<Emphasis Type="Italic">Ab initio</Emphasis> and DFT investigation of electrophilic addition reaction of bromine to <Emphasis Type="Italic">endo,endo</Emphasis>-tetracyclo[4.2.1.1<Superscript>3,6</Superscript>.0<Superscript>2,7</Superscript>]dodeca-4,9-diene

Full geometric optimization of endo,endo-tetracyclo[4.2.1.1^3,6.0^2,7]dodeca-4,9-diene (TTDD) has been carried out by ab initio and DFT/B3LYP methods and the structure of the molecule investigated. The double bonds of TTDD molecule are endo pyramidalized. The structure of π-orbitals and their mutual interactions for TTDD molecule were investigated. The cationic intermediates and products obtained as a result of the addition reaction have been studied using the HF/6-311G(d), HF/6-311G(d,p) and B3LYP/6-311G(d) methods. The bridged bromonium cation isomerized into the more stable N- and U-type cations and the difference between the stability of these cations is small. The N- and U-type reaction products are obtained as a result of the reaction, which takes place via the cations in question. The stability of exo, exo and exo, endo isomers of N-type product are nearly the same and the formation of both isomers is feasible. The U-type product basically formed from the exo, exo-isomer. Although the U-type cation was 0.68 kcal mol⁻¹ more stable than the N-type cation, the U-type product was 4.79 kcal mol⁻¹ less stable than the N-type product. Figure The energy diagram of TTDD–Br₂ system (kcal mol⁻¹)(MP2/6-311G*//HF/6-311G*)     

Ab initio and DFT study on the electrophilic addition reaction of bromine to tetracyclo[5.3.0.02,6.03,10]deca–4,8–diene

The electronic and geometric structures of tetracyclo[5.3.0.0^2,6.0^3,10]deca-4,8-diene (hypostrophene) have been investigated by ab initio and DFT/B3LYP methods using the 6-31G* and 6-311G* basis sets. The double bonds of hypostrophene are endo-pyramidalized. The cationic intermediates and products formed in the addition reaction have been investigated using the HF/6-311G*, HF/6-311G**, and B3LYP/6-311G* methods. The bridged bromonium cation was more stable than the U-type cation. Considering that the bridged cation does not isomerize to the less stable U-type cation, it is not possible for the U-type product to be obtained in the reaction. The bridged bromonium cation transformed into the more stable N-type cation and the N-type product was obtained via this cation. The thermodynamic stability of the exo, exo and exo, endo isomers of the N-type dibromide molecule were almost identical. The N-type product was 16.6 kcal mol⁻¹ more stable than the U-type product. Figure General energy diagram of the hypostrophene–bromine (HS–Br₂) system (kcal mol⁻¹) (MP2/6-311G*//HF/6-311G*)     

DFT and MP2 study on the electrophilic addition reaction of bromine to exo-tricyclo[3.2.1.02.4]oct-6-ene

The geometry and electronic structure of exo-tricyclo[3.2.1.0^2,4]oct-6-ene (exo-TCO) was investigated using DFT methods. The two faces of the endo-pyramidalised double bond of the molecule are not equivalent. The exo face of the double bond has regions with high electron density (q _i,HOMO) and greater negative potential. Molecular complexes of exo-TCO with bromine were investigated using the B3LYP/6-311++G(d,p) method; the exo-TCO . . . Br₂(exo) molecular complex was found to be relatively more stable than the exo-TCO . . . Br₂(endo) complex. The cationic intermediates of the reaction were studied by DFT and MP2 methods. The solvent effect was evaluated using the self-consistent isodensity polarised continuum model (SCI-PCM). The exo-bromonium cation was found to be more stable than the endo-bromonium cation. Exo-facial selectivity due to electronic and steric factors was observed upon addition of bromine to exo-TCO. The multicentre nonclassical delocalised bromocarbonium cation IV and the exo-bridged-bromonium cation I are more stable than the rearrangement cation V. The reaction products are formed via exo-bridged-bromonium I and nonclassical IV cations, which are the most stable intermediates and whose stabilities barely differ. The mechanism of the addition reaction is also discussed.     

