Laplacian Of Electron Density Research Articles

Unveiling the high regioselectivity and stereoselectivity within the synthesis of spirooxindolenitropyrrolidine: A molecular electron density theory perspective

AbstractA 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.

DFT Studies of the Toxicity of Para-Substituted Ortho-Benzoquinones

Toxicity descriptors based on Cu(II) coordination ability of para-substituted ortho-benzoquinones and subsequent O → Cu electron density transfer are introduced. Geometries of quinones and of their Cu(II) complexes are optimized using DFT treatment. The transferred electron density is evaluated using the copper charge or the Laplacian of electron density at the Cu-O bond critical points. The toxicity of quinones with electron-withdrawing substituents is much more sensitive to the extent of electron density transfer. Quinone O atoms exhibit equal trends for electron-donating substituents only.

Non-covalent interactions abetted supramolecular arrangements of N-Substituted benzylidene acetohydrazide to direct its solid-state network

Intra-molecular hydrogen bond modulation of compounds positively impacts their solubility, permeability and as well as potency in the field of medicinal chemistry. Herein, N-substituted benzylidene acetohydrazide derivative: (Z)-2-((6-chloropyridin-2-yl)oxy)-N'-(2-hydroxy-3-methoxybenzylidene)acetohydrazide (HOBAH), a novel solid state network was synthesized efficiently via sono-chemical approach. The structural characterization of HOBAH was achieved by single crystal analysis which exposed intra-molecular NH…O, OH…N bonding and intermolecular NH…O, OH…O and comparatively weak CH…O hydrogen bonding being responsible for the crystal packing. Theoretical calculations by applying the density functional theory (DFT) at DFT/B3LYP/6–311G(d,p) were completed. The characteristic of HOBAH was evaluated from a relaxed PES scan analysis and the HOBAH conformations with minimum energy have been identified. Hirshfeld surface (HS) and the quantum theory of atoms in molecules (QT-AIM) analyses bolstered in quantifying the existing non-covalent interactions. QT-AIM analysis unveiled that strong NH…O-H and CO…H-O hydrogen bonds (HBs) and other van der Waals interactions were responsible for the stabilization of these solid state networks. All non-covalent interactions with positive laplacian of electron density (∇2ρ) values from QT-AIM analysis corroborated well with the internal charge transfer and the hyper-conjugative interactions explored by NBO analysis. Moreover, all significant results were endorsed by both NPA and FMO evaluations. FMO analysis later assisted in the calculation of global reactivity indices. However, local reactivity indices were computed with Fukui function calculations. Lastly, molecular electrostatic potential (MEP) was plotted which confirmed the nucleophilic and electrophilic sites of HOBAH as elaborated by the reactivity indices.

Electride Characteristics of Some Binuclear Sandwich Complexes of Alkaline Earth Metals, M2(η5-L)2 (M = Be, Mg; L = C5H5-, N5-, P5-, As5-).

Ab initio calculations have been performed for a series of binuclear sandwich complexes, M2(η5-L)2. It has been observed that the eclipsed and staggered conformations have almost equal amount of energies. The M-M bond lengths are comparable with those in the free M2 molecules (M = Be, Mg). The nuclear-independent chemical shift (NICS) values indicate the aromaticity of these complexes. The stability of Be2(η5-L)2 complexes is higher than that of the Mg2(η5-L)2 complexes. The natural bond orbital (NBO) analysis and electron density descriptors proved the existence of a single covalent M-M bond in an M22+ fragment. It has been observed that each M-M bond contains a non-nuclear attractor (NNA) at the center of the respective bond. The Laplacian of electron density [∇2ρ(r)] is negative at the NNAs. The energy decomposition analysis (EDA) showed that M22+ and 2L- represent the bonding interaction in the complexes. All of the designed binuclear sandwich complexes behave as electrides.

Halogen bonds and other noncovalent interactions in the crystal structures of trans-1,2-diiodo alkenes: an ab initio and QTAIM study.

A series of interatomic interactions interpretable as halogen bonds involving I…I, I…O, and I…C(π), as well as the noncovalent interactions I…H and O…O, were observed in the crystal structures of trans-1,2-diiodoolefins dimers according to ab initio calculations and the quantum theory of "atoms in molecules" (QTAIM) method. The interplay between each type of halogen bond and other noncovalent interactions was studied systematically in terms of bond length, electrostatic potential, and interaction energy, which are calculated via ab initio methods at the B3LYP-D3/6-311++G(d,p) and B3LYP-D3/def2-TZVP levels of theory. Characteristics and nature of the halogen bonds and other noncovalent interactions, including the topological properties of the electron density, the charge transfer, and their strengthening or weakening, were analyzed by means of both QTAIM and "natural bond order" (NBO). These computational methods provide additional insight into observed intermolecular interactions and are utilized to explain the differences seen in the crystal structures. Graphical abstract The contour map presents the regions of electronic concentration and depletion along each bond in one dimer. The blue points denote the BCPs. The blue lines denote positive Laplacian of electron density, which indicate the ionic interactions, van der Waals or intermolecular interactions, and the red lines denote negative Laplacian of electron density which indicate the covalent bonds.

Computational Characterization of the Substrate Activation in the Active Site of SARS-CoV-2 Main Protease

Molecular dynamics simulations with the QM(DFT)/MM potentials are utilized to discriminate between reactive and nonreactive complexes of the SARS-CoV-2 main protease and its substrates. Classification of frames along the molecular dynamic trajectories is utilized by analysis of the 2D maps of the Laplacian of electron density. Those are calculated in the plane formed by the carbonyl group of the substrate and a nucleophilic sulfur atom of the cysteine residue that initiates enzymatic reaction. Utilization of the GPU-based DFT code allows fast and accurate simulations with the hybrid functional PBE0 and double-zeta basis set. Exclusion of the polarization functions accelerates the calculations 2-fold, however this does not describe the substrate activation. Larger basis set with d-functions on heavy atoms and p-functions on hydrogen atoms enables to disclose equilibrium between the reactive and nonreactive species along the MD trajectory. The suggested approach can be utilized to choose covalent inhibitors that will readily interact with the catalytic residue of the selected enzyme.

Discrimination of enzyme–substrate complexes by reactivity using the electron density analysis: peptide bond hydrolysis by the matrix metalloproteinase-2

The results of quantum mechanics/molecular mechanics calculations of electron density changes upon oligopeptide hydrolysis by the matrix metalloproteinase-2 are utilized to discriminate between reactive and non-reactive enzyme–substrate complexes. Electron density depletion regions on the carbonyl carbon atom attacked by a catalytic water molecule are found on the 2D maps of electron density Laplacian in the reactive complexes. Also, the computed Fukui function quantitatively describes reactivity of the nucleophilic and electrophilic sites.

Computational investigation of the carmustine (BCNU) alkylation mechanism using the QTAIM, IQA, and NBO models

Although several studies have attempted to deduce by theoretical calculations the reaction mechanism of carmustine with DNA, no study has presented data on the reaction sites and the behavior of the electrons of the participating molecules. Thus, the objective of this paper is to apply the NBO (Natural Bond Orbital) model from the donor-acceptor point of view and the QTAIM (Quantum Theory: Atoms in Molecules) theory from the Laplacian of electronic density and the energy partition formalism IQA (Interacting Quantum Atoms) to quantify the interactions present in the alkylation between carmustine and DNA. The results showed that the decomposition of carmustine forms the chloroethyl ion and the 2-chloroethyldiazene hydroxide molecule, which subsequently breaks down to form 2-chloroethanol and N2. The NBO, QTAIM, and IQA data demonstrated that the ionic carbon of the chloroethyl ion suffers a nucleophilic attack from the O6-guanine. In the alkylation between intermediate 1,O6-ethanoguanine and cytosine, the bond between the CO of the intermediate ring breaks with a subsequent nucleophilic attack of the N of the cytosine with the C of the ring of the molecule 1,O6-ethanoguanine, forming a bridge of ethane between the guanine and cytosine bases.

