Competition between O-H and S-H Intermolecular Interactions in Conformationally Complex Systems: The 2-Phenylethanethiol and 2-Phenylethanol Dimers.

Noncovalent interactions involving sulfur centers play a relevant role in biological and chemical environments. Yet, detailed molecular descriptions are scarce and limited to very simple model systems. Here we explore the formation of the elusive S-H···S hydrogen bond and the competition between S-H···O and O-H···S interactions in pure and mixed dimers of the conformationally flexible molecules 2-phenylethanethiol (PET) and 2-phenylethanol (PEAL), using the isolated and size-controlled environment of a jet expansion. The structure of both PET-PET and PET-PEAL dimers was unraveled through a comprehensive methodology that combined rotationally resolved microwave spectroscopy, mass-resolved isomer-specific infrared laser spectroscopy, and quantum chemical calculations. This synergic experimental-computational approach offered unique insights into the potential energy surface, conformational equilibria, molecular structure, and intermolecular interactions of the dimers. The results show a preferential order for establishing hydrogen bonds following the sequence S-H···S < S-H···O ≲ O-H···S < O-H···O, despite the hydrogen bond only accounting for a fraction of the total interaction energy.

Equilibrium structures of selenium compounds: The torsionally flexible molecule of selenophenol.

The equilibrium structure of selenophenol has been investigated using rotational spectroscopy and high-level quantum mechanical calculations, offering electronic and structural insight into the scarcely studied selenium compounds. The jet-cooled broadband microwave spectrum was measured in the 2-8 GHz cm-wave region using broadband (chirped-pulse) fast-passage techniques. Additional measurements up to 18 GHz used narrow-band impulse excitation. Spectral signatures were obtained for six isotopic species of selenium (80Se, 78Se, 76Se, 82Se, 77Se, and 74Se), together with different monosubstituted 13C species. The (unsplit) rotational transitions associated with the non-inverting µa-dipole selection rules could be partially reproduced with a semirigid rotor model. However, the internal rotation barrier of the selenol group splits the vibrational ground state into two subtorsional levels, doubling the dipole-inverting µb transitions. The simulation of the double-minimum internal rotation gives a very low barrier height (B3PW91: 42 cm-1), much smaller than for thiophenol (277 cm-1). A monodimensional Hamiltonian then predicts a huge vibrational separation of 72.2 GHz, justifying the non-observation of µb transitions in our frequency range. The experimental rotational parameters were compared with different MP2 and density functional theory calculations. The equilibrium structure was determined using several high-level ab initio calculations. A final Born-Oppenheimer (reBO) structure was obtained at the coupled-cluster CCSD(T)_ae/cc-wCVTZ level of theory, including small corrections for the wCVTZ → wCVQZ basis set enlargement calculated at the MP2 level. The mass-dependent method with predicates was used to produce an alternative rm(2) structure. The comparison between the two methods confirms the high accuracy of the reBO structure and offers information on other chalcogen-containing molecules.

Sulfur-arene interactions: the S⋯π and S-H⋯π interactions in the dimers of benzofuran⋯sulfur dioxide and benzofuran⋯hydrogen sulfide.

Non-covalent interactions between sulfur centers and aromatic rings play important roles in biological chemistry. We examined here the sulfur-arene interactions between the fused aromatic heterocycle benzofuran and two prototype sulfur divalent triatomics (sulfur dioxide and hydrogen sulfide). The weakly-bound adducts were generated in a supersonic jet expansion and characterized with broadband (chirped-pulsed) time-domain microwave spectroscopy. The rotational spectrum confirmed the detection of a single isomer for both heterodimers, consistent with the computational predictions for the global minima. The benzofuran⋯sulfur dioxide dimer exhibits a stacked structure with sulfur closer to benzofuran, while in benzofuran⋯hydrogen sulfide the two S-H bonds are oriented towards the bicycle. These binding topologies are similar to the corresponding benzene adducts, but offer increased interaction energies. The stabilizing interactions are described as S⋯π or S-H⋯π, respectively, using a combination of density-functional theory calculations (dispersion corrected B3LYP and B2PLYP), natural bond orbital theory, energy decomposition and electronic density analysis methods. The two heterodimers present a larger dispersion component, but nearly balanced by electrostatic contributions.

π-Stacking Isomerism in Polycyclic Aromatic Hydrocarbons: The 2-Naphthalenethiol Dimer.

