Anne Zehnacker

Chirality Recognition between Neutral Molecules in the Gas Phase

Noncovalent interactions are particularly intriguing when they involve chiral molecules, because the interactions change in a subtle way upon replacing one of the partners by its mirror image. The resulting phenomena involving chirality recognition are relevant in the biosphere, in organic synthesis, and in polymer design. They may be classified according to the permanent or transient chirality of the interacting partners, leading to chirality discrimination, chirality induction, and chirality synchronization processes. For small molecules, high-level quantum chemical calculations for such processes are feasible. To provide reliable connections between theory and experiment, such phenomena are best studied in vacuum isolation at low temperature, using rotational, vibrational, electronic, and photoionization spectroscopy. We review these techniques and the results which have become available in recent years, with special emphasis on dimers of permanently chiral molecules and on the influence of conformational flexibility. Analogies between the microscopic mechanisms and macroscopic phenomena and between intra- and intermolecular cases are drawn.

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.

Binding energy of hydrogen-bonded complexes of the chiral molecule 1-phenylethanol, as studied by 2C-R2PI: comparison between diastereoisomeric complexes with butan-2-ol and the singly hydrated complex

The relative gas phase binding energy of the two diastereoisomeric complexes of R-1-phenylethanol with R- and S-butan-2-ol formed in a supersonic expansion has been obtained from fragmentation measurements following two-colour resonance two-photon ionisation of the complex. The homochiral species (Rr) is found to be more stable than the heterochiral complex (Rs) by about 0.7 kcal mol−1. The present study also points out two possible reasons for an underestimation of the absolute binding energy when using a photofragmentation technique: (i) when the adiabatic ionisation threshold of the chromophore (here, 1-phenylethanol) is not accessible by photoionisation because of a too large geometry change between the neutral species and the ion, only lower limits of the binding energies can be drawn; and (ii) when the solvent (here, butan-2-ol) exists under different conformers, the most stable form of the complex can involve a conformation different from the most stable one in the isolated fragment. The lowest-energy fragmentation channel in the ion nevertheless corresponds to the formation of the most stable form of the fragments. In the present case, this latter effect may contribute to an anomalous low binding energy of the complexes of 1-phenylethanol with butan-2-ol compared to the 1:1 hydrate.

Chiral recognition between lactic acid derivatives and an aromatic alcohol in a supersonic expansion: electronic and vibrational spectroscopy

Jet-cooled diastereoisomeric complexes formed between a chiral probe, (+/-)-2-naphthyl-1-ethanol, and chiral lactic acid derivatives have been characterised by laser-induced fluorescence and IR fluorescence-dip spectroscopy. Complexes with non chiral alpha-hydroxyesters and chiral beta-hydroxyesters have also been studied for the sake of comparison. DFT calculations have been performed to assist in the analysis of the vibrational spectra and the determination of the structures. The observed 1 : 1 complexes correspond to the addition of the hydroxy group of the chromophore on the oxygen atom of the hydroxy in alpha-position relative to the ester function. Moreover, (+/-)-methyl lactate and (+/-)-ethyl lactate complexes with (+/-)-2-naphthyl-1-ethanol show an enantioselectivity in the size of the formed adducts: while fluorescent 1 : 1 complexes are the most abundant species observed when mixing (S)-2-naphthyl-1-ethanol with (R)-methyl or ethyl lactate, they are absent in the case of the SS mixture, which only shows 1 : 2 adducts. This property has been related to steric hindrance brought by the methyl group on the hydroxy-bearing carbon atom.

IR-UV investigation of the structure of the 1-phenylethanol chromophore and its hydrated complexes

The structure of the 1-phenylethanol molecule and its hydrated complexes has been investigated by means of laser-induced fluorescence and IR fluorescence-dip spectroscopy in the region of the OH vibration, coupled with DFT calculations. The isolated chromophore has a gauche conformation with the OH group slightly interacting with the aromatic cycle. In the singly hydrated complex, the water molecule acts as a proton acceptor from the OH group of the chromophore and is involved as a donor in the OH–π interaction with the aromatic ring. The 1:2 water complex consists of a water dimer acting as an acceptor from the OH group of 1-phenylethanol and as a donor to its aromatic ring.

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.

Role of conformational isomerism in solvent-mediated charge transfer in chiral (S) 1,2,3,4-tetrahydro-3-isoquinoline methanol (THIQM): condensed-phase to jet-cooled spectroscopic studies.

Intramolecular charge-transfer reaction in chiral (S) 1,2,3,4-tetrahydro-3-isoquinoline methanol (THIQM) has been investigated in the condensed phase and in jet-cooled conditions by means of laser-induced fluorescence, dispersed emission, resonance-enhanced two-photon ionization, and IR-UV double resonance experiments, as well as quantum chemical calculations. In the condensed phase, THIQM only shows local emission in nonpolar and protic solvents and dual emission in aprotic polar solvents, where the solvent-polarity dependent Stokes shifted emission is ascribed to a state involving charge transfer from the nitrogen lone pair to the benzene π-cloud. Ab initio calculations reveal two low-energy conformers, which are observed in jet-cooled conditions. In the most stable conformer, THIQM(I), the CH(2)OH substituent acts as a hydrogen bond donor to the nitrogen lone pair in the equatorial position, while the second most stable conformer, THIQM(II), corresponds to the opposite NH···O hydrogen bond, with the nitrogen lone pair in the axial position. The two low-energy jet-cooled conformers of THIQM evidenced from the laser-induced fluorescence and dispersed emission spectra only show structured local emission. Complexes with usual solvents reproduce the condensed phase properties. The jet-cooled complex with aprotic polar solvent acetonitrile shows both local emission and charge transfer emission as observed in solution. The jet-cooled hydrate mainly shows local emission due to the unavailability of the nitrogen lone pair through intermolecular hydrogen bonding.

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.

Conformation-dependent intramolecular exciplex formation in jet-cooled bichromophores

Abstract Bichromophore compounds consisting of anthracene and naphthalene subunits linked by the alkyl (CH 2 ) 3 and the ethereal CH 2 –O–CH 2 chain have been studied under supersonic jet conditions in the region of the first electronic transition of anthracene by laser-induced fluorescence. Intramolecular exciplex formation has been observed in the 1-substituted naphthalene derivative involving the CH 2 –O–CH 2 spacer, whereas the trimethylene bridge compound as well as the 2-substituted naphthalene ethereal derivative exhibit only the resonance fluorescence characteristic of a locally excited anthracene molecule. These different behaviours reproduce the photophysical properties of these bichromophores in solution and have been discussed in terms of ground-state geometries.

Fluorescence emission in fluid solution and supersonic jet of symmetrical bisbenzenes incorporating a three membered flexible chain

Abstract Intramolecular excimer formation in symmetrical bichromophore compounds consisting of two benzene, anisole, and 2,6-dimethylbenzene groups connected by a highly flexible O-CH2-O chain has been evidenced from steady state and time resolved fluorescence studies. The thermodynamic and kinetic parameters have been determined in methanol and for one of them in methylcyclohexane as a function of temperature. While the activation energy for the conformational change required for excimer formation is similar for both solvents, the preexponential factors deduced from Arrhenius plots appear to be larger in methanol than in methylcyclohexane. The parallel investigation of fluorescence excitation and dispersed emission spectra of bis-p-methoxy-phenoxymethane in supersonic expansion has shown that two conformers coexist in the jet and that the intrinsic barrier for excimer formation in the isolated molecule is larger than 2.3 kcal mol−1.