Maria Eugenia Sanz

Non‐covalent interactions play a fundamental role in molecular recognition and receptor‐ligand binding, being vital in biological and chemical processes like olfaction. Here we use broadband rotational spectroscopy to investigate the gas‐phase complexes of the odorant carvone with ethanol and phenol, mimicking interactions with serine and tyrosine amino acid side chains. Eight carvone‐ethanol and two carvone‐phenol isomers were identified, each characterized by OH⋅⋅⋅O hydrogen bonds binding to the lone pair of carvone in trans with respect to the methyl group of the carvone ring. Secondary interactions, including CH⋅⋅⋅O and CH⋅⋅⋅π, further modulate the structural preferences of the complexes. A shift to higher‐energy conformers of carvone and ethanol is observed. Our results characterize binding motifs and participating non‐covalent interactions, which may serve as a proxy for exploring general principles relevant to odorant–receptor recognition.

Volatile Organic Compounds (VOCs), especially oxygenated aromatic species, constitute a major class of atmospheric pollutants and important precursors of secondary organic aerosol. We report here a high-resolution rotational study of 5-methyl-2-nitrophenol using Fourier transform microwave spectroscopy in combination with quantum chemical calculations. A broadband survey spectrum was first recorded in the 2-8 GHz range using chirp-excitation. Higher-resolution measurements were then performed using the cavity-based resonator mode of the Passage and Resonance In Synergy (PARIS) spectrometer, extending also the frequency coverage to 2-20 GHz. Quantum chemical calculations at the B3LYP-D3BJ/6-311++G(d,p) and MP2/6-311++G(d,p) levels of theory were used to optimize the molecular structure and guide spectral assignment. Splittings due to methyl internal rotation and hyperfine structure arising from the 14N nuclear quadrupole coupling were observed, analyzed, and fitted using the XIAM and BELGI-Cs-hyperfine programs to measurement accuracy. A threefold barrier to internal rotation of 78.89342(24) cm-1 was derived. The results contribute to the understanding of structure-dynamics relationships in functionalized aromatic molecules relevant to atmospheric chemistry.

Understanding the interactions of chiral molecules with water is crucial, given the central role that water plays in chemical and biological processes. We report the investigation of the amino alcohol prolinol, a widely used chiral catalyst and auxiliary in asymmetric synthesis, and its interactions with one to three water molecules by applying broadband rotational spectroscopy. Bare prolinol adopts two low-energy conformations stabilized by an intramolecular O-H···N hydrogen bond. Upon complexation with a single water molecule, four prolinol-H₂O isomers are identified, showing addition and insertion structures, where the original prolinol conformations are conserved. Notably, complexation with two and three water molecules induces prolinol to adopt its highest energy conformations, which lie more than 9.5 kJ mol^-1 above the global minimum and feature an intramolecular N-H···O hydrogen bond. In prolinol-(H₂O)_2,3, water acts as a conformational switch for prolinol, binding to both the amino and hydroxyl groups. Combined NMR studies and molecular dynamics simulations reveal that, in bulk water, prolinol exists as a highly flexible conformational ensemble, with no evidence of a stable intramolecular hydrogen bond, and mainly samples the same conformational space as that displayed in prolinol-(H₂O)_2,3. Our results illustrate how stepwise hydration proceeds and reveal the profound changes that water can induce in flexible chiral molecules. These findings provide a solid foundation for future experiments and modeling of solvation-induced processes.

An atomic‐level knowledge of the aggregation of archetypal molecular systems is essential to accurately model supramolecular structures and the transition from gas to liquid phase. The structures and forces involved in ethanol aggregation have been investigated using microwave spectroscopy and extensive quantum chemical calculations. Four isomers of the ethanol trimer have been observed and identified based on comparisons between experimental and predicted spectroscopic parameters, and considering collisional relaxation in the supersonic expansion. All observed isomers exhibit O−H O hydrogen bonds between the hydroxyl groups forming a six‐membered ring. Additionally, secondary C−H O hydrogen bonds and H H dispersion contacts participate in the stabilization of the complexes with remarkably similar energy contributions. Structures where there is a mixture of gauche and trans conformations of ethanol are favored, with gauche conformations being predominant and no evidence of homochirality synchronization. Our results underscore the critical changes involved in aggregation as the size of the system increases and shed light on the unique properties and behavior of ethanol in chemical and biological systems.

An atomic‐level knowledge of the aggregation of archetypal molecular systems is essential to accurately model supramolecular structures and the transition from gas to liquid phase. The structures and forces involved in ethanol aggregation have been investigated using microwave spectroscopy and extensive quantum chemical calculations. Four isomers of the ethanol trimer have been observed and identified based on comparisons between experimental and predicted spectroscopic parameters, and considering collisional relaxation in the supersonic expansion. All observed isomers exhibit O−H O hydrogen bonds between the hydroxyl groups forming a six‐membered ring. Additionally, secondary C−H O hydrogen bonds and H H dispersion contacts participate in the stabilization of the complexes with remarkably similar energy contributions. Structures where there is a mixture of gauche and trans conformations of ethanol are favored, with gauche conformations being predominant and no evidence of homochirality synchronization. Our results underscore the critical changes involved in aggregation as the size of the system increases and shed light on the unique properties and behavior of ethanol in chemical and biological systems.

Insight into the arrangements of water molecules around solutes is important to understand how solvation proceeds and to build reliable models to describe water-solute interactions. We report the stepwise solvation of fenchone, a biogenic ketone, with 4-7 water molecules. Multiple hydrates were observed using broadband rotational spectroscopy, and the configurations of four fenchone-(H₂O)₄, three fenchone-(H₂O)₅, two fenchone-(H₂O)₆, and one fenchone-(H₂O)₇ complexes were characterized from the analysis of their rotational spectra in combination with quantum-chemical calculations. Interactions with fenchone deeply perturb water configurations compared with the pure water tetramer and pentamer. In two fenchone-(H₂O)₄ complexes, the water tetramer adopts completely new arrangements, and in fenchone-(H₂O)₅, the water pentamer is no longer close to being planar. The water hexamer interacts with fenchone as the least abundant book isomer, while the water heptamer adopts a distorted prism structure, which forms a water cube when including the fenchone oxygen in the hydrogen bonding network. Differences in hydrogen bonding networks compared with those of pure water clusters show the influence of fenchone's topology. Specifically, all observed hydrates except one show two water molecules binding to fenchone through each oxygen lone pair. The observation of several water arrangements for fenchone-(H₂O)_4-7 complexes highlights water adaptability and provides insight into the solvation process.

The structure and interactions of oxygenated aromatic molecules are of atmospheric interest due to their toxicity and as precursors of aerosols. Here, we present the analysis of 4-methyl-2-nitrophenol (4MNP) using chirped pulse and Fabry–Pérot Fourier transform microwave spectroscopy in combination with quantum chemical calculations. The rotational, centrifugal distortion, and ¹⁴N nuclear quadrupole coupling constants of the lowest-energy conformer of 4MNP were determined as well as the barrier to methyl internal rotation. The latter has a value of 106.4456(8) cm⁻¹, significantly larger than those from related molecules with only one hydroxyl or nitro substituent in the same para or meta positions, respectively, as 4MNP. Our results serve as a basis to understand the interactions of 4MNP with atmospheric molecules and the influence of the electronic environment on methyl internal rotation barrier heights.