Molecular Structure of Salicylic Acid and Its Hydrates: A Rotational Spectroscopy Study.

We present a study of salicylic acid and its hydrates, with up to four water molecules, done by employing chirped-pulse Fourier transform microwave spectroscopy. We employed the spectral data set of the parent, 13C, and 2H isotopologues to determine the molecular structure and characterize the intra- and intermolecular interactions of salicylic acid and its monohydrate. Complementary theoretical calculations were done to support the analysis of the experimental results. For the monomer, we analyzed structural properties, such as the angular-group-induced bond alternation (AGIBA) effect. In the microsolvates, we analyzed their main structural features dominated by the interaction of water with the carboxylic acid group. This work contributes to seeding information on how water molecules accumulate around this group. Moreover, we discussed the role of cooperative effects further stabilizing the observed inter- and intramolecular hydrogen bond interactions.

Accurate Experimental Structure of 1-Chloronaphthalene.

The structure of isolated 1-chloronaphthalene has been investigated in a supersonic expansion by high-resolution chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy in the 2-8 GHz frequency range. Accurate values of the rotational, centrifugal distortion, and nuclear quadrupole coupling constants for the only availabe conformer have been determined. The intensity of the spectrum allowed us to observe all the heavy atoms isotopologues in natural abundance, determining their rotational constants. From the extensive experimental dataset we derived accurate structures for 1-chloronaphthalene using different methodologies and compared with related compounds.

Conformational isomerism in trans-3-methoxycinnamic acid: From solid to gas phase.

The rotational spectrum of laser ablated trans-3-methoxycinnamic acid has been observed in the 2-8 GHz range using chirped-pulse Fourier transform microwave spectroscopy coupled to a supersonic jet and adapted to support a laser ablation vaporization system (LA-CP-FTMW). Eight stable conformers were theoretically predicted to exist at B3LYP-D3BJ/6-311++(2d,p) level, all of which were experimentally detected. The experimental rotational parameters data evidence the essentially planar structures for all the conformers. The relative population distribution of conformers in the supersonic jet was investigated from relative intensity measurements. Cooling in the jet brings rotational temperatures close to 1 K for all the conformers. The theoretical predictions for the rotational constants and electric dipole moments show good agreement with the experimental constants and selection rules observed. The population distribution of conformers in the supersonic jet was found to be close to the equilibrium distribution calculated at temperatures lower than the stagnation temperature. Finally, the correlation of the observed conformers structures with those found in condensed phases was investigated.

Structure and dynamics of 3'-aminoacetophenone and 4'-aminoacetophenone from rotational spectroscopy.

The rotational spectra of 4'-aminoacetophenone, and those of two conformers (Z and E arrangement of the CO and NH2 groups) of 3'-aminoacetophenone and their 13C and 15N isotopologues were investigated both in the microwave (2-8 GHz) and millimetre (59.6-74.4 GHz) frequency regions using chirped pulse Fourier transform and free-jet absorption techniques, respectively. The spectra consist of µa and µb type lines that show a hyperfine structure due to both the nuclear quadrupole coupling of the 14N nucleus and the methyl internal rotation. Relative intensity measurements show that the Z form in 3'-aminoacetophenone is favoured with respect to E and the measured energy difference upper limit is about 5.5(1) kJ mol-1. Barriers to methyl internal rotation are V3 = 7.04(2) and 6.530(6) kJ mol-1 for 3'(Z)- and 4'-aminoacetophenone, respectively. Flexible model analyses of the amino inversion motion based on ab initio potential energy paths, suggest that the corresponding vibrational splitting increases up to 78% from aniline to 3'(E)-, 3'(Z), and 4-aminoacetophenone. However, due to supersonic expansion cooling, no splitting related to amine inversion is observed.

The Role of the Transient Atropisomerism and Chirality of Flurbiprofen Unveiled by Laser-Ablation Rotational Spectroscopy.

The combination of atropisomerism and chirality in flurbiprofen is shown to be relevant concerning its pharmacological activity. The two most stable conformers of a total of eight theoretically predicted for each R- or S- flurbiprofen enantiomers have been isolated in the cooling conditions of a supersonic jet and structurally characterized by laser ablation Fourier transform microwave spectroscopy. The detected conformers, whose structure is mainly defined by three dihedral angles, only differ in the sign of the phenyl torsion angle giving rise to Sa and Ra atropisomers. A comparison with the structures available for the R- and S- enantiomers complexed to COX isoforms reveals that the enzymes select only the Sa atropisomers, resulting in a diastereoisomer-specific recognition. The most stable gas phase conformer is exclusively selected when using the S- enantiomer while the second is recognized only for the R- enantiomer. These experimental results highlight the importance of atropisomerism in drug design.

Characterizing the n→π* interaction of pyridine with small ketones: a rotational study of pyridine⋯acetone and pyridine⋯2-butanone.

