Adaptive Response to Solvation in Flexible Molecules: Oligo Hydrates of 4-Hydroxy-2-butanone.

Structural changes induced by water play a pivotal role in chemistry and biology but remain challenging to predict, measure, and control at molecular level. Here we explore size-governed gas-phase water aggregation in the flexible molecule 4-hydroxy-2-butanone, modeling the conformational adaptability of flexible substrates to host water scaffolds and the preference for sequential droplet growth. The experiment was conducted using broadband rotational spectroscopy, rationalized with quantum chemical calculations. Two different isomers were observed experimentally from the di- to the pentahydrates (4-hydroxy-2-butanone-(H2O)n=2-5), including the 18O isotopologues for the di- and trihydrates. Interestingly, to accommodate water molecules effectively, the heavy atom skeleton of 4-hydroxy-2-butanone reshapes in every observed isomer and does not correspond to the stable conformer of the free monomer. All solvates initiate from the alcohol group (proton donor) but retain the carbonyl group as secondary binding point. The water scaffolds closely resemble those found in the pure water clusters, balancing between the capability of 4-hydroxy-2-butanone for steering the orientation and position of the water molecules and the ability of water to modulate the monomer's conformation. The present work thus provides an accurate molecular description on how torsionally flexible molecules dynamically adapt to water along progressing solvation.

Probing the n → π* carbonyl-carbonyl interactions in the formaldehyde-trifluoroacetone dimer by rotational spectroscopy.

The non-covalent bonding features of carbonyl-carbonyl interactions have been investigated in the dimer of formaldehyde and trifluoroacetone using high resolution rotational spectroscopy combined with quantum chemical calculations. The observation of all possible isotopic substitutions for the heavy atoms in the complex enabled the determination of the accurate structure, characterized by the antiparallel arrangement of the two C=O bonds. The two moieties are connected through a dominant n → π* interaction enhanced by one weak C-H⋯O hydrogen bond, as revealed by supporting natural bond orbital analysis and symmetry-adapted perturbation theory analysis. Further computational investigations on 17 related adducts stabilized by carbonyl-carbonyl n → π* interactions show how the interaction strength is regulated by the incorporation of either electron-donating or withdrawing functional groups.

Aqueous microsolvation of 4-hydroxy-2-butanone: competition between intra- and inter-molecular hydrogen bonds.

The rotational spectra of 4-hydroxy-2-butanone and its monohydrate were investigated by Fourier transform microwave spectroscopy complemented by quantum chemical calculations. One conformer of 4-hydroxy-2-butanone, with the intramolecular O-H⋯O hydrogen bond, has been observed in the pulsed jet. Rotational spectra of the six isotopologues (including four 13C and one 18O mono-substitution species) in natural abundance were measured and assigned, enabling the accurate structural determination of the molecular skeleton. The most stable isomer of its monohydrate, in which water inserts into the intramolecular hydrogen bond and serves the dual role of being a proton donor and acceptor, was also detected. The rotational spectra of HOD, DOH, D2O and H218O isotopologues were also measured allowing the accurate evaluation of the parameters of the intermolecular hydrogen bonds. This rotational spectroscopic investigation demonstrates that upon complexation, the weak intramolecular hydrogen bond in the monomer is replaced by two strong intermolecular O-H⋯O hydrogen bonds, leading to a change in the orientation of the -OH group of 4-hydroxy-2-butanone.

The LAM of the Rings: Large Amplitude Motions in Aromatic Molecules Studied by Microwave Spectroscopy.

Large amplitude motions (LAMs) form a fundamental phenomenon that demands the development of specific theoretical and Hamiltonian models. In recent years, along with the strong progress in instrumental techniques on high-resolution microwave spectroscopy and computational capacity in quantum chemistry, studies on LAMs have become very diverse. Larger and more complex molecular systems have been taken under investigation, ranging from series of heteroaromatic molecules from five- and six-membered rings to polycyclic-aromatic-hydrocarbon derivatives. Such systems are ideally suited to create families of molecules in which the positions and the number of LAMs can be varied, while the heteroatoms often provide a sufficient dipole moment to the systems to warrant the observation of their rotational spectra. This review will summarize three types of LAMs: internal rotation, inversion tunneling, and ring puckering, which are frequently observed in aromatic five-membered rings such as furan, thiophene, pyrrole, thiazole, and oxazole derivatives, in aromatic six-membered rings such as benzene, pyridine, and pyrimidine derivatives, and larger combined rings such as naphthalene, indole, and indan derivatives. For each molecular class, we will present the representatives and summarize the recent insights on the molecular structure and internal dynamics and how they help to advance the field of quantum mechanics.

