Solute-solvent interactions in cryosolutions: a study of halothane-ammonia complexes.

The formation of C-H···N bonded complexes of halothane with ammonia has been studied using infrared and Raman spectroscopy of solutions in the liquid rare gases argon, krypton and xenon, of supersonic jet expansions and of room temperature vapor phase mixtures. For the solutions and for the vapor phase experiments, the formation of complexes with 1:1 and 1:2 stoichiometry was observed. The complexation enthalpy for the 1:1 complex was determined to be -20 (1) kJ mol(-1) in the vapor phase, -17.0 (5) kJ mol(-1) in liquid xenon and -17.3 (6) kJ mol(-1) in liquid krypton. For the 1:2 complex in liquid xenon, the complexation enthalpy was determined to be -31.5 (12) kJ mol(-1). Using the complexation enthalpies for the vapor phase and for the solutions in liquid xenon and krypton, a critical assessment is made of the Monte Carlo Free Energy Perturbation approach to model solvent influences on the thermodynamical properties of the cryosolutions. The influences of temperature and solvent on the complexation shifts of the halothane C-H stretching mode are discussed.

C-X···π halogen and C-H···π hydrogen bonding: interactions of CF3X (X = Cl, Br, I or H) with ethene and propene.

Using FTIR and Raman spectroscopy, the formation of halogen bonded complexes of the trifluorohalomethanes CF(3)Cl, CF(3)Br and CF(3)I with ethene and propene dissolved in liquid argon has been investigated. For CF(3)Br and CF(3)I, evidence was found for the formation of C-X···π halogen bonded 1:1 complexes. At a higher ratio of CF(3)I/propene, weak absorptions due to a 2:1 complex were also observed. Using spectra recorded at different temperatures, the complexation enthalpies for the complexes were determined to be -5.3(2) kJ mol(-1) for CF(3)Br·ethene, -7.5(2) kJ mol(-1) for CF(3)I·ethene, -5.6(1) kJ mol(-1) for CF(3)Br·propene, -8.8(1) kJ mol(-1) for CF(3)I·propene and -16.5(6) kJ mol(-1) for (CF(3)I·)(2)propene. The complexation enthalpies of the hydrogen bonded counterparts, with CF(3)H as the Lewis acid, were determined to be -4.6(4) kJ mol(-1) for CF(3)H·ethene and -5.1(2) kJ mol(-1) for CF(3)H·propene. For both hydrogen bonded complexes, a blue shift, by +4.8 and +4.0 cm(-1), respectively, was observed for the C-H stretching mode. The results from the cryospectroscopic study are compared with ab initio calculations at the MP2/aug-cc-pVDZ(-PP) level.

On the weakly C-H···π hydrogen bonded complexes of sevoflurane and benzene.

A vibrational assignment of the anaesthetic sevoflurane, (CF(3))(2)CHOCH(2)F, is proposed and its interaction with the aromatic model compound benzene is studied using vibrational spectroscopy of supersonic jet expansions and of cryosolutions in liquid xenon. Ab initio calculations, at the MP2/cc-pVDZ and MP2/aug-cc-pVDZ levels, predict two isomers for the 1 : 1 complex, one in which the near-cis, gauche conformer of sevoflurane is hydrogen bonded through its isopropyl-hydrogen atom, the other in which the same conformer is bonded through a bifurcated hydrogen bond with the fluoromethyl hydrogen atoms. From the experiments it is shown that the two isomers are formed, however with a strong population dominance of the isopropyl-bonded species, both in the jet and liquid phase spectra. The experimental complexation enthalpy in liquid xenon, ΔH(o)(LXe), of this species equals -10.9(2) kJ mol(-1), as derived from the temperature dependent behaviour of the cryosolution spectra. Theoretical complexation enthalpies in liquid xenon were obtained by combining the complete basis set extrapolated complexation energies at the MP2/aug-cc-pVXZ (X = D,T) level with corrections derived from statistical thermodynamics and Monte Carlo Free Energy Perturbation calculations, resulting in a complexation enthalpy of -11.2(3) kJ mol(-1) for the isopropyl-bonded complex, in very good agreement with the experimental value, and of -11.4(4) kJ mol(-1), for the fluoromethyl-bonded complex. The Monte Carlo calculations show that the solvation entropy of the isopropyl-bonded species is considerably higher than that of the fluoromethyl-bonded complex, which assists in explaining its dominance in the liquid phase spectra.