Ab initio and DFT study on the electrophilic addition of bromine to endo-tricyclo[3.2.1.02,4]oct-6-ene

Full geometric optimization of endo-tricyclo[3.2.1.0^2,4]oct-6-ene (endo-TCO) by ab initio and DFT methods allowed us to investigate the structure of the molecule. The double bond is endo-pyramidalized and its two faces are no longer found to be equivalent. The exo face of the double bond has regions with far more electron density (q_i,HOMO) and more negative electrostatic potential. The endo-TCO-Br₂ system was investigated at the B3LYP/6-311+G** level and the endo-TCO···Br₂(exo) molecular complex was found to be relatively more stable than the endo-TCO···Br₂(endo) complex. The cationic intermediates of the reaction were studied by ab initio and DFT methods. The bridged exo-bromonium cation(I) is relatively more stable than the endo-bromonium cation(II). An absolute exo-facial selectivity should be observed in the addition reaction of Br₂ to endo-TCO, which is caused by steric and electronic factors. The nonclassical rearranged cation IV was found to be the most stable ion among the cationic intermediates and the ionic addition occurs via the formation of this cation. The mechanism of the addition reaction is also discussed.     

Computational Study of the Sulfonylated Amino Acid Hydroxamates Binding to the Zinc Ion within the Active Site of Carbonic Anhydrase

Abstract

The B3LYP/6–311+G(d,p) method and three ONIOM extrapolation methods ONI-OM (B3LYP/6–311+G(d,p): AM1); ONIOM(B3LYP/6–311+G(d,p): MNDO); ONIOM (B3LYP/6–311+G(d,p): HF/3-21G(d)) were used to characterize the complexes of Zn²⁺ cation with anionic sulfonylated amino acid hydroxamates (RSO₂NH-AA-CON(-)OH), possessing an unsubstituted RSO₂NH—amino acyl moiety. According to the R moiety we distinguish between pentafluorophenyl and 4-methoxyphenyl derivates. The amino acid hydroxamates included in the study were the Gly, Ala, and Leu derivates. Of the inhibitors investigated, the weakest zinc affinity exhibits the pentafluorophenyl derivate with Gly amino acid and the strongest affinity the 4-methoxyphenyl derivate with Leu amino acid. The inhibitors form bidentate coordination bonds with the zinc cation by means of the sulfonyl oxygen and the ionized hydroxamate nitrogen atoms, respectively. The zinc affinities computed using the B3LYP/6–311 +G(d,p)//HF/6–31 +G(d,p) method are in very good agreement with the full density functional theory (DFT) B3LYP/6–311+G(d,p)//B3LYP/6- 311+G(d,p) method and this method can be adopted to model larger complexes of inhibitors with the active site of carbonic anhydrase.     

Density functional theory investigation of electrophilic addition reaction of bromine to tricyclo[4.2.2.22,5]dodeca-1,5-diene1

The geometry and the electronic structure of tricyclo[4.2.2.2^2,5]dodeca-1,5-diene (TCDD) molecule were investigated by DFT/B3LYP and /B3PW91 methods using the 6-311G(d,p) and 6-311++G(d,p) basis sets. The double bonds of TCDD molecule are syn-pyramidalized. The structure of π-orbitals and their mutual interactions for TCDD molecule were investigated. Potential energy surface (PES) of the TCDD-Br₂ system was studied by B3LYP/6-311++G(d,p) method and the configurations [molecular charge-transfer (CT) complex, transition states (TS1 and TS2), intermediate (INT) and product (P)] corresponding to the stationary points (minima or saddle points) were determined. Initially, a molecular CT-complex forms between Br₂ and TCDD. With a barrier of 22.336 kcal mol^-1 the CT-complex can be activated to an intermediate (INT) with energy 15.154 kcal mol^-1 higher than that of the CT-complex. The intermediate (INT) then transforms easily (barrier 5.442 kcal mol^-1) into the final, N-type product. The total bromination is slightly exothermic. Accompanying the breaking of Br-Br bond, C1-Br, C5-Br and C2-C6 bonds are formed, and C1 = C2 and C5 = C6 double bonds transform into single bonds. The direction of the reaction is determined by the direction of intramolecular skeletal rearrangement that is realized by the formation of C2-C6 bond.

