Rovibronic signatures of molecular aggregation in the gas phase: subtle homochirality trends in the dimer, trimer and tetramer of benzyl alcohol.

[EN]Molecular aggregation is of paramount importance in many chemical processes, including those in living beings. Thus, characterization of the intermolecular interactions is an important step in its understanding. We describe here the aggregation of benzyl alcohol at the molecular level, a process governed by a delicate equilibrium between OHMIDLINE HORIZONTAL ELLIPSISO and OHMIDLINE HORIZONTAL ELLIPSIS pi hydrogen bonds and dispersive interactions. Using microwave, FTIR, Raman and mass-resolved double-resonance IR/UV spectroscopic techniques, we explored the cluster growth up to the tetramer and found a complex landscape, partly due to the appearance of multiple stereoisomers of very similar stability. Interestingly, a consistently homochiral synchronization of transiently chiral monomer conformers was observed during cluster growth to converge in the tetramer, where the fully homochiral species dominates the potential energy surface. The data on the aggregation of benzyl alcohol also constitute an excellent playground to fine-tune the parameters of the most advanced functionals.The Gottingen part of the project was partly funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 271107160/SPP1807. We thank M. Lange and E. K. M. M. Sennert for the measurement of the FTIR spectrum and E. Meyer for help with the measurement of the Raman spectrum. Computational resources from the GWDG and the Gottingen Faculty of Chemistry (DFG - 405832858/INST 186/1294-1 FUGG) are acknowledged. We thank the Gottingen chemistry workshops for valuable support. This publication was supported financially by the Open Access Grant Program of the DFG and the Open Access Publication Fund of the University of Gottingen. The Bilbao and Valladolid groups acknowledge funding from the Spanish Ministerio de Ciencia e Innovacion (MICINN-FEDER PGC2018-098561-B-C21 and PGC2018-098561-B-C22). Bilbao's group also thank the SGIKER (UPV/EHU, MICIU-FEDER) for the computational and laser resources. The Hamburg part of this work was financially supported by the Deutsche Forschungsgemeinschaft (SCHN1280/4-2, project number 271359857) in the context of the priority program SPP 1807 "Control of London dispersion interactions in molecular chemistry". P. Pinacho would like to thank the Alexander von Humboldt Foundation for a postdoctoral fellowship

The furan microsolvation blind challenge for quantum chemical methods: First steps

© 2018 Author(s). Herein we present the results of a blind challenge to quantum chemical methods in the calculation of dimerization preferences in the low temperature gas phase. The target of study was the first step of the microsolvation of furan, 2-methylfuran and 2,5-dimethylfuran with methanol. The dimers were investigated through IR spectroscopy of a supersonic jet expansion. From the measured bands, it was possible to identify a persistent hydrogen bonding OH-O motif in the predominant species. From the presence of another band, which can be attributed to an OH-π interaction, we were able to assert that the energy gap between the two types of dimers should be less than or close to 1 kJ/mol across the series. These values served as a first evaluation ruler for the 12 entries featured in the challenge. A tentative stricter evaluation of the challenge results is also carried out, combining theoretical and experimental results in order to define a smaller error bar. The process was carried out in a double-blind fashion, with both theory and experimental groups unaware of the results on the other side, with the exception of the 2,5-dimethylfuran system which was featured in an earlier publication

The first microsolvation step for furans : new experiments and benchmarking strategies

The site-specific first microsolvation step of furan and some of its derivatives with methanol is explored to benchmark the ability of quantum-chemical methods to describe the structure, energetics, and vibrational spectrum at low temperature. Infrared and microwave spectra in supersonic jet expansions are used to quantify the docking preference and some relevant quantum states of the model complexes. Microwave spectroscopy strictly rules out in-plane docking of methanol as opposed to the top coordination of the aromatic ring. Contrasting comparison strategies, which emphasize either the experimental or the theoretical input, are explored. Within the harmonic approximation, only a few composite computational approaches are able to achieve a satisfactory performance. Deuteration experiments suggest that the harmonic treatment itself is largely justified for the zero-point energy, likely and by design due to the systematic cancellation of important anharmonic contributions between the docking variants. Therefore, discrepancies between experiment and theory for the isomer abundance are tentatively assigned to electronic structure deficiencies, but uncertainties remain on the nuclear dynamics side. Attempts to include anharmonic contributions indicate that for systems of this size, a uniform treatment of anharmonicity with systematically improved performance is not yet in sight

Quantifying Conformational Isomerism in Chain Molecules by Linear Raman Spectroscopy: The Case of Methyl Esters

