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Thalidomide is a drug that presents two enantiomers with markedly different pharmacological and toxicological activities. It is sadly famous due to its teratogenic effects mostly caused by the preferential docking of the (S)-enantiomer to the target protein cereblon (CRBN). To compare the structure of the bound CRBN thalidomide enantiomers with that of the isolated molecule, the rotational spectrum of laser-ablated thalidomide has been studied by chirp-pulsed Fourier transform microwave spectroscopy in supersonic jets complemented by theoretical computations. A new setup of the laser ablation nozzle used is presented. Two stable equatorial and axial conformers of thalidomide have been predicted corresponding to the two possible bent conformations exhibited by the glutarimide moiety. Only the most stable equatorial conformer has been detected. The comparison of its structure with those of the (S)- and (R)-enantiomers bound to CBRN shows that the bound (S) species is only slightly distorted. On the contrary, the bound (R)-enantiomer exhibits a highly distorted structure which affects the degree of puckering of the glutarimide ring and especially to the orientation of the phtalimide and glutarimide subunits. This is consistent with a less stable (R)-enantiomer and the known preference of (S)-thalidomide to bind CRBN, which starts the process leading to teratogenic effects.

Microsolvated complexes of ethyl carbamate (urethane) with up to three water molecules formed in a supersonic expansion have been characterized by high-resolution microwave spectroscopy. Both chirped-pulse and cavity Fourier transform microwave spectrometers covering the 2-13 GHz frequency range have been used. The structures of the complexes have been characterized and show water molecules closing sequential cycles through hydrogen bonding with the amide group. As is the case in the monomer, the ethyl carbamate-water complexes exhibit a conformational equilibrium between two conformers close in energy. The interconversion barrier between both forms has been studied by analyzing the spectra obtained using different carrier gas in the expansion. Complexation of ethyl carbamate with water molecules does not appear to significantly alter the potential energy function for the interconversion between the two conformations of ethyl carbamate.

Producción Científica, The rotational spectrum of the weakly bound complex pentafluoropyridineꞏꞏꞏformaldehyde has been investigated using Fourier transform microwave spectroscopy. From the analysis of the rotational parameters of the parent species and of the 13C and 15N isotopologues, the structural arrangement of the adduct has been unambiguously established. The full ring fluorination of pyridine has a dramatic effect on its binding properties: It alters the electron density distribution at the π-cloud of pyridine creating a π-hole and changing its electron donor-acceptor capabilities. In the complex, formaldehyde lies above the aromatic ring with one of the oxygen lone pairs, as conventionally envisaged, pointing toward its centre. This lone pairꞏꞏꞏπ-hole interaction, reinforced by a weak C-HꞏꞏꞏN interaction, indicates an exchange of the electron-acceptor roles of both molecules when compared to the pyridineꞏꞏꞏformaldehyde adduct. Tunnelling doublets due to the internal rotation of formaldehyde have also been observed and analysed leading to a discussion on the competition between lone pairꞏꞏꞏπ-hole and π ꞏꞏꞏπ staking interactions., Ministerio de Economía y Competitividad (grant CTQ2016-75253-P), Ministerio de Ciencia, Innovación y Universidades de España (project PGC2018-094644-B-C22), Comunidad Autónoma de Madrid (grant P2018 / EMT-4329 AIRTEC-CM)

15‐crown‐5 ether (15C5) and its complexes with water (w) have been studied using broadband Fourier transform microwave spectroscopy in a supersonic jet. A new conformer of 15C5 has been observed and established as the new global minimum out of a total of nine isolated structures. In addition, two 15C5‐w and two 15C5‐w2 clusters have been observed. The cluster structures have been unambiguously identified through the observation of water 18O isotopologue spectra. In all the clusters, at least one water molecule, located close to the axis of the 15C5 ring, interacts through two simultaneous hydrogen bonds to the endocyclic oxygen atoms. This interaction reshapes the 15C5 ring to reduce its rich conformational landscape to only two open structures, related to those found in complexes with Li+ or Na+ ions. In the most abundant 15C5‐w2 form, the two water molecules repeat the same interaction scheme while binding to opposite sides of the ring. In the second most abundant dihydrated form the two water molecules lie on the same side of the ring. This finding is exceptionally rare because water‐water interactions typically prevail over the formation of additional solutewater contacts, and it showcases the particular binding features of crown ethers., Ministerio de economia, industria y competitividad CTQ2016-75253-P

