Why betaine crystallizes in high local Cs symmetry. An ab initio MO and DFT study of anhydrous betaine and betaine monohydrate

A theoretical study of the structure, charge distribution, rotational barrier and fundamental vibrations of anhydrous betaine (CH₃)₃NCH₂COO (trimethylglycine) was carried out and compared with available experimental data. Calculations were carried out at HF, MP2 and B3LYP levels using a 6-31+G(d,p) basis set. The calculated rotational barrier of the betaine carboxylic group is 40.5 kJ/mol at the MP4(SDQ)/6-311G(d,p)//HF/6-31+G(d,p) level of theory. The rotation of the carboxylic group changes the molecule from a highly symmetric (C _s ) conformation into a twisted conformation resulting in shortening of the molecule by about 50 pm. Natural population analysis (NPA) indicates intramolecular interaction between the carboxylic oxygen and the nearest methyl hydrogens resulting in internal hydrogen bonding. MP4(SDQ)/6-311G(d,p) single-point NPA calculations on a betaine monohydrate model taken from the X-ray geometry show an expected weakening in the internal hydrogen bond. Calculations explain why betaine preferentially crystallizes in high local C _s symmetry. Received: 24 March 1998 / Accepted: 3 September 1998 / Published online: 7 December 1998     

Gas phase and water solution conformational analysis of the herbicide diuron (DCMU): an ab initio study

In the present work, the conformational equilibrium for the herbicide diuron (DCMU) has been investigated using high level ab initio calculations. The solvent effect was included through two different continuum models: (1) the real cavity IPCM method and (2) the standard dipole Onsager model SCRF. The effect due to solute-solvent hydrogen-bond interactions was analyzed considering a hybrid discreet-continuum model. At the Hartree-Fock level, the gas phase results showed that only the trans forms (A and B) are present in the equilibrium mixture, with the relative concentrations found to be 33% (A) and 67% (B) (HF/6-311+G**//6-31G**). When the electronic correlation effect is included (MP2/6-31G*//HF/6-31G*), a relative stabilization of the cis forms was observed, with the conformational distribution calculated as 38% (A), 50% (B), 6% (C) and 6% (D). The trans conformations were found to be completely planar, which has been considered to be a prerequisite for the herbicide binding. In water solution, the trans conformation A should be the most abundant conformer, the IPCM and SCRF values being ca. 100% and ca. 85% respectively. The IPCM calculations with the isodensity level set to 0.0005 present a conformational distribution close to that obtained from the hybrid model [92% (A) and 8% (B)], which has been considered our best solvent approach. Regarding the biological action of urea-type herbicides, the results presented here are important, because some QSAR studies have suggested that the partition coefficient is related to the herbicide activity, so the conformational equilibrium may play a role in the biological action. Received: 23 February 1998 / Accepted: 28 May 1998 / Published online: 19 August 1998     

Bis-periazulene: a simple Kekulé biradical with a triplet ground state

B3LYP/6-31G* calculations on bis-periazulene (cyclohepta[def]-fluorene) predict a triplet ground state for this molecule. The singlet has an aromatic 14π-electron periphery but is 2 kcal/mol higher in energy. The results agree with earlier predictions by Heilbronner. Received: 19 August 1998 / Accepted: 6 October 1998 / Published online: 23 February 1999     

An ab initio Molecular Orbital Study of the Conformational Properties of all-( Z )-Cyclododeca-1,4,7,10-tetraene

 Ab initio HF/6-31G^* and MP2/6-31G^*//HF/6-31G^* methods were used to calculate the structure optimization and conformational interconversion pathways for all-(Z )-cyclododeca-1,4,7,10-tetraene. This compound adopts the symmetrical crown (C _4v) conformation. Ring inversion takes place via symmetrical intermediates, such as boat-chair (BC, C _s) and twist (C _2h) conformers and requires about 22.3 kJ · mol⁻¹. The calculated strain energies for BC and twist conformers are 5.9 and 13.5 kJ · mol⁻¹. The results of semiempirical AM1 calculations for structural parameters and relative energies of the important geometries of the title compound are in good agreement with the results of ab initio methods.     

