Structural and dynamical features of the 2,2,2-trifluoroethanolammonia complex.

The 1 : 1 adduct of 2,2,2-trifluoroethanol (TFE) with ammonia was investigated using a combination of chirped pulse and cavity-based Fourier transform microwave spectroscopy and computational methods. Rotational spectra of the most stable TFENH3 conformer and seven deuterium and 15N isotopologues were identified, and this led to a determination of partial rs and ro structures. The observed complex exhibits a gauche conformation of TFE with ammonia inserted into the existing intramolecular hydrogen-bonded ring of TFE. The adduct is stabilised by a delicate interplay between the primary O-HN hydrogen-bond and secondary N-HF interactions between TFE and ammonia. Evidence for several internal-dynamics effects was found in the rotational spectra. The ammonia subunit shows an almost free internal rotation. Tunneling between the gauche forms, g+ and g-, of TFE is quenched by the hydrogen-bond interactions with ammonia.

Conformational Landscape of m-Anisic Acid and Its Complexes with Formic Acid.

Four conformers of m-anisic acid were observed in a supersonic expansion using Fourier transform microwave spectroscopy. These conformers correspond to different relative orientations of the acid and methoxy groups and have their planar skeletons stabilized by resonance. When formic acid was present in the jet, the spectra of four m-anisic acid-formic acid heterodimer conformers were detected. The complexes are formed from the interaction of formic acid with each of the four observed conformers of m-anisic acid through the typical acid-acid sequential cycle with a double O-H···O═C hydrogen bond interaction in a pseudo eight-membered ring arrangement. The four heterodimer forms retain the same four m-anisic acid conformational geometries and the same relative abundances of the m-anisic acid monomeric forms in the supersonic expansion. This proves that a kinetic mechanism dominates the formation of complexes in the jet.

The rich conformational landscape of perillyl alcohol revealed by broadband rotational spectroscopy and theoretical modelling.

The rotational spectrum of perillyl alcohol, a naturally occurring, chiral, dietary monoterpene, was investigated using a chirped pulse Fourier transform microwave spectrometer and a cavity-based Fourier transform microwave spectrometer. To aid the assignment of the dense chirped pulse spectrum obtained, extensive theoretical conformational searches were carried out. In one approach, several one and two-dimensional scans along three dihedral angles associated with the rotational motions of the -OH, -CH2OH, and -C(CH2)CH3 groups were performed. These scans, combined with the equatorial and axial positions of the -C(CH2)CH3 group, resulted in 54 conformers. The same conformers were identified in the second approach where a semi-classical conformational search code was used. The relative stabilities of the conformers and the interconversion barriers among them were explored extensively at the DFT B3LYP-D3(BJ)/def2-TZVP and B3LYP-D3(BJ)/6-311++G(2d,p), as well as local MP2/aug-cc-pVQZ levels of theory, and 12 conformers were ultimately identified as possibly observable candidates in a molecular jet expansion. Rotational spectra of eight out of the 12 candidates were observed experimentally and analyzed. The non-observation of the remaining four conformers may be attributed to their low abundances. The study points out the importance of identifying all conformers of relevant abundance, even those which could not be detected experimentally, in order to properly benchmark the theoretical relative stabilities with the experimental ones. A comprehensive study of the conformational distribution of perillyl alcohol contributes to our understanding of its structural properties which may influence its functions.

Competition Between Intra- and Intermolecular Hydrogen Bonding: o-Anisic Acid⋠⋠⋠Formic Acid Heterodimer.

Four conformers of the heterodimer o-anisic acid-formic acid, formed in a supersonic expansion, have been probed by Fourier transform microwave spectroscopy. Two of these forms have the typical double intermolecular hydrogen-bond cyclic structure. The other two show the o-anisic acid moiety bearing a trans-COOH arrangement supported by an intramolecular O-H⋅⋅⋅O bond to the neighbor methoxy group. In these conformers, formic acid interacts with o-anisic acid mainly through an intermolecular O-H⋅⋅⋅O hydrogen bond either to the O-H or to the C=O moieties, reinforced by other weak interactions. Surprisingly, the most abundant conformer in the supersonic expansion is the complex in which the o-anisic acid is in trans arrangement with the formic acid interacting with the O-H group. Such a trans-COOH arrangement in which the intramolecular hydrogen bond dominates over the usually observed double intermolecular hydrogen bond interaction has never been observed previously in an acid-acid dimer.