The water adducts of triacetone triperoxide (TATP) have been observed by using broadband rotational spectroscopy. This work opens a new way for the gas-phase detection of this improvised explosive. The observed clusters exhibit unusual water dynamics and rarely observed multicenter interactions. TATP-H2O is formed from the D3 symmetry conformer of TATP with water lying close to the C3 axis. Water rotation around this axis with a very low barrier gives rise to the rotational spectrum of a symmetric top. The main interaction of the monohydrate is a four-center trifurcated donor Ow-H⋅⋅⋅O hydrogen bond, not observed previously in the gas phase, reinforced by a weak four-center trifurcated acceptor C−H⋅⋅⋅Ow interaction. Surprisingly, all structural signatures show the weakness of these interactions. The complex TATP-(H2O)2 is formed from the monohydrated TATP by the self-association of water., SB, AM, and JCL acknowledge the Ministerio de Economía y Competitividad (Grant CTQ2016-75253-P) for financial support. JGC, ARC, and TT acknowledge the NATO Science for Peace and Security Programme (Grant SPS G5536), Junta de Castilla y León, Consejería de Educación y Cultura y Fondo Social Europeo (Grant BU263P18) and the Ministerio de Ciencia e Innovación (Grant PID2019-111215RB-100) for financial support.

The conformational landscape of the bicyclic molecule 2-decalone has been studied in a jet-cooled expansion by using rotational spectroscopy. The investigation covered the frequency region 7-19 GHz using broadband fast-passage IMPACT Fourier-transform microwave techniques. The introduction of the asymmetric carbonyl substituent in the double-chair decalin skeleton originates two distinct inverting conformers with cis ring junction, which were independently identified and characterized in the gas phase. Additionally, a single trans conformer was detected, as expected for the non-inverting equatorial ring junction. Accurate rotational parameters and quartic centrifugal distortion constants have been determined for the three observed species. A population estimation is given for the observed conformations based on relative intensities. Supporting ab initio calculations up to MP2/cc-pVTZ complement the experimental work.

Producción Científica, 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 neighbour 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., Ministerio de economia, industria y competitividad CTQ2016-75253-P

The microsolvated complexes of formanilide, generated in a supersonic expansion, have been observed by Fourier transform microwave spectroscopy. Three 1:1 and one 1:2 formanilide‐water adducts have been observed and their structure characterized by the measurement of isotopologue rotational spectra. In one of the monohydrated complexes and in the dihydrated complex formanilide adopts a cis‐configuration. In these species water closes sequential cycles with the cis amino and carbonyl groups through a network of N‐H∙∙∙O and O‐H∙∙∙O hydrogen bonds. Furthermore, in these complexes cis‐formanilide has almost the same non planar configuration observed in the monomer. In the two monohydrated complexes detected with trans‐formanilide, a planar skeleton is detected with water interacting solely with either the amino (N‐H∙∙O bond) or the carbonyl group (O‐H∙∙∙O=C bond). The observed tunnelling splittings show a rich intermolecular dynamics in those complexes. The results seem to indicate that complexation with water switches the configuration of formanilide from trans, more stable for the bare monomer, to cis, more stable for the hydrated complexes., Ministerio de economia, industria y competitividad CTQ2016-75253-P

The conformation of ortho-anisic acid and its monohydrated clusters generated in a supersonic jet has been studied by rotational spectroscopy to analyze the structural implications of ortho substitution. The dominant monomer species shows a trans-COOH arrangement stabilized by an intramolecular O–H...O hydrogen bond from the acid to the methoxy group. The spectra of two non-planar skeleton monomer forms with a cis-COOH arrangement have also been detected. A tunneling doublet has been observed for the most stable cis-COOH conformer. The periodic potential energy function for the COOH internal rotation connecting these cis forms has been estimated from the experimental data. For the first time a water complex with an acid in a trans-COOH configuration has been observed. This is more abundant than the other weak form observed for the complex, characterized by a cis-COOH arrangement. The observation of the rotational spectra of salicylic acid, methyl salicylate and methyl 2-methoxybenzoate, formed upon heating of ortho-anisic acid, gives additional interest in the chemistry of ortho substituted benzoic acids., Ministerio de economia, industria y competitividad CTQ2016-75253-P

