Three-dimensional docking of alcohols to ketones: an experimental benchmark based on acetophenone solvation energy balances.

The two hydrogen bond solvation sites exhibited by the carbonyl group in acetophenone are influenced by alkylation of the methyl group in both the acetophenone and in the prototype solvent methanol, largely due to London dispersion forces. Phenyl docking and alkyl docking preferences can be realized at will by appropriate substitution. In particular, cyclopropylation helps to stabilize the opposite phenyl docking site. In all cases, the energy gap is small enough to allow for a simultaneous detection even under low temperature conditions. This density functional prediction is checked experimentally by jet FTIR spectroscopy and largely confirmed. A spurious out-of-plane solvation preference predicted for cyclopropylphenylketone with tert-butyl alcohol by B3LYP-D3 calculations is not confirmed experimentally. It is unlikely that this discrepancy is due to zero-point energy effects. Instead, the second most stable alkyl-side solvation motif predicted with a more in-plane coordination is found in the jet expansion. Overall, the ability of carbonyl solvation balances to benchmark subtle electronic structure effects for non-covalent interactions without major nuclear motion corrections is supported.

Dispersion-controlled docking preference: multi-spectroscopic study on complexes of dibenzofuran with alcohols and water.

The structural preferences within a series of dibenzofuran-solvent complexes have been investigated by electronic, vibrational, and rotational spectroscopic methods probing supersonic jet expansions. The experimental study is accompanied by a detailed theoretical analysis including dispersion-corrected density functional theory, symmetry adapted perturbation theory, as well as coupled cluster approaches. The complementary, multi-spectroscopic results reveal a preferred OHO structure for the smallest complex of dibenzofuran-water, whereas for the methanol complex an OHπ isomer is simultaneously observed. For the largest complex, dibenzofuran-tert-butyl alcohol, only a π-bound structure is found. These comprehensive investigations show that a completely inverse trend regarding the docking preference is observed by comparing the present results with the ones for analogous diphenyl ether complexes. This can be rationalized on the basis of the planarity/non-planarity and rigidity/flexibility of the different systems, providing valuable insight into the interplay between different non-covalent interactions. This analysis is a further step towards a quantitative description of very delicate energetic balances with the overall goal of yielding reliable structural predictions for non-covalently bound systems.

The donor OH stretching-libration dynamics of hydrogen-bonded methanol dimers in cryogenic matrices.

FTIR spectra of the methanol dimer trapped in neon matrices are presented. The fundamental, overtone and combination bands involving the donor OH libration and stretching motions were observed in order to extract relevant anharmonicity constants. We find a stretching-libration coupling constant of +43(5) cm(-1) and a diagonal librational anharmonicity constant of -71(5) cm(-1). The spectra are compared to a number of VPT2 calculations and a torsionally localized monomer model in order to enhance previous explanations of the observable OH stretching red-shift upon dimerization.

The effect of hydrogen bonding on torsional dynamics: a combined far-infrared jet and matrix isolation study of methanol dimer.

The effect of strong intermolecular hydrogen bonding on torsional degrees of freedom is investigated by far-infrared absorption spectroscopy for different methanol dimer isotopologues isolated in supersonic jet expansions or embedded in inert neon matrices at low temperatures. For the vacuum-isolated and Ne-embedded methanol dimer, the hydrogen bond OH librational mode of the donor subunit is finally observed at ~560 cm(-1), blue-shifted by more than 300 cm(-1) relative to the OH torsional fundamental of the free methanol monomer. The OH torsional mode of the acceptor embedded in neon is observed at ~286 cm(-1). The experimental findings are held against harmonic predictions from local coupled-cluster methods with single and double excitations and a perturbative treatment of triple excitations [LCCSD(T)] and anharmonic. VPT2 corrections at canonical MP2 and density functional theory (DFT) levels in order to quantify the contribution of vibrational anharmonicity for this important class of intermolecular hydrogen bond vibrational motion.

Femtisecond single-mole infrared spectroscopy of molecular clusters.

The sensitivity limitations of Fourier transform infrared (FTIR) spectroscopy for the detection of molecular clusters formed in rarefied gas expansions can be overcome by synchronizing intense gas pulses at a low duty cycle with rapid interferometer scans. This turns the broadband FTIR approach into a universal cluster spectroscopy tool applicable from the far (200 cm(-1)) to the near (8000 cm(-1)) IR. It nicely complements more selective and more restricted laser-based techniques and it provides a gas-phase variant of the matrix-isolation method, the main drawback being substance consumption. A survey over the capabilities, limitations and perspectives of this high-throughput nozzle approach to cluster FTIR spectroscopy is given.

Communication: The highest frequency hydrogen bond vibration and an experimental value for the dissociation energy of formic acid dimer.