Rotational spectroscopy of chiral tetrahydro-2-furoic acid: Conformational landscape, conversion, and abundances.

The conformational landscape of tetrahydro-2-furoic acid (THFA), a chiral carboxylic acid which is often used as a precursor in syntheses of pharmaceuticals, was investigated using rotational spectroscopy and theoretical modeling. Extensive manual searches were carried out to identify possible conformers related to the relative orientations of the carbonyl and hydroxyl groups in the COOH functional group, the COOH rotation, and the ring puckering motions in the system. A large number of initial conformational geometries were generated in parallel using a joint semiempirical-molecular dynamics simulation program. The final geometry optimizations were carried out at the B3LYP-D3(BJ)/def2-TZVP, B3LYP-D3(BJ)/6-311++G(2d,p), and MP2/6-311G++(2d,p) levels of theory. Eight conformers within a relative energy span of 10 kJ mol-1 after zero-point energy corrections were identified. Rotational spectra of three conformers were detected experimentally and assigned, as were the spectra of all the 13C isotopologues of the most stable conformer. Based on the achieved experimental sensitivity and the predicted relative abundances at the sample source, some conformers are unexpectedly missing or experience significant depletion, whereas others show noticeable enrichment. Detailed analyses of the conformational conversion barriers were carried out to satisfactorily explain the observed phenomena. The combined experimental rotational spectroscopic and theoretical investigation provides significant insights into the complex conformational landscape of THFA.

Rotational spectra and theoretical study of tetramers and trimers of 2-fluoroethanol: dramatic intermolecular compensation for intramolecular instability.

Using broadband rotational spectroscopy aided by high level ab initio calculations, we probe structural diversity and emerging bulk behavior in trimeric and tetrameric aggregates of the transiently chiral 2-fluoroethanol (FE). One FE tetramer which is homochiral and features a highly compact arrangement that is stabilized by a water tetramer-like H-bond ring and a network of fully bifurcated C-HF H-bonds, and two higher energy FE trimers which feature a water trimer-like H-bond ring, were observed experimentally in a jet expansion. The three most stable FE trimers predicted within a few kJ mol-1 are all made of the most stable FE subunit and are detected experimentally. Unexpectedly, two out of the three most stable FE tetramers exclusively consist of much less stable subunits. For example, one FE tetramer that contains four less stable subunits, which are in total ∼40 kJ mol-1 less stable than their global minimum counterparts, is predicted to be of similar stability as the tetramer containing four global minimum subunits. High level theoretical modeling is essential in providing a comprehensive picture of the energetic and structural landscapes of the FE tetramer, an intriguing system at the interface between gas- and bulk-phase behavior, where the conformational specificity seen in the gas-phase is still experimentally relevant but plays a diminished role relative to the intermolecular topology and cooperative stability.

IR, Raman, and Vibrational Optical Activity Spectra of Methyl Glycidate in Chloroform and Water: The Clusters-in-a-liquid Solvation Model.

Solvent effects, in particular those involving water as the solvent, are of significant interest to the chemistry and physics communities. IR, vibrational circular dichroism (VCD), Raman, and Raman optical activity (ROA) spectra of methyl glycidate in two very different solvents, namely CCl4 and water, have been measured experimentally and simulated theoretically. The observed spectra in CCl4 could be well modelled using the polarizable continuum model for the solvent, whereas the situation is much different in water. The experimental VCD spectrum of methyl glycidate in water reveals strong induced VCD signatures in the water bending region, indicating the presence of the relatively long-lived methyl glycidate-watern complexes. We applied the clusters-in-a-liquid approach to identify the dominant methyl glycidate-water1,2 complexes which are the long-lived species responsible for all the spectra observed in water. We examined the influences of solvent dielectric environment and the hydrogen-bonding interactions on the conformational distribution of methyl glycidate. The geometry optimizations, frequency calculations, IR, VCD, Raman and ROA intensity calculations were performed at the B3LYP/6-311++G(2d,p) and aug-cc-pVTZ levels of theory with D3BJ dispersion correction. It is particularly satisfying to note that the clusters-in-a-liquid approach has captured all main experimental features in IR, VCD, Raman and ROA spectra of methyl glycidate in water.