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 the 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 eightmembered 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., Ministerio de economia, industria y competitividad CTQ2016-75253-P

The rotational spectrum of the pyridine–formaldehyde adduct generated in a supersonic expansion has been analyzed using Fourier transform microwave spectroscopy. The spectrum shows the quadrupole coupling hyperfine structure due to the presence of 14N. The spectra of the parent, 13C and 15N isotopologues have been observed to investigate its structure. The complex shows a Cs symmetry with the plane of pyridine bisecting the pi* interaction together with a weak C-H...O bond., Ministerio de economia, industria y competitividad CTQ2016-75253-P

2-Azetidinone-water clusters can be considered as appropriate models for investigating the interaction of the peptide functional group with water. The rotational spectra of 2-azetidinone-(H2O)n (n = 1, 2) complexes have been studied in the 6-18 GHz frequency range using a molecular beam Fourier transform microwave spectrometer. Two different isomers have been observed for the 1 : 1 adduct. The most stable (1 : 1a) is stabilized by two hydrogen bonds O-H···O=C and N-H···O with water closing a ring with the peptide group. For the other conformer (1 : 1b), water is placed on the other side of the carbonyl group stabilized by O-H···O=C and C-H···O hydrogen bonds. In 2-azetidinone-(H2O)2 the water molecules close a ring with the peptide group forming three different hydrogen bonds: O-H···O=C, O-H···O and N-H···O. The spectra of the parent and several isotopologues of each cluster have been investigated in order to determine their structures. The hydrogen bond geometries show that the dominant interaction is the O-H···O=C hydrogen bond, in good agreement with the observed preference of water to interact with this group in proteins. A comparison between the geometries of the different observed adducts shows clearly how cooperative hydrogen bonding plays an important role in the stabilization of these complexes. No detectable structural changes have been observed for 2-azetidinone upon hydration with one water molecule.

Chemistry - a European journal 24(3), 721 - 729 (2018). doi:10.1002/chem.201704644, In the current work we present a detailed analysis of the chiral molecule pulegone, which is a constituent of essential oils, using broadband rotational spectroscopy. Two conformers are observed under the cold conditions of a molecular jet. We report an accurate experimentally determined structure for the lowest energy conformer. For both conformers, a characteristic splitting pattern is observed in the spectrum, resulting from the internal rotation of the two non‐equivalent methyl groups situated in the isopropylidene side chain. The determined energy barriers are 1.961911(46) kJ mol$^{−1}$ and 6.3617(12) kJ mol$^{−1}$ for one conformer, and 1.96094(74) kJ mol$^{−1}$ and 6.705(44) kJ mol$^{−1}$ for the other one. Moreover, a cluster of the lowest energy conformer with one water molecule is reported. The water molecule locks one of the methyl groups by means of a hydrogen bond and some secondary interactions, so that we only observe internal rotation splittings from the other methyl group with an internal rotation barrier of 2.01013(38) kJ mol$^{−1}$. Additionally, the chirality‐sensitive microwave three‐wave mixing technique is applied for the differentiation between the enantiomers, which can become of further use for the analysis of essential oils., Published by Wiley-VCH, Weinheim

3,3-dimethyloxetane (DMO) has a nonplanar ring equilibrium configuration ( ϕ = 17.5°) and a double minimum potential function, with a barrier of 47 cm −1 , for ring-puckering vibration. In a previous work, the observation of endocyclic 13 C and 18 O monosubstituted isotopologues allowed to conclude that the ring is puckered, consistent with the observed ring-puckering potential function. However, an interesting feature was observed for the 13 C substitutions at the methyl carbon atoms. While two different, axial and equatorial, 13 C-methyl groups spectra are predicted from a rigid nonplanar ring DMO model, only one spectrum was found. This behavior evidences that the two methyl groups of DMO are equivalent as could be expected for a planar ring. In this work we show how consideration of the potential function and the dynamical path for ring-puckering motion allows to reproduce the experimental results.

