DFT Molecular Orbital Calculations Research Articles

Synthesis, Crystal Structures, Density Functional Theory (DFT) Calculations and Molecular Orbital Calculations of Two New Metal-Free Macrocyclic Schiff Bases Derived from 2,6-Dibenzoyl-4-alkylphenol and Diamines

Two new phenol-based metal-free macrocyclic Schiff bases, cyclo-bis{2-[benz(N-propan-1,3-diyl)imidoyl][6-benzimidoyl][4-methyl]phenol} and cyclo-bis{2-[benz(N-butan-1,4-diyl)imidoyl][6-benzimidoyl][4-tert-butyl]phenol} have been synthesized and their structures determined by single crystal X-ray crystallography. The DFT geometry optimization calculations were performed to compare experimental and theoretical results. A comparison of the dihedral angles between mean planes of the central phenolato rings and peripheral phenyl rings in the crystal with the DFT theoretical calculations has been included for each molecule. Electronic transitions have been predicted by DFT molecular orbital calculations and compared with experimental absorption spectral data. A one-pot synthesis, crystal structure and theoretical calculations of 20- and 22-membered macrocyclic ligands are reported.

Gas-phase structure of nickel dichloride. An electron-diffraction investigation augmented by ab initio and DFT calculations

The structure of nickel dichloride in the vapor at ca. 1050 K has been studied experimentally by electron diffraction and theoretically by ab initio and DFT molecular orbital calculations. The molecule is found to have a linear equilibrium structure, and from all levels of theory it is predicted to have a triplet ground state. Theory also predicts the existence of a singlet state about 30 kcal/mol less stable than the triplet where the molecule is triangular with a bond angle in the range of about 110°̊ – 117°̊. Two models of the experimental structure were investigated. Model A consisted of 11 “pseudoconformers” distributed at even intervals over the range 180°̊ ≤ ∠(ClNiCl) ≤ 130°̊ for which the main refined parameter was the distribution (relative weighting) of the pseudoconformers based on an assumed bending potential of the form V(Δθ) = V2(Δθ)2, where Δθ is the difference of the ClNiCl angle from linearity. In this model the pseudoconformational weighting led to averages for the bond- and nonbond distances. Model B was simpler, defined only by values of the bond distance and bond angle. The structural results for Model A are 〈rg(NiCl)〉 = 2.067(6) Å, 〈rg(Cl⋅⋅Cl)〉 = 4.037(28) Å, 〈lg(NiCl)〉 = 0.081(6) Å, and 〈lg(Cl⋅⋅Cl)〉 = 0.136(52) Å; in this case the rms amplitudes are for the frame (no contributions from the bending mode). For Model B they are 〈rg(NiCl)〉 = 2.059(5) Å, 〈rg(Cl⋅⋅Cl)〉 = 4.041(89) Å, 〈lg(NiCl)〉 = 0.081(6) Å, and 〈lg(Cl⋅⋅Cl)〉 = 0.159(60) Å; the uncertainties are estimated 2σ. The theoretical prediction of a linear ground state for nickel dichloride is confirmed by experimental values of about 156̊° for the bond angle ∠(ClNiCl) in each model, which differs from the theoretical 180̊° due to the effects of vibrational averaging that arise nearly entirely from the bending mode. The structure is discussed.

Benzothiazole analogues: Synthesis, characterization, MO calculations with PM6 and DFT, in silico studies and in vitro antimalarial as DHFR inhibitors and antimicrobial activities

Benzothiazole analogues are of interest due to their potential activity against malarial and microbial infections. In search of suitable antimicrobial and antimalarial agents, we report here the synthesis, characterization and biological activities of benzothiazole analogues (J 1-J 10). The molecules were characterized by IR, Mass, 1H NMR, 13C NMR and elemental analysis. The in vitro antimicrobial activity was investigated against pathogenic strains; the results were explained with the help of DFT and PM6 molecular orbital calculations. In vitro cytotoxicity and genotoxicity of the molecules were studied against S. pombe cells. In vitro antimalarial activity was studied. The active compounds J 1, J 2, J 3, J 5 and J 6 were further evaluated for enzyme inhibition efficacy against the receptor Pf-DHFR, computational and in vitro studies were carried out to examine their candidatures as lead dihydrofolate reductase inhibitors.

