An ab initio study of the conformational preferences of Hoechst 33258 in gas-phase and aqueous solution environments

A quantum mechanical study of the conformational preferences of Hoechst 33258, a synthetic minor groove-binding drug, has been performed in both gas-phase and aqueous solution. Gas-phase calculations were performed at the HF/6-31G(d) and MP2/6-31G(d) levels of theory, whereas calculations in the aqueous solution phase were performed using the PCM model with the 6-31G(d) basis set. The molecule was divided into three fragments, which were submitted to a systematic and detailed conformational study. The results clearly indicate that Hoechst 33258 does not adopt a planar conformation in either the gas-phase or aqueous solution. Thus, a folded conformation is not induced by binding of the molecule to DNA, but is an intrinsic property of the compound. Received: 3 March 1998 / Accepted: 29 May 1998 / Published online 19 August 1998     

Ab initio conformational maps in the gas phase and aqueous solution for a prototype of the glycosidic linkage

Ab initio conformational maps for methoxyethoxymethane (MEM) in both the gas phase and aqueous solution have been constructed using two different approaches. The results obtained allow us to conclude that a rigid conformational map is able to predict the regions of the minima, in the potential energy surface of MEM, in full agreement with those found in the relaxed conformational map, in both phases studied. This is a good indication that ab initio rigid conformational maps may be reliably used to sort the stablest conformers of disaccharides in aqueous solution. Besides that, in the MEM case, the solvation effects do not give rise to any new local minimum in its potential energy surface, but just change the relative energies of the stablest conformers found in the gas phase. This may be an indication that even in aqueous solution the anomeric effect is still the determinant effect defining the conformation of the molecule.Proceedings of the 11th International Congress of Quantum Chemistry satellite meeting in honor of Jean-Louis Rivail     

Comparison of conformer distributions in the crystalline state with conformational energies calculated by ab initio techniques

Summary The conformational preferences of 12 molecular substructures in the crystalline state have been determined and compared with those predicted for relevant model compounds by ab initio molecular orbital calculations. Least-squares regression shows that there is a statistically significant correlation between the crystal-structure conformer distributions and the calculated potential-energy differences, even though the calculations relate to a gas-phase environment. Torsion angles associated with high strain energy (>1 kcal mol^-1) appear to be very unusual in crystal structures and, in general, high-energy conformers are underrepresented in crystal structures compared with a gas-phase, room-temperature Boltzmann distribution. It is concluded that crystal packing effects rarely have a strong systematic effect on molecular conformations. Therefore, the conformational distribution of a molecular substructure in a series of related crystal structures is likely to be a good guide to the corresponding gas-phase potential energy surface.     

Cis- and trans-3-hexene: infrared spectrum in liquid argon solution, ab initio calculations of equilibrium geometry, normal coordinate analysis, and vibrational assignments

The infrared spectra of cis-3-hexene and trans-3-hexene dissolved in liquid argon have been obtained at temperatures from 93 to 120 K. The absorptions were observed with a low-temperature cell and a Fourier transform infrared spectrophotometer. Ab initio molecular orbital calculations were performed to obtain the equilibrium geometry, vibrational frequencies, force fields, and infrared intensities. The calculations were done at the Hartree-Fock level using 6-31G basis set. The Cartesian force fields from ab initio calculations have been converted to the force field in symmetry coordinates. The scale factors of ab initio calculated force fields were determined. Normal coordinate calculations were performed using a scaled quantum mechanical (SQM) force field. Vibrational normal modes calculated for the lowest energy rotamers of cis- and trans-3-hexene have been assigned to infrared absorption bands observed in liquid argon solution. The assignments were based on calculated frequencies and potential energy distributions. The equilibrium geometries of the two lowest energy rotamers (symmetry C₂ and C_s) of cis-3-hexene and of the three lowest energy rotamers (symmetry C_i, C₂, and C₁) of trans-3-hexene were calculated. Variable temperature studies of the infrared spectrum of cis- and trans-3-hexenes dissolved in liquid argon were done to obtain the ΔH of conversion between the rotamers C₂ and C_s of cis-3-hexene and between the rotamers C_i, C₂, and C₁ of trans-3-hexene.     

