The Shapes of Sulfonamides: A Rotational Spectroscopy Study.

Benzenesulfonamides are a class of molecules of extreme interest in the biochemical field because many of them are active against a variety of diseases. In this work, the pharmacophoric group benzensulfonamide, its derivatives para-toluensulfonamide and ortho-toluensulfonamide, and the bioactive molecule sulfanilamide, were investigated using rotational spectroscopy to determine their conformations and the influence of different substituents on their structures. For all species, the hyperfine structure due to the 14N atom was analyzed, and this provided crucial information for the unambiguous identification of the observed conformation of all molecules. In addition, for ortho-toluensulfonamide, the vibration-rotation hyperfine structure related to the methyl torsion was analyzed, and the methyl group rotation barrier was determined. For benzensulfonamide, partial rS and r0 structures were established from the experimental rotational constants of the parent and two deuterated isotopic species. In all compounds except ortho-toluensulfonamide, the amino group of the sulfonamide group lies perpendicular to the benzene plane with the aminic hydrogens eclipsing the oxygen atoms. In ortho-toluensulfonamide, where weak attractive interactions occur between the nitrogen lone pair and the methyl hydrogen atoms, the amino group lies in a gauche orientation, retaining the eclipsed configuration with respect to the SO2 frame. A comparison of the geometrical arrangements found in the PDB database allowed us to understand that the bioactive conformations are different from those found in isolated conditions. The conformations within the receptor are reached with an energy cost, which is balanced by the interactions established in the receptor.

Characterizing hydrogen and tetrel bonds in clusters of CO2 with carboxylic acids.

The interaction between carbon dioxide and planar carboxylic acids has been investigated through the analysis of the microwave spectrum of the acrylic acid·CO2 complex and quantum chemical modeling of the R-COOH·(CO2)1,16 clusters, where R = H, CH2CH. As regards the 1 : 1 compounds, two species, involving the s-cis and s-trans conformers of acrylic acid were observed. For both of them, a similar bidentate interaction arises between the carbonyl group of CO2 and the carboxylic group of the organic acid, leading to the formation of a planar six-membered ring. The binding energy is estimated to be De ≃ 21 kJ mol-1, 1/3 being the energy contributions of the tetrel to hydrogen bonds, respectively. In the 1 : 16 clusters, the ring arrangement is broken, allowing for the interaction of the acid with several CO2 molecules. The CO2 molecules completely surround formic acid, whereas, in the case of acrylic acid, they tend to avoid the allyl chain.

Structure, Dynamics, and Accurate Laboratory Rotational Frequencies of the Acrylonitrile-Methanol Complex.

The hydrogen-bonded complex between acrylonitrile (CH2═CHCN) and methanol has been characterized spectroscopically in the millimeter wave range (59.6-74.4 GHz) using a free jet absorption millimeter wave spectrometer. Precise values of the rotational and centrifugal distortion constants were obtained from the measured frequencies of the complex of acrylonitrile with CH3OH and CD3OD. The analysis of the splittings of the rotational lines due to the hindered internal rotation of the methanol methyl group led to the determination of a V3 value of 221.9(7) and 218(5) cm-1 for the complexes of CH3OH and CD3OD, respectively, and these values are about 40% lower than that of free methanol. The structure of the observed conformation is in agreement with the global minimum determined at the MP2/aug-cc-pVTZ level of calculation, and the counterpoise corrected intermolecular binding energy, obtained at the same theoretical level, is De = 26.3 kJ mol-1.

The axial/equatorial conformational landscape and intramolecular dispersion: new insights from the rotational spectra of monoterpenoids.