1,2,4-Triazole and 1,3,4-oxadiazole analogues: Synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities

1,2,4-Triazole and 1,3,4-oxadiazole analogues are of interest due to their potential activity against microbial and malarial infections. In search of suitable antimicrobial and antimalarial compounds, we report here the synthesis, characterization and biological activities of 1,2,4-triazole and 1,3,4-oxadiazole analogues (SS 1-SS 10). The molecules were characterized by IR, mass, 1H NMR, 13C NMR and elemental analysis. The in vitro antimicrobial activity was investigated against pathogenic strains, the results were explained with the help of DFT and PM6 molecular orbital calculations. In vitro cytotoxicity and genotoxicity of the molecules were studied against S. pombe cells. In vitro antimalarial activity was studied. The active compounds were further evaluated for enzyme inhibition efficacy against the receptor Pf-DHFR computationally as well as in vitro to prove their candidature as lead dihydrofolate reductase inhibitors.

Synthesis and structure of dithizonato complexes of antimony(III), copper(II) and tin(IV)

In view of the important role of dithizone in trace metal analyses, new structural aspects and approaches used to probe metal complexes of dithizone are of interest. Three X-ray diffraction structures are reported, dichloridobis(dithizonato)tin(IV), dichlorido(dithizonato)antimony(III), and bis(dithizonato)copper(II). During synthesis of the tin complex, auto-oxidation of SnIICl2 to SnIV occurred without chloride liberation. The SbIII complex revealed a unique distorted see-saw geometry which is, as for the other complexes, predicted by DFT molecular orbital calculations. The computed products of the lowest energy reactions are in agreement with experimentally obtained reaction products, which, together with molecular orbital renderings serve as a tool toward prediction of modes of coordination in these complexes. The S–M–N bond angle in the five-membered coordination ring shows a linear relationship with the corresponding metal ionic radii.

The DMDO Hydroxylation of Hydrocarbons via the Oxygen Rebound Mechanism.

Both DFT and G4 molecular orbital calculations have been employed to reexamine the mechanism of dimethyldioxirane (DMDO) oxidation of saturated hydrocarbons and the epoxidation of alkenes. The UM062X DFT functional provided the most accurate bond O-O dissociation energies for a series of typical peroxides. A diradicaloid process initiated by an O-O homolytic bond cleavage involving abstraction of hydrogen from the C-H bond followed by a final product forming "oxygen rebound" step best describes the DMDO oxidation of saturated hydrocarbons. In contrast, this study showed that the DMDO epoxidation of alkenes is a concerted process best described with the B3LYP DFT functional.

Molecular Structures of Isomeric Ortho, Meta, and Para Bromo-Substituted α-Methylsulfonyl-α-diethoxyphosphoryl Acetophenones by X-ray and DFT Molecular Orbital Calculations

The X-ray single crystal analysis of isomeric ortho, meta, and para bromo-substituted α-methylsulfonyl-α-diethoxyphosphoryl acetophenones showed that this class of compound adopts synclinal (gauche) conformations for both [-P(O)(OEt)2] and [-S(O)2Me] groups, with respect to the carbonyl functional group. The phosphonate, sulfonyl, and carbonyl functional groups are joined through an intramolecular network of attractive interactions, as detected by molecular orbital calculations at the M06-2X/6-31G(d,p) level. These interactions are responsible for the more stable conformations in the gas phase, which also persist in the solid-state structures. The main structural distinction in the title compounds relates to the torsion angle of the aryl group (with respect to the carbonyl group), which gives rise to different interactions in the crystal packing, due to the different positions of the Br atom.