Infrared and Raman spectra, conformational stability, ab initio calculations of structure, and vibrational assignment of 2-hexyne

The infrared spectra (3500–50 cm⁻¹) of the gas and solid and the Raman spectra (3500–50 cm⁻¹) of the liquid and solid have been recorded for 2-hexyne, CH₃–CC–CH₂CH₂CH₃. Variable temperature studies of the infrared spectrum (3500–400 cm⁻¹) of 2-hexyne dissolved in liquid krypton have also been recorded. Utilizing four anti/gauche conformer pairs, the anti(trans) conformer is found to be the lower energy form with an enthalpy difference of 74±8 cm⁻¹ (0.88±0.10 kJ/mol) determined from krypton solutions over the temperature range −105 to −150 °C. At room temperature it is estimated that there is 42% of the anti conformer present. Equilibrium geometries and energies of the two conformers have been determined by ab initio (HF and MP2) and hybrid DFT (B3LYP) methods using a number of basis sets. Only the HF and DFT methods predict the anti conformer as the more stable form as found experimentally. A vibrational assignment is proposed based on the force constants, relative intensities, depolarization ratios from the ab initio and DFT calculations and on rotational band contours obtained using the calculated equilibrium geometries. From calculated energies it is shown that the CH₃ group exhibits almost completely free rotation which is in agreement with the observation of sub-band structure for the degenerate methyl vibrations from which values of the Coriolis coupling constants, ζ, have been determined. The results are compared to similar properties of some corresponding molecules.     

Infrared, and Raman spectra, conformational stability, normal coordinate analysis, ab initio calculations, and vibrational assignment of 1-chlorosilacyclobutane

The infrared spectra (3500–40 cm⁻¹) of gaseous and solid and the Raman spectra (3500–30 cm⁻¹) of liquid and solid 1-chlorosilacyclobutane, c-C₃H₆SiClH, have been obtained. Both the axial and equatorial conformers with respect to the chlorine atom have been identified in the fluid phases. Variable temperature (−105 to −150°C) studies of the infrared spectra of the sample dissolved in liquid krypton have been carried out. From these data, the enthalpy difference has been determined to be 211±17 cm⁻¹ (2.53±0.21 kJ/mol), with the equatorial conformer being the more stable form and the only conformer remaining in the annealed solid. At ambient temperatures, approximately 26% of the axial conformers are present in the vapor phase. A complete vibrational assignment is proposed for the equatorial conformer, and many of the fundamentals of the axial conformers have also been identified. The vibrational assignments are supported by normal coordinate calculations utilizing ab initio force constants. Complete equilibrium geometries, conformational stabilities, harmonic force fields, infrared intensities, Raman activities, and depolarization ratios have been determined for both rotamers by ab initio calculations employing the 6-31G(d) basis set at the levels of restricted Hartree–Fock (RHF) and/or Moller–Plesset (MP) to second order. Structural parameters have also been obtained using MP2/6-311+G(d,p) ab initio calculations. The r₀ parameters for both conformers are obtained from a combination of the ab initio predicted values and the twelve previously reported microwave rotational constants. The results are discussed and compared to those obtained for some similar molecules.     

双核Au(Ⅰ)配合物[Y+]2[Au(i-mnt)]2(Y+=[n-Bu4N]+,K+,[Ph4As]+)发光机制的从头计算研究

用从头算方法研究[Au(i-mnt)]22-(i-mnt=i-marononitriledithiolate)的电子吸收和磷光发射性质,利用MP2和CIS方法分别优化了[Au(i-mnt)]22-基态和激发态几何结构.计算的基态Au(Ⅰ)—Au(Ⅰ)键长为0.2825nm,表明Au(Ⅰ)之间存在弱吸引作用.采用SCRF方法中IPCM模型模拟配合物在乙氰溶液中的行为,计算得到的最大吸收波长为315.5nm,指认X1Ag→A1Au来源于i-mnt配体内电荷转移跃迁.在436.2nm处得到具有B3Au→1Ag跃迁的磷光发射,指认为i-mnt配体内电荷转移和金属到配体电荷转移跃迁,与500nm乙氰溶液的发射相对应,为金属修饰的有机配体发光机制.     

