By mono-chlorination of propane-1,2-diol its conformational complexity can be significantly enhanced. The Cl atom allows for a stabilization of conformers with an anti-periplanar arrangement of the OC-CO dihedral angle which has not been detected for any other vicinal diol in the gas phase. We assigned a total of eight different conformers in our chirped-pulse Fourier transform microwave (CP-FTMW) spectra with the 35Cl and 37Cl isotopologues for each case. Furthermore, the conformational landscape was analyzed in great detail including transition state calculations. In addition to the monomeric species, the Ne complex of the global minimum was also observed. From the nuclear quadrupole coupling constants, the presence of weak OH⋯Cl bonding is assessed. We further investigate the shifts induced in the energetic landscape by the chlorine atom with density functional and explicitly correlated wavefunction theory based methods. To understand the potential role of dispersion in the stabilization of some key conformers, local energy decomposition accompanied by dispersion interaction densities was employed.

Sugars are essential biomolecules, serving as metabolic fuels, nucleic acid backbone components and structural or energy-storage polymers. A central question in origin-of-life research is how monosaccharides formed on the primitive Earth, as laboratory experiments under prebiotic conditions yield insufficient concentrations. The detection of ribose, glucose and other monosaccharides in asteroids and meteorites suggests an exogenous origin, possibly in the interstellar medium (ISM) before meteoritic parent-body formation. However, no sugar has been observed in the ISM so far. Here we report the discovery of erythrulose, a chiral four-carbon ketose, in the ISM. The detection was achieved through ultrasensitive, broadband spectral surveys of the Galactic Centre molecular cloud G+0.693-0.027, using the Yebes 40 m and IRAM 30 m telescopes. Erythrulose appears to be at least eight times more abundant than analogous three-carbon sugars, which remain undetected in our ultrasensitive observations. Quantum chemical and astrochemical models indicate that erythrulose forms efficiently on interstellar dust grains from simpler two-carbon aldehydes and alcohols. As ketoses readily isomerize into aldoses in aqueous conditions, interstellar erythrulose could have contributed to the sugar inventory available for early metabolic and replication processes.

To gain molecular-level insights into how weak intramolecular noncovalent interactions govern the conformational preference of large semivolatile organic compounds, benzyl benzoate (BnBz), an ester with terminal benzyl and phenyl groups, was investigated using chirped-pulse Fourier transform microwave spectroscopy and quantum chemical calculations. Systematic conformational searches followed by DFT calculations identified four BnBz conformers: two low-energy species with a planar benzoate (C6H5-COO) motif and two significantly higher-energy conformers with a nonplanar benzoate moiety. The rotational spectra of the two most stable conformers, BnBz-g and BnBz-t, along with 16 of their 13C isotopologues, were observed and assigned. The DFT-predicted stability ordering of these two conformers is reversed when based on zero-point-corrected energies and free energies. Experimental results confirm BnBz-g as the global minimum, resolving the theoretical ambiguity and underscoring the importance of benchmarking computational predictions with conformer-specific data. The conformational conversion barrier was investigated both experimentally using helium, neon, and argon as carrier gases, and computationally, revealing a low barrier height of less than 5 kJ mol-1. Noncovalent interactions analyses indicate that multiple CH···O hydrogen bonds govern the structural preferences of the low-energy conformers, while additional model calculations show that the π-π stacking motif becomes more prominent with the addition of further bridging methylene groups.

Methyl lactate, a chiral molecule with multiple functional groups, has played a pivotal role in advancing experimental and theoretical chiroptical methods. Leveraging conformer-specific jet-cooled rotational spectroscopy in tandem with extensive conformational searches and quantum chemical calculations, we investigated chirality self-recognition in the methyl lactate dimer. The experimental fingerprint-like spectral patterns, including methyl rotor tunneling splittings, allowed the definite identification of one heterochiral and two homochiral binary conformers from a large number of low-energy candidates. Nuclear spin statistics analyses and methyl internal rotor parameters reveal different nuclear tunneling dynamics in the homochiral versus heterochiral environments and highlight the associated chirality-driven symmetry preference in the observed conformers. The results provide comprehensive experimental data for benchmarking quantum chemical calculations of chiral properties and pave the way for the exploration of this prototypical dimer across different frequency ranges using other spectroscopic tools.