2-Amino-3-methylpyridinium, 2-amino-4-methylbenzothiazolium and 2-amino-5-chloropyridinium salts. Experimental and theoretical findings

Reaction between 2-amino-3-methylpyridine, 2-amino-4-methylbenzothiazole with salicylic acid, and 2-amino-5-chloropyridine with 3-chlorobenzoic acid were carried out and respective molecular salts 1–3 were obtained. During reactions, proton transfer from acid to endocyclic N of the base was observed. Structural elucidation of all compounds was carried out with the help of FT-IR and X-ray Diffraction for single crystals. The acid/base pairs in a molecular salt are held together with the help of H- and charge-assisted bonding and additional non-covalent bonding extend the supramolecular structure. All hydrogen bonds and secondary interactions have been discussed and a detailed comparison of experimental data with theoretical calculations through AIM, NBO and Wiberg bond index analysis has been made. The non-covalent character was mainly typified by positive values of Laplacian of electronic density. The theoretical studies demonstrate that other than classical H-bonds, the non-classical and secondary non-covalent interactions are very important to direct supramolecular structure of the respective molecular salt. The DFT calculations with solvent model SMD proved a good alternative to deduce the molecular salt formation when the 0>ΔpKa>3. Moreover, global reactivity descriptors (GRD) have been calculated utilizing the energies of FMOs. The calculated values for HOMO of compounds 1–3, -5.469, -5.642 and -6.435, respectively indicate that the compounds adopt the numerical order in terms of electron donation/Lewis basicity. The molecular salt formation is more feasible for heterosynthon 1 and least for 3.

Investigation of bond topological and electrostatic properties of plumbagin molecule: An experimental and theoretical charge density study

Plumbagin is a naturally occurring derivative with several medicinal properties including antioxidants, antifungal, antimalarial, leprosy and antitumor properties; their structural and electrostatic properties are yet to be determined. The crystal structure of plumbagin has been solved; it shows that the compound crystallizes in P21/c space group with two molecules in the asymmetric unit. The electron density distribution of both molecules have determined from multipole model refinement. Among all the C–O bonds of both molecules (I & II), the OH group connected C–O bond and the methyl group connected C–C bond exhibits less electron density and the negative Laplacian of electron density as well. Further, the electrostatic potential (ESP) surface of two plumbagin molecules show some difference in their electronegative regions. The carbonyl O-atoms exhibit high electronegative ESP regions which are the key reactive locations of plumbagin when bind with the active site of target protein and in the ESP map, an aromatic π-cloud also observed in one of the molecule. The electron density distribution of O–H⋅⋅⋅O intermolecular interactions between the molecules I and II, reveals that these interactions are found very stronger than the other interactions in the crystal.

Hydrogen vs. Halogen Bonds in 1-Halo-Closo-Carboranes.

A theoretical study of the hydrogen bond (HB) and halogen bond (XB) complexes between 1-halo-closo-carboranes and hydrogen cyanide (NCH) as HB and XB probe has been carried out at the MP2 computational level. The energy results show that the HB complexes are more stable than the XBs for the same system, with the exception of the isoenergetic iodine derivatives. The analysis of the electron density with the quantum theory of atoms in molecules (QTAIM) shows the presence of a unique intermolecular bond critical point with the typical features of weak noncovalent interactions (small values of the electron density and positive Laplacian and total energy density). The natural energy decomposition analysis (NEDA) of the complexes shows that the HB and XB complexes are dominated by the charge-transfer and polarization terms, respectively. The work has been complemented with a search in the CSD database of analogous complexes and the comparison of the results, with those of the 1-halobenzene:NCH complexes showing smaller binding energies and larger intermolecular distances as compared to the 1-halo-closo-carboranes:NCH complexes.

Reply to the Comment on “Realization of Lewis Basic Sodium Anion in the NaBH3− Cluster”

AbstractWe reply to the comment by S. Pan and G. Frenking who challenged our interpretation of the Na−:→BH3 dative bond in the recently synthesized NaBH3− cluster. Our conclusion remains the same as that in our original paper (https://doi.org/10.1002/anie.201907089 and https://doi.org/10.1002/ange.201907089). This conclusion is additionally supported by the energetic pathways and NBO charges calculated at UCCSD and CASMP2(4,4) levels of theory. We also discussed the suitability of the Laplacian of electron density (QTAIM) and Adaptive Natural Density Partitioning (AdNDP) method for bond type assignment. It seems that AdNDP yields more sensible results. This discussion reveals that the complex realm of bonding is full of semantic inconsistencies, and we invite experimentalists and theoreticians to elaborate this topic and find solutions incorporating different views on the dative bond.

Experimental and theoretical charge density analysis of skin whitening agent kojic acid

The charge density analysis from high resolution X-ray diffraction at 100 K was carried out to understand the structure properties relationship and binding fashion in anti-Tyrosinase Kojic acid. The experimental results were validated from periodic theoretical calculations using B3LYP/6–311++g(2 d, 2p) level of theory. The experimental electron density and Laplacian of electron density was calculated and compared from theoretical displaying the distribution of respective charges in the crystal field of Kojic acid molecule. An analysis of the electrostatic potential surface provides insight into anti-melanogenesis function.