The highest frequency hydrogen bond fundamental of formic acid dimer, ν(24) (B(u)), is experimentally located at 264 cm(-1). FTIR spectra of this in-plane bending mode of (HCOOH)(2) and band centers of its symmetric D isotopologues (isotopomers) recorded in a supersonic slit jet expansion are presented. Comparison to earlier studies at room temperature reveals the large influence of thermal excitation on the band maximum. Together with three B(u) combination states involving hydrogen bond fundamentals and with recent progress for the Raman-active modes, this brings into reach an accurate statistical thermodynamics treatment of the dimerization process up to room temperature. We obtain D(0) = 59.5(5) kJ/mol as the best experimental estimate for the dimer dissociation energy at 0 K. Further improvements have to wait for a more consistent determination of the room temperature equilibrium constant.

Comment on "Theoretical investigations into the enantiomeric and racemic forms of α-(trifluoromethyl)lactic acid" by R. Tonner, V. A. Soloshonok and P. Schwerdtfeger, Phys. Chem. Chem. Phys., 2011, 13, 811-817.

It is argued that differences between homo- and heterochiral dimers of the title compound in the gas phase cannot be responsible for the different sublimation behaviour of racemic and enantiomerically pure crystals near room temperature.

The benefits of alternation and alkylation: large amplitude hydrogen bond librational modes of alcohol trimers and tetramers.

Intermolecular hydrogen bond librational modes in cyclic trimers and tetramers of methanol and t-butyl alcohol isolated at low temperature in pulsed supersonic jet expansions are observed by direct absorption spectroscopy in the far-infrared region. The large amplitude librational modes probe the strength and directionality of the intermolecular hydrogen bonds. In addition, their frequency and intensity is very sensitive to the angle which the alkyl groups form with the hydrogen bonded ring. Theoretical predictions which fail to describe the trends in cluster size, alkylation and symmetry splitting reported in this work are likely to miss important ingredients of the underlying intermolecular interaction. Analysis of the vibrational correlation diagram between planar and puckered tetramer structures circumvents some deficiencies of approximate treatments.

Probing the stiffness of the simplest double hydrogen bond: the symmetric hydrogen bond modes of jet-cooled formic acid dimer.

Formic acid dimer is held together and kept planar by two strong hydrogen bonds, which give rise to intermolecular vibrations. Raman active fundamentals, overtones, and combination bands involving out-of-plane bending and stretching vibrations of the hydrogen bonds are recorded under jet-cooled, vacuum-isolated conditions between 100 and 750 cm(-1) and assigned with the help of isotope substitution. Individual anharmonicity effects are shown to be very small (x(i,j) = -(1+/-2) cm(-1)), where they are accessible by experiment. However, they may accumulate to substantial differences between harmonic and anharmonic fundamental excitations. Preliminary experimental evidence for the most elusive fundamental vibration of formic acid dimer, symmetric OH torsion, is presented. A rigorous experimental reference frame for existing and future high level quantum chemical and dynamical treatments of this important prototype system is provided. The effects of clustering beyond the dimer on the low frequency dynamics are found to be small, whereas argon coating gives rise to blueshifts.

Hydrogen bonding lights up overtones in pyrazoles.

The spectral complexity in the NH stretching mode of hydrogen-bonded pyrazoles is traced back to an extensive Fermi resonance system involving combinations and overtones of at least four aromatic ring modes with significant in plane hydride bending character. The couplings are shown to be inherent in the monomer, but hydrogen bonding is required to bring them into resonance with the NH stretching chromophore. A cost-efficient variational "monomers-in-clusters" model is presented and applied to a five-dimensional subspace of pyrazole. Spectra of substituted pyrazoles confirm the robustness of the coupling, which remains dark in strained dimers, but lights up in linearly hydrogen-bonded trimers.

Raman jet spectroscopy of formic acid dimers: low frequency vibrational dynamics and beyond.

The vibrational dynamics of formic acid dimer is quite regular at low fundamental excitation frequencies, whereas it evolves into a complex and irregular vibrational signature in the OH stretching region. This is evidenced by the first Raman investigation of the jet-cooled formic acid dimer and its three deuterated isotopomers. Subtle isotope effects in the inter-monomer stretching mode, which is directly observed for the first time at 194 cm(-1), find an interpretation based on hydrogen bond weakening due to quantum delocalization of the protons. The reported high-frequency jet spectra should provide essential experimental stepping stones towards a more complete understanding of this planar prototype for strong double hydrogen bonding.

Cooperative organic hydrogen bonds: the librational modes of cyclic methanol clusters.

Intermolecular hydrogen bond libration modes of isolated cyclic methanol trimers (approximately 613 cm(-1)) and tetramers (695 and 760 cm(-1)) are observed in pulsed jet Fourier transform infrared spectra and found to exhibit sizeable anharmonicity and mode coupling effects, opening the way for a microscopic interpretation of the broad librational bands of alcohols. The correlation of experimental OH stretching and OH libration band intensities provides important constraints for theoretical band strengths, cluster densities, and size assignments.

Proton tunneling estimates for malonaldehyde vibrations from supersonic jet and matrix quenching experiments.