Herein, we present the first experimental observation of isolated progesterone, an endogenous steroid, placed in the gas phase by laser ablation and characterized in a supersonic expansion by Fourier transform microwave techniques. Guided by quantum-chemical calculations, we assigned the rotational spectrum of the most stable structure. The internal rotation of the acetyl methyl group led to the observation of A-E doublets in the spectrum, which were analyzed, resulting in a V3 barrier of 2.4425 ± 0.0025 kJ mol-1. By fitting over 250 transitions, we determined accurate rotational constants that enabled us to compare the gas phase geometrical parameters with those of crystalline forms and complexes with progesterone receptors. Our results indicate that the A ring of progesterone that contains the ketone group is surprisingly flexible, despite its rigid appearance. This finding is particularly significant, since this ring is an active biological site that is involved in strong intermolecular interactions. Notably, progesterone C21H30O2 is the largest molecule investigated using laser ablation rotational spectroscopy.

Contrary to popular belief, the interstellar medium (ISM) is not empty; it is filled with atoms, dust particles, and molecules. Some of these molecules may have been the very building blocks of life that, delivered to Earth via comets and meteorites, could have given rise to Life itself. A large-area single-dish telescope with superb sensitivity, field-of-view and multi-band instruments will allow us to explore the limits of chemical complexity in the interstellar medium, across our Galaxy and in external galaxies, determining whether amino acids, sugars, or RNA/DNA nucleobases can form in space.

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.

Glycerol, a flexible triol, has found widespread use in biological and industrial applications due to its intricate intra- and intermolecular hydrogen (H)-bonding capability. Using a combination of experimental broadband rotational spectroscopy and high-level quantum chemistry calculations, we probed low-energy isomers of binary and ternary glycerol aggregates. Seven binary isomers and one ternary isomer were identified experimentally, with the aid of theoretical modeling. The experimental results offer critical benchmarks for theoretical geometry and relative energy ordering predictions across various levels of theory, especially for systems unusually rich in OH groups. Importantly, by detecting these isomers experimentally, we can trace the evolution of the 3D H-bonding networks up to the trimer, thereby gaining molecular-level insights into the initial stages of glycerol self-aggregation. The observed binary and ternary isomers reveal a delicate interplay of intra- and intermolecular H-bonds. The H-bonding networks of their respective most stable isomers show remarkable similarities to those of the observed isomers of (H2O)6 and (H2O)9 clusters. These findings shed new light on the origin of glycerol's miscibility with water and its related biological functions.

The conformational landscapes of four 1-O-methylated monosaccharides-methyl α-glucose, methyl β-glucose, methyl α-galactose, and methyl β-galactose-were characterized using jet-cooled broadband rotational spectroscopy, supported by density functional theory calculations. A newly designed, simple pulsed nozzle assembly was used to introduce the sugar samples into a jet expansion without thermal degradation, eliminating the need for a complex and expensive laser ablation system. Ten conformers were experimentally identified by assigning their rotational spectra, and the intricate methyl internal rotation splittings were analysed. Notably, methylation alters the directionality of intramolecular hydrogen bonding of α-galactose highlighting its impact on structural preference. Natural bond orbital, intrinsic bond strength, and non-covalent interaction analyses were conducted to explore the interplay between hydrogen bonding and hyperconjugation. A set of σ to σ* neutral hyperconjugative interactions was found to override a strong hydrogen bond, driving a preference for the gauche conformers.

This work aims to spectroscopically characterize and provide for the first time direct experimental frequencies of the ground vibrational state and two excited states of the simplest alkynyl thiocyanate (HCCSCN) for astrophysical use. Both microwave (8-16 GHz) and millimeter wave regions (50-120 GHz) of the spectrum have been measured and analyzed in terms of Watson's semirigid rotor Hamiltonian. A total of 314 transitions were assigned to the ground state of HCCSCN and a first set of spectroscopic constants have been accurately determined. Spectral features of the molecule were then searched for in Sgr B2(N), NGC 6334I, G+0.693-0.027 and TMC-1 molecular clouds. Upper limits to the column density are provided.

Four conformations of the widely used insect repellent DEET have been observed in the gas phase by broadband microwave spectroscopy. The relative orientation of the alkyl chains provide flexibility resulting in a populated potential energy surface.