Producción Científica, Water self-association dominates the formation of microsolvated molecular clusters which may give rise to complex structures resembling those of pure water clusters. We present a rotational study of the complex formamide−(H2O)3 formed in a supersonic jet and several monosubstituted isotopologues. Formamide and water molecules form a four-body sequential cycle through N−H···O, O−H···O, and O−H···O=C hydrogen bonds, resulting in a chiral structure with a nonplanar skeleton that can be overlapped to that of water pentamer. The analysis of the 14N-nucleus quadrupole coupling effects shows the depletion of the electron density of the N atom lone pair with respect to the bare formamide that affects the amide group C−N and C=O distances. The study of the observed tunneling doublets shows that formamide−(H2O)3 follows a path to invert its structure driven by the flipping of water subunits and passing through successive nonplanar configurations, a motion reminiscent of the pseudorotation of water pentamer., Ministerio de economia, industria y competitividad CTQ2016-75253-P

Producción Científica, The rotational spectrum of formamide2-H2O formed in a supersonic jet has been characterized by Fourier transform microwave spectroscopy. This adduct provides a simple model of water mediated interaction involving the amide linkages, as occur in protein folding or amide association processes, showing the interplay between self-association and solvation. Mono-substituted 13C, 15N, 18O and 2H isotopologues have been observed to investigate the structure. The adduct forms an almost planar three body sequential cycle. The two formamide molecules link on one side through an N-H···O hydrogen bond and on the other side through a water-mediated interaction with the formation of C=O···H-O and O···H-N hydrogen bonds. The analysis of the quadrupole coupling effects due to the presence of two 14N-nuclei reveal the subtle inductive forces associated to cooperative hydrogen bonding. These forces are involved in the changes detected in the C=O and C-N bond distances with respect to bare formamide., 2018-03-03, Ministerio de Economía, Industria y Competitividad (CTQ2013-40717-P), Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA334U14)

none 6 si The rotational spectra of two conformers of the 1:1 adduct of fluoroacetic acid with water have been assigned by pulsed jet Fourier transform microwave spectroscopy. Their shapes differ according to the trans and cis forms of the fluoroacetic acid moiety. This is in contrast to the rotational spectrum of the monomer, for which the cis form has not been observed. Details of the hydrogen bond, structure, dynamics and energetic features of the two species are given. Feng, Gang; Gou, Qian; Evangelisti, Luca; Spada, Lorenzo; Blanco, Susana; Caminati, Walther Feng, Gang; Gou, Qian; Evangelisti, Luca; Spada, Lorenzo; Blanco, Susana; Caminati, Walther

The trimer of difluoromethane, (CH2F2)3, has been characterized by supersonic jet Fourier transform microwave spectroscopy. The rotational spectrum displays all types (a, b and c) of transitions, showing that the adduct does not possess any element of molecular symmetry. The investigation of the three 13C species in natural abundance indicates that the three carbon atoms form a triangle where the C-C distances are 3.648(2), 3.825(8) and 3.942(6) Å, respectively. The three subunits are held together by nine CHF weak hydrogen bonds.

The neutral form of the non-coded amino acid sarcosine ( N -methylglycine) has been studied in the gas phase using laser-ablation molecular-beam Fourier transform microwave (LA-MB-FTMW) spectroscopy. Two conformers have been unequivocally identified by comparing the experimental values of rotational and quadrupole coupling constants with those predicted by ab initio calculations at the MP2/6-311++G(d,p) level. The most stable conformer is stabilized by an intramolecular hydrogen bond N–H⋯O C and a cis -COOH arrangement, whereas the second conformer exhibits an intramolecular hydrogen bond N⋯H–O and trans -COOH. The conformational behaviour of sarcosine is discussed in the context of those of glycine and N , N -dimethylglycine.

Microsolvated formamide clusters have been generated in a supersonic jet expansion and characterized using Fourier transform microwave spectroscopy. Three conformers of the monohydrated cluster and one of the dihydrated complex have been observed. Seven monosubstituted isotopic species have been measured for the most stable conformer of formamide...H(2)O, which adopts a closed planar ring structure stabilized by two intermolecular hydrogen bonds (N-H...O(H)-H...O=C). The two higher energy forms of formamide...H(2)O have been observed for the first time. The second most stable conformer is stabilized by a O-H...O=C and a weak C-H...O hydrogen bond, while, in the less stable form, water accepts a hydrogen bond from the anti hydrogen of the amino group. For formamide...(H(2)O)(2), the parent and nine monosubstituted isotopic species have been observed. In this cluster the two water molecules close a cycle with the amide group through three intermolecular hydrogen bonds (N-H...O(H)-H...O(H)-H...O=C), the nonbonded hydrogen atoms of water adopting an up-down configuration. Substitution (r(s)) and effective (r(0)) structures have been determined for formamide, the most stable form of formamide...H(2)O and formamide...(H(2)O)(2). The results on monohydrated formamide clusters can help to explain the observed preferences of bound water in proteins. Clear evidence of sigma-bond cooperativity effects emerges when comparing the structures of the mono- and dihydrated formamide clusters. No detectable structural changes due to pi-bond cooperativity are observed on formamide upon hydration.