π-Stacking is a common descriptor for face-to-face attractive forces between aromatic hydrocarbons. However, the physical origin of this interaction remains debatable. Here we examined π-stacking in a model homodimer formed by two thiol-substituted naphthalene rings. Two isomers of the 2-naphthalenethiol dimer were discovered using rotational spectroscopy, sharing a parallel-displaced crossed orientation and absence of thiol-thiol hydrogen bonds. One of the isomers presents C2 symmetry, structurally analogous to the global minimum of the naphthalene dimer. The experimental data were rationalized with molecular orbital calculations, revealing a shallow potential energy surface. Noncovalent interactions are dominated by dispersion forces according to SAPT energy decomposition. In addition, the reduced electronic density shows a diffuse and extended region of inter-ring interactions, compatible with the description of π-stacking as a competition between dispersion and Pauli repulsion forces.

The evolution towards cyclic structures in the aggregation of aromatic alcohols: the dimer, trimer and tetramer of 2-phenylethanol.

Gas-phase spectroscopic studies of alcohol clusters offer accurate information on the influence of non-covalent interactions on molecular recognition, and are of paramount importance to model supramolecular and biological chemical processes. Here, we examine the role of the aliphatic side chain in the self-aggregation of aromatic alcohols, using a multi-methodological gas-phase approach which combines microwave spectroscopy and mass-resolved electronic and vibrational laser spectroscopy. Spectroscopic and electronic structure computations were carried out for the dimer, trimer and tetramer of 2-phenylethanol, extending previous investigations on smaller aromatic alcohols. While the conformational flexibility of the ethyl group anticipates a variety of torsional isomers, the intra- and inter-molecular interactions restrict molecular conformations and favour particularly stable isomers. The conformational landscape of the clusters is very shallow and multiple competing isomers were rotationally and/or vibrationally detected, including three dimer species, two trimers and two tetramers. Cluster growth is associated with a tendency to form cyclic hydrogen bond structures.

Hydrogen Bonding in the Dimer and Monohydrate of 2-Adamantanol: A Test Case for Dispersion-Corrected Density Functional Methods.

Weakly-bound intermolecular clusters constitute reductionist physical models for non-covalent interactions. Here we report the observation of the monomer, the dimer and the monohydrate of 2-adamantanol, a secondary alcohol with a bulky ten-carbon aliphatic skeleton. The molecular species were generated in a supersonic jet expansion and characterized using broadband chirped-pulse microwave spectroscopy in the 2-8 GHz frequency region. Two different gauche-gauche O-H···O hydrogen-bonded isomers were observed for the dimer of 2-adamantanol, while a single isomer was observed for the monomer and the monohydrate. The experimental rotational parameters were compared with molecular orbital calculations using density functional theory (B3LYP-D3(BJ), B2PLYP-D3(BJ), CAM-B3LYP-D3(BJ), ωB97XD), additionally providing energetic and electron density characterization. The shallow potential energy surface makes the dimer an interesting case study to benchmark dispersion-corrected computational methods and conformational search procedures.

Torsional chirality and molecular recognition: the homo and heterochiral dimers of thenyl and furfuryl alcohol.

Furfuryl alcohol and thenyl alcohol contain a labile torsional chiral center, producing transiently chiral enantiomers interconverting in the nanosecond time-scale. We explored chiral molecular recognition using the weakly-bound intermolecular dimers of both alcohols, freezing stereomutation. Supersonic jet broadband microwave spectroscopy revealed homo and heterochiral diastereoisomers for each alcohol dimer and the structural characteristics of the clusters. All dimers are primarily stabilized by a moderately intense O-H⋯O hydrogen bond, but differ in the secondary interactions, which introduce additional hydrogen bonds either to the ring oxygen in furfuryl alcohol or to the π ring system in thenyl alcohol. Density-functional calculations (B2PLYP-D3(BJ)/def2-TZVP) show no clear preferences for a particular stereochemistry in the dimers, with relative energies of the order 1-2 kJ mol-1. The study suggests opportunities for the investigation of chiral recognition in molecules with torsional barriers in between transient and permanent interconversion regimes.

Rovibronic signatures of molecular aggregation in the gas phase: subtle homochirality trends in the dimer, trimer and tetramer of benzyl alcohol.