Halogen bonding to a divalent sulfur atom: an experimental study of the interactions of CF3X (X = Cl, Br, I) with dimethyl sulfide.

Using FTIR and Raman spectroscopy, the formation of halogen bonded complexes of the trifluorohalomethanes CF(3)Cl, CF(3)Br and CF(3)I with dimethyl sulfide (DMS) dissolved in liquid krypton has been investigated. For CF(3)Br and CF(3)I, evidence was found for the formation of C-XS halogen bonded 1:1 complexes. At higher concentrations of CF(3)I weak absorptions due to a 2:1 complex were also observed. Using spectra recorded at temperatures between 118 and 163 K, the complexation enthalpies for the complexes were determined to be -9.5(5) kJ mol(-1) for CF(3)Br·DMS, -17.4(1) kJ mol(-1) for CF(3)I·DMS and -30.8(16) kJ mol(-1) for (CF(3)I·)(2)DMS. The results from the cryospectroscopic study are compared with ab initio calculations at the MP2/aug-cc-pVDZ(-PP) level. Apart from vibrational modes localized in the trifluorohalomethanes and the DMS moieties, for both CF(3)Br and CF(3)I, an additional band, which we assign as the intermolecular stretching mode in the complex, was identified in the infrared and Raman spectra.

The complexes of halothane with benzene: the temperature dependent direction of the complexation shift of the aliphatic C-H stretching.

The formation of C-H...π bonded complexes of halothane with benzene(-d(6)) has been studied using infrared and Raman spectroscopy of solutions in liquid krypton, in supersonic jet expansions and in room temperature vapour phase. The formation of complexes with 1 ∶ 1 and 2 ∶ 1 stoichiometry was observed. The complexation enthalpy in liquid krypton for the 1 ∶ 1 complex was determined to be -9.8(2) kJ mol(-1) and the enthalpy for the addition of a second halothane molecule to the 1 ∶ 1 complex was determined at -7.0(3) kJ mol(-1). The stretching mode of the halothane C-H bond involved in the formation of the complex in the jets was observed to blue shift by 7.7(10) cm(-1). In contrast, for the solutions of liquid krypton and the room temperature measurements a small red shift was observed. Supported by ab initio calculations and Monte Carlo simulations, this shift was explained by the differences in thermal populations of the van der Waals vibrations of the complex in the different experiments.

ONSH: optimization of oxidative alkylamination reactions through study of the reaction mechanism.

Oxidative alkylamination of electron-deficient (hetero)aromatic compounds, via the nucleophilic substitution of hydrogen, is a methodology that has made significant progress since the introduction of AgPy(2)MnO(4) as oxidant. This oxidant generally gives good conversions and yields, whereas the use of KMnO(4) only sometimes works equally well. In order to rationalize this, the reaction mechanism of oxidative alkylamination has been studied. 3-Nitropyridine (1), 1,3-dinitrobenzene (2), and quinazoline (3) were chosen as model substrates and n-butylamine and pyrrolidine as model alkylamines. The rate-limiting step of the mechanism for these substrate/alkylamine combinations was determined. With the use of (1)H NMR spectroscopy thermodynamic properties of sigma(Eta)-adduct formation were deduced and the effect of additives on the adduct formation was investigated. The fundamental insights resulting from these studies led to the identification of a cheap additive (tetrabutylammonium chloride), which in combination with the standard and cheap oxidant KMnO(4) generally gave excellent yields, similar to the ones previously obtained with more expensive AgPy(2)MnO(4).

Infrared spectra of (12)CF(2)=(12)CH(2) and (12)CF(2)=(13)CH(2), quantum-chemical calculations of anharmonicity, and analyses of resonances.