The complex thiirane–trifluoromethane (C2H4S⋯HCF3) has been observed in a supersonic expansion using Fourier-transform microwave spectroscopy. Its structure was derived from the rotational spectra of the parent and three minor 34S and 13C isotopomers observed in natural abundance. The thiirane–trifluoromethane dimer exhibits an equilibrium Cs symmetry stabilized by one C–H⋯S and two C–H⋯F–C weak hydrogen bonds. The rotational spectrum shows A–E splittings due to the internal rotation of trifluoromethane in the complex around an axis close to its C–H bond, suggesting that the C–H⋯S linkage is the primary hydrogen bond interaction in the dimer.

The jet-cooled rotational spectrum of neutral alanine has been studied using laser-ablation molecular-beam Fourier transform microwave spectroscopy (LA-MB-FTMW). The spectra of the two most stable forms were observed in the frequency range 6-18 GHz for the parent, (15)N alanine, three single (13)C species, and four single D species. The (14)N nuclear quadrupole coupling hyperfine structures have been resolved, and their comparison with those calculated theoretically confirms unambiguously the conformer assignments. The independent structures of both conformers have been determined experimentally for the first time using r(s) and r(0) procedures. In both cases, the amino acid backbone is nonplanar. For the most stable conformer I, the COOH group adopts a cis configuration and an asymmetric bifurcated hydrogen bond is formed between the amino group and carbonyl oxygen (r(N-H(a)...O=C) = 2.70(2) A and r(N-H(b)...O=C) = 2.88(2) A). For conformer IIa, the COOH group adopts a trans configuration and is stabilized by a O-H...N hydrogen bond (r(O-H...N) = 1.96(2) A). The relative conformer abundances in the supersonic expansion have also been investigated.

The free jet millimeter-wave absorption spectra of the propylene oxide–Ar complex is reported. The Ar atom lies, with respect to the plane of the COC ring, on the same side of the methyl group (syn conformer). This is in contrast with the results of MP2/6-311++G∗∗ calculations, which give the anti conformer slightly more stable. The ab initio geometry of the syn species is, however, in agreement with the experimental findings. The dissociation energy has been estimated, from the DJ centrifugal distortion constant, to be about 3 kJ/mol.

Two different axial and equatorial hydrogen-bonded conformers of the complex formed by pentamethylene sulfide and hydrogen fluoride have been generated in a pulsed supersonic expansion and characterised by means of Fourier transform microwave spectroscopy. The ground-state rotational spectra of six isotopomers (C5H10S⋅⋅⋅HF, C5H10S⋅⋅⋅DF, C5H1034S⋅⋅⋅HF, 13CαC4H10S⋅⋅⋅HF, 13CβC4H10S⋅⋅⋅HF and 13CγC4H10S⋅⋅⋅HF) have been analysed for both conformers in the frequency range 5.5–18.5 GHz. The rotational parameters were used to derive Cs structures for the conformers, with hydrogen fluoride pointing to the domain of the nonbonding electron pairs at either the axial or equatorial position of the sulfur atom. The axial form was found to be the more stable, in contrast with the observation for the pentamethylene sulfide⋅⋅⋅HCl complex. No equatorial-to-axial relaxation was observed when He or Ar were used as the carrier gas. The conformational behaviour is compared with that of related six-membered rings and discussed in terms of the existence of secondary hydrogen bonding between the halogen atom and the nearest H atoms of the methylene groups of the ring. No significant structural distortion of pentamethylene sulfide upon complexation was detected from a comparison with the structure of the isolated monomer. Finally, an ab initio study was carried out to complement the experimental results.