Molecular aggregation is of paramount importance in many chemical processes, including those in living beings. Thus, characterization of the intermolecular interactions is an important step in its understanding. We describe here the aggregation of benzyl alcohol at the molecular level, a process governed by a delicate equilibrium between OH⋯O and OH⋯π hydrogen bonds and dispersive interactions. Using microwave, FTIR, Raman and mass-resolved double-resonance IR/UV spectroscopic techniques, we explored the cluster growth up to the tetramer and found a complex landscape, partly due to the appearance of multiple stereoisomers of very similar stability. Interestingly, a consistently homochiral synchronization of transiently chiral monomer conformers was observed during cluster growth to converge in the tetramer, where the fully homochiral species dominates the potential energy surface. The data on the aggregation of benzyl alcohol also constitute an excellent playground to fine-tune the parameters of the most advanced functionals.

How accurate is the determination of equilibrium structures for van der Waals complexes? The dimer N2O⋯CO as an example.

Plausible methods for accurate determination of equilibrium structures of intermolecular clusters have been assessed for the van der Waals dimer N2O⋯CO. In order to assure a large initial dataset of rotational parameters, we first measured the microwave spectra of the 15N2O⋯12CO and 15N2O⋯13CO isotopologs, expanding previous measurements. Then, an anharmonic force field was calculated ab initio and a semi-experimental equilibrium structure was determined. The dimer structure was also calculated at the coupled-cluster level of theory using very large basis sets with diffuse functions and counterpoise correction. It was found that the contributions of the diffuse functions and the counterpoise correction are not additive and do not compensate each other although they have almost the same value but opposite signs. The semi-experimental and ab initio structures were found to be in fair agreement, with the equilibrium distance between the centers of mass of both monomers being 3.825(13) Å and the intermolecular bond length r(C⋯O) = 3.300(9) Å. In this case, the mass-dependent method did not permit us to determine reliable intermolecular parameters. The combination of experimental rotational constants and results of ab initio calculations thus proves to be very sensitive to examine the accuracy of structural determinations in intermolecular clusters, offering insight into other aggregates.

Switching Hydrogen Bonding to π-Stacking: The Thiophenol Dimer and Trimer.

We used jet-cooled broadband rotational spectroscopy to explore the balance between π-stacking and hydrogen-bonding interactions in the self-aggregation of thiophenol. Two different isomers were detected for the thiophenol dimer, revealing dispersion-controlled π-stacked structures anchored by a long S-H···S sulfur hydrogen bond. The weak intermolecular forces allow for noticeable internal dynamics in the dimers, as tunneling splittings are observed for the global minimum. The large-amplitude motion is ascribed to a concerted inversion motion between the two rings, exchanging the roles of the proton donor and acceptor in the thiol groups. The determined torsional barrier of B2 = 250.3 cm-1 is consistent with theoretical predictions (290-502 cm-1) and the monomer barrier of 277.1(3) cm-1. For the thiophenol trimer, a symmetric top structure was assigned in the spectrum. The results highlight the relevance of substituent effects to modulate π-stacking geometries and the role of the sulfur-centered hydrogen bonds.

Molecular Rotation Spectrum of Tetracyclic Quinolizidines: Observation of trans-Matrine and the Elusive cis-Matrine.

We characterized the bis-quinolizidine tetracyclic alkaloid (5S, 6S, 7R, 11R)-matrine in a supersonic jet expansion, using chirped-pulsed broadband microwave spectroscopy. Previous crystal diffraction analyses suggested 16 diastereoisomers associated with matrine's four carbon stereocenters but were inconclusive whether the lactamic nitrogen atom would additionally produce separated trans-/cis- diastereoisomers or if both species may interconvert through low potential barriers. Our experiment simultaneously detected trans- and cis-matrine through their rotational spectrum, confirming the possibility of conformational rearrangement in matrine alkaloids. The two matrine conformers mainly differ in the envelope or half-chair lactamic ring, as evidenced by the experimental rotational and nuclear quadrupole coupling parameters. Molecular orbital calculations with ab initio (MP2) and density functional methods (B3LYP-D3(BJ) and MN15) were tested against the experiment, additionally offering an estimation of the cis-/trans- barrier of 24.9-26.9 kJ mol-1. The experiment illustrates the structural potential of chirped-pulsed broadband microwave spectroscopy for high-resolution rotational studies of biomolecules in the range of 20-40 atoms.

Sulfur hydrogen bonding and internal dynamics in the monohydrates of thenyl mercaptan and thenyl alcohol.