Complexes formed by pyridine and small ketones such as acetone and 2-butanone have been generated in a supersonic jet and characterized by broadband Fourier transform microwave spectroscopy combined with high-level theoretical computations. The spectra of the complexes show a quadrupole coupling hyperfine structure due to the presence of a nitrogen atom and the splittings owing to the low barriers of the internal rotation of the methyl groups bonded to the carbonyl group. The corresponding barriers have been determined from the analysis of the spectra. We show in both complexes that pyridine closes a cycle with a ketone carbonyl group through an N⋯CO n→π* tetrel interaction and a C-H⋯O contact. The n→π* tetrel bond involves the pyridine N atom lone pair and the ketone carbonyl group with a geometry approaching the Bürgi-Dunitz trajectory for the nucleophilic attack to a carbonyl group.

The Conformations of Isolated Gallic Acid: A Laser-Ablation Rotational Study.

The rotational spectrum of laser-ablated gallic acid has been recorded using CP-FTMW spectroscopy. Two rotamers have been detected, and their rotational spectra have been assigned and analyzed to obtain the molecular spectroscopic parameters. The observed rotamers have been unambiguously identified in the light of theoretical computations, based on the comparison of the experimental line intensities and rotational parameters with the rotational constants and electric dipole moments predicted from theoretical calculations. The values of the planar inertial moments confirm that the observed conformers are planar, and their relative stability and population have been determined from relative intensity measurements. The B3LYP-D3/6-311++G(2d,p) level has been shown to be the best method among a series of levels normally used to predict the rotational parameters in rotational spectroscopy. In the observed conformers, the three adjacent OH groups are arranged in a sequential form, and the only difference between them lies in the orientation of the COOH group. Although weak attractive OH···O interactions seem to exist, the analysis of the electron density topology does not show the existence of any critical point corresponding to these interactions.

Decoding the Structure of Non-Proteinogenic Amino Acids: The Rotational Spectrum of Jet-Cooled Laser-Ablated Thioproline.

The broadband rotational spectrum of jet-cooled laser-ablated thioproline was recorded. Two conformers of this system were observed and identified with the help of DFT and ab initio computations by comparison of the observed and calculated rotational constants and 14N quadrupole coupling constants as well as the predicted energies compared to the observed relative populations. These conformers showed a mixed bent/twisted arrangement of the five-membered ring similar to that of the related compound thiazolidine with the N-H bond in axial configuration. The most stable form had the COOH group in an equatorial position on the same side of the ring as N-H. The arrangement of the C=O group close to the N-H bond led to a weak interaction between them (classified as type I) characterized by a noncovalent interaction analysis. The second form had a trans-COOH arrangement showing a type II O-H···N hydrogen bond. In thioproline, the stability of conformers of type I and type II was reversed with respect to proline. We show how the conformation of the ring depends on the function associated with the endocyclic N atom when comparing the structures of isolated thioproline with its zwitterion observed in condensed phases and with peptide forms.

How Aromatic Fluorination Exchanges the Interaction Role of Pyridine with Carbonyl Compounds: The Formaldehyde Adduct.

The rotational spectrum of the weakly bound complex pentafluoropyridine⋅⋅⋅formaldehyde has been investigated using Fourier transform microwave spectroscopy. From the analysis of the rotational parameters of the parent species and of the 13 C and 15 N 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 pair⋅⋅⋅π-hole interaction, reinforced by a weak C-H⋅⋅⋅N interaction, indicates an exchange of the electron-acceptor roles of both molecules when compared to the pyridine⋅⋅⋅formaldehyde 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 pair⋅⋅⋅π-hole and π⋅⋅⋅π stacking interactions.

A new MALDI-TOF approach for the quick sequence type identification of Legionella pneumophila.

BACKGROUND: Recently, MALDI-TOF has emerged as a quick tool for bacterial typing. The aim was to evaluate if MALDI-TOF based typing of Legionella pneumophila can achieve the same discriminatory power as that of the Sequence Based Typing (SBT) method. METHODS: The Sequence Type (ST) was obtained from the 90 strains included in the training set and an in-house MALDI-TOF library based on the Main Spectra Profile (MSP) was generated for the identification of such ST. Then, our library was validated by three procedures: a) creating a dendrogram, b) searching for specific peaks present exclusively in each MSP entry, and c) analysing a validation set composed of 14 strains with known ST. Fully characterized L. pneumophila ATCC 33152, which belongs to ST 36, was used as a control strain. RESULTS: In the training set, 17 strains belonged to ST 1, 1 to ST 20, 63 to ST 22, 1 to ST 146, 6 to ST 578, and 2 to ST 1086. Specific peaks present in each MSPs spectrum, which are considered type-specific biomarkers, ranged from 2 to 11; more concretely, MSP for ST 1 identification shows 2 specific peaks; MSP for ST 20 identification: 9 specific peaks; MSP for ST 22 and ST 36 identification: 11 specific peaks; MSP for ST 146 identification: 5 specific peaks; and MSP for ST 578 and ST 1086 identification: 3 specific peaks. Using the validation set (nine strains belonging to ST 22 and five to ST 1), MALDI-TOF assigned accurately the ST in 30 min per tested strain with a full match. CONCLUSIONS: The ST of L. pneumophila can be identified and reported in few minutes directly from colonies grown on BCYE agar using MALDI-TOF.