A computer-aided quantum chemical study of the N<Stack><Subscript>15</Subscript><Superscript>−</Superscript></Stack> cluster

Ab initio (RHF, MP2) and Density Functional Theory (DFT) methods have been used to examine six isomers of the N15m cluster with the 6-31+G* basis set. Different from the known odd-numbered anionic N7m, N9m, and N11m clusters, in which the open-chain structures are the most stable species, the most stable N15m isomer is structure 1 (C1), which may be considered as a complex between the fragments cyclic N5m (D5h) and staggered N10 (D2d). The decomposition pathways of structure 2 (CS), containing two aromatic N5 rings connected by a N5 chain, and the open-chain structure 3 (C2v) were studied at the B3LYP/6-31+G* level of theory. Relative energies were refined at the level of B3LYP/6-311+G(3df,2p)//B3LYP/6-31+G*+ZPE (B3LYP/6-31+G*). The barriers for N2 and N5m (D5h) fission reactions for structure 2 are predicted to be 18.2 and 14.2 kcal x mol(-1), respectively. The corresponding N2+N3m fission barrier for structure 3 is predicted to be 11.2 kcal x mol(-1). Supplementary material is available for this article if you access the article at http://dx.doi.org/10.1007/s00894-003-0118-0. A link in the frame on the left on that page takes you directly to the supplementary material. Figure Structure 1 of the N15m cluster, showing bond distances in A and bond angles in degrees     

Structures and aromaticity of Cationic closo-$$ B_{n} H_{{n - 3}} {\left( {CO} \right)}^{ + }_{3} $$ (n = 5−12)

Structures and stabilities of tricarbonyl closo-boranes cation, BnHn-3(CO)3+ (n = 5-12), isolobal with cationic closo-carboranes C3Bn-3Hn+, have been investigated at the B3LYP/6-311+G** level of theory. The most stable positional isomers of individual cluster are in agreement with those of closo-C3Bn-3Hn+ clusters except for n = 8 and 10. Energetic analysis identifies closo-B6H3(CO)3+, closo-B10H7(CO)3+ and closo-B12H9(CO)3+ as the most stable cages. It is also found that closo-BnHn-3(CO)3+ is much less strained than closo-C3Bn-3Hn+. The negative nucleus independent chemical shifts (NICS) at the cage center reveal three-dimensional aromaticity of the closo-BnHn-3(CO)3+ cages. The CO stretching frequencies have been computed in advance to aid experimental study.     

Quantum-chemical investigation of the elementary molecular mechanisms of pyrimidine-purine transversions

Purine-purine mispairs of DNA (thus involving template base in anti-conformation along the glycosidic bond and base of the incoming nucleotide - in syn-conformation) leading to pyrimidine-purine "transversions"-type point mutations were revealed and characterized at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in vacuum approach adequately modeling hydrophobic environment of the active centre of high-fidelity replicative DNA-polymerases.     

Studies on molecular structure and tautomerism of a vitamin B<Subscript>6</Subscript> analog with density functional theory

This work presents a computational study on the molecular structure and tautomeric equilibria of a novel Schiff base L derived from pyridoxal (PL) and o-phenylenediamine by using the density functional method B3LYP with basis sets 6-31 G(d,p), 6-31++G(d,p), 6-311 G(d,p) and 6-311++G(d,p). The optimized geometrical parameters obtained by B3LYP/6-31 G(d,p) method showed the best agreement with the experimental values. Tautomeric stability study of L inferred that the enolimine form is more stable than its ketoenamine form in both gas phase and solution. However, protonation of the pyridoxal nitrogen atom (LH) have accelerated the formation of ketoenamine form, and therefore, both ketoenamine and enolimine forms could be present in acidic media.     