The monohydrates of thenyl alcohol and thenyl mercaptan have been probed in a supersonic jet expansion using chirped-pulse and Fabry-Perot Fourier-transform microwave spectroscopy. The rotational spectra revealed a single isomer for each of the dimers. The thenyl alcohol hydrate is stabilized by an O-HOw hydrogen bond between the alcohol and water, with water acting as a proton acceptor and additionally engaging in an Ow-Hπ interaction with the thenyl ring. Conversely, water behaves as a proton donor in the thenyl mercaptan hydrate, linking to the thiol group though an Ow-HS hydrogen bond and secondary Ow-Hπ interactions with the ring. In both dimers water retains internal mobility, as tunneling doublings in the spectrum confirm an internal rotation motion of water inside the cluster. The experimental results have been complemented with density-functional-theory molecular orbital calculations, binding energy decomposition and a topological analysis of the electronic density, providing a comparative description of the effects of hydrogen bonding of water to the alcohol and thiol groups in the dimers, relevant to understand hydrogen bonding to sulfur centers.

Rotational Spectrum, Tunneling Motions, and Intramolecular Potential Barriers in Benzyl Mercaptan.

The rotational spectrum of benzyl mercaptan (parent and four isotopologues) has been assigned in a supersonic jet expansion using chirped-pulse Fourier transform microwave spectroscopy. The spectrum is characterized by torsional tunneling doublings, strongly perturbed by Coriolis interactions. The experimental rotational constants reveal that the sulfur atom is located above the ring plane in a gauche conformation. The torsion dihedral θ0 = φ (SCα-C1C2) is approximately 74°, according to a flexible molecular model calculation reproducing the energy separation (ΔE01 ∼ 2180.4 MHz) between the first two torsional substates. The global minimum configuration is 4-fold degenerate, corresponding to potential minima with θ0 ≈ ±74° and ±(180-74)°. The four equivalent minima are separated by potential barriers at θ = ±90°, 0°, or 180°. The tunneling splittings are caused by the potential barrier at θ = ± 90°, while the barriers at torsions of 0° or 180° are too large to generate detectable splittings. The tunnelling barrier has been determined as 248 cm-1, similar to the value obtained with high-level MP2 ab initio calculations (259 cm-1), but smaller than in benzyl alcohol (280 cm-1).

Rotational spectroscopy of organophosphorous chemical agents: cresyl and phenyl saligenin phosphates.

Cresyl and phenyl saligenin phosphates have been probed in a jet expansion by broadband chirp-excitation microwave spectroscopy, revealing the most stable conformations and their structural properties. The rotational parameters offer a high-resolution univocal route for characterization of organophosphorous agents and a testbed for computational models.

How flexible is the disulfide linker? A combined rotational-computational investigation of diallyl disulfide.

The symmetrically substituted diallyl disulfide adopts a non-symmetric conformation in the gas-phase, as observed with supersonic-jet rotational spectroscopy. The determination of the equilibrium structure with a predicate mixed regression illustrates both the benefits of the mass-dependent method for moderately large molecules and the structural peculiarities of the disulfide bridge.

The S-S Bridge: A Mixed Experimental-Computational Estimation of the Equilibrium Structure of Diphenyl Disulfide.

The disulfide bridge (-S-S-) is an important structural motif in organic and protein chemistry, but only a few accurate equilibrium structures are documented. We report the results of supersonic-jet microwave spectroscopy experiments on the rotational spectra of diphenyl disulfide, C6 H5 -S-S-C6 H5 (including all 13 C and 34 S monosubstituted isotopologues), and the determination of the equilibrium structure by the mixed estimation (ME) method. A single conformation of C2 symmetry was observed in the gas phase. This disulfide is a challenging target since its structure is determined by 34 independent parameters. Additionally, ab initio calculations revealed the presence of three low-frequency vibrations (<50 cm-1 ) associated to phenyl torsions which would prevent the calculation of an accurate force field. For this reason, instead of the semiexperimental method, we used the mass-dependent (rm ) method to fit the structural parameters concurrently to moments of inertia and predicate parameters, affected with appropriate uncertainties. The predicates were obtained by high-level quantum-chemical computations. A careful analysis of the results of different fits and a comparison with the ab initio optimizations confirms the validity of the used methods, providing detailed structural information on the title compound and the disulfide bridge.