An ab initio Molecular Orbital Study of the Conformational Properties of all-(Z)-Cyclododeca-1,4,7,10-tetraene

Summary.  Ab initio HF/6-31G^* and MP2/6-31G^*//HF/6-31G^* methods were used to calculate the structure optimization and conformational interconversion pathways for all-(Z )-cyclododeca-1,4,7,10-tetraene. This compound adopts the symmetrical crown (C _4v) conformation. Ring inversion takes place via symmetrical intermediates, such as boat-chair (BC, C _s) and twist (C _2h) conformers and requires about 22.3 kJ · mol⁻¹. The calculated strain energies for BC and twist conformers are 5.9 and 13.5 kJ · mol⁻¹. The results of semiempirical AM1 calculations for structural parameters and relative energies of the important geometries of the title compound are in good agreement with the results of ab initio methods. Received July 9, 2001. Accepted September 26, 2001     

Density functional calculations of the pseudorotational flexibility of tetrahydrofuran

The flexibility of the five-membered ring in tetrahydrofuran was investigated using quantum mechanical methods involving density functional, Hartree-Fock, and many-body perturbation theory (MP2, MP4) calculations. We found that motion along the pseudorotational path of tetrahydrofuran is nearly free. The 0.1 kcal/mol energy barrier for pseudorotation, calculated at the highest MP4(SDQ)/6-311++G(2d,p)//MP2/6-311++G(2d,p) level of theory, agrees well with the experimental value of 0.16±0.03 kcal/mol. Similar results were obtained with the S-VWN, B3-LYP and B-LYP density functional calculations using the 6-31G(d) set of atomic orbitals. Also the density functional dipole moments and geometries were in good agreement with both the MP2 and experimental benchmarks. However, all density functional methods that utilized the default integration grid in the Gaussian 94 program were found to provide false stationary points of the C ₁ symmetry near the pseudorotational angle of 100°. These stationary points disappeared when a denser spherical-product grid was used. Overall, the hybrid B3-LYP functional was found to be the most promising quantum mechanical method for the modeling of biomolecules containing the furanose ring. Received: 17 June 1997 / Accepted: 20 November 1997     

An ab initio study of electrophilic aromatic substitution

Proton affinities are calculated at all reactive positions for the normal benzenoid hydrocarbons, benzene, naphthalene, phenanthrene and anthracene, a strained benzenoid hydrocarbon, biphenylene, and a nonalternant hydrocarbon, fluoranthene, and the results are compared to experimental protodetritiation rates. Methods used include PM3 and Hartree-Fock calculations at the STO-3G, 3-21G*, 6-31G* and MP2//6-31G* levels. Generally good agreement is found between theory and experiment with 6-31G* giving the best correlations. Received: 11 June 1998 / Accepted: 3 September 1998 / Published online: 23 February 1999     

Complexes of ammonia with propane and cyclopropane: electrostatic guidelines for ab initio treatment

A model based on the molecular electrostatic potential (MESP) is employed for the investigation of structures and energies of complexes of ammonia with propane and cyclopropane. The electrostatic model geometries are employed as starting points for an ab initio investigation at the self-consistent field and second-order M?ller-Plesset (MP2) levels. The most stable structures of C₃H₆..NH₃ and C₃H₈..NH₃ complexes have the interaction energies of 10.07 kJ/mol and 8.15 kJ/mol, respectively, at the MP2/6-31G(d,p) level. The energy rank order of the structures is not altered with the use of the 6-31++G(d,p) basis set, and the basis␣set superposition error has little effect. The interaction energy decomposition analysis shows that the electrostatic component is dominant over the other ones. MESP topography thus seems to offer valuable hints for predicting the structures of weakly bonded complexes. Received: 8 July 1998 / Accepted: 4 August 1998 / Published online: 2 November 1998     

Theoretical study on decomposition of γ-halo allylalkoxide and β-halo acrylate ions

β, γ-Substituted γ-halo allylalkoxide ions decompose to form a halogen ion, formaldehyde, and an alkyne under mild conditions, for example at room temperature. The E isomer does not differ from the Z isomer in terms of activation energy. We attempted to shed light on the mechanism of the reaction by using ab initio molecular orbital calculations. The observed propensity was confirmed by the present calculation on model molecules, γ-chloro allylalkoxide ions. We conducted further calculations and compared the alkoxide results with a similar reaction of β-haloacrylate ions that release carbon dioxide instead of formaldehyde. This similar reaction needs heating as high as 150°C. The activation energy of the acrylate ions (36–39 kcal mol⁻¹) was calculated to be about 10 kcal mol⁻¹ higher than that of the alkoxide ions. The activation energy of the E acrylate ion is smaller by 0.8 kcal mol⁻¹ than that of the Z isomer at the MP2/6-31+G**//RHF/6-31+G* level of theory. This is consistent with experimental results. While the ready deprotonation from the carboxylic group does not activate the acrylate ion very much, the alkoxide ion is destabilized to a great degree in the process of anion formation. The difficulty in deprotonation that proceeds from the neutral molecule is seen in the difference in the activation energies for the decomposition of the corresponding anions. Therefore, the pK _a of a hydroxy or a carboxylic group plays the leading role in determining the magnitude of activation energies of allyl halides with a negatively charged fragment. Received: 2 July 1998 / Accepted: 9 September 1998 / Published online: 8 February 1999     