Connecting Classical QSAR and LERE Analyses Using Modern Molecular Calculations, LERE-QSAR (VI): Hydrolysis of Substituted Hippuric Acid Phenyl Esters by Trypsin.

The reaction mechanism of trypsin was studied by applying DFT and ab initio molecular orbital (MO) calculations to complexes of trypsin with a congeneric series of eight para-substituted hippuric acid phenyl esters, for which a previous quantitative structureactivity relationship (QSAR) study revealed nice linearity of Hammett substitution constant σ(-) with logarithmic values of the MichaelisMenten and catalytic rate constants. Based on the LERE procedure, we performed QSAR analyses on each elementary reaction step during the acylation process. The present calculations showed that the rate-determining step during the acylation process is the transition state (TS) between the enzymesubstrate complex (ES) and tetrahedral intermediate (TET), and that the proton transfer occurs from Ser195 to His57, not between His57 and Asp102. The LERE-QSAR analysis statistically suggested that the variation of overall free-energy changes leading to formation of TS is governed mostly by that of activation energies required to form TS from ES. In spite of a very limited number of congeneric ligands in the current work, it is critically essential to clarify and verify physicochemical meanings of a typical QSAR/Chemoinformatics parameter, Hammett σ(-) based on quantum chemical calculations on the proteinligand kinetics; how Hammett σ(-) behaves in terms of proteinligand interaction energies.

Computationally Designed Atovaquone Prodrugs Based on Bruice’s Enzyme Model

DFT molecular orbital calculations at B3LYP 6-31G (d,p) and B3LYP/311+G (d,p) levels and molecular mechanics (MM2) calculations of kinetic properties for Bruice's systems 1-5 indicate that the rate enhancement in the cyclization of di-carboxylic semi-esters 1-5 is solely the result of strain effects and not proximity orientation 'reactive rotamer effect". Furthermore, it was found that the activation energy in systems 1-5 and atovaquone ProD1- ProD5 is largely dependent on the difference in the strain energies of the tetrahedral intermediates and reactants, and no correlation was found between the cyclization rate and distance between the nucleophile and the electrophile (rGM). Using the experimental t1/2 (the time needed for the conversion of 50% of the reactants to products) value for the cyclization reaction of di-carboxylic semi-ester 1 and the calculated log krel values for prodrugs ATQ ProD1- ProD5 the t1/2 values for the interconversion of ATQ ProD1- ProD5 to the parent drug were calculated. Thet1/2 values were: ATQ ProD3, 22.44 hours; ATQ ProD1, ATQ ProD2 and ATQ ProD4, few seconds and ATQ ProD5 few years. Therefore, the interconversion rate of atovaquone prodrugs to atovaquone can be programmed according to the nature of the prodrug linker.

Mechanism and kinetic studies for OH radical-initiated atmospheric oxidation of methyl propionate

DFT molecular orbital theory calculations were carried out to investigate OH radical-initiated atmospheric oxidation of methyl propionate. Geometry optimizations of the reactants as well as the intermediates, transition states and products were performed at the B3LYP/6-31G(d,p) level. As the electron correlation and basis set effect, the single-point energies were computed by using various levels of theory, including second-order Møller–Plesset perturbation theory (MP2) and the coupled-cluster theory with single and double excitations including perturbative corrections for the triple excitations (CCSD(T)). The detailed oxidation mechanism is presented and discussed. The results indicate that the formation of 3-oxo-methyl propionate (HC(O)CH2C(O)OCH3) is thermodynamically feasible and the isomerization of alkoxy radical IM17 (CH3CH(O)C(O)OCH3) can occur readily under the general atmospheric conditions. Canonical variational transition-state (CVT) theory with small curvature tunneling (SCT) contribution was used to predict the rate constants. The overall rate constants were determined, k(T)(CH3CH2COOCH3 + OH) = (1.35 × 10−12)exp(−174.19/T) cm3 molecule−1 s−1, over the possible atmospheric temperature range of 180–370 K.