A rapid method for analyzing the chemical bond from energy densities calculations at the bond critical point

The quantum theory atoms in molecules (QTAIM) method has been used in this paper to characterize various bonding interactions in molecules and solid compounds. By using DFT-PAW calculations, complete electron density Laplacian distributions have been obtained and related to energies densities calculated at the bond critical points. From the analysis of these results a simple and rapid method, based solely on local energies densities calculations, is proposed to diagnose the bonding state, the polarizability and the deformation of the charge distribution.

Experimental and theoretical charge density, intermolecular interactions and electrostatic properties of metronidazole.

Metronidazole is a radiosensitizer; it crystallizes in the monoclinic system with space group P21/c. The crystal structure of metronidazole has been determined from high-resolution X-ray diffraction measurements at 90 K with a resolution of (sin θ/λ)max = 1.12 Å-1. To understand the charge-density distribution and the electrostatic properties of metronidazole, a multipole model refinement was carried out using the Hansen-Coppens multipole formalism. The topological analysis of the electron density of metronidazole was performed using Bader's quantum theory of atoms in molecules to determine the electron density and the Laplacian of the electron density at the bond critical point of the molecule. The experimental results have been compared with the corresponding periodic theoretical calculation performed at the B3LYP/6-31G** level using CRYSTAL09. The topological analysis reveals that the N-O and C-NO2 exhibit less electron density as well as negative Laplacian of electron density. The molecular packing of crystal is stabilized by weak and strong inter- and intramolecular hydrogen bonding and H...H interactions. The topological analysis of O-H...N, C-H...O and H...H intra- and intermolecular interactions was also carried out. The electrostatic potential of metronidazole, calculated from the experiment, predicts the possible electrophilic and nucleophilic sites of the molecule; notably, the hydroxyl and the nitro groups exhibit large electronegative regions. The results have been compared with the corresponding theoretical results.

One pot synthesis of novel pregnane-sulphur prodrugs, spectroscopic investigation, conformational analysis, chemical reactivity, Fukui function and their mathematical model

Novel sulphur derivatives have been synthesized for the first time from 16-Dehydropregnenolone acetate (16-DPA) by adopting thia-Michael addition reaction yielding 2-[(3β-acetoxy) pregn–5-ene-20-one −16 –thio] propanoic acid, 2-[(3β-acetoxy) pregn–5-ene-20-one–16–thio] ethanoic acid, 3β-acetoxy 16α-(2-hydroxyethylthio)-pregn-5-ene-20-one and 3β-acetoxy-16β-(2-amino phenylthio)-pregn-5-ene-20-one. All the compounds were characterized with the help of 1H, 13C NMR, FT-IR spectroscopy and mass spectrometry. The molecular geometry and vibrational frequency of these compounds were calculated in ground state by density functional theory (DFT/B3LYP) using 6-31G (d, p) basis set. Conformational analysis of all the compounds was carried out to determine the most stable conformation. The electronic properties such as HOMO-LUMO energy were calculated by using time dependent density functional theory (TD-DFT). The topological parameters-electron density (ρBCP), Laplacian of electron density (∇2ρ(rBCP)), energy parameters-kinetic electron energy density (GBCP), potential electron density (VBCP) and the total electron energy density (HBCP) at the bond critical points (BCP) were analyzed by ‘Atoms in molecules’ AIM theory. Local reactivity descriptors like Fukui functions (fk+, fk−, fk0), local softness (sk+, Sk−, Sk0) and local electrophilicity indices (ωk+, ωk−, ωk0) analysis were performed to find out the reactive sites within the molecules. Molecular electrostatic potential of the synthesized compounds were also determined. Lastly a nonlinear mathematical model has been proposed and analyzed to study the effect of catalysts on these reactions. Local and global stability analysis of the mathematical model along with the persistence of the system was checked using theory of nonlinear ordinary differential equations.