The formation of a hydrogen bond between methylene cyclobutane and hydrogen chloride has been investigated in the region 8–18 GHz using molecular-beam Fourier transform microwave spectroscopy. The rotational spectrum of an endo conformer in which methylene cyclobutane retains a puckered conformation and HCl is bonded in T-shape to the methylenic group has been observed. Searches for the exo form using Ar, Ne or He as carrier gases were unsuccessful. A Cs symmetry r0-like structure has been obtained for this conformer from the rotational data of three observed isotopomers (C5H8⋯H35Cl, C5H8⋯H37Cl, and C5H8⋯DCl). Ab initio calculations at MP2/6-311+G(d,p) level have been used to complement the analysis. These calculations predict the existence of both endo and exo conformers close in energy.

Seven isotopomers of the hydrogen-bonded heterodimer tetrahydrofuran⋯HF have been investigated in the frequency range 6–18 GHz using molecular-beam Fourier transform microwave spectroscopy. The rotational spectra of C4H8O⋯HF and C4H8O⋯DF exhibit small tunneling splittings, which were not observed for C4D8O⋯HF and the four single 13C isotopomers. These observations analyzed in terms of symmetry considerations allow us to conclude that these splittings are due to pseudorotation within the tetrahydrofuran subunit of the complex and not to HF inversion. The spectroscopic parameters of the complex have been interpreted in terms of a geometry in which tetrahydrofuran has a conformation close to the twisted ring form, with HF lying on the plane bisector to the COC ring angle.

The rotational spectrum of 1,4-anhydrothreitol (a C4 anhydrosugar) has been assigned by free jet millimeter wave spectroscopy. The structure, characterized by a distorted ring and one O-H∙∙∙O hydrogen bond involving an alcoholic group and the ring oxygen, corresponds to the B3LYP/6-31G** predicted global conformational minimum. Since C2 sugars have already been observed, and C3 sugars have been extensively searched in the interstellar medium, (with controversial results) we propose 1,4-anhydrothreitol to be of interest for astrochemical observation.

g-Aminobutyric acid (GABA) is arguably the most important inhibitory neurotransmitter in the brain and brainstem/spinal cord. Owing to the high torsional flexibility of its heavyatom backbone, this molecular system has a large number of low-energy conformers (see Figure 1). Identifying the stable conformers of GABA can be relevant to understanding the selectivity of the biological processes in which the neurotransmitter participates. This can be done by placing GABA on a supersonic jet such that conformers are cooled down and trapped in their energy minima. In such an isolated environment the conformers with sufficient population can be detected and studied by spectroscopic methods. In this context, several methods have made great contributions to the elucidation of the structures of biomolecules in the gas phase. In the present work we have observed and characterized nine conformers of GABA using Fourier transform microwave spectroscopy in supersonic jets combined with laser ablation. Microwave spectroscopy, considered the most definitive gas-phase structural probe, can distinguish between different conformational structures since they have unique moments of inertia and give separate rotational spectra. In general, large molecules, in particular those of biological importance, have low vapor pressures and tend to degrade upon heating, making them unsuited for structural studies in the gas phase. Recently, rotational studies of biomolecules have entered in a new stage with the LAMB-FTMW experiment, which combines laser ablation (LA) with molecular beam Fourier transform microwave spectroscopy (MB-FTMW), an approach that overcomes the problems of thermal decomposition associated with conventional heating methods. To date, different aand b-amino acids have been studied using this technique, making it possible to characterize their preferred conformations. Even in conformationally challenging systems these can be identified by rotational spectroscopy, as has been illustrated with the assignment of seven low-energy conformers of serine and threonine, six of cysteine, and four of b-alanine and proline. In the present work, we have examined the conformations of GABA. In this system the separation of the polar amino and carboxylic groups, characteristic of many families of neurotransmitters, opens new conformational possibilities with respect to a-amino acids if one considers the balance of intramolecular forces that contribute to stabilizing the different conformations. The five hindered rotations around the single bonds generate a plethora of conformational species (Figure 1). An overall picture of the conformational landscape obtained from theoretical predictions at the MP2/6-311++G(d,p) level confirms the conformational richness of GABA: the 30 feasible conformers shown in Figure 1 were localized with relative energies below 900 cm . These conformers are labeled by two letters (a, G, or g) followed by a number. The first letter refers to the configuration at Ca and the second one to the configuration at Cg : a means anti conformers, G gauche conformers with positive value of the torsional angle CCOOH-Ca-Cb-Cg or N-Cg-Cb-Ca, and g gauche conformers Figure 1. Predicted low-energy conformers of GABA. The nine observed conformers are circled.