Notable Effects of Metal Salts on UV–Vis Absorption Spectra of α-, β-, γ-, and δ-Tocopheroxyl Radicals in Acetonitrile Solution. The Complex Formation between Tocopheroxyls and Metal Cations

The measurements of the UV-vis absorption spectra of α-, β-, γ-, and δ-tocopheroxyl (α-, β-, γ-, and δ-Toc(•)) radicals were performed by reacting aroxyl (ArO(•)) radical with α-, β-, γ-, and δ-tocopherol (α-, β-, γ-, and δ-TocH), respectively, in acetonitrile solution including three kinds of alkali and alkaline earth metal salts (LiClO(4), NaClO(4), and Mg(ClO(4))(2)) (MX or MX(2)), using stopped-flow spectrophotometry. The maximum wavelengths (λ(max)) of the absorption spectra of the α-, β-, γ-, and δ-Toc(•) located at 425-428 nm without metal salts increased with increasing concentrations of metal salts (0-0.500 M) in acetonitrile and approached some constant values, suggesting (Toc(•)···M(+) (or M(2+))) complex formations. Similarly, the values of the apparent molar extinction coefficient (ε(max)) increased drastically with increasing concentrations of metal salts in acetonitrile and approached some constant values. The result suggests that the formations of Toc(•) dimers were suppressed by the metal ion complex formations of Toc(•) radicals. The stability constants (K) were determined for Li(+), Na(+), and Mg(2+) complexes of α-, β-, γ-, and δ-Toc(•). The K values increased in the order of NaClO(4) < LiClO(4) < Mg(ClO(4))(2), being independent of the kinds of Toc(•) radicals. Furthermore, the K values increased in the order of δ- < γ- < β- < α-Toc(•) radicals for each metal salt. The alkali and alkaline earth metal salts having a smaller ionic radius of the cation and a larger charge of the cation gave a larger shift of the λ(max) value, a larger ε(max) value, and a larger K value. The result of the DFT molecular orbital calculations indicated that the α-, β-, γ-, and δ-Toc(•) radicals were stabilized by the (1:1) complex formation with metal cations (Li(+), Na(+), and Mg(2+)). Stabilization energy (E(S)) due to the complex formation increased in the order of Na(+) < Li(+) < Mg(2+) complexes, being independent of the kinds of Toc(•) radicals. The calculated result also indicated that the metal cations coordinate to the O atom at the sixth position of α-, β-, γ-, and δ-Toc(•) radicals.

Raman Optical Activity and Raman Spectra of Amphetamine Species—Quantum Chemical Model Calculations and Experiments

Theoretical calculations and preliminary measurements of vibrational Raman optical activity (ROA) spectra of different species of amphetamine (amphetamine and amphetamine-H+) are reported for the first time. The quantum chemical calculations were carried out as hybrid ab initio DFT-molecular orbital calculations by use of the Gaussian 03W program, based on complete geometry minimizations of the conformational energy of the S-(+)-amphetamine molecule, the S-(+)-amphetamine-H+ ion, and the R-(–)-amphetamine molecule. Following this, harmonic frequency calculations have been made, providing information about the cation vibrational bands, expected in salts of single anions (chlorides) as well as in salts of anions with internal bonds (sulfates, hydrogen phosphates, etc.). It shows that the kind of anion should be given better attention, as so far it has often not been the case, when the spectra are employed for identification purposes. The DFT calculations show that the most stable conformations are those allowing for close contact between the aromatic ring and the amine hydrogen atoms. The internal rotational barrier within the same amphetamine enantiomer has a considerable influence on the Raman and ROA spectra. As predicted the experimental ROA spectra were found to depend on the chirality. Two street samples, provided by the London Police, were also measured and compared to the calculated ROA spectra. The street samples were found to contain different enantiomers of the protonated amphetamine-H+ sulfate. According to the present study the AMPH+ ion in aqueous sulfate solution seems to adopt a conformation in which the phenyl and ammonium groups are in transpositions, similar to what has been found in the solid state.

