r0pt Figure The active sites of odorant receptors are sensitive to chirality. It is well known that some enantiomers of chiral odorants smell differently or have a completely different odour threshold. To start gaining an understanding of the interactions involved in chirality recognition, we investigated the complex of carvone and 1-phenylethanol (1PE) using a combination of chirped pulse Fourier transform microwave spectroscopy and quantum-chemical methods. Carvone is a chiral odorant whose R enantiomer smells like spearmint while its S enantiomer smells of caraway. 1PE is a chiral alcohol with an aromatic benzene ring that can establish different types of hydrogen bonds and dispersion interactions. Several isomers of (R)-carvone···(S)-1PE (RS) and (S)-carvone···(S)-1PE (SS) complexes have been observed, and identified from the comparison between experimental and calculated rotational constants and dipole moment components. Carvone and 1PE are bound through an O-H···O hydrogen bond and secondary C-H···π interactions. Homochiral SS complexes show an additional C-H···O interaction. We will discuss binding preferences as well as the balance of intermolecular interactions.

r0pt Figure Amino alcohols are found in a large variety of biologically important compounds, such as natural products, synthetic drugs and a growing number of ligands and chiral auxiliares for asymmetric synthesis. Their conformational analysis is of interest to improve our understanding of stereocontrol, and a first step to investigate the interactions involved in the molecular recognition and self-assembly processes in which they participate. Here we present the investigation of the amino alcohol prolinol using chirped pulse Fourier transform microwave spectroscopy. Prolinol was previously studied by FTIR spectroscopyJ. J. Lee,S. Hesse, M. A. Suhm, J. Mol. Spectrosc. 976, 397 (2010). where it was speculated that two conformers contributed to the spectrum. We have identified two conformers of isolated prolinol and determined their effective and substitution structures. In addition, its clusters with 1 to 3 water molecules have also been observed. The conformations of prolinol in the monohydrates resemble those of the isolated monomer. However, upon complexation with two and three water molecules there is a significant alteration in the conformational preference of prolinol. J. J. Lee,S. Hesse, M. A. Suhm, J. Mol. Spectrosc. 976, 397 (2010).,

Studying water's interaction with small molecules has been crucial for developing an understanding of solvation at the molecular level. Our current work focuses on heterocycles that contain multiple sites for potential interaction with water. Here, we will describe the interactions of 1:1 complexes of oxazole and N-methylpyrrolidone with water. Both heterocycles have two obvious sites for potential hydrogen bond activity and we seek to understand the competition between these sites for association. The computational analysis of these complexes found four structures of oxazole with water and four structures of N-methylpyrrolidone with water. In both cases, there are structures where water acts as a hydrogen bond donor and structures where water acts as a hydrogen bond acceptor. Matrix isolation FTIR experiments identified several transitions that could be attributed to weakly-bound complexes of each system. In addition to normal water, and HDO complexes with oxazole and N-methylpyrrolidone were also observed. The spectra obtained can be interpreted with the aid of our computational work. Possible interpretations of the experimental and computational results will be presented here.

We present a jet-cooled rotational spectroscopic study of a binary complex made of furfural and n-hexane. Six different dimeric conformers were experimentally identified. These dimers are stabilized by several weak CH-O hydrogen bonds, where hexane acts as the proton donor. The experimental conformational cooling studies with different carrier gases have been coupled with associated DFT calculations to analyze the intricate conformational landscape, which is characterized by multiple shallow minima that are close in energy. The combined experimental and theoretical results provide a qualitative picture of the conformational interconversion landscape, the relative stability of the observed conformers, and importantly, an unusual enantiotopic element recognition in the binary aggregates of furfural and n-hexane.

Large systems, such as steroid hormones are a challenge to study with rotational spectroscopy, but gaining insight into the conformation and interaction with other molecules and functional groups is crucial to understand mechanisms and pathways better in the human body. For that reason a smaller system was choosen to replicate the hormones and used to study the interaction of hydroxy groups within complexes. r0pt Figure Decahydro-2-naphthol (C₁₀H₁₇OH) will hereby be the common complex partner. Decahydro-2-napthol has two saturated hexane rings with one being substituted by a hydroxy group. The molecule has eight stereoisomers which are four enantiomer pairs, which cannot be differentiated in a rotational spectrum. From these four pairs, three have been observed in the spectrum of the monomer, one trans and two cis species. The rotational spectra were recorded between 2-8 GHz with the chirped pulse Fourier transform microwave spectrometer COMPACT. The complexes were studied in a cold and isolated environment generated by a supersonic expansion. Here, we will compare the effect of different hydroxy species on the conformation of decahydro-2-naphthol and how the non-hydroxy part of the partner molecule affects the conformation of the overall complex.