We investigated the Fourier transform microwave spectra of the hydrated forms of the N-methylformamide (NMF) in a supersonic expansion and assigned the rotational spectra of two mono-hydrated species. The conformation of each molecular complex was reliably determined on the basis of the values of the rotational constants, of the relative intensities of a- and b-type transitions, and of the features of the 14N quadrupole hyperfine structure of the rotational transitions. In both complexes water acts as a proton donor and NMF has a trans configuration of the peptidic group. In the most stable of these conformers, water is also weakly bound to the methyl group.

The conformational preferences of the simplest amine neurotransmitter 2-phenylethylamine have been investigated using molecular beam Fourier transform microwave (MB-FTMW) spectroscopy. Two new conformers have been observed together with the two previously reported by Godfrey et al. [J. Am. Chem. Soc., 1995, 117, 8204]. The (14)N nuclear quadrupole hyperfine structure has been resolved for all four conformers. Comparison of the experimental rotational and quadrupole coupling constants with those calculated theoretically provides a conclusive test for the identification of all conformers. The two most stable conformers present a gauche (folded) disposition of the alkyl-amine chain and are stabilised by a weak NH...pi interaction between the amino group and the aromatic ring. The other two conformers show an anti (extended) arrangement of the alkyl-amine chain. Tunnelling splittings have been observed in the spectrum of one of the anti conformers. The post expansion relative abundances in the supersonic jet have been also investigated and related to the conformer energies.

The molecular beam Fourier transform microwave spectrum of cyclobutanone-trifluoromethane has been assigned and measured. The carbon atom of trifluoromethane lies in the plane of the heavy atoms of cyclobutanone. The complex is stabilized by one C-H...O=C and two C-H...F-C weak hydrogen bonds. The C-H...O=C interaction, involving one carbonylic oxygen, is studied for the first time in detail with rotationally resolved spectroscopy. The two C-H...F-C weak hydrogen bonds involve two fluorine atoms of trifluoromethane and two hydrogens of the same methylenic group in the alpha position.

The oxirane-trifluoromethane dimer generated in a supersonic expansion has been characterized by Fourier transform microwave spectroscopy. The rotational spectra of the parent species and of its two 13C isotopomers in combination with ab initio calculations have been used to establish a Cs geometry for the dimer with the two monomers bound by one C-HâââO and two C-HâââF-C hydrogen bonds. An overall bonding energy of about 6.7 kJ/mol has been derived from the centrifugal distortion analysis. The lengths of the C-HâââO and C-HâââF hydrogen bonds, r(OâââH) and r (FâââH), are 2.37 and 2.68 Å, respectively. The C-HâââF-C interactions give rise to the HCF3 internal rotation motion barrier of 0.55(1) kJ/mol, which causes the A-E splittings observed in the rotational spectra. The analysis of the structural and energetic features of the C-HâââO and C-HâââF-C interactions allows us to classify them as weak hydrogen bonds. Ab initio calculations predict these weak interactions to produce blue shifts in the C-H vibrational frequencies and shortenings of the C-H lengths.

Producción Científica, The complexes of 12-crown-4 ether (12C4) with water, generated in a supersonic jet, have been studied using broadband Fourier transform microwave spectroscopy. Three 1:1 and one 1:2 clusters have been observed and their structures unambiguously identified through the observation of isotopologue spectra. The structures of the clusters are based on networks of O-H···O and C-H···O hydrogen bonds. The most abundant 1:1 cluster is formed from the most stable S4 symmetry conformer of 12C4, even though it is not the energetically favored water complex. Interestingly, the structures of the most stable water cluster and the other remaining observed 1:1 and 1:2 complexes are formed from the third or the fifth most abundant conformers of 12C4. This shows the existence of a mechanism that changes the configuration of 12C4 so that the host-guest interactions can be maximized, even for a “soft” ligand like water., 2018-03-03, Ministerio de Economía, Industria y Competitividad (CTQ2013-40717-P), Junta de Castilla y León (programa de apoyo a proyectos de investigación – Ref. VA334U14), Deutsche Forschungsgemeinschaft SPP1807(SCHN1280/4-1)