Rotational spectroscopy of the methyl glycidate-water complex: conformation and water and methyl rotor tunnelling motions.

Methyl glycidate is a chiral epoxy ester whose structure and characteristic functional groups can be used to model biological events involving much larger chiral esters on the molecular scale. Since biological molecules function in aqueous solution, it is of interest to obtain detailed knowledge of the initial few steps of solvation using high resolution spectroscopy. In the current study, rotational spectra of methyl glycidate monohydrate were investigated by using a chirped-pulse and a cavity-based Fourier transform microwave spectrometer. Quantum theory of atoms in molecules and non-covalent interaction analyses were performed for the observed monohydrate to characterize non-covalent interactions in the system. In the observed monohydrate, methyl glycidate takes on its most stable monomeric form, while water serves as a hydrogen bond donor to the carbonyl group and as a hydrogen bond acceptor to the hydrogen atom of the CH2 group on the epoxide ring, and additionally forms a close contact to the epoxide oxygen atom. Unexpectedly, water tunnelling splittings on the order of tens to hundreds of kHz were detected. A water tunnelling path was proposed and a surprisingly low tunnelling barrier of about 2 kJ mol-1 was calculated. The proposed tunnelling path is asymmetric in the forward and backward tunnelling directions, demonstrating the complicated dynamics of water motions in the system. In addition, splittings due to the methyl internal rotation were observed and analyzed.

Tunnelling and barrier-less motions in the 2-fluoroethanol-water complex: a rotational spectroscopic and ab initio study.

The pure rotational spectrum of the 2-fluoroethanol (2-FE)water complex was measured using a chirped pulse Fourier-transform microwave spectrometer and a cavity-based Fourier-transform microwave spectrometer. In the detected 2-FEwater conformer, 2-FE serves as a proton donor, in contrast to its role in the observed ethanolwater conformer, while water acts simultaneously as a hydrogen bond donor and acceptor, forming a hydrogen-bonded ring with an OHO and an OHF hydrogen bond. Comparison to the calculated dipole moment components suggests that the observed structure sits between the two most stable minima identified theoretically. This conclusion is supported by extensive deuterium isotopic data. Further analysis shows that these two minima are connected by a barrier-less wagging motion of the non-bonded hydrogen of the water subunit. The observed narrow splitting with a characteristic 3 : 1 intensity ratio is attributed to an exchange of the bonded and non-bonded hydrogen atoms of water. The tunneling barrier of a proposed tunneling path is calculated to be as low as 5.10 kJ mol-1. A non-covalent interaction analysis indicates that the water rotation motion along the tunneling path has a surprisingly small effect on the interaction energy between water and 2-FE.

Rotational spectra of two six-membered heterocyclic N-methyl-piperidinol compounds: Conformations by OH rotation, N-methyl inversion, and ring puckering.

Rotational spectra of two nitrogen containing six-membered heterocycles which are commonly used in syntheses of pharmaceuticals, namely, N-methyl-3-piperidinol (NMP3) and N-methyl-4-piperidinol (NMP4), were measured using a broadband chirped pulse and a cavity based Fourier transform microwave spectrometer. The possible conformers due to the OH rotation, N-methyl inversion, and ring puckering were investigated theoretically for these two heterocycles. The substituent position of the hydroxyl group with respective to the N atom in the heterocyclic ring has a strong influence on the preferred conformations. While one dominant conformer, favoring the OH⋯N close contact, was predicted for NMP3, several close energy conformers with OH pointing at different directions were predicted for NMP4. In contrast, only one conformer was identified for each compound experimentally. The 14N nuclear quadrupole hyperfine structures were observed for all rotational transitions and analyzed. In addition, rotational spectra of all 13C and 15N isotopologues of NMP4 were studied in their natural abundance, leading to a definite identification of the NMP4 conformer observed. The differences in the conformational landscapes and the OH motions in the two compounds are presented and also discussed in the context of the 1,3-diaxial interaction rule commonly used in organic chemistry.