Rearrangements in icosahedral boranes and carboranes revisited

The structure, stability, and intermolecular rearrangements between ortho-, meta-, and para-C2B10H12 and were investigated using the hybrid density functional B3LYP/6-31G(d) for vibrational frequencies, as well as B3LYP/6-311+G(2d,p) for single-point electronic energies. The general trends in free energies of rearrangement between ortho-C2B10H12 to meta-C2B10H12 and meta-C2B10H12 to para-C2B10H12 presented here are consistent with experimental reaction temperatures. In addition, the majority of the rearrangements can be viewed in terms of concerted diamond-square-diamond steps and triangular face rotations.     

Structure and electronic properties of azadirachtin

We performed a combined DFT and Monte Carlo ¹³C NMR chemical-shift study of azadirachtin A, a triterpenoid that acts as a natural insect antifeedant. A conformational search using a Monte Carlo technique based on the RM1 semiempirical method was carried out in order to establish its preferred structure. The B3LYP/6-311++G(d,p), wB97XD/6-311++G(d,p), M06/6-311++G(d,p), M06-2X/6-311++G(d,p), and CAM-B3LYP/6-311++G(d,p) levels of theory were used to predict NMR chemical shifts. A Monte Carlo population-weighted average spectrum was produced based on the predicted Boltzmann contributions. In general, good agreement between experimental and theoretical data was obtained using both methods, and the ¹³C NMR chemical shifts were predicted highly accurately. The geometry was optimized at the semiempirical level and used to calculate the NMR chemical shifts at the DFT level, and these shifts showed only minor deviations from those obtained following structural optimization at the DFT level, and incurred a much lower computational cost. The theoretical ultraviolet spectrum showed a maximum absorption peak that was mainly contributed by the tiglate group.     

Conformational preferences of α,α-trehalose in gas phase and aqueous solution

This work presents an investigation on the conformational preferences of α,α-trehalose in gas phase and aqueous solution. Eighty-one systematically selected structures were studied at the B3LYP/6-311++G(d,p)//B3LYP/6-31G(d) level, giving rise to 40 unique conformers. The 19 lower energy structures and some selected other were further re-optimized at the B3LYP/6-311++G(d,p) level. The main factors accounting for the conformer’s stability were pointed out and discussed. NBO and QTAIM analyses were performed in some selected conformers in order to address the anomeric and exo-anomeric effects as well as intramolecular hydrogen bonding. The effect of solvent water on the relative stability of the conformers was accounted for by applying the conductor-like polarizable continuum model, CPCM.     

Absolute configuration of (−)-myrtenal by vibrational circular dichroism

The VCD spectrum of the monoterpene (−)-myrtenal (1) was compared with theoretical spectra using ab initio density functional theory (DFT) calculations at the B3LYP/6-31G(d,p), B3LYP/6-31G+(d,p), B3LYP/6-311G+(d,p), B3LYP/DGDZVP, and B3PW91/DGTZVP levels of theory. Conformational analysis of 1 indicated that the lowest energy conformer was s-trans-C2-C10, which contributes more than 98.5% to the total conformational population regardless of the employed level of theory. The use of a recently developed confidence level algorithm demonstrated that VCD spectra calculated for the main conformer, using the indicated hybrid functionals and basis set, gave no significant changes, from where it follows that B3LYP/DGDZVP calculations provide a superior balance between computer cost and VCD spectral accuracy. The DGDZVP basis set demanded around a quarter the time than the 6-311G+(d,p) basis set while providing similar results. The spectral comparison also provided evidence that the levorotatory enantiomer of myrtenal has the 1R absolute configuration.     