Methyl Internal Rotation in Fruit Esters: Chain-Length Effect Observed in the Microwave Spectrum of Methyl Hexanoate.

The gas-phase structures of the fruit ester methyl hexanoate, CH3-O-(C=O)-C5H11, have been determined using a combination of molecular jet Fourier-transform microwave spectroscopy and quantum chemistry. The microwave spectrum was measured in the frequency range of 3 to 23 GHz. Two conformers were assigned, one with Cs symmetry and the other with C1 symmetry where the γ-carbon atom of the hexyl chain is in a gauche orientation in relation to the carbonyl bond. Splittings of all rotational lines into doublets were observed due to internal rotation of the methoxy methyl group CH3-O, from which torsional barriers of 417 cm-1 and 415 cm-1, respectively, could be deduced. Rotational constants obtained from geometry optimizations at various levels of theory were compared to the experimental values, confirming the soft degree of freedom of the (C=O)-C bond observed for the C1 conformer of shorter methyl alkynoates like methyl butyrate and methyl valerate. Comparison of the barriers to methyl internal rotation of methyl hexanoate to those of other CH3-O-(C=O)-R molecules leads to the conclusion that though the barrier height is relatively constant at about 420 cm-1, it decreases in molecules with longer R.

Spectroscopic Characterization of 3-Aminoisoxazole, a Prebiotic Precursor of Ribonucleotides.

The processes and reactions that led to the formation of the first biomolecules on Earth play a key role in the highly debated theme of the origin of life. Whether the first chemical building blocks were generated on Earth (endogenous synthesis) or brought from space (exogenous delivery) is still unanswered. The detection of complex organic molecules in the interstellar medium provides valuable support to the latter hypothesis. To gather more insight, here we provide the astronomers with accurate rotational frequencies to guide the interstellar search of 3-aminoisoxazole, which has been recently envisaged as a key reactive species in the scenario of the so-called RNA-world hypothesis. Relying on an accurate computational characterization, we were able to register and analyze the rotational spectrum of 3-aminoisoxazole in the 6-24 GHz and 80-320 GHz frequency ranges for the first time, exploiting a Fourier-transform microwave spectrometer and a frequency-modulated millimeter/sub-millimeter spectrometer, respectively. Due to the inversion motion of the -NH2 group, two states arise, and both of them were characterized, with more than 1300 lines being assigned. Although the fit statistics were affected by an evident Coriolis interaction, we were able to produce accurate line catalogs for astronomical observations of 3-aminoisoxazole.

Stacked but not Stuck: Unveiling the Role of π→π* Interactions with the Help of the Benzofuran-Formaldehyde Complex.

The 1:1 benzofuran-formaldehyde complex has been chosen as model system for analyzing π→π* interactions in supramolecular organizations involving heteroaromatic rings and carbonyl groups. A joint "rotational spectroscopy-quantum chemistry" strategy unveiled the dominant role of π→π* interactions in tuning the intermolecular interactions of such adduct. The exploration of the intermolecular potential energy surface led to the identification of 14 low-energy minima, with 4 stacked isomers being more stable than those linked by hydrogen bond or lone-pair→π interactions. All energy minima are separated by loose transition states, thus suggesting an effective relaxation to the global minimum under the experimental conditions. This expectation has been confirmed by the experimental detection of only one species, which was unambiguously assigned owing to the computation of accurate spectroscopic parameters and the characterization of 11 isotopologues. The large number of isotopic species opened the way to the determination of the first semi-experimental equilibrium structure for a molecular complex of such a dimension.

Determination of the "Privileged Structure" of 8-Hydroxyquinoline.

An accurate semi-experimental equilibrium structure of 8-hydroxyquinoline (8-HQ) has been determined combining experiment and theory. The cm-wave rotational spectrum of 8-HQ was recorded in a pulsed supersonic jet using broadband dual-path reflection and narrowband Fabry-Perot-type resonator Fourier-transform microwave spectrometers. Accurate rotational and quartic centrifugal distortion constants and 14 N quadrupole coupling constants are determined. Rotational constants of all 13 C, 18 O and 15 N singly substituted isotopologues in natural abundance and those of a chemically synthesized OD isotopologue were used to obtain geometric parameters for all the heavy atoms and the hydroxyl hydrogen from a number of structure determination models. Theoretical approaches allowed for the determination of a semi-experimental equilibrium structure, reSE in which computed rovibrational and electronic corrections were utilized to convert vibrational ground state constants into equilibrium constants. Despite the molecule having only a horizontal plane of symmetry and possessing 11 individual heavy atoms, microwave spectroscopy has allowed for a reliable and accurate structure determination. A mass dependent, rm2 structure was determined and proved to be equally reliable by comparison with the B3LYP-D3(BJ)/aVTZ equilibrium structure.

