Katia Le Barbu-Debus

Intra- vs. intermolecular hydrogen bonding : dimers of alpha-hydroxyesters with methanol

Intermolecular hydrogen bonding competes with an intramolecular hydrogen bond when methanol binds to an alpha-hydroxyester. Disruption of the intramolecular OH...O=C contact in favour of a cooperative OH...OH...O=C sequence is evidenced by FTIR spectroscopy for the addition of methanol to the esters methyl glycolate, methyl lactate and methyl alpha-hydroxyisobutyrate in seeded supersonic jet expansions. Comparison of the OH stretching modes with quantum-chemical harmonic frequency calculations and 18O labelling of methanol unambiguously prove the insertion of methanol into the intramolecular hydrogen bond. This is in marked contrast to UV/IR hole burning studies of the homologous system methyl lactate: (+/-)-2-naphthyl-1-ethanol, where only addition complexes were found and the intramolecular hydrogen bond was conserved. This switch in hydrogen bond pattern from aliphatic to aromatic heterodimers is thought to reflect not only a kinetic propensity but also a thermodynamic preference for addition complexes when dispersion forces become more important in aromatic systems.

Chirality influence on the aggregation of methyl mandelate

The methyl ester of mandelic acid is investigated by a wide range of techniques to unravel its aggregation pattern and the influence of relative chirality of the aggregating monomers. Matrix isolation confirms that a single monomer conformation prevails. The electronic spectrum of the dimers is strongly affected by the relative monomer chirality. Vibrational effects are more subtle and can be explained in terms of the most stable homo- and heteroconfigurational dimer structures, when compared to results of MP2 and DFT-D computations. Selective IR/UV double resonance techniques and wide-band FTIR spectroscopy provide largely consistent spectroscopic fingerprints of the chirality discrimination phenomena. The dominant homochiral dimer has two intermolecular O–H⋯OC hydrogen bonds whereas the more strongly bound heterochiral dimer involves only one such hydrogen bond. This is a consequence of the competition between dispersion and intramolecular or intermolecular hydrogen bonding. Aromatic interactions also play a role in trimers and larger clusters, favoring homochiral ring arrangements. Analogies and differences to the well-investigated methyl lactate system are highlighted. Bulk phases show a competition between different hydrogen bond patterns. The enantiopure, racemic, and 3 : 1 crystals involve infinite hydrogen-bonded chains with different arrangements of the aromatic groups. They exhibit significantly different volatility, the enantiopure compound being more volatile than the racemic crystal. The accumulated experimental and quantum-chemical evidence turns methyl mandelate into a model system for the role of competition between dispersion forces and hydrogen bond interactions in chirality discrimination.

Conformational Analysis of Quinine and Its Pseudo Enantiomer Quinidine: A Combined Jet-Cooled Spectroscopy and Vibrational Circular Dichroism Study

Laser-desorbed quinine and quinidine have been studied in the gas phase by combining supersonic expansion with laser spectroscopy, namely, laser-induced fluorescence (LIF), resonance-enhanced multiphoton ionization (REMPI), and IR-UV double resonance experiments. Density funtional theory (DFT) calculations have been done in conjunction with the experimental work. The first electronic transition of quinine and quinidine is of π-π* nature, and the studied molecules weakly fluoresce in the gas phase, in contrast to what was observed in solution (Qin, W. W.; et al. J. Phys. Chem. C2009, 113, 11790). The two pseudo enantiomers quinine and quinidine show limited differences in the gas phase; their main conformation is of open type as it is in solution. However, vibrational circular dichroism (VCD) experiments in solution show that additional conformers exist in condensed phase for quinidine, which are not observed for quinine. This difference in behavior between the two pseudo enantiomers is discussed.

Fluorescence spectroscopy of jet-cooled chiral (±)-indan-1-ol and its cluster with (±)-methyl- and ethyl-lactate

The laser-induced fluorescence excitation, dispersed fluorescence, and IR-UV double resonance spectra of chiral (+/-)-indan-1-ol have been measured in a supersonic expansion. Three low energy conformers of the molecule have been identified, and the ground state vibrational modes of each conformer are tentatively assigned with the aid of quantum chemistry calculations. The frequencies of the nu(OH) and nu(CH) stretch modes of the two most abundant conformers have been measured by fluorescence dip IR spectroscopy and have been used for their assignment. The dispersed fluorescence spectra clearly indicate the coupling of low-frequency modes, as was seen in other substituted indanes such as 1-aminoindan and 1-amino-2-indanol. (R)- and (S)-indan-1-ol distinctly form different types of clusters with (R)- and (S)- methyl- and ethyl-lactate. Both hetero- and homochiral clusters are characterized by complex spectra which exhibit a progression built on low-frequency intermolecular modes.

Laser spectroscopy of a chiral drug in a supersonic beam: conformation and complexation of s-(+)-Naproxen

Abstract The S 0 –S 1 electronic transition of jet-cooled Naproxen has been investigated by laser-induced fluorescence excitation and emission spectroscopy. Two electronic transitions separated by 102 cm −1 have been evidenced and attributed to the presence of two conformers. With the help of DFT calculations, the structure of these conformers has been shown to correspond to a rotation by 180° of the chiral substituent with respect to the aromatic plane. When associated with alcohols, both conformers of the chromophore form complexes which give rise to different microscopic solvent shifts of the S 0 –S 1 transition. In the case of complexation with R- or S-2-butanol, the hetero- and homo-chiral pairs are characterised by different spectroscopic patterns, which allow a clear discrimination between them.