Hyperfine interactions in aqueous solution of Cr3+: an ab initio molecular dynamics study

We performed an ab initio molecular dynamics simulation of the paramagnetic transition metal ion Cr³⁺ in aqueous solution. Isotropic hyperfine coupling constants between the electron spin of the chromium ion and nuclear spins of all water molecules have been determined for instantaneous snapshots extracted from the trajectory. The coupling constant of first sphere oxygen, A _iso(¹⁷O_I)=1.9±0.3 MHz, is independent on Cr–O_I distance but increases with the tilt angle for the water molecule approaching 180°. First sphere hydrogen spins have A _iso(¹ H_I)=2.1±0.2 MHz which decreases with increasing tilt angle and shows a Cr–H_I distance dependence. The hyperfine coupling constants for second sphere ¹⁷O is negative and an order of magnitude smaller (−0.20±0.02 MHz) compared to first sphere.     

Electronic structure and conformational properties of (carboxy-alkenyl)-phosphonic acids

The general conformational properties and electronic structure of (carboxy-alkenyl)-phosphonic derivatives were determined at RHF/STO-3G^* level. In all the series, low rotation barriers were found for the two C=C/P=O conformers. In the compounds in which the interactions between the carboxylic and phosphonic moieties are smaller, the most stable conformers are the C=C/P=O s-cis ones. In most of the conformers, the C=C/C=O system presents the disposition s-cis. The Z-(2-carboxy-vinyl) and Z-(2-carboxy-propenyl) phosphonic acids present intramolecular hydrogen bonds, existing in at least four conformer with internal hydrogen bonds. These last compounds were more rigorously studied at RHF/3-21G^* and RHF/6-31G^** levels. The most stable conformer shows a trans structure for the C=C/P=O angle, with an intramolecular hydrogen bond located between the hydroxylic hydrogen of phosphonic group and the carbonyl oxygen of carboxylic moiety. A secondary conformer is found with a double intramolecular hydrogen bond between two hydroxylic hydrogens of the phosphonic moiety and the oxygen of carboxylic bond. Another secondary conformer appears with an intramolecular hydrogen bond between the oxygen of the phosphoryl bond and the hydroxylic hydrogen of the carboxylic group. A study of the topology of charge densities is carried out. This analysis reveals bonds with an ionic participation. A very weak π conjugation, variable with the conformers, is found in the C=C/P=O system, as well as a strongly polarized P=O partial triple bond. The intramolecular hydrogen bonds give rise to cyclic structures.     

Anharmonic force field and spectroscopic constants of silene: an ab initio study

High-level ab initio calculations with large basis sets are reported for silene, H₂C=SiH₂. Correlated harmonic force fields are obtained from coupled cluster CCSD(T) calculations with the cc-pVQZ basis (cc-pVTZ for H) while the anharmonic force fields are computed at the MP2/TZ2Pf level. There is excellent agreement with the available experimental data, in particular the equilibrium geometry and the fundamental vibrational frequencies. Many other spectroscopic constants are predicted for the C _{2 v} isotopomers of silene. Received: 27 May 1998 / Accepted: 23 July 1998 / Published online: 9 October 1998     

Vibrational analysis of a rate-slowing conformational kinetic isotope effect

An enthalpy-entropy approach to analyzing a rate-slowing conformational kinetic isotope effect (CKIE) in a deuterated doubly-bridged biaryl system is described. The computed isotope effect (k_H/k_D?=?1.075, 368?K) agrees well with the measured value (k_H/k_D?=?1.06, 368?K). The rate-slowing (normal isotope effect) nature of the computed CKIE is shown to originate from a vibrational entropy contribution defined by the twenty lowest frequency normal modes in the ground state and transition state structures. This normal entropy contribution is offset by an inverse vibrational enthalpy contribution, which also arises from the twenty lowest frequency normal modes. Zero point vibrational energy contributions are found to be relatively small when all normal modes are considered. Analysis of the H_ZPE, H_vib, and S_vib energy terms arising from the low frequency vibrational modes reveals their signs and magnitudes are determined by larger vibrational energy differences in the labeled and unlabeled ground state structures.     