Racemization of the gastrointestinal antisecretory chiral drug esomeprazole magnesium via the pyramidal inversion mechanism: A theoretical study

The pyramidal inversion mechanisms of the 6‐methoxy and the 5‐methoxy tautomers of (S)‐omeprazole were studied, employing ab initio and DFT methods. The conformational space of the model molecule (S)‐2‐[(3‐methyl‐2‐pyridinyl)methyl]sulfinyl‐1H‐benzimidazole was calculated, with respect to rotations around single bonds, at the B3LYP/6‐311G(d,p) level. All of the resulting conformations were used as starting points for full optimizations of (S)‐omeprazole, at B3LYP/6‐31G(d), B3LYP/6‐311G(d,p), B3LYP/6‐311++G(d,p), B3LYP/6‐311G(2df,2pd), MP2/6‐31G(d), and MP2/6‐311G(d,p) levels. Four distinct pathways were found for enantiomerization via the pyramidal inversion mechanism for each of the tautomers of (S)‐omeprazole. Each transition state, in which the sulfur, the oxygen and the two carbon atoms connected directly to the sulfur are in one plane, connects two diastereomeric minima. The enantiomerization is completed by free rotation around the sulfur–methylene bond, and around the methylene–pyridine ring bond. The effective Gibbs' free energy barrier for racemization ΔG of the two tautomers of (S)‐omeprazole are 39.8 kcal/mol (5‐methoxy tautomer) and 40.0 kcal/mol (6‐methoxy tautomer), indicating that the enantiomers of omeprazole are stable at room temperature (in the gas phase). The 5‐methoxy tautomer of (S)‐omeprazole was found to be slightly more stable than the 6‐methoxy tautomer, in the gas phase. The energy barrier (ΔG^?) for the(S,M) (S,P) diastereomerization of (S)‐omeprazole due to the rotation around the pyridine chiral axis was very low, 5.8 kcal/mole at B3LYP/6‐311G(d,p). Chirality 2010. © 2010 Wiley‐Liss, Inc.     

Theoretical investigations of the hydrolysis pathway of verdoheme to biliverdin

Conversion of iron(II) verdoheme to iron biliverdin in the presence of OH(-) was investigated using B3LYP method. Both 3-21G and 6-31G* basis sets were employed for geometry optimization calculation as well as energy stabilization estimation. Calculation at 6-31G* level was found necessary for a correct spin state estimation of the iron complexes. Two possible pathways for the conversion of iron verdoheme to iron biliverdin were considered. In one path the iron was six-coordinate while in the other it was considered to be five-coordinate. In the six-coordinated pathway, the ground state of bis imidazole iron verdoheme is singlet while that for open chain iron biliverdin it is triplet state with 4.86 kcal/mol more stable than the singlet state. The potential energy surface suggests that a spin inversion take place during the course of reaction after TS. The ring opening process in the six-coordinated pathway is in overall -2.26 kcal/mol exothermic with a kinetic barrier of 9.76 kcal/mol. In the five-coordinated pathway the reactant and product are in the ground triplet state. In this path, hydroxyl ion attacks the iron center to produce a complex, which is only 1.59 kcal/mol more stable than when OH(-) directly attacks the macrocycle. The activation barrier for the conversion of iron hydroxy species to the iron biliverdin complex by a rebound mechanism is estimated to be 32.68 kcal/mol. Large barrier for rebound mechanism, small barrier of 4.18 kcal/mol for ring opening process of the hydroxylated macrocycle, and relatively same stabilities for complexes resulted by the attack of nucleophile to the iron and macrocycle indicate that five-coordinated pathway with direct attack of nucleophile to the 5-oxo position of macrocycle might be the path for the conversion of verdoheme to biliverdin.     