Chiral recognition between alpha-hydroxylesters: a double-resonance IR/UV study of the complexes of methyl mandelate with methyl glycolate and methyl lactate.

Chiral recognition between alpha hydroxylesters has been studied in jet-cooled complexes of methyl mandelate with methyl lactate. The complex with nonchiral methyl glycolate has also been studied for the sake of comparison. The hydrogen-bond topology of the complexes has been interrogated by means of IR/UV double-resonance spectroscopy in the range of 3 mum. A theoretical approach has been conducted in conjunction with the experimental work to assist in the analysis of the spectra. Owing to the conformational flexibility of the subunits at play, emphasis has been put on the methodology used for the exploration of the potential-energy surface. The hydrogen-bond topology is very similar in the homo- and heterochiral complexes. It involves insertion of the hydroxyl group of methyl mandelate within the intramolecular hydrogen bond of methyl lactate or methyl glycolate, resulting in a five-membered ring. This contrasts with methyl lactate clusters previously studied by FTIR spectroscopy in a filet jet.

How do Pseudoenantiomers Structurally Differ in the Gas Phase? An IR/UV Spectroscopy Study of Jet‐Cooled Hydroquinine and Hydroquinidine

The gas-phase structures of the cinchona alkaloids, hydroquinine and its pseudoenantiomer hydroquinidine, are studied in a supersonic expansion by means of laser-induced fluorescence and IR/UV double-resonance spectroscopy. Vibrational spectroscopy combined with density functional calculations show that the conformational properties of the two pseudoenantiomers are identical. In both cases, they exist in two isoenergetic forms, with similar IR spectra. Both conformers are similar to the most stable cis-γ-open form of quinine; they differ from each other by the position of the ethyl substituent attached to the quinuclidine ring. Further differences between the two conformers are observed in the laser-induced fluorescence spectrum. The first electronic transition is characterized by time-dependent density functional theory and RI-cc2 calculations, and is of ππ* nature. The results described here emphasize the role of the ethyl substituent in the structural differences between pseudoenantiomers of cinchona alkaloids.

Mass Spectrometry Study and Infrared Spectroscopy of the Complex Between Camphor and the Two Enantiomers of Protonated Alanine: The Role of Higher-Energy Conformers in the Enantioselectivity of the Dissociation Rate Constants

The properties of the protonated complexes built from S camphor and R or S alanine were studied in a Paul ion trap at room temperature by collision-induced dissociation (CID) and infrared multiple-photon dissociation spectroscopy (IRMPD), as well as molecular dynamics and ab initio calculations. While the two diastereomer complexes display very similar vibrational spectra in the fingerprint region, in line with similar structures, and almost identical calculated binding energies, their collision-induced dissociation rates are different. Comparison of the IRMPD results to computed spectra shows that the SS and SR complexes both contain protonated alanine strongly hydrogen-bonded to the keto group of camphor. The floppiness of this structure around the NH⁺...O=C hydrogen bond results in a complex potential energy surface showing multiple minima. Calculating the dissociation rate constant within the frame of the transition state theory shows that the fragmentation rate larger for the heterochiral SR complex than the homochiral SS complex can be explained in terms of two almost isoenergetic low-energy conformers in the latter that are not present for the former.

Jet-cooled hydrates of Chiral (S) 1,2,3,4-tetrahydro-3-isoquinoline methanol (THIQM): structure and mechanism of formation

The mechanism of formation of hydrates of chiral (S) 1,2,3,4-tetrahydro-3-isoquinoline (THIQM) with two water molecules has been investigated in jet-cooled condition by means of resonance-enhanced two-photon ionization and IR-UV double resonance experiments. Quantum chemical calculations reveal that only one isomer of the THIQM is involved in the THIQM-(H(2)O)(2) complex formation, in contrast with what was observed for THIQM-(H(2)O). Anharmonic vibration calculations allowed unambiguous assignment of THIQM-(H(2)O)(2) to a complex resulting from the addition of a water molecule on the most stable THIQM-(H(2)O) complex. A sequential mechanism for complex formation has been deduced from these results.

Laser-induced fluorescence and single vibronic level emission spectroscopy of chiral (R)-1-aminoindan and some of its clusters in a supersonic jet

Two low energy conformers of the chiral (R)-1-aminoindan molecule are identified in supersonic jet and their ground and excited states vibrational spectroscopy has been investigated by laser-induced fluorescence (LIF) excitation and single vibronic level (SVL) emission spectroscopy. Ab initio calculations confirm the existence of two lowest-energy structures, where the amino group is in equatorial position with its lone pair directed opposite to the aromatic electron cloud. Harmonic frequencies have been calculated for these two conformers at the DFT level with B3LYP functional. A low-frequency progression of 118 cm(-1) and 114 cm(-1), respectively, appears in the fluorescence excitation spectrum of the two conformers, with its ground state counterpart at approximately 147 cm(-1). It has been assigned to the puckering motion coupled with the ring flapping mode. The other calculated low-frequency mode corresponds to the puckering motion coupled with the ring twisting mode and its ground state frequency has been observed at 119 cm(-1) and 111 cm(-1) from SVL spectra. Both conformers form similar 1 : 1 water clusters, whose 0-0 transitions are shifted to the blue by 41 cm(-1) and 44 cm(-1), respectively, and whose SVL spectra are similar. Interestingly, one of the conformers seems to preferentially make complexes with (S)-methyllactate, while the other one shows selective complexation to (R)-methyllactate.