Infrared spectra obtained in gas and liquid argon phases are reported for (12)CF(2) horizontal line(12)CH(2) and (12)CF(2) horizontal line(13)CH(2). These spectra firmly establish the positions of nu(3)(A(1)) and nu(6)(A(2)) for both isotopomers. Using anharmonicity constants from MP2 calculations, Fermi resonances affecting nu(1)(A(1)), nu(2)(A(1)), nu(3), and nu(8)(B(1)) are analyzed. Deperturbed fundamental frequencies from these analyses are used in conjunction with unaffected fundamentals and ab initio anharmonicity data to predict all 12 "observed" harmonic frequencies. A Darling-Dennison type resonance between 2nu(6) and nu(11) + nu(12) is diagnosed, the calculation of which from ab initio data requires modification of the existing second-order treatment of such constants, where Fermi resonance type terms are also present. Predictions are made of many overtone and combination band frequencies, aiding assignment of observed spectra. From the isolated CH stretching frequency obtained here of 3125.4 cm(-1), the C-H equilibrium bond length is predicted to be 1.0762(11) A.

On the nu(1) (CO(2) )/2 nu(2) (CO(2) ) resonance in the complex of carbon dioxide with dimethyl ether.

Infrared and Raman spectra of solutions in liquid argon and krypton containing dimethyl ether or its fully deuterated isotopomer and (12)CO(2) or (13)CO(2) are investigated. The spectra lead to new data on the nu(1) (CO(2) )/2 nu(2) (CO(2) ) resonances appearing in the complex of CO(2) with the ether. The experimental data, and their interpretation, is supported by MP2/6-311++G(2d,2p) calculations of the cubic and quartic force constants and of the first and higher order dipole moment derivatives required for the modelling of the Fermi and Darling-Dennison resonances observed.

C-X...O halogen bonding: interactions of trifluoromethyl halides with dimethyl ether.

The formation of weakly bound molecular complexes between dimethyl ether (DME) and the trifluoromethyl halides CF(3)Cl, CF(3)Br and CF(3)I dissolved in liquid argon and in liquid krypton is investigated, using Raman and FTIR spectroscopy. For all halides evidence is found for the formation of C-X...O halogen-bonded 1:1 complexes. At higher concentrations of CF(3)Br, a weak absorption due to a 1:2 complex is also observed. Using spectra recorded at temperatures between 87 and 125 K, the complexation enthalpies for the complexes are determined to be -6.8(3) kJ mol(-1) (DME x CF(3)Cl), -10.2(1) kJ mol(-1) (DME x CF(3)Br), -15.5(1) kJ mol(-1) (DME x CF(3)I), and -17.8(5) kJ mol(-1) [DME(x CF(3)Br)(2)]. Structural and spectral information on the complexes is obtained from ab initio calculations at the MP2/6-311++G(d,p) and MP2/6-311++G(d,p)+LanL2DZ* levels. By applying Monte Carlo free energy perturbation calculations to account for the solvent influences, and statistical thermodynamics to estimate the zero-point vibrational and thermal influences, the ab initio complexation energies are converted into complexation enthalpies for the solutions in liquid argon. The resulting values are compared with the experimental data deduced from the cryosolutions.

Cryospectroscopic and ab initio studies of haloform-trimethylamine H-bonded complexes.

The FTIR spectra of F(2)ClCH and Cl(3)CH(D) in mixtures with trimethylamine (TMA) have been studied in liquefied Kr in approximately 800-4000 cm(-1) frequency range. Spectroscopic evidence of a medium strength H-bond formation with conventional features has been found between these weak CH "proton donors" and TMA. The relative stability of the complexes has been determined in a series of temperature (T = 118-157 K) measurements of integrated intensities of vibrational bands ascribed to monomer and complex species. The complexes found are characterized by the red shift of the nu(1)(CH) stretching vibration of the haloforms studied. In the case of chloroform, the substantial red shift is accompanied by a noticeable broadening effect and by a marked growth of the intensity of this band. The spectroscopic changes caused by the complex formation have been also registered for vibrations of TMA. Specifically, the bands situated in the frequency domain of CH stretching vibrations of TMA show a weak blue shift, whereas the NC stretching vibrations are red-shifted. Ab initio MP2/6-311++G(2d,2p) a priori counterpoise corrected calculations, made for a series of haloforms and TMA, reproduce the main spectroscopic observations. The results obtained also suggest that the vibrational mode coupling between vicinal C-H and C-B (B = Hal, N) bonds is to a great extent responsible for the sign of these bond length changes and for the sign of the frequency shifts of the respective stretching vibrations upon complex formation.