The conformational preferences of the ester group have the potential to facilitate the large amplitude folding of long alkyl chains in the gas phase. They are monitored by Raman spectroscopy in supersonic jet expansions for the model system methyl butanoate, after establishing a quantitative relationship with quantum–chemical predictions for methyl methanoate. This requires a careful analysis of experimental details, and a simulation of the rovibrational contours for near-symmetric top molecules. The technique is shown to be complementary to microwave spectroscopy in quantifying coexisting conformations. It confirms that a C−O−C(=O)–C–C chain segment can be collapsed into a single all-trans conformation by collisional cooling, whereas alkyl chain isomerism beyond this five-membered chain largely survives the jet expansion. This sets the stage for the investigation of linear alkyl alkanoates in terms of dispersion-induced stretched-chain to hairpin transitions by Raman spectroscopy

Low Temperature Infrared Spectroscopy Study of Pyrazinamide: From the Isolated Monomer to the Stable Low Temperature Crystalline Phase

A structural and spectroscopic analysis of the anti-tuberculosis drug pyrazinamide (PZA) was carried out. The PZA molecule was predicted theoretically to possess two conformers differing by internal rotation around the C−C(═O) bond, with the E conformer (Cs symmetry point group; N−C−C═O dihedral: 180°) being ca. 30 kJ mol−1 more stable than the Z form (C1 point group; N−C−C═O dihedral: ca. ± 42°). In consonance with both the large energy difference and low energy barrier between the Z and E conformers, upon isolation in low temperature argon and xenon matrices, only the E form could be observed and characterized spectroscopically. In the argon matrix, this conformer was found to exist in at least three matrix sites, of different stability. In a supersonic jet, besides the monomer (E), the most stable dimer of PZA with two equivalent NH···O═ hydrogen bonds could also be identified. Its spectrum reveals rapid energy flow out of the excited NH stretching mode mediated by one of the heteroatoms in the ring. Finally, the IR spectra of the amorphous solid resulting from fast cooling of the vapor of the compound (initially in the α crystalline phase) onto the cold substrate of the cryostat (10 K) and of the crystalline phase resulting from warming the amorphous solid were also recorded and interpreted. The obtained crystalline phase was found to be the thermodynamically most stable δ polymorph of PZA

Attaching Onto or Inserting Into an Intramolecular Hydrogen Bond: Exploring and Controlling a Chirality-Dependent Dilemma for Alcohols

Prereactive complexes in noncovalent organocatalysis are sensitive to the relative chirality of the binding partners and to hydrogen bond isomerism. Both effects are present when a transiently chiral alcohol docks on a chiral α-hydroxy ester, turning such 1:1 complexes into elementary, non-reactive model systems for chirality induction in the gas phase. With the help of linear infrared and Raman spectroscopy in supersonic jet expansions, conformational preferences are investigated for benzyl alcohol in combination with methyl lactate, also exploring p-chlorination of the alcohol and the achiral homolog methyl glycolate to identify potential London dispersion and chirality effects on the energy sequence. Three of the four combinations prefer barrierless complexation via the hydroxy group of the ester (association). In contrast, the lightest complex predominantly shows insertion into the intramolecular hydrogen bond, such as the analogous lactate and glycolate complexes of methanol. The experimental findings are rationalized with computations, and a uniform helicality induction in the alcohol by the lactate is predicted, independent of insertion into or association with the internal lactate hydrogen bond. p-chlorination of benzyl alcohol has a stabilizing effect on association because the insertion motif prevents a close contact between the chlorine and the hydroxy ester. After simple anharmonicity and substitution corrections, the B3LYP-D3 approach offers a fairly systematic description of the known spectroscopic data on alcohol complexes with α-hydroxy esters

Detailed Assignment of the CH Chromophores in Methyl Mandelate and Mandelic Acid: A Multi-Experimental Approach Using Polarized FTIR Microspectroscopy of Sublimated Crystals

A sublimation cell for the characterization of microcrystals using Fourier transform infrared (FTIR) microspectroscopy was constructed and applied to methyl mandelate and mandelic acid. It was possible to assign different CH chromophores in the FTIR spectra. Comparison to quantum chemical calculations, attenuated total reflectance infrared (ATR-IR) spectra of related compounds, and isotope labeling was used to support the assignments. Vibrational transition dipole vectors were deduced from crystal rotation and polarization experiments. The direction of these vectors can be used to constrain the absolute orientation of the molecules in the crystal as well as for the assignment of further vibrational bands