Infrared and Raman spectra, conformational stability, normal coordinate analysis, ab initio calculations, and vibrational assignment of 1-fluoro-1-methylsilacyclobutane

The infrared (3500–40 cm⁻¹) spectra of gaseous and solid 1-fluoro-1-methylsilacyclobutane, c-C₃H₆SiF(CH₃), have been recorded. Additionally, the Raman spectrum (3500–30 cm⁻¹) of the liquid has been recorded and quantitative depolarization values have been obtained. Both the axial and equatorial (with respect to the methyl group) conformers have been identified in the fluid phases. Variable temperature (−55–−100°C) studies of the infrared spectra of the sample dissolved in liquid xenon have been carried out. From these data, the enthalpy difference has been determined to be 267±10 cm⁻¹ (3.19±0.12 kJ mol⁻¹), with the axial conformer being the more stable form and the only conformer remaining in the polycrystalline solid. A complete vibrational assignment is proposed for the axial conformer and many of the fundamentals for the equatorial conformer have also been identified. The vibrational assignments are supported by normal coordinate calculations utilizing ab initio force constants. Complete equilibrium geometries have been determined for both rotamers by ab initio calculations employing the 6-31G* and 6-311++G** basis sets at the levels of restricted Hartree–Fock (RHF) and/or Moller–Plesset (MP) to second order. The results are discussed and compared to those obtained for some similar molecules.     

Molecular structure and conformational analysis of chiral alcohols. Application to the enantioselectivity study of lipases

The molecular structures of the chiral compounds 1-phenylethanol, 2-hexanol and 1-phenylethanol acetate have been studied theoretically by ab initio methods. Conformational analysis and electronic structure studies have been carried out with these molecules at STO-3G^* and 6-31G^* basis sets. For the study of the interaction of lipases with substrates, a simplified model of the tetrahedral intermediate has been calculated at the 6-31G^*//4-31G^* level. Molecular mechanics simulations of the interaction of these compounds with the lipases of Candida rugosa, Pseudomonas cepacia and Rhizomucor miehei have been used to study the enantioselectivity of these lipases in the transesterification reaction of the chiral alcohols. The theoretical results have been compared with experimental data and good agreement was observed. It can be concluded that the enantioselectivity of these lipases is controlled by the formation of a tetrahedral intermediate, whereas Michaelis complex formation has a much lower significance.     

On the vibrational spectra and conformational stability of 1,1-dimethylhydrazine from temperature dependent FT-IR spectra of krypton solutions and ab initio calculations

Variable temperature (−105 to −150 °C) studies of the infrared spectra (3500–400 cm⁻¹) of 1,1-dimethylhydrazine, (CH₃)₂NNH₂, in liquid krypton have been carried out. No convincing spectral evidence could be found for the trans conformer which is expected to be at least 600 cm⁻¹ less stable than the gauche form. The structural parameters, dipole moments, conformational stability, vibrational frequencies, and infrared and Raman intensities have been predicted from MP2/6-31G(d) ab initio calculations. The predicted infrared and Raman spectra are compared to the experimental ones. The adjusted r₀ parameters from MP2/6-311+G(d,p) calculations are compared to those reported from an electron diffraction study. The energy differences between the gauche and trans conformers have been obtained from MP2 ab initio calculations as well as from density functional theory by the B3LYP method calculations from a variety of basis sets. All of these calculations indicate an energy difference of 650–900 cm⁻¹ with the B3LYP calculations predicted the larger values. The potential function governing the conformational interchange has been predicting from both types of calculations and comparisons have been made. The barrier to internal rotation by the independent rotor model of the inner methyl group is predicted to have a value of 1812 cm⁻¹ and that of the outer one of 1662 cm⁻¹ from ab initio MP2/6-31G(d) calculations. These values agree well with the experimentally determined values of 1852±16 and 1558±12 cm⁻¹, respectively, from a fit of the torsional transitions with the coupled rotor model. For the coupled rotor model the predicted V′₃₃ (sin 3τ₀ sin 3τ₁ term) value which ranged from 190 to 232 cm⁻¹ is in reasonable agreement with the experimental value of 268±3 cm⁻¹ but the predicted V₃₃ (cos 3τ₀ cos 3τ₁ term) value of −73 to −139 cm⁻¹ is 25% smaller and of the opposite sign of the experimental value of 333±22 cm⁻¹. These theoretical and spectroscopy results are compared to similar quantities of some corresponding molecules.     