Static electric properties of LiH: explicitly correlated coupled cluster calculations

Explicitly correlated MBPT-R12 and coupled cluster [up to CCSD(T)-R12] methods have been used in calculations of various (vibrationless) electrical properties for the LiH molecule, including the dipole and quadrupole moments, dipole and quadrupole polarizability tensors, dipole hyperpolarizability tensors, and the second dipole hyperpolarizability tensors. Generally, with extension of the basis set the R12 method did not lead to faster convergence for the calculated properties towards the basis limit. Nevertheless, R12 calculations serve as useful indicators to judge the reliability of the results, and substantially help in determining the accuracy. Results obtained with the 11s8p6d5f/9s8p6d5f basis and CCSD(T)-R12 calculated within this work should be close to the basis set limit. Received: 8 June 1998 / Accepted: 23 July 1998 / Published online: 7 October 1998     

Conformational Isomerism and Chlorotropy Mechanisms of Chloromethyl- and Trichloromethyldichlorophosphines

³⁵Cl NQR spectroscopy and MP2//RHF/6-31⁺⁺G(d,p) and MNDO-PM3 calculations were used to study the conformational and chlorotropic isomerism of chlorodimethyldichlorophosphine (I) and trichloromethyldichlorophosphine (II). The experimental ³⁵Cl NQR spectrum is in complete accord with the staggered conformation of phosphine II obtained using an RHF/6-31⁺⁺G(d,p) calculation. The rotational barrier of the CCl₃ group is 38.1 kJ/mol. On the other hand, the spectrum of phosphine I is in accord with a gauche conformation, which agrees with experiment only upon taking account of electron correlation (MP2). The ylide and phosphinic chlorotropic isomers for I and II are thermodynamically stable with greater stability found for II. The chlorotropic phosphine–ylide conversion in system I proceeds exclusively through a sigmatropic transition state in qualitative accord with nonempirical and semiempirical calculations. Such a conversion is theoretically possible in system II by means of dissociation of the P⁺—C^– ylide bond.     

Conformational flexibility of 1,3-cyclohexadiene and its aza analogs

The conformational flexibility of 1,3-cyclohexadiene and its analogs — pyridine and pyrimidine derivatives— was studied by HF/6-31G** ab initio quantum chemical calculations. The potential surface calculations and normal vibration shape analysis show that the molecules exhibit two weakly coupled ring deformation modes. One of the modes may be described as rotation around the C(sp₃)-C(sp₂) bond leading to a transition state of the ring inversion process. The other mode involves flattening of the butadiene fragment and a loss of planarity for endocyclic double bonds without any pronounced changes in the conformation of the saturated part of the molecule. An accurate calculation of the ring inversion barrier demands inclusion of electron correlation effects. Translated fromZhurnal Strukturnoi Khimii, Vol. 41, No. 3, pp. 474-479, May-June, 2000.     

Ab Initio and DFT Studies on the Structure,Infrared Spectrum,and Thermodynamic Properties of Hoechst 33258

Ab initio and DFT(B3LYP) levels of theory, with basis sets of 3–21G, 6–31G*, and LanL2DZ, have been applied to the specific DNA binder Hoechst 33258. All calculations lead to a structure with two benzimidazole groups and one phenyl group being coplanar. Atoms H₃₃ and H₃₇ bear large positive charges, and the distance between the two atoms is about 5 Å, which allows the molecule interacting with the negative sites of neighboring bases in the DNA helix and thus facilitates Hoechst 33258 to gravitate on AT‐rich regions in the minor groove of DNA, owing to the deeper negative potential in such sequences. The most stable conformer corresponds to the dihedral angles of ca. 0° for ?_{1‐2‐14‐15} and ?_{27‐26‐5‐4}, and 180° for ?_{20‐19‐11‐12}. This fact provides clear evidence that Hoechst 33258 has an arc‐like shape with coplanar aromatic rings. Both the HOMO and the LUMO are made up of the P_z orbitals of the non‐hydrogen atoms in two benzimidazole groups and one phenyl group. On going from the ground state to the first singlet excited state, the lengths of the single bonds between the aromatic rings decrease, and the aromatic rings are more conjugated with each other in the excited state. The heat of formation (ΔH_f) of Hoechst 33258, evaluated from the isodesmic reaction, is 406.32 kJ/mol at the B3LYP/6–31G* level.     