X-ray diffraction and QTAIM calculations of the non-covalent intermolecular fluorine-fluorine interactions in tris(trifluoroacetylacetonato)-manganese(III)

An X-ray study was conducted on tris(trifluoroacetylacetonato)-manganese(III). The two different molecules in the unit cell exhibit a distorted octahedral geometry and moderate compression Jahn–Teller distortion respectively. A number of F⋯H and F⋯F intermolecular interactions were observed in the packing of the crystals in the solid state. The crystal packing effects could lead to the observed compressed Jahn–Teller distortion, instead of the expected elongation Jahn–Teller distortion. A Quantum Theory of Atoms in Molecules (QTAIM) study on selected molecular pairs identified intermolecular bond paths (BP) between fluorine atoms with bond critical points (BCP) which have positive electron density (ρ) and Laplacian of electron density (∇2ρ) values, which are indicative of weak F···F non-covalent bonding interactions.

DFT, spectroscopic, DSC/TGA, electronic, biological and molecular docking investigation of 2,5-thiophenedicarboxylic acid: A promising anticancer agent

The molecular structural and various spectroscopic parameters (FT-IR, FT-Raman and UV–Visible) were determined by using quantum mechanical computation for 2,5-thiophenedicarboxylic acid (2,5-TDCA) molecule: a potential anticancer agent. The optimized geometrical parameters (monomer, dimer and trimer) were computed by B3LYP/6-311 + G(d,p) method and compared with related XRD data. The spectral studies of 2,5-TDCA molecule were adopted by recording FT-IR (4000-400 cm−1) and FT-Raman (3500-50 cm−1) spectroscopic techniques. The fundamental vibrational modes were computed for monomer and dimer, the vibrational assignments were done by finding Total Energy Distribution (TED) for each normal modes of vibrations by VEDA software. Mulliken charage analysis for monomer, dimer and trimer were analyzed by the same method. The UV–Vis absorption spectrum was recorded and correlated with electronic properties by TD-DFT method in gas and acetone phase by B3LYP/6-311 + G(d,p) method. The charge transfers happen within 2,5-TDCA molecule as well as in dimer form were investigated by using Natural Bond Orbital (NBO) approach. The MEP analysis was utilized for predicting the electrophilic and nucleophilic site in the 2,5-TDCA molecule. Total Density of State (TDOS) and Partial Density of State (PDOS) were also computed by Gauss Sum software. The non-covalent interaction of 2,5-TDCA was studied by adopting Reduced Density Gradient (RDG) and color filled electron density diagram. Thermodynamic properties have been performed by computing various thermodynamical parameters. The Electron density, Laplacian of electron density, Lagrangian Kinetic Energy, Hamiltonian Kinetic Energy and H-Bond energy at the bond critical point using Atoms in Molecule (AIM) theory reveal that there is a possibility of strong intermolecular hydrogen bonds. The DSC/TGA analysis was carried out to find the decomposition of molecule with respect to temperature. The biological activity of the 2,5-TDCA molecule were studied by using molecular docking analysis to identify hydrogen bond length and binding energies with different cancer protein. The 2,5-TDCA compound has been screened and found to exhibit anti-bacterial activity.

New lithium-electride design: material properties of Lin@porphyrin

The material with electride features have cavity-trapped electrons in the molecular structure. In this work, we select the porphyrin species as backbone to design new electrides. In this regard, addition of Li-atoms to porphyrin backbone (Li@porphyrin species) has been investigated at density functional theory (DFT) framework, systematically. According to our results, the Li@porphyrin systems have high thermodynamic stability and can be incorporated in either lithium electride (Li10Pr species) or lithium salt (Li1Pr and Li5Pr species) categories. This categorization is in terms of the computational study of four factors, non nuclear attractor (NNA), electron density laplacian (), electron localization function (ELF) and non linear optical (NLO) property. Therefore, Lithium:porphyrin ratio in the Li@porphyrin systems is very important criterion to provide porphyrin based lithium electride.

Realization of Lewis Basic Sodium Anion in the NaBH3− Cluster

AbstractWe report a Na:−→B dative bond in the NaBH3− cluster, which was designed on the principle of minimum‐energy rupture, prepared by laser vaporization, and characterized by a synergy of anion photoelectron spectroscopy and electronic structure calculations. The global minimum of NaBH3− features a Na−B bond. Its preferred heterolytic dissociation conforms with the IUPAC definition of dative bond. The lone electron pair revealed on Na and the negative Laplacian of electron density at the bond critical point further confirm the dative nature of the Na−B bond. This study represents the first example of a Lewis adduct with an alkalide as the Lewis base.