Torsion potentials and electronic structure of trifluoromethoxy- and trifluoromethylthiobenzene: an ab initio study

Potential functions of internal rotation about the C_sp²X bonds in molecules C₆H₅XCF₃ (X=O, S) were calculated at the second-order Møller-Plesset perturbation level of theory with 6-31G(d) basis set. The profile of the potential function and the rotation barrier (ΔE^#=3.0 kJ/mol) found for C₆H₅OCF₃ suggest that, depending on experimental conditions, there can be either free rotation about the C_sp²O bond or the conformational equilibrium is shifted to the side of the orthogonal form. The rotational barrier for C₆H₅SCF₃ is 14.7 kJ/mol and the molecule exists in the stable orthogonal conformation. The nature of hybridization, energy and population of lone electron pairs (LPs) on the oxygen and sulfur atoms were considered by using the Natural Bond Orbital (NBO) method. The energy of interactions of the LPs with antibonding π^∗-orbitals of the aromatic moiety were estimated for different conformations. The distribution of electron density in the molecules was discussed. The results were compared with analogous calculations on the molecules C₆H₅XCH₃.     

Unusual conformational properties of 1,3-dimethyl-1,1,3,3-tetrakis(trimethylsilyl)trisilane: A preparative, X-ray, Raman spectroscopic and ab initio study

The heptasilane Me(SiMe₃)₂SiSiH₂SiMe(SiMe₃)₂ was synthesized from Me(SiMe₃)₂SiK and H₂Si(OSO₂CF₃)₂. Crystals suitable for a X-ray single crystal analysis could be grown, with the somewhat surprising result that the two dihedral angles (H₃)CSiSi(H₂)Si are different in the crystal (24.58(10)° and 31.67(11)°). SiSiSi-bonds angles are widened, with values up to 117°. Ab initio calculations at the density functional B3LYP level employing 6-311G(d) basis sets predict minima for five conformers 1-5 with relative energies 0.0, 3.1, 8.2, 10.8 and 18.1 kJ/mol, respectively. Moreover, SiSiSiSi dihedral angles spanning the range 43.5-172.3° are predicted, reflecting the small forces which are required for distorting these angles.In the Raman spectrum of a solution in toluene, three lines at 350, 340 and 330 cm⁻¹ are observed in a wavenumber range which is typical for the SiSi-pulsation of methylated oligosilanes. The relative intensity ratio of the bands is temperature dependent, reflecting the changes in conformer concentrations that occur according to Boltzman’s law. Supported by the ab initio calculations, the Raman band at 350 cm⁻¹ is assigned to an ‘averaged’ conformer 1 and 2, because a rapid interconversion between 1 and 2 has to be assumed due to a small barrier separating them. The bands with wavenumbers 340 and 330 cm⁻¹ originate from conformers 3 and 4. From the Raman spectra, relative energies 0.0 (1 + 2), 2.2 (3) and 6.3 (4) kJ/mol are deduced, the presence of 5 is not observed. Caused by solvent effects, these values differ somewhat from the ab initio results.     

Tautomeric and conformational equilibrium of 2-nitrosophenol and 9,10-phenanthrenequinonemonooxime: ab initio and NMR study

The tautomeric and conformational equilibrium of 2-nitrosophenol and 9,10-phenanthrenequinonemonooxime was studied by ab initio methods. The geometry optimizations of the structures investigated were done without any geometrical restrictions at HF/6-31G** and MP2/6-31G** levels of theory. The transition structures for tautomeric and rotameric conversions were located. To correct for electron correlation, single-point calculations were carried out up to MP4/6-311G*//MP2/6-31G* level of theory.

Ab initio calculations for 2-nitrosophenol in agreement with the available experimental data define the nitroso form as more stable. It was found that the influence of the correlation energy on the relative stabilities is smaller for the rotamers of the nitroso tautomer but substantially (4–6 kcal/mol) for the oxime forms. It was found that the barrier height of tautomerization reaction is 10.24 kcal/mol.