FTIR tunneling splittings for a range of fundamental excitations of malonaldehyde are determined from adiabatic cooling and symmetry breaking experiments in three different molecular states (isolated, coated by Ar layers and embedded in bulk Ar matrices), showing that there is room for improvement in available theoretical models.

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.

Comparative FTIR spectroscopy of HX adsorbed on solid water: Ragout-jet water clusters vs ice nanocrystal arrays.

In addition to revealing the stretch-mode bands of the smallest mixed clusters of HCl and HBr (HX) with water, the ragout-jet FTIR spectra of dense mixed water-acid supersonic jets include bands that result from the interaction of HX with larger water clusters. It is argued here that low jet temperatures prevent the water-cluster-bound HX molecules from becoming sufficiently solvated to induce ionic dissociation. The molecular nature of the HX can be deduced directly from the observed influence of changing from HCl to HBr and from replacing H2O with D2O. Furthermore, the band positions of HX are roughly coincidental with bands assigned to molecular HCl and HBr adsorbed on ice nanocrystal surfaces at temperatures below 100 K. It is also interesting that the HX band positions and widths approximate those of HX bound to the surface of amorphous ice films at <60 K. Though computational results suggest the adsorbed HX molecules observed in the jet expansions are weakly distorted by single coordination with surface dangling-oxygen atoms, on-the-fly trajectories indicate that the cluster skeletons undergo large-amplitude low-frequency vibrations. Local HX solvation, the extent of proton sharing, and the HX vibrational spectra undergo serious modulation on a picosecond time scale.

Hybrid diatomics-in-molecules-based quantum mechanical/molecular mechanical approach applied to the modeling of structures and spectra of mixed molecular clusters Arn(HCl)m and Arn(HF)m.

A new hybrid QM/DIM approach aimed at describing equilibrium structures and spectroscopic properties of medium size mixed molecular clusters is developed. This methodology is applied to vibrational spectra of hydrogen chloride and hydrogen fluoride clusters with up to four monomer molecules embedded in argon shells Arn(H(Cl/F))m (n = 1-62, m = 1-4). The hydrogen halide complexes (QM part) are treated at the MP2/aug-cc-pVTZ level, while the interaction between HX molecules and Ar atoms (MM part) is described in terms of the semiempirical DIM methodology, based on the proper mixing between neutral and ionic states of the system [Grigorenko et al., J. Chem. Phys. 104, 5510 (1996)]. A detailed analysis of the resulting topology of the QM/DIM potential energy (hyper-)surface in the triatomic subsystem Ar-HX reveals more pronounced nonadditive atomic induction and dispersion contributions to the total interaction energy in the case of the Ar-HCl system. An extension of the original analytical DIM-based potential in the frame of the present model as well as the current limitations of the method are discussed. A modified algorithm for the gradient geometry optimization, along with partly analytical force constant matrix evaluation, is developed to treat large cages of argon atoms around molecular clusters. Calculated frequency redshifts of HX stretching vibrations in the mixed clusters relative to the isolated hydrogen-bonded complexes are in good agreement with experimental findings.

Spectroscopic characterization of N(2)O aggregates: from clusters to the particulate state.

Collisional cooling is used to generate N(2)O particles with radii ranging from the subnanometer to the submicrometer region. The vibrational dynamics of the aggregates is studied by Fourier transform infrared spectroscopy. In the region of the stretching fundamentals and combination bands, the infrared spectra of the particles exhibit characteristic size-dependent features. For the very small particles, the results obtained from collisional cooling are compared for the first time with corresponding results from supersonic jet expansions. It turns out that with both methods very similar clusters are generated. A pronounced temperature dependence of a combination band maximum in the collisional cooling cell spectra is found. This correlation is exploited to estimate cluster temperatures in supersonic jet spectra.

Ragout-jet FTIR spectroscopy of cluster isomerism and cluster dynamics: from carboxylic acid dimers to N2O nanoparticles.

Direct absorption supersonic jet Fourier transform spectroscopy provides a panoramic view of the dynamics of molecular clusters over the entire IR spectral range. The new and generally applicable ragout-jet technique compensates for the sensitivity limits inherent in the incoherent FTIR approach by the use of synchronized giant gas pulses expanding into a large vacuum buffer. A modification based on fragmented interferograms is proposed and demonstrated, by which the spectral resolution can be extended to the limit of the available FTIR spectrometer. The power of the method is illustrated for two classes of compounds. For acetic acid and its isotopomers, the supersonic jet spectra of dimers and oligomers are investigated for the first time, concentrating on the very complex OH/CH stretching domain and on the more regular C=O/C-O stretching range. Issues of cluster isomerism, hydrogen exchange tunneling, anharmonic resonances, intermolecular Franck-Condon sequences, methyl group substitution and cluster coating with argon are explored. For the more weakly interacting nitrous oxide, stretching fundamentals and combination bands of clusters in the 1-3 nm range are studied as a function of composition. Surface vibrations are investigated in detail and modeled quantum mechanically. The semiempirical AM1 approach is found to provide a remarkably accurate description of the cluster structure, energetics and dynamics.