Ab initio study of tautomerism and hydrogen bonding of β-carbonylamine in the gas phase and in water solution

All the possible conformations of the three tautomeric isomers of simple β-carbonylamine were fully optimized at ab initio MP2/6-31G** and B3LYP/6-31G** levels in order to determine the conformational equilibrium and the energies of the O—H···N and O···H—N hydrogen bridges. For the most interesting conformations, further calculations in water solution were also carried out. It was found that carbonylamine is the most stable tautomer, followed by enolimine and carbonylimine. This order of stability does not change in solution. O—H···N is the strongest hydrogen bridge, but in solution its energy as well as that of the O···H—N one are dramatically lowered. The deprotonation energy was also calculated and discussed. Received: 16 September 1999 / Accepted: 3 February 2000 / Published online: 5 June 2000     

Solvent influence on the rotational isomerism in terephthalaldehyde

Experimental and theoretical studies were carried out in order to investigate the rotational isomerism of terephthalaldehyde. The dipole moment measurements and infrared spectroscopy in Ar matrix and using various solvents were performed experimentally. In order to supplement the experimental study, both static and dynamical theoretical calculations were performed. IR spectra and potential energy distribution (PED) were calculated for both cis and trans isomers of terephthalaldehyde in gas phase using B3LYP/6-31G(d,p) level of theory. Further calculations consisted of conformational analysis were performed in order to estimate the rotational barrier and relative stabilities of isomers. The DFT theory with B3LYP functional and four double-zeta and triple-zeta basis sets served as framework for this part of calculations. Semiempirical AM1 and PM3 methods were also used for gas-phase modeling. Molecular dynamics using MM3 force field was applied to study the preferences of solvent molecules’ orientation around the studied molecule. Additionally, the effect of solvent polarity on the Gibbs energy of the trans ⇌ cis equilibrium was analyzed in terms of the continuum dielectric medium models.     

Comprehensive DFT and MO studies on glyoxilic acid oxime and related ions in gas phase and solution: Conformations,basicities and acidities

Density functional (BLYP, B3LYP and BHLYP) and highly correlated MP2 and CCSD(T) calculations have been performed to investigate conformers, energy barriers, intramolecular H-bond strength, gas-phase basicity and deprotonation energies of glyoxilic acid oxime (gao) and related ions in gas phase and in aqueous solution (SCRF-PCM method). BHLYP/6-311G(d,p) and B3LYP/6-31++G(d) predictions for the global minimum conformer of gao were consistent with experiment. BLYP level overestimated the H-bond and stabilized incorrectly the H-bonded conformer. The calculations in solution indicated destabilization of H-bonded conformers due to the small polarizability and weaken of the H-bond. The same global minimum structures in gas phase and aqueous solution were found for gao-neutral (ectt) and gao-dianion (e⁻²), whereas they were different for gao-anion because of the strong decrease of the conformational energies in solution. The global minimum structures of the neutral, anion and dianion of gao, obtained in solution, are in agreement with experiment. The gas-phase basicity (GB) and molecular electrostatic potential (MEP) calculations revealed the same sites for electrophilic attack, supported by the nature of HOMO: the carbonylic oxygen for the neutral, the carboxylic oxygen for the anion and the oxime nitrogen for the dianion. MEP results in gas phase and in solution suggested a region between the two atoms, but not on one atom in accordance with bidentate binding of gao ions to a metal. The BHLYP/6-31++G(d,p) molecular properties of gao were in best consistent with CCSD(T) results. The thermodynamical properties (GB and bond deprotonation energy) of gao were better estimated at B3LYP level.     

Conformational analysis of carbonic anhydrase inhibitors using ab initio molecular orbital methods. 1. Rotational isomerism in methane sulfonamide anion, CH3-SO2-NH−

Ab initio calculations have been performed on methane sulfonamide anion. Geometries have been optimized using Hartree-Fock basis sets up to 6-31+G*, and single-point calculations employing those Hartree-Fock geometries have been performed at levels up to MP2/6-311++G**. In addition, geometry optimizations for the 0°, 90°, 150°, and 180° conformers have been carried out at the MP2/6-31G*, MP2/6-31+G*, and MP2/6-311++G** levels. Vibrational frequencies have been calculated using the HF/4-31G*, MP2/6-31G*, and MP2/6-31+G* geometries. All calculations at or above the 4-31G* level agree that H—N—S—C ˜90° is the global minimum. The H—N—S—C = 180° conformer is clearly higher in energy although the relative energy of this conformer varies from 0.36 to 1.03 kcal/mol for the post-HF calculations depending on basis set. The H—N—S—C = 180° conformer appears to be a very shallow local minimum. However, the potential energy surface is quite flat in this region, and the highest-level calculations, including MP2 optimizations and vibrational frequency analysis, are ambiguous on this point. The conformer with an H—N—S—C torsion of 0° is a transition state with a relative energy ˜8 kcal/mol. Received: 3 December 1996 / Accepted: 2 January 1997