The structure of the 9,10-phenanthrenequinonemonooxime was studied by solid and liquid state NMR spectroscopy. Ab initio calculations in agreement with our experimental data predict that the compound exists as oxime tautomer and the syn-oxime is most stable. It was found that the solvent influence on the relative stabilities of both isomers: syn- and anti-oxime. While in chloroform solution the syn-oxime is preferred but in DMSO anti-oxime is more stable in energy.

At the MP4/6-311G*//MP2/6-31G**+ZPE level of theory the barrier of tautomerization was predicted to be 10.96 kcal/mol and the rotational barrier around the single C–O bond in the syn-oxime was found to be 7.57 kcal/mol. The rotation is facile and this explains the absence of nitroso tautomers in solution.     

Equilibrium structure of the carbon dioxide-water complex in the gas phase: an ab initio and density functional study

High-level ab initio (MP2/6-311++G(2d,2p) geometry, Gaussian-2, MP4(SDTQ) and QCISD(T) binding energies) and density-functional (Becke3LYP/6-311++G(2df,2pd)) calculations have been performed on the charge-transfer complex between water and carbon dioxide. The complex appears to have two equivalent non-planar minima of C_s symmetry. Minima are separated by transition states with C₁ symmetry, whereas the totally planar structure with C_2v symmetry is a second-order transition state. All the critical points lie at approximately the same energy (less than 0.05 Kj mol⁻¹ difference). Therefore, the experimentally observable structure should be planar. The best equilibrium intermolecular distance for this complex calculated at the MP2/6-311++G(2d,2p) level is 2.800 Å. Our best estimate of the observable intermolecular distance (corrected for anharmonicity) is 2.84 Å, in agreement with the experimentally derived value of 2.836 Å. Our best estimate of the binding energy at the QCISD(T) level, taking into account the variation of the distance owing to anharmonicity and the use of more sophisticated theoretical treatments, is −12.0 ± 0.2 kJ mol⁻¹. Our best estimate of the barrier to internal rotation, also at the MP2/6-311++G(2d,2p) level, is 4.0 kJ mol⁻¹, outside the error limits of the experimental determination (3.64 ± 0.04 kJ mol⁻¹). Density functional theory at the level employed here gives an equilibrium intermolecular distance that is too large (2.857 Å), a binding energy that is too small (8.1 kJ mol⁻¹), attributable neither to geometry nor to the basis set, and also a barrier to internal rotation that is slightly too small (3.39 kJ mol⁻¹). The overall picture is, however, reasonably good.     

Using Raman Spectroscopy and ab initio Calculations to Investigate Intermolecular Hydrogen Bonds in Binary Mixture (Tetrahydrofuran+Water)

We analyzed the properties and structures of the hydrogen-bonded complexes of tetrahydrofuran(THF) and water by means of experimental Raman spectra and ab initio calculations.The optimized geometries and vibrational frequencies of the neat THF molecule and its hydrogen-bonded complexes with water(THF/H2O) were calculated at the MP2/6-311+G(d,p) level of theory.We found that the intermolecular hydrogen bonds which are formed from the binary mixtures of the neat THF and water with different molar ratios could...     

Chemisorption of HSi(OH)3 on silica surfaces: an ab initio periodic study

The study of the grafting of trialkoxysilane R′Si(OR)₃ molecules on amorphous silica has been undertaken at the Hartree–Fock level using a biperiodic model for the surface. Different types of slab cut out from the model system Edingtonite (a tetragonal silica structure with five SiO₂ groups per unit cell) have been used to simulate isolated and interacting silanol sites at the amorphous silica surface, while only the simple case of HSi(OH)₃ has been considered for the interacting molecule. In a first step, for each type of surface the geometrical parameters have been optimised and the surface formation energy determined. The geometrical structure of the grafted molecule is compared with that of the isolated one. The geometrical strains of the surfaces with either isolated or interacting silanols are also compared before and after the grafting reactions. The calculated values of the chemisorption energies show that the grafting process is favored on isolated silanols only if correlation effects are included.