A VCD robust mode analysis of induced chirality: the case of pulegone in chloroform.

Vibrational modes in an achiral molecule may acquire rotational strength by complexation to a chiral molecule, as happens for achiral solvent molecules complexed to a chiral solute. We investigate this transfer of chirality in vibrational circular dichroism for the pulegone molecule in CDCl(3) solvent from the point of view of the robustness concept introduced recently. It turns out that the transfer of chirality yields nonrobust modes, which means that, although they are observed in vibrational circular dichroism (VCD) experiments, the sign of these modes cannot be predicted reliably with standard (Density Functional Theory) VCD calculations. This limits the usefulness of the induced chirality phenomenon for obtaining information on the intermolecular interactions that give rise to it.

C-H bonds with a positive dipole gradient can form blue-shifting hydrogen bonds: the complex of halothane with methyl fluoride.

The complex of halothane (CF(3)CBrClH) with ([D(3)])methyl fluoride is investigated theoretically by means of ab initio calculations at the MP2/6-311++G(d,p) level and experimentally by infrared spectroscopy of solutions in liquid krypton. The complexation energy is calculated to be -12.5 kJ mol(-1). The dipole moment of halothane monomer as a function of the C-H stretching coordinate is calculated with different methodologies and the value of (partial differential(mu)/partial differential(Q(1)))0 is found to be positive. In the spectra, formation of a 1:1 complex is observed. The standard complexation enthalpy is measured to be -8.4(2) kJ mol(-1). The C-H stretching vibration of halothane shows a blueshift of +15.4 cm(-1) on complexation, and its infrared intensity ratio epsilon(complex)/epsilon(monomer) is found to be 1.39(7). The frequency shift is analyzed by a Morokuma analysis, and the infrared intensities are rationalized by using a model which includes the mechanical and electrical anharmonicity of the C-H stretching vibration.

Solvent effects on IR and VCD spectra of natural products: an experimental and theoretical VCD study of pulegone.

The VCD spectra of pulegone, dissolved in CDCl3, CD2Cl2 and CS2 have been recorded in the frequency range from 1000 to 3000 cm(-1). The assignment of the absolute configuration was performed by comparing the experimental data with theoretical spectra computed at the B3LYP/6-311+G(d,p) level. Analysis of the agreement in several spectral regions revealed significant shortcomings when comparing with vacuum calculations. It is shown that the agreement improves when the solvent effects are taken into account by a continuum model. For the measurements in CDCl3 and CD2Cl2 further improvement was found when considering explicitly 1 : 1 complexes between a pulegone and a CDCl3 or CD2Cl2 solvent molecule in vacuo, while the best agreement was obtained when embedding these in a continuum model. The presence of the chiral solute was found to induce a VCD active C-D stretch band which could be modeled also at ab initio level.

Role of nitrogen lewis basicity in boronate affinity chromatography of nucleosides.

Urinary modified nucleosides have a potential role as cancer biomarkers, and most of the methods used in their study have utilized low-pressure phenylboronate affinity chromatography materials for the purification of the cis-diol-containing nucleosides. In this study, a boronate HPLC column was surprisingly shown not to trap the nucleosides as would be expected from experience with the classic Affigel 601 resin but showed only partial selectivity toward cis-diol groups while other groups exhibited better retention. In aprotic conditions, trapping of nucleosides was possible; however, the selectivity toward cis-diol-containing compounds was lost with the Lewis basicity of available nitrogens being the main determinant of retention. The experimental findings are compared to and confirmed by DFT calculations.

Intermolecular interactions between halothane and dimethyl ether: a cryosolution infrared and Ab initio study.