Intramolecular non-covalent interactions determine the conformational preferences of many molecules, and their understanding is relevant for a proper description of molecular structure. Here, by using rotational spectroscopy in combination with quantum chemistry calculations, we show that intramolecular dispersion forces involving a three-carbon substituent influence the relative energies and conformational landscape of the three monoterpenoids carvone, limonene and perillaldehyde. New equatorial and axial conformers have been identified for all three molecules. Comparison of experimental data with ab initio and density functional calculations shows that axial conformers are stabilised by dispersion interactions between the cyclohexene ring and the isopropenyl group of the monoterpenoids, and that an accurate account of these interactions is challenging for theoretical methods. This work demonstrates the potential of rotational spectroscopy for investigating non-covalent interactions and provides critical benchmarks for theory. Our results will inform future investigations of axial/equatorial isomerism and impact understanding of intramolecular dispersion in larger species.

Regarding the torsional flexibility of the dihydrolipoic acid's pharmacophore: 1,3-propanedithiol.

The conformational space of antioxidant dihydrolipoic acid has been explored through the investigation of its pharmacophore, 1,3-propanedithiol. Five of the possible 25 non-equivalent isomers (namely: gGGg', gGGg, g'AGg, gAGg and g'AGg') were observed in the 59.6-74.4 GHz frequency region using free-jet absorption rotational spectroscopy. Furthermore, for three of them, the 34S mono-substituted isotopologues were also detected in natural abundance. Theoretical simulations show that the balance of steric and electronic intramolecular interactions arises on a shallow conformational potential energy surface and suggest that in polar solvents the flexibility of the dithiol chain is greater than that in the isolated phase.

Millimeter Wave Spectrum of the Weakly Bound Complex CH2═CHCN·H2O: Structure, Dynamics, and Implications for Astronomical Search.

The weakly bound 1:1 complex between acrylonitrile (CH2═CHCN) and water has been characterized spectroscopically in the millimeter wave range (59.6-74.4 GHz) using a Free Jet Absorption Millimeter Wave spectrometer. Precise values of the rotational and quartic centrifugal distortion constants have been obtained from the measured frequencies of the normal and isotopically substituted water moiety (DOH, DOD, H(18)OH). Structural parameters have been estimated from the rotational constants and their differences among isotopologues: the complex has a planar structure with the two subunits held together by a O-H···N (2.331(3) Å) and a C-H···O (2.508(4) Å) interaction. The ab initio intermolecular binding energy, obtained at the counterpoise corrected MP2/aug-cc-pVTZ level of calculation, is De = 24.4 kJ mol(-1).

How CO2 Interacts with Carboxylic Acids: A Rotational Study of Formic Acid-CO2.

The rotational spectra of the 1:1 formic acid-carbon dioxide molecular complex and of its monodeuterated isotopologues are analysed in the 6.5-18.5 and 59.6-74.4 GHz frequency ranges using a pulsed jet Fourier transform microwave spectrometer and a free-jet absorption millimetre wave spectrometer, respectively. Precise values of the rotational and quartic centrifugal distortion constants are obtained from the measured frequencies, and quadrupole coupling constants are determined from the deuterium hyperfine splittings. Structural parameters are estimated from the moments of inertia and their differences among isotopologues: the complex has a planar structure with the two subunits held together by a HC(O)OH⋅⋅⋅O=C=O (2.075 Å) and a HC(OH)O⋅⋅⋅CO2 (2.877 Å) interactions. The ab initio intermolecular binding energy, obtained at the counterpoise corrected MP2/aug-cc-pVTZ level of calculation, is De =17 kJ mol(-1).

Proton transfer in homodimers of carboxylic acids: the rotational spectrum of the dimer of acrylic acid.

The dimer of acrylic acid can exist in two forms, depending on the entgegen or zusammen orientations of the two allyl groups. The latter one (zusammen) has a permanent value of the µ(b) dipole moment component, which allowed measuring its pulsed jet Fourier transform microwave (MW) spectrum. From the tunneling splitting, originating in the concerted proton transfer of the two carboxylic hydrogen atoms and measured for four isotopologues of such a bimolecule, we could determine the barrier and dynamics of the proton transfer.