A Direct Link from the Gas to the Condensed Phase: A Rotational Spectroscopic Study of 2,2,2-Trifluoroethanol Trimers.

Rotational spectra of the three most stable conformers (I, II, III) of the ternary 2,2,2-trifluoroethanol (TFE) cluster were measured using Fourier transform microwave spectrometers, and unambiguously assigned with the aid of ab initio calculations. The most stable conformer, I, contains one trans-TFE subunit which is unstable in its isolated gas phase form. The study offers new insights into how the trans conformation is stabilized in TFE clusters of increasing size, and eventually becomes a dominant conformation in the liquid phase. A detailed analysis shows that while O-H⋅⋅⋅O-H and O-H⋅⋅⋅F-C hydrogen bonds are the most significant attractive interactions which stabilize all three conformers, the main driving force for the stability of I over III, which has all gauche-TFE subunits, is the attractive interaction of C-F⋅⋅⋅F-C contact pairs. A new type of three-point F⋅⋅⋅F⋅⋅⋅F attractive contact interaction is also identified.

Hydration of the simplest α-keto acid: a rotational spectroscopic and ab initio study of the pyruvic acid-water complex.

Intermolecular interactions between pyruvic acid, the simplest α-keto acid, and water are important in bio- and atmospheric chemistry. In this context, the pure rotational spectrum of the pyruvic acid-water complex was measured from 7 to 15 GHz using a cavity-based Fourier-transform microwave spectrometer. In the detected isomer, water acts as a hydrogen bond donor and acceptor, bridging the acidic hydrogen and the keto oxygen. Both a- and b-type transitions were observed; however, c-type transitions were not observed, due to vibrational averaging of the effectively barrier-less wagging motion of the free hydrogen of the water subunit, which results in an effective ground state structure with a plane of symmetry. The mass distribution out of the ab-plane, corrected for the out-of-plane hydrogen atoms of the methyl group, confirms that the complex has a plane of symmetry. The observed transitions exhibit splittings due to internal rotations of the water subunit and the methyl group. The proposed internal rotation of water nominally breaks one hydrogen bond, so it is remarkable that the barrier was calculated to be as low as 5.2 kJ mol-1; however, a non-covalent interactions analysis indicates that water rotation has surprisingly little effect on the interactions between the water and pyruvic acid subunits. The barrier to methyl internal rotation was determined to be about 4.6 kJ mol-1 experimentally, significantly higher than that of the pyruvic acid monomer. In general, the structure and dynamics investigated here provide insights into the interactions between pyruvic acid and water that dictate the fate of pyruvic acid in aqueous aerosols and living cells.

The Clusters-in-a-Liquid Approach for Solvation: New Insights from the Conformer Specific Gas Phase Spectroscopy and Vibrational Optical Activity Spectroscopy.

Vibrational optical activity spectroscopies, namely vibrational circular dichroism (VCD) and Raman optical activity (ROA), have been emerged in the past decade as powerful spectroscopic tools for stereochemical information of a wide range of chiral compounds in solution directly. More recently, their applications in unveiling solvent effects, especially those associated with water solvent, have been explored. In this review article, we first select a few examples to demonstrate the unique sensitivity of VCD spectral signatures to both bulk solvent effects and explicit hydrogen-bonding interactions in solution. Second, we discuss the induced solvent chirality, or chiral transfer, VCD spectral features observed in the water bending band region in detail. From these chirality transfer spectral data, the related conformer specific gas phase spectroscopic studies of small chiral hydration clusters, and the associated matrix isolation VCD experiments of hydrogen-bonded complexes in cold rare gas matrices, a general picture of solvation in aqueous solution emerges. In such an aqueous solution, some small chiral hydration clusters, rather than the chiral solutes themselves, are the dominant species and are the ones that contribute mainly to the experimentally observed VCD features. We then review a series of VCD studies of amino acids and their derivatives in aqueous solution under different pHs to emphasize the importance of the inclusion of the bulk solvent effects. These experimental data and the associated theoretical analyses are the foundation for the proposed "clusters-in-a-liquid" approach to account for solvent effects effectively. We present several approaches to identify and build such representative chiral hydration clusters. Recent studies which applied molecular dynamics simulations and the subsequent snapshot averaging approach to generate the ROA, VCD, electronic CD, and optical rotatory dispersion spectra are also reviewed. Challenges associated with the molecular dynamics snapshot approach are discussed and the successes of the seemingly random "ad hoc explicit solvation" reported before are also explained. To further test and improve the "clusters-in-a-liquid" model in practice, future work in terms of conformer specific gas phase spectroscopy of sequential solvation of a chiral solute, matrix isolation VCD measurements of small chiral hydration clusters, and more sophisticated models for the bulk solvent effects would be highly valuable.

Unusual H-Bond Topology and Bifurcated H-bonds in the 2-Fluoroethanol Trimer.

By using a combination of rotational spectroscopy and ab initio calculations, an unusual H-bond topology was revealed for the 2-fluoroethanol trimer. The trimer exhibits a strong heterochiral preference and adopts an open OH⋅⋅⋅OH H-bond topology while utilizing two types of bifurcated H-bonds involving organic fluorine. This is in stark contrast to the cyclic OH⋅⋅⋅OH H-bond topology adopted by trimers of water and other simple alcohols. The strengths of different H-bonds in the trimer were analyzed by using the quantum theory of atoms in molecules. The study showcases a remarkable example of a chirality-induced switch in H-bond topology in a simple transient chiral fluoroalcohol. It provides important insight into the H-bond topologies of small fluoroalcohol aggregates, which are proposed to play a key role in protein folding and in enantioselective reactions and separations where fluoroalcohols serve as a (co)solvent.

Structure and tunneling dynamics in a model system of peptide co-solvents: rotational spectroscopy of the 2,2,2-trifluoroethanol⋯water complex.

The hydrogen-bonding topology and tunneling dynamics of the binary adduct, 2,2,2-trifluoroethanol (TFE)⋯water, were investigated using chirped pulse and cavity based Fourier transform microwave spectroscopy with the aid of high level ab initio calculations. Rotational spectra of the most stable binary TFE⋯water conformer and five of its deuterium isotopologues were assigned. A strong preference for the insertion binding topology where water is inserted into the existing intramolecular hydrogen-bonded ring of TFE was observed. Tunneling splittings were detected in all of the measured rotational transitions of TFE⋯water. Based on the relative intensity of the two tunneling components and additional isotopic data, the splitting can be unambiguously attributed to the tunneling motion of the water subunit, i.e., the interchange of the bonded and nonbonded hydrogen atoms of water. The absence of any other splitting in the rotational transitions of all isotopologues observed indicates that the tunneling between g+ and g- TFE is quenched in the TFE⋯H2O complex.

Chirality induction and amplification in the 2,2,2-trifluoroethanol⋠⋠⋠propylene oxide adduct.

Chirality induction and amplification in a model system, that is, the 2,2,2-trifluoroethanol (TFE)⋅⋅⋅propylene oxide (PO) adduct, were investigated using free-space and cavity-based Fourier transform microwave spectroscopy, complemented with high level ab initio calculations. Rotational spectra of four out of eight predicted TFE⋅⋅PO adducts were assigned, and the remaining four were shown to relax to the geometries of the four observed in a jet expansion. The g+ TFE⋅⋅⋅S-PO adduct was found to be favored over that of g- TFE⋅⋅⋅S-PO by a factor of 2.8 at 60 K. This difference contrasts the TFE dimer for which an extreme case of chirality synchronization was previously reported. All TFE⋅⋅⋅PO conformers observed take on the open arrangement, in contrast to 2-fluoroethanol⋅⋅⋅PO, which prefers the closed arrangement. Furthermore, perfluorination at CH3 increases the hydrogen-bonding energy by about 70 % over its ethanol counterpart.

