectivities were predicted from interaction energy calculations. Finally, the transition states were successfully located and the extent of bond formation analyzed. The catalytic acceleration was rationalized by density functional theory (DFT) calculated activation parameters. The rate constant ratios with Eyring's transition state theory (TST) rate equation and total partition functions were also theoretically evaluated to further rationalize the observed catalytic acceleration. Graphical abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

A B3LYP/6-31G* study was carried out for the reactions of 1-pyrroline-1-oxide (N1) with methyl cinnamate (E1) and benzylidene acetophenone (E2) for getting a quantitative rationalization of the experimental findings. The product ratios were determined by NMR studies of the crude reaction mixtures. The conformation and stereochemistry of the isolated cycloadducts were finally confirmed by 2D NMR and X-ray diffraction. The endo/exo-selectivities were predicted through the computation of activation parameters on the basis of assumed concerted mechanism. The regioselectivity and reactivity were amply predicted by local and global electrophilicity indices and were found to be in good agreement with the experimental findings which were supportive of polar character and of the direction of charge transfer (CT) accompanying the cycloaddition. It was found that the cycloaddition involving methyl cinnamate was endo-selective, while that with benzylidene acetophenone produced the exo-isomer as the major adduct. Copyright © 2010 John Wiley & Sons, Ltd. A B3LYP/6-31G* study has been carried out to calculate the activation parameters, global and local electrophilicity indexes for the cycloaddition of 1-pyrroline-1-oxide with methyl cinnamate and benzylidene acetophenone. Results of theoretical calculations were supported by NMR and X-Ray diffraction studies. [ABSTRACT FROM AUTHOR]

A DFT/B3LYP/6-31G* study was carried out to predict the regio- and stereoselectivities of 1,3-dipolar cycloadditions of C,N-disubstituted aldonitrones to chalcones in terms of FMO theory, DFT-based reactivity indices, and activation energy calculations. The structures of the resultant 2,3,4,5-tetrasubstituted isoxazolidines were determined by means of NMR spectroscopy and X-ray analysis. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The [3 + 2] cycloaddition (32CA) reaction of an α-santonin derivative, which has an exocyclic C–C double bond, with p-bromophenyl nitrile oxide yielding only one spiroisoxazoline, has been studied within the molecular electron density theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. Analysis of the conceptual density functional theory (CDFT) reactivity indices and the global electron density transfer (GEDT) account for the non-polar character of this zwitterionic-type 32CA reaction, which presents an activation enthalpy of 13.3 kcal·mol−1. This 32CA reaction takes place with total ortho regioselectivity and syn diastereofacial selectivity involving the exocyclic C–C double bond, which is in complete agreement with the experimental outcomes. While the C–C bond formation involving the β-conjugated carbon of α-santonin derivative is more favorable than the C–O one, which is responsible for the ortho regioselectivity, the favorable electronic interactions taking place between the oxygen of the nitrile oxide and two axial hydrogen atoms of the α-santonin derivative are responsible for the syn diastereofacial selectivity. [ABSTRACT FROM AUTHOR]