The structure of isolated thalidomide as reference for its chirality-dependent biological activity: a laser-ablation rotational study.

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.

Microwave Detection of Wet Triacetone Triperoxide (TATP): Non-Covalent Forces and Water Dynamics.

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-H2 O 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-(H2 O)2 is formed from the monohydrated TATP by the self-association of water.

Perfluorination of Aromatic Compounds Reinforce Their van der Waals Interactions with Rare Gases: The Rotational Spectrum of Pentafluoropyridine-Ne.

The rotational spectrum of the pentafluoropyridine-Ne complex, generated in a supersonic jet, has been investigated using chirped-pulse microwave Fourier transform spectroscopy in the 2-8 GHz range. The spectra of the 20Ne and 22Ne species have been observed, and the rotational constants have been used to determine the structure of the complex. This structure, and those of the previously experimentally studied complexes benzene-Ne and pyridine-Ne, are an excellent benchmark for the theoretical calculations on these adducts. These complexes and hexafluorobenzene-Ne have been investigated at the CCSD/6-311++G(2d,p) level. The calculations reproduce the experimental structures well and show how the van der Waals complexes are stronger for the perfluorinated compound.

Microsolvation of ethyl carbamate conformers: effect of carrier gas on the formation of complexes.

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.

Terpenoids: shape and non-covalent interactions. The rotational spectrum of cis-verbenol and its 1 : 1 water complex.

Verbenols are aromatic terpenoids whose bioactivity is attracting considerable experimental efforts. Exploiting the chirped-pulse Fourier transform technique, the rotational spectra of cis-verbenol, its hydroxyl deuterated form, and all 13C-monosubstituted isotopologues have been assigned, allowing for the structure determination, as the knowledge of its shape is crucial to understanding its molecular activity. Unlike in the solid state, in the gas phase, the most stable conformer exhibits an anti HO-CH arrangement, analogous to that of simpler allyl alcohol compounds. Observation of the 1 : 1 water complex showed that the conformation of cis-verbenol is still anti where water not only acts mainly as a proton donor to the hydroxyl group, but also as a proton acceptor, forming a secondary C-HO interaction with the hydrogen atom of alkyl verbenol.

Pyridine-acetaldehyde, a molecular balance to explore the n→π* interaction.

The complex pyridine-acetaldehyde is formed through an n→π* interaction and a C-HO contact. The acetaldehyde methyl group internal rotation induces a phase-locked intermolecular oscillation along the Bürgi-Dunitz coordinate. Surprisingly, this sort of molecular balance extracts energy through the n→π* interaction to reduce the size of the internal rotation barrier.

Structure of Butyl Carbamate and of Its Water Complex in the Gas Phase.

The structure of butyl carbamate and of its complex with water generated in a supersonic expansion has been characterized by Fourier transform microwave spectroscopy. Up to 13 low-energy conformations of the monomer have been predicted that differ in the relative orientation of the butyl chain and the amide group. However, only three conformations have been observed experimentally. The remaining low-energy conformers are expected to interconvert into the observed rotamers through collisional relaxation processes in the supersonic jet. The values of the C-O-Cα-Cß dihedral angle observed for the two most stable conformers of butyl carbamate, with extended configurations, can be directly correlated with the values of this angle in the two experimentally observed conformers of the shorter-chain molecule, ethyl carbamate. The less stable form shows a weak C-H···O═C intramolecular hydrogen bond from the terminal methyl group to the carbamate C═O group, stabilizing a folded configuration. For the most stable butyl carbamate monomer the complex with one molecule of water has been observed. In that complex the water molecule attaches to the amide group in a cyclic arrangement using two hydrogen bonds. The results indicate that water does not substantially alter the conformational behavior of butyl carbamate.

[Quality of mammography and breast cancer screening in ArgentinaQualidade da mamografia e prevenção do câncer de mama na Argentina]. / Calidad de la mamografía y tamizaje del cáncer de mama en Argentina.

This paper presents results from the mammography quality plan of the National Breast Cancer Program at Argentina's National Cancer Institute, which focused on improving mammography quality in the public health-care sector and on using mammography to implement breast cancer screening. Plan implementation started in 2011, based on the premise that poor quality mammography impedes early diagnosis of breast cancer. At the time, there was little awareness in Argentina of the importance of quality control, and constant changes in lines of authority in the health system tended to hinder organized implementation of the program. The plan consisted of quality review and control of mammography facilities, training of technical and medical human resources, and implementation of an accreditation system for mammography services by the National Cancer Institute. Perception by involved personnel of the importance of quality improved; an overview was obtained of the state of mammography at the national level regarding quality, technology, quantity of equipment, and opportunities for implementation of screening; technical and medical personnel were trained using different methods; and standardization of mammography reading was promoted in the participating provinces.

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.