Van der Waals interactions of the disulfide bond revealed: A microwave spectroscopic study of the diethyl disulfide-argon complex.

The van der Waals complex formed between diethyl disulfide (DEDS) and an argon atom was investigated by pulsed-jet Fourier transform microwave spectroscopy in conjunction with quantum chemical computations. One set of transition lines belonging to the configuration of the global potential energy minimum was measured and assigned. The rotational constants A, B, and C were accurately determined to be 1262.5758(1) MHz, 845.402 12(9) MHz, and 574.006 38(8) MHz, respectively. The distance between the argon atom and the center of mass of the DEDS subunit is 4.075(16) Å. Quantum theory of atoms in molecules and non-covalent interaction analyses reveal that the interactions take place between the argon atom and four sites of the DEDS subunit. Furthermore, the usage of the energy decomposition analysis approach provides further understanding of the characteristics of the van der Waals interactions. Additionally, ab initio calculations and symmetry-adapted perturbation theory analysis of the binary complexes of DEDS with He, Ne, Kr, and Xe atoms were carried out to get further insight into the characteristics of the van der Waal interactions of the disulfide bond.

The Characteristics of Disulfide-Centered Hydrogen Bonds.

The disulfide-centered hydrogen bonds in the three different model systems of diethyl disulfide⋅⋅⋅H2 O/H2 CO/HCONH2 clusters were characterized by high-resolution Fourier transform microwave spectroscopy and quantum chemical computations. The global minimum energy structures for each cluster are experimentally observed and are characterized by one of the three different S-S⋅⋅⋅H-C/N/O disulfide-centered hydrogen bonds and two O⋅⋅⋅H-C hydrogen bonds. Non-covalent interaction and natural bond orbital analyses further confirm the experimental observations. The symmetry-adapted perturbation theory (SAPT) analysis reveals that electrostatic is dominant in diethyl disulfide⋅⋅⋅H2 O/HCONH2 clusters being consistent with normal hydrogen bonds, whilst dispersion takes over in diethyl disulfide⋅⋅⋅H2 CO cluster. Our study gives accurate structural parameters for the disulfide bond involved non-covalent clusters providing important benchmarking data for the theoretical evaluation of more complex systems.

A Journey from Thermally Tunable Synthesis to Spectroscopy of Phenylmethanimine in Gas Phase and Solution.

Phenylmethanimine is an aromatic imine with a twofold relevance in chemistry: organic synthesis and astrochemistry. To tackle both aspects, a multidisciplinary strategy has been exploited and a new, easily accessible synthetic approach to generate stable imine-intermediates in the gas phase and in solution has been introduced. The combination of this formation pathway, based on the thermal decomposition of hydrobenzamide, with a state-of-the-art computational characterization of phenylmethanimine laid the foundation for its first laboratory observation by means of rotational electric resonance spectroscopy. Both E and Z isomers have been accurately characterized, thus providing a reliable basis to guide future astronomical observations. A further characterization has been carried out by nuclear magnetic resonance spectroscopy, showing the feasibility of this synthetic approach in solution. The temperature dependence as well as possible mechanisms of the thermolysis process have been examined.

The Scent of Maibowle - π Electron Localization in Coumarin from Its Microwave-Determined Structure.

The microwave spectra of the natural substance coumarin, a planar aromatic molecule with the specific scent of maibowle, a popular fruit punch served in spring and early summer, were recorded using a molecular jet Fourier transform microwave spectrometer working in the frequency range from 4.0 to 26.5 GHz. The rotational constants and centrifugal distortion constants were determined with high precision, reproducing the spectra to experimental accuracy. The spectra of all singly-substituted 13 C and 18 O isotopologues were observed in their natural abundances to determine the experimental heavy atom substitution rs and semi-experimental equilibrium reSE structures. The experimental bond lengths and bond angles were compared to those obtained from quantum chemical calculations and those of related molecules reported in the literature with benzene as the prototype. The alternation of the C-C bond lengths to the value of 1.39 Šfound for benzene reflects the localization of π electrons in coumarin, where the benzene ring and the lactone-like chain -CH=CH-(C=O)-O- are fused. The large, negative inertial defect of coumarin is consistent with out-of-plane vibrations of the fused rings.