The question of “How many water molecules trigger the dissociation of an acid” has been subjects of extensive investigations. Previous microwave and infrared studies collectively characterized the HCl(H₂O)_n, (n = 1-3) as undissociated complexes¹⁻³. For n ≥ 4, studies using IR spectroscopy in helium nanodroplets claimed to observe dissociated HCl, resulting in controversial spectral assignments⁴⁻⁶. To address this topic, we investigated the HCl-water clusters produced in a supersonic jet expansion using broadband rotational spectroscopy. In Fig.1, we incorporated the nuclear quadrupole coupling tensor obtained from the assignments of HCl(H₂O)_n clusters in the Townes-Daily model. Our results support that the observed HCl(H₂O)₄ exists as an undissociated complex. In H⁺Cl⁻(H₂O)₅ and H⁺Cl⁻(H₂O)₇, HCl dissociate spontaneously upon the formation of three hydrogen bonds with water. This forms contacting ion pairs. 1.JCP, 118, 10120–10136 (2003). 2.J.Phys.Chem. A 104, 6970–6978 (2000). 3.JCP, 112, 5767–5776 (2000). 4.Science 324, 1545–1548 (2009). 5.J.Phys.Chem.Lett. 1, 2233–2238 (2010). 6.JCP, 139, 154304 (2013). c0pt

Anisaldehydes constitute a common family of natural products formed by a phenyl ring substituted with both aldehyde and methoxy functional groups. The investigation of the stepwise hydration and the dimerization of these small-sized molecules can provide valuable insights into the intricate map of intermolecular interactions taking place upon solvation, serving as models for other molecular systems. In this work, the microsolvation and dimerization of the ortho isomer of anisaldehyde have been investigated through a combination of broadband microwave spectroscopy and high-quality quantum chemical calculations. A total of seven microsolvated complexes from one and up to five water molecules generated in a supersonic expansion have been experimentally detected in the range of 2 to 8 GHz. The theoretically predicted most stable homodimer of o-anisaldehyde has been also found in the rotational spectrum. A structural feature common to all microsolvated clusters observed is the dominant O-H···O=C hydrogen bond interaction accompanied by a variety of interactions and cluster configurations. Interestingly the dimer is stabilized by the formation of two n → π^∗ tetrel interactions established between the aldehyde and the methoxy functional groups. A further analysis of the intermolecular interactions highlights that the predominant contribution at play in microsolvates is electrostatic while in the dimer dispersion forces predominate.

Molecular switches regulate several biological processes, also having numerous applications in the field of molecular nanotechnology; inspired by nature, these simple molecular machines may be integrated in responsive drug-delivery systems [1] and in molecular computers [2]. The workings of some of these molecules comprise an on-off hydrogen bond, which may be achieved by combining a chiral molecule with an oxime functional group. Despite their unquestionable importance, the intricate working mechanisms of such systems remain largely unexplored [3-5]. In this framework, rotational spectroscopy is a highly appropriate technique to investigate the configurational dynamics of molecular switches in a controlled environment. In this contribution, we present a rotational study of a prototype switch, camphorquinone oxime, captured in the cold conditions of a supersonic jet expansion. Using CP-FTMW spectroscopy in the 2-8 GHz range, and supported by auxiliary quantum chemistry calculations, we investigated the stepwise growth of a solvation layer around the molecule. We observed that the closed state is preferred when the switch is in its isolated form. However, in the presence of water the oxime functionality is strongly perturbed, stabilizing in the open conformation. This effect is increasingly more pronounced with the growth of the water hydrogen-bonding network around the oxime site. We will discuss this conformers’ energy-inversion effect, relating it to the inter- and intra-molecular forces and dynamics that are established in the first solvation layer. References: [1] W. Viricel, A. Mbarek, J. Leblond. Angewandte Chem. Int. Ed., 2015, 54 (43), 12743-12747 [2] F. M. Raymo. Advanced Materials, 2002, 14 (6), 401-414. [3] L. Greb, A. Eichhöfer, J.-M. Lehn, Angew. Chem. Int. Ed., 2015, 54, 14345-14348 [4] S. Kassem, T. van Leeuwen, A. S. Lubbe, et al., Chem. Soc. Rev., 2017, 46, 2592-2621 [5] C. H. Pollok, T. Riesebeck, C. Merten, Angew. Chem. Int. Ed., 2017, 56, 1925-1928