Theoretical investigation of hydrogen bonding effects on oxygen, nitrogen, and hydrogen chemical shielding and electric field gradient tensors of chitosan/HI salt

A density functional theory study has been carried out to calculate the (17)O, (15)N, (13)C, and (1)H chemical shielding as well as (17)O, (14)N, and (2)H electric field gradient tensors of chitosan/HI type I salt. These calculations were performed using the B3LYP functional and 6-311++G (d,p) and 6-31++G (d,p) basis sets. Calculated EFG and chemical shielding tensors were used to evaluate the (17)O, (14)N, and (2)H nuclear quadruple resonance, NQR, and (17)O, (15)N, (13)C, and (1)H nuclear magnetic resonance, NMR, parameters in the cluster model, which are in good agreement with the available experimental data. The difference in the isotropic shielding (sigma(iso)) and quadrupole coupling constant (C(Q)) between monomer and target molecule in the cluster was analyzed in detail. It was shown that both EFG and CS tensors are sensitive to hydrogen-bonding interactions, and calculating both tensors is an advantage. A different influence of various hydrogen bond types, N-Hcdots, three dots, centeredI, O-Hcdots, three dots, centeredI, and N-Hcdots, three dots, centeredO was observed on the calculated CS and EFG tensors. On the basis of this study, nitrogen and O-6 are the most important nuclei to confirm crystalline structure of chitosan/HI. These nuclei have large change in their CS and EFG tensors because of forming intermolecular hydrogen bonds. Moreover, the quantum chemical calculations indicated that the intermolecular hydrogen-bonding interactions play an essential role in determining the relative orientation of CS and EFG tensors of O-6 and nitrogen atoms in the molecular frame axes.     

Theoretical potential functions and vibrational analysis for halocarbonyl azides CXO-NNN (X=F,Cl and Br)

The structural stability of halocarbonyl azides CXO-NNN (X=F, Cl and Br) was investigated by DFT and MP2 calculations using the 6-311++G** basis set. From the calculations, the molecules were found to have an s-cis<--> s-trans conformational equilibrium with cis being the lower -energy form. Full energy optimizations were carried out for the transition states and the minima at the B3LYP/6 -311++G** and MP2/6 -311++G** levels, from which the rotational barriers were calculated to be of the order 8-10 kcal x mol(-1). The vibrational frequencies were computed at the DFT -B3LYP level and the vibrational assignments for the normal modes of the stable conformers were made on the basis of normal coordinate calculations.     

Experimental and theoretical study on the 1:1 supramolecular complexes of formamide with adrenaline

The electron transfer properties were investigated for supramolecular complexes of formamide (FA) with adrenaline (Ad) at graphite electrode and paraffine soaked graphite electrode using cyclic voltammetry (CV). The experimental results show that FA affected the electron transfer properties of Ad. The formed supramolecular complexes by hydrogen bond (H-bond) interaction between FA and Ad slowed down the diffusion ability of adrenaline, which makes it hard to donate electron and be oxidized. The H-bond interaction energies calculation for the supramolecular complexes of FA with Ad at MP2/6-311+G(d,p)//B3LYP/6-311+G(d,p) level have also been performed. The calculational results confirm the experimental fact that FA can form stable supramolecular complexes with Ad.     

Theoretical 49Ti NMR chemical shifts

⁴⁹Ti chemical shifts for a total of 20 titanium complexes are reported, and several levels of theory are evaluated in order to identify a reliable approach for the calculation of titanium NMR data. The popular B3LYP/6–31G(d)//B3LYP/6–31G(d) proves to give very good agreement with experimental data over a range from 1,400 to −1,300 ppm. The MP2/6–31G(d)//MP2/6–31G(d) level computes even smaller average deviations but fails for TiI₄. This behavior together with its huge demand for computational resources requires careful handling of this theoretical level. In addition, NMR data for five titanium fulvene (or related) complexes are given. Dedicated to Professor Dr. Paul von Ragué Schleyer on the occasion of his 75th birthday