Torsional Energy Barriers in Dimethyl Ether and Perfluoro-Dimethyl Ether: Electronic Structure Contributions

The optimized geometries, torsional energy barriers and atomic charge in dimethyl ether and perfluoro-dimethyl ether have been investigated with density functional theory (dft) molecular orbital calculations. The optimized dimethyl ether (DME) and perfluoro-dimethyl ether (PFDME) geometries have been obtained and are in good agreement with experimental results. The torsional energy barriers for both the DME and PFDME have been calculated by incrementally increasing the dihedral angle and performing a full-geometry optimization. The DME and PFDME barriers have been compared, and the geometries of the transition states for both molecules are given. The net atomic charges of both the optimized and transition state species are calculated for both DME and PFDME and shown to be consistent with a stereoelectronic effect (anomeric) that mixes an anti-bonding C–H-centered molecular orbital and an oxygen lone pair. The effects of this antiperiplanar electronic interaction are discussed, and the calculated torsion energy barriers are justified using a simplified second-order bonding model.

DFT molecular orbital calculations of initial step in decomposition pathways of TNAZ and some of its derivatives with –F, –CN and –OCH3 groups

1,3,3-Trinitroazetidine (TNAZ) and its derivatives are highly desirable energetic compounds, which can be used in explosive and/or propellant formulations. In this paper, the quantities of activation barriers, enthalpies, entropies and free energies of a few initial steps in the decomposition pathways of TNAZ and some of its derivatives with –F, –CN and –OCH3 groups have been computed by means of DFT with B3LYP/6–31G** model. The initial decomposition pathways including NO2 fission, HONO elimination and direct ring-opening reaction are investigated. For all of molecules, the results essentially confirm that the N–NO2 fission is the convenient pathway in the kinetics and thermodynamic properties of their decomposition.

Analysis of anomeric effects in some oxa diaza spiro decan derivatives by DFT molecular orbital calculations

The conformational behavior of oxa diaza spiro decan derivative compounds has been investigated using DFT calculations at the B3LYP/cc-pVDZ level of theory. Natural bond orbital (NBO) analysis of the total energy behavior yielded the orbital-interaction factors contributing to the conformational equilibria. The relative energies, NBO analysis and structural parameters predicted that steric and anomeric effects determine the stabilization of the axial and/or equatorial conformers. The dipole moments of the optimized systems were used to estimate the electrostatic contributions to the anomeric effect. The results of calculations indicated that the axial conformers are the most stable in all of the studied compounds. Finally, the strain energy barriers for the most stable conformers were calculated at HF/6-311G*//HF/6-311G* level of theory. Interconversion between chair and twist conformations takes place via the half-chair as transition state. The lowest calculated strain energy for this process is 42.41 kJ mol −1.

Effects of substitution on the effective molarity (EM) for five membered ring-closure reactions – A computational approach

DFT molecular orbital calculations of kinetic parameters for ring closing reactions of substituted 4-bromobutyl alcohols 1–5 and 4-bromobutyl amines 6–10 (Brown’s system) indicate that accelerations in ring closing rate in both systems are largely the result of strain effects as opposed to the currently advanced proximity orientation. Furthermore, the calculated effective molarity (EM) values derived from the DFT data reveal that replacing the nitrogen (6–10, Brown’s system) with an oxygen (1–5, alcoholic analog) results in a decrease in demands on directional flexibility to form 5-membered ring, thus enhancing the rate of the cyclization reaction. In the absence of experimental data the DFT approach could be utilized to predict effective molarities (EM) for intramolecular processes.