This atomic-resolution study reveals glucose changes due to oxidation, exploring key carbohydrate aspects like hydrogen bonding, ring-puckering, anomeric effect, and tautomeric selection. Results confirm mutarotation suppression in the gas phase.

We explored the conformational landscape of N-acetyl-alpha-d-glucosamine (alpha-GlcNAc), a fundamental chemical scaffold in glycobiology. Solid samples were vaporized by laser ablation, expanded in a supersonic jet, and characterized by broadband chirped pulse Fourier transform microwave spectroscopy. In the isolation conditions of the jet, three different structures of GlcNAc have been discovered. These are conclusively identified by comparing the experimental values of the rotational constants with those predicted by theoretical calculations. The conformational preferences are controlled by intramolecular hydrogen bond networks formed between the polar groups in the acetamido group and the hydroxyl groups and dominated in all cases by a strong OHO & boxH;C interaction. We reported an exception to the gauche effect due to the enhanced stability observed for the Tg(+) conformer. All the structures present the same disposition of the acetamido group, which explains the highly selective binding of N-acetylglucosamine with different amino acid residues. Thus, the comprehensive structural data provided here shall help to shed some light on the biological role of this relevant amino sugar.

The rotational spectra of a mixture of 2,4-pentanediol (PDL) isomers, comprising both the meso isomers [(2R, 4S) and (2S, 4R)] and the racemic isomers [(2R, 4R) and (2S, 4S)], were recorded using a chirped-pulse Fourier transform microwave spectrometer coupled to a supersonic jet expansion. The conformational landscapes of meso- and racemic-PDL were examined using the Conformer-Rotamer Ensemble Sampling Tool and high-level quantum chemical calculations, generating 26 and 25 conformers, respectively. Five sets of rotational transitions were observed and assigned, with two attributed to meso-PDL and the remaining three attributed to racemic-PDL. Furthermore, tunneling splittings were observed for both meso-PDL conformers, and the nudged elastic band method was utilized to map the corresponding tunneling pathways and obtain tunneling barriers. To rationalize relative abundances of the observed conformers and the non-observation of other low-energy conformers, possible conversion pathways among meso-PDL conformers and racemic-PDL conformers were also explored. Finally, ten carbon-13 isotopologues, five from each of the lowest-energy meso- and racemic-PDL conformers, were detected in natural abundance and used to establish the corresponding geometries. These results offer valuable insights into the stereoisomeric behaviors and conformational preferences within flexible diols.

The conformational space of cis-1,2-cyclohexanediol, a model molecule for cyclic vicinal diols, was investigated using rotational spectroscopy and density functional theory calculations. Four low energy conformers within an energy window of 5 kJ mol−1 were identified computationally. A rotational spectrum of jet-cooled cis-1,2-cyclohexanediol was recorded with a chirped pulse Fourier transform microwave spectrometer. Two sets of rotational transitions were observed and could be assigned to conformers of cis-1,2-cyclohexanediol. The non-observation of other low energy conformers was explained by conformational conversion barrier height calculations and results from experimental spectra recorded with different carrier gases. Eight isotopologues, including those with 13C and 18O, of the lowest energy conformer were observed, allowing the determination of the semi-experimental equilibrium structure, reSE. Interestingly, the structural analysis revealed that the C–O bond length of the intramolecular hydrogen-bond donor is shorter than that of the acceptor. This appears to be a general characteristic of vicinal diols and can be used as a novel hydrogen-bond marker in such compounds.

The 1 : 2 adduct of 1-phenyl-2,2,2-trifluoroethanol (PhTFE), a chiral fluoroalcohol, with two water molecules (PhTFE & ctdot;2H(2)O) was investigated via chirped pulse Fourier-transform microwave (CP-FTMW) spectroscopy and theoretical calculations. A systematic search of the PhTFE & ctdot;2H(2)O conformational landscape identified 38 stable minima at the B3LYP-D3BJ/def2-TZVPPD level of theory, 27 of which are within an energy window of 10 kJ mol(-1) after applying zero-point energy corrections. Rotational spectra of a single PhTFE & ctdot;2H2O conformer along with eight deuterated and three oxygen-18 isotopologues were assigned. Interestingly, the observed PhTFE & ctdot;2H(2)O conformer contains PhTFE II, the second most stable monomer conformer, and the most stable PhTFE I dihydrate is ca. 4 kJ mol(-1) higher in energy. In contrast, PhTFE I & ctdot;H2O was identified experimentally and theoretically as the most stable 1 : 1 conformer. Furthermore, the observed dihydrate structure experiences large amplitude motions connecting three theoretical minima which differ only in which water oxygen lone pairs are involved in the hydrogen-bonds, i.e., the free OH pointing directions. Additionally, the ortho and para-H2O tunnelling splittings were detected and attributed to the interchange water hydrogen atoms which interact with the aromatic part of PhTFE but not for the water interacting with PhTFE hydroxy group. Extensive theoretical modelling was carried out to gain insight into the associated large amplitude motions including tunnelling, supported by the experimental isotopic and tunnelling splitting data.