Rotational spectroscopy has in recent years unlocked investigations into increasingly intricate molecular species. At the University of Coimbra, we are leveraging the high sensitivity and broadband capabilities of molecular rotational resonance (MRR) spectroscopy combined with cold molecular jets to study molecular organization in weakly-bound complexes. Supported by high-performance computing resources for quantum chemical calculations, studies of structural heterogeneity and conformational proofreading are at reach for increasingly more complex systems[1-3]. In this contribution, we will discuss aggregation mechanisms, energy reordering of equilibrium states, and chirality recognition during the stepwise growth of molecular clusters. References: [1] S. R. Domingos, A. Cnossen, W. J. Buma, W. R. Browne, B. L. Feringa, M. Schnell. “Cold Snapshot of a Molecular Rotary Motor Captured by High-Resolution Rotational Spectroscopy” Angew. Chem. Int. Ed. 2017, 56, 11209-11212. [2] S. R. Domingos, C. Pérez, N. M. Kreienborg, C. Merten, M. Schnell “Dynamic chiral self-recognition in aromatic dimers of styrene oxide revealed by rotational spectroscopy” Commun. Chem. 2021, 4(32). [3] S. R. Domingos, K. Martin, N. Avarvari, M. Schnell. “Water docking bias in [4]helicene” Angew. Chem. Int. Ed. 2019, 58, 11257-11261.

The van der Waals complex of trimethylamine (TMA) and carbon dioxide (CO₂) has been investigated for the first-time using cavity-based Fourier transform microwave spectroscopy. B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVTZ calculations were also used to model the structure, spectropic constants (rotational, centrifugal, and hyperfine constants), and the dipole moment. Five K = 0 rotational transitions were assigned and fit to (B + C)/2 = 1499.8620 (1) MHz. 18 nuclear quadrupole hyperfine components were assigned and fit to χ_aa = -5.294 (1) MHz. Progress towards assignment of higher K transitions and tunneling splitting will also be discussed.

Rotational spectra of clusters of trifluoroethylene (TFE) with CO₂ up to a heptamer, TFE...(CO₂)₆, have been assigned using microwave spectroscopy combined with novel intensity-variation analysis techniques. The chirped-pulse Fourier-transform microwave spectrometer (CP-FTMW) at the University of Virginia was used to record 2-8 GHz spectra that are averages of 1 million FIDs at two different CO₂ concentrations. Intensity ratios of transitions in the two spectra were used to extract subsets of data consisting of transitions exhibiting similar intensity variation between the two spectra. This provided simplified datasets, facilitating assignment of weak transitions, and leading to identification of at least eight clusters containing up to six CO₂ molecules. A similar analysis has been performed on hexafluoropropene (HFP) mixtures with CO₂, and in addition to multiple HFP...(CO₂)_n clusters, this has led to identification of several (HFP)_n and HFP...Ne_n species.

The potential energy surfaces of the 3,4,5-trifluorobenzoic acid monomer were scanned along C-C-C=O and O=C-O-H dihedral angles at the B3LYP/6-311G level to analyze its conformational landscape. Two conformations were identified and reoptimized at the B3LYP/aug-cc-pVTZ and MP2/aug-cc-pVTZ levels. The geometries of the relevant conformers are rationalized regarding the interactions between the carboxylic group and the substituted fluorine atoms. Only the planar global minimum conformation of the monomer was observed experimentally. The rotational spectra were recorded using a chirped pulse Fourier transform spectrometer in the frequency range of 6 – 12.5 GHz and analyzed for both the monomer and its complex with formic acid. The spectra of the parent, seven ¹³C, and one deuterium singly substituted isotopologues of the monomer were analyzed and fitted to measurement accuracy for a semi-rigid asymmetric top molecule. Theoretical and spectroscopic studies were performed on the complex formed by 3,4,5-trifluorobenzoic acid and formic acid, which undergoes double proton transfer. Proton tunneling is a widely studied phenomenon that is present in various biological and chemical processes. The rotational constants, centrifugal distortion constants, and tunneling energy difference were determined for the 3,4,5-trifluorobenzoic acid and formic acid complex. The complex prefers a co-planar structure. The tunneling splittings are due to the concerted proton transfer of the two carboxylic hydrogens. The proton tunneling process in this complex will be compared to related complexes. The agreement between the calculated and experimental parameters is very good for both the monomer and the complex.