Structural studies of trans-N 2S 2 copper macrocycles

The X-ray crystal structures of two related trans-N 2S 2 copper macrocycles are reported. One was isolated with the copper in the divalent form and the other with copper in its univalent form affording a valuable insight into the changes of geometry and metrical parameters that occur during redox processes in macrocyclic copper complexes. A variable temperature NMR study of the copper(I) complex is reported, indicative of a chair-boat conformational change within the alkyl chain backbone of the macrocycle. It was possible to extract the relevant kinetic and thermodynamic parameters (ΔG ‡, 57.8 kJ mol −1; ΔH ‡, 52.1 kJ mol −1; ΔS ‡, −19.2 J K −1 mol −1) for this process at 298 K. DFT molecular orbital calculations were used to confirm these observations and to calculate the energy difference (26.2 kJmol −1) between the copper(I) macrocycle in a planar and a distorted tetrahedral disposition.

The influence of crystal packing effects upon the molecular structures of Ph3Sn(CH2)nSnPh3, n = 1 to 8, as determined by X-ray crystallography and DFT molecular orbital calculations. Supramolecular aggregation patterns sustained by C–H⋯π interactions

Crystallography shows that with the exception of the n = 1 and n = 6 derivatives, molecules of dinuclear Ph3Sn(CH2)nSnPh3, n = 1 to 8, display extended conformations where a pair of triphenyltin moieties are linked by methylene bridges of varying length. Discernable supramolecular aggregation patterns stabilised by C–H⋯π contacts lead to chains and ladders or even 2D arrays in most of the solid-state structures. In all but the n = 1 molecule, with inherent steric hindrance which precludes the adoption of molecular symmetry, symmetry is evident in all of the geometry optimised structures calculated using DFT methods; non-systematic variations in geometric parameters apparent in the experimental structures do not persist in the theoretical structures. The greatest disparity between the experimental and theoretical structures is found for the n = 6 compound, featuring a hexamethylene bridge. The linear conformation calculated in the gas-phase distorts to form a curved molecule to allow the more efficient crystal packing of spherical molecules, as for the spherical n = 1 molecule. In the remaining structures, the global crystal packing is based on the stacking of rod-like molecules.

Out-of-plane Deformation of the Azulene Ring along Its Short Molecular Axis in Crystal and Theoretical Structures of 1,3-Diheterolyl- and 1,3-Diphenylazulenes

Crystal structures of four simple azulene derivatives, 1,3-diheterolyl-and 1,3-diphenylazulenes, were determined by X-ray diffraction analysis. Three of them showed clear out-of-plane deformation of the azulene ring along its short molecular axis, and one showed a similar but very small deformation. Structural and conformational analyses on substituted azulenes were also performed by DFT molecular orbital calculations. Based on the results of the calculations it was indicated that azulenes could exhibit such deformation depending on their conformations except one case, supporting the results of X-ray analysis. A similar deformation was also found in the crystal structure of a previously reported 1,3-disubstituted azulene whose data were collected from an X-ray crystal structure database.

Disulfido iron–manganese carbonyl cluster complexes: Synthesis, structure, bonding and properties of the radical CpFeMn 2(CO) 7(μ 3-S 2) 2

Two new compounds CpFeMn 2(CO) 7(μ 3-S 2) 2 ( 2) and Cp 3Fe 3Mn(CO) 4(μ 3-S 2) 2(μ 3-S) ( 3) were obtained by the treatment of [CpFeMn(CO) 5(μ 3-S 2)] 2 ( 1) with CO at room temperature in the presence of room light. Compound 2 contains two triply bridging disulfido ligands on opposite sides of an open FeMn 2 triangular cluster. EPR and temperature-dependent magnetic susceptibility measurements show that it is paramagnetic with one unpaired electron per formula equivalent. The electronic structure of 2 was established by DFT and Fenske-Hall (FH) molecular orbital calculations which show that the unpaired electron occupies a low lying antibonding orbital that is located principally on the iron atom. The cyclic voltammogram of 2 exhibits one reversible one-electron oxidation wave at +0.34 V and one irreversible one-electron reduction wave at −0.66 V vs. Ag/AgCl. Compound 3 contains three iron atoms and one manganese atom with two triply bridging disulfido ligands and one triply bridging sulfido ligand and has no unpaired electrons. The molecular structures of compounds 2 and 3 were established by single crystal X-ray diffraction analyses.