The rotational spectra of four substituted benzoic acids, i.e., para-aminobenzoic acid, para-nitrobenzoic acid, para-chlorobenzoic acid, and para-hydroxybenzoic acid were recorded with a chirp-pulse Fourier transform microwave spectrometer and analysed in terms of rotational constants and, where applicable, nuclear quadru-pole coupling constants and tunnelling motions. In all instances, the experimentally identified conformer con-tains a carboxylic acid group in the cis-arrangement. In the case of para-hydroxybenzoic acid, spectra of two conformers were observed which differ in the orientation of the para-OH group. Quantum chemical calculations at the B3LYP-D3BJ/def2-TZVP and B2PLYP-D3BJ/cc-pCVTZ levels show that the trans-conformers are about 23 kJ mol- 1 higher in energy than the global minimum cis-conformers. In general, the calculated rotational con-stants are in good agreement with the experimental derived ones. Agreement between calculated and experi-mental14N and 35/37Cl nuclear quadrupole coupling constants is somewhat worse and necessitated the use of the B2PLYP functional in the case of para-nitrobenzoic acid to reduce the discrepancy. Conversion barriers between possible conformers were calculated to explain the absence of tunnelling splittings and/or higher energy con-formers in the experimental spectra. An analysis of the electron density distribution was used to rationalize the calculated out-of-plane excursions of the carboxylic acid group in the trans-conformers.

Two competing solvation pathways of 3-methylcatechol (MC), an atmospherically relevant aromatic molecule, with up to five water molecules were explored in detail by using a combination of broadband rotational spectroscopy and computational chemistry. Theoretically, two different pathways of solvation emerge: the commonly observed droplet pathway which involves preferential binding among the water molecules while the solute serves as an anchor point for the formation of a water cluster, and an unexpected wetting pathway which involves interactions between the water molecules and the aromatic face of MC, i.e., a wetting of the π-surface. Conclusive identification of the MC hydrate structures, and therefore the wetting pathway, was facilitated by rotational spectra of the parent MC hydrates and several H2 18 O and 13 C isotopologues which exhibit splittings associated with methyl internal rotation and/or water tunneling motions. Theoretical modelling and analyses offer insights into the tunneling and conversion barriers associated with the observed hydrate conformers and the nature of the non-covalent interactions involved in choosing the unusual wetting pathway.

Tetrahydro-2H-pyran-2-ol (THP) is an alcohol containing pyranose ring.The lack of substituents in THP minimizes the conformational flexibility and the non-covalent interactions within the structure, drastically simplifying the system in relation to physiologically relevant carbohydrates, such as glucose.This makes THP a prototypical system to study various phenomena and dynamics of carbohydrate chemistry.Such phenomena include the anomeric effect, which describes the preference for the axial conformation over the less hindered and more energetically favoured equatorial conformation.When in solution, THP is in equilibrium with its linear counterpart, 5-hydroxypentanal, and readily interconverts between its two chiral forms.A high resolution gas phase study of THP may not only confirm phenomena such as the anomeric affect, but also allow for the study of chiral interconversion in the gas phase.An in-depth study of THP will also lay a foundation for future gas phase carbohydrate systems with more physiological relevance.However, before we can study the various phenomena and dynamics, it is first beneficial to study the structure of THP in great detail.To elucidate the THP structure we analyzed rotational spectra measured with a chirped-pulse Fourier transform microwave spectrometer, operating in the 2-6 GHz range.In addition to the monomers, some dimer conformations were assigned to the rotational spectrum.The intermolecular interactions within the dimers were then visualized using a non-covalent interactions (NCI) analysis.