The complex of halothane (CHClBrCF(3)) and dimethyl ether has been investigated experimentally in solutions of liquid krypton using infrared spectroscopy and theoretically using ab initio calculations at the MP2/6-311++G(d,p) level. The formation of a 1:1 complex was experimentally detected. The most stable ab initio geometry found is the one in which the C--H bond of halothane interacts with the oxygen atom of dimethyl ether. The complexes in which the chlorine or the bromine atom of halothane interacts with the oxygen atom of the ether were found to be local energy minima and were less stable by 14.5 and 9.3 kJ mol(-1), respectively, than the global minimum. The formation of a single complex species was observed in the infrared spectra; the standard complexation enthalpy of this complex was determined to be -12.3(8) kJ mol(-1). Analysis of the observed complexation shifts supports the identification of the complex as the hydrogen-bonded species. The C--H stretching vibration of halothane was found to show a redshift upon complexation of 19(2) cm(-1). The infrared intensity ratios epsilon(complex)/epsilon(monomer) for the fundamental and its first overtone were measured to be 6.5(1) and 0.31(1). The frequency shift was analyzed using Morokuma-type analysis, and the infrared intensity ratios were rationalized using a model including the mechanical and electric anharmonicity of the C--H stretching fundamental.

A DFT conformational analysis and VCD study on methyl tetrahydrofuran-2-carboxylate.

DFT calculations were performed on (S)-methyl tetrahydrofuran-2-carboxylate to facilitate the interpretation of IR and VCD spectra. The potential energy surface could not be described unambiguously using the 6-31G* basis set in combination with different density functionals including B1LYP, B3LYP, B3P86, B3PW91, B98, BHandH, BHandHLYP, MPW1PW91 and PBE1PBE. In contrast, a uniform conformational picture could be found using the cc-pVTZ basis set. Using this large basis set and the collection of nine functionals from above, the dipole and rotational strengths were calculated, and compared to experimental values which were extracted from the experimental IR and VCD spectra for (+)-(S)-methyl tetrahydrofuran-2-carboxylate. A detailed analysis on the agreement between experiment and simulated spectra was performed by assigning the experimental bands based on the harmonic fundamentals obtained for all functionals except BHandH, which performs badly over the whole line. Assessing the dipole strengths, all tested functionals perform equally well. For the rotational strengths, differences can be observed: B3LYP, B1LYP and B98 give the highest correlation with experiment, while PBE1PBE gives the lowest correlation. Comparable conclusions are obtained using a neighborhood similarity measure.

Infrared spectra of the complexes of trifluoroethene with dimethyl ether, acetone, and oxirane: a cryosolution study.

Infrared spectra of solutions of trifluoroethene and dimethyl ether, acetone, or oxirane in liquid krypton and liquid argon have been studied. For each Lewis base the formation of a 1:1 complex with the Lewis acid was observed. The C-H stretching of trifluoroethene being perturbed by a strong Fermi resonance, the complexes with trifuloroethene-d were also investigated and showed that in each case the hydrogen bond between the acid and base is of the traditional, red-shifting type. The structures of the complexes were investigated using ab initio calculations. These indicate that with dimethyl ether and acetone two different isomeres can be formed, but with a single one detected in the solution in each case. The Fermi resonance in the complex with unlabeled trifluoroethene is discussed using data derived form ab initio potential and dipole hypersurface calculations. The complexation enthalpies of the complexes were obtained from temperature dependent studies of the solutions and are discussed in relation to the ab initio complexation energies and Monte Carlo free energy perturbation calculations of solvent effects.

Intermolecular association of tetrahydrofuran-2-carboxylic acid in solution: a vibrational circular dichroism study.

Carboxylic acids are known for their strong intermolecular associations. With chiral carboxylic acids, this behavior can be studied using vibrational circular dichroism (VCD). Tetrahydrofuran-2-carboxylic acid 1, a chiral building block for beta-lactam antibiotics, is studied by emphasizing the effect of the dimerization. Experimental results indicate that for solutions of 1 in CDCl3 and CS2, a complex equilibrium exists between the monomers and dimers. B3LYP/aug-cc-pVTZ calculations are performed on both monomer and dimer structures. To simulate IR and VCD spectra, populations for monomer and dimers were approximated using a semiquantitative model. A good agreement between experimental and simulated spectra is obtained by taking into account both the monomeric and the dimeric structures, weighted using the experimentally determined populations.