Perfluorobutyric acid and its monohydrate: a chirped pulse and cavity based fourier transform microwave spectroscopic study.

Rotational spectra of perfluorobutyric acid (PFBA) and its monohydrate were studied with a broadband chirped pulse and a narrow-band cavity based Fourier transform microwave spectrometer, and high-level ab initio calculations. Extensive conformational searches were performed for both the acid and its monohydrate at the MP2/6-311++G(2d,p) level of theory. Two and three conformers were predicted to exist for PFBA and its monohydrate, respectively. One set of rotational transitions was observed and assigned for each, PFBA and its monohydrate. Based on the measured broadband spectra, we confidently conclude that only one dominant conformer exists in each case. The orientation of the hydroxyl group in PFBA was determined by using isotopic analysis. Comparison of the observed transition intensities and the calculated electric dipole moment components allowed us to identify the most stable monohydrate conformation, which takes on an insertion hydrogen-bonding topology. Comparisons to the shorter chain analogues, that is, trifluoroacetic acid, perfluoropropionic acid, and their monohydrates, are made to elucidate the general trend in their conformational preference and binding topologies.

Direct Spectroscopic detection of the orientation of free OH groups in methyl lactate-(water)(1,2) clusters: hydration of a chiral hydroxy ester.

Hydration of chiral molecules is a subject of significant current interest in light of recent experimental observations of chirality transfer from chiral solutes to water in solution and the important roles which water plays in biological events. Using a broadband chirped pulse and a cavity based microwave spectrometer, we detected spectroscopic signatures of the mono- and dihydrates of methyl lactate, a chiral hydroxy ester. Surprisingly, these small hydration clusters show highly specific binding preferences. Not only do they strongly prefer the insertion H-bonding topology, but they also favor specific pointing direction(s) for their non-H-bonded hydroxy group(s). We observed that the particular dihydrate conformer identified is not the most stable one predicted. This work highlights the superior capability of high-resolution spectroscopy to identify specific water binding topologies, and provides quantitative data to test state-of-the-art theory.

Chirality Synchronization in Trifluoroethanol Dimer Revisited: The Missing Heterochiral Dimer.

Chirality self-recognition in the dimer of transient chiral 2,2,2-trifluoroethanol (TFE) is studied using chirped pulse and cavity-based Fourier transform microwave spectroscopy with the aid of ab initio calculations. The broad-band and extreme high-resolution capabilities enable us to assign rotational spectra of the most stable homo- and heterochiral dimers and analyze their structural and dynamical properties in detail. A strong preference for the homochiral over the heterochiral diastereomers is observed. The current study unambiguously identifies the structure of the most stable homochiral dimer and supports the identification by the previous low-resolution infrared study. More importantly, it also indisputably detects the so far elusive, most stable heterochiral dimer.

Chirped-pulse and cavity-based Fourier transform microwave spectroscopy of a chiral epoxy ester: methyl glycidate.

Rotational spectra of a chiral epoxy ester, methyl glycidate, were measured using a chirped-pulse and a cavity-based Fourier transform microwave spectrometer. The two lowest energy conformers where the epoxy oxygen and the ester oxygen atoms are in the syn and anti relative orientation with respect to each other were identified experimentally. Spectra of four (13)C isotopologues of the lowest energy conformer of methyl glycidate were also measured and assigned. All of the observed rotational transitions are split into doublets due to the presence of the ester methyl internal rotor. The rotational constants and the internal rotation barrier height for the ester methyl group were determined for both conformers of methyl glycidate and for the four (13)C isotopologues of the most stable conformer. A value for the interconversion barrier between the two most stable conformers was estimated. Furthermore, comparison to strawberry aldehyde, a larger derivative of methyl glycidate, shows how the syn-anti conformational equilibrium shifts as a result of the additional bulky substituents at the epoxy ring and at the ester oxygen atom.