XeOCS: relatively straightforward?

We report a benchmark-quality equilibrium-like structure of the XeOCS complex, obtained from microwave spectroscopy. The experiments are supported by a wide array of highly accurate calculations, expanding the analysis to the complexes of He, Ne, Ar, Kr, Xe, and Hg with OCS. We investigate the trends in the structures and binding energies of the complexes. The assumption that the structure of the monomers does not change significantly upon forming a weakly bound complex is also tested. An attempt at reproducing the r structure of the XeOCS complex with correlated wavefunction theory is made, highlighting the importance of relativistic effects, large basis sets, and inclusion of diffuse functions in extrapolation recipes.

Reactivity and rotational spectra: the old concept of substitution effects.

The internal rotation of methyl groups and nuclear quadrupole moments of the halogens Cl, Br, I in o-halotoluenes cause complex spectral fine and hyperfine structures in rotational spectra arising from angular momentum coupling. Building on the existing data regarding o-fluorotoluene and o-chlorotoluene, the investigations of o-bromotoluene and o-iodotoluene allow for a complete analysis of the homologous series of o-halogenated toluenes. The trend in the methyl barriers to internal rotation rising with the size of the halogen can be rationalised by repulsion effects as predicted by MP2 calculations. Furthermore, the analysis of the observed quadrupole coupling serves as a quantitative intra-molecular probe, e.g. for the explanation of the relative reaction yields in the nitration of halotoluenes, related to the different π-bond character of the C-X bond depending on the position of substitution.

The puzzling hyper-fine structure and an accurate equilibrium geometry of succinic anhydride.

An accurate semiexperimental equilibrium structure of succinic anhydride has been determined from a combination of experiment and theory. The cm-wave and mm-wave rotational spectra of succinic anhydride, 3,4-dihydrofuran-2,5-dione, were recorded in a pulsed supersonic jet using Fourier-transform microwave spectroscopy and in a free-jet using mm-wave absorption spectroscopy. Many lines in the cm-wave spectrum show fine structure and after eliminating all other possibilities the origin of this fine structure is determined to be from spin-spin interaction. Accurate rotational and quartic centrifugal distortion constants are determined. Assignments of 13C and 18O singly substituted isotopologues in natural abundance were used to obtain a substitution geometry for the heavy atoms of succinic anhydride. Theoretical approaches permitted the calculation of a Born-Oppenheimer ab initio structure and the determination of a semiexperimental equilibrium structure in which computed rovibrational corrections were utilized to convert vibrational ground state rotational constants into equilibrium constants. The agreement between the semiexperimental structure and the Born-Oppenheimer ab initio structure is excellent. Succinic anhydride has been shown to have a planar heavy atom equilibrium structure with the effects of a large amplitude vibration apparent in the resultant rotational constants.

Conformational preference determined by inequivalent n-pairs: rotational studies on acetophenone and its monohydrate.

Acetophenone and its complex with water have been investigated by using pulsed jet Fourier transform microwave spectroscopy complemented with quantum chemical calculations. Rotational spectra of the acetophenone monomer comprising nine isotopologues were measured and assigned, enabling the accurate structural description of the carbon skeleton. The most stable isomer of the monohydrate of acetophenone was detected in the supersonic jet expansion. Water serves as a proton donor and acceptor forming an O-HO[double bond, length as m-dash]C hydrogen bond and a secondary C-HO-H weak hydrogen bond with acetophenone through a six-membered ring. The water molecule lies almost in the plane of the aromatic ring. Bader's quantum theory of atoms in molecules, Johnson's non-covalent interaction, electron localization function and natural bond orbital analyses were applied to characterize the nature of the non-covalent interactions in the target complex. All rotational transitions are split into two components arising from the hindered methyl internal rotation. Upon the complexation, the V3 barrier to internal rotation of -CH3 slightly decreases, with 7.50(3) kJ mol-1 for the monomer, and 7.04(5) kJ mol-1 for the acetophenone-H2O dimer, respectively.

Chalcogen bond and internal dynamics of the 2,2,4,4-tetrafluoro-1,3-dithietanewater complex.

The rotational spectrum of the 2,2,4,4-tetrafluoro-1,3-dithietanewater complex has been investigated by high resolution rotational spectroscopy. Experimental evidence and quantum theoretical analyses revealed that the two moieties are linked together through a dominant SO chalcogen bond. Two secondary FO interactions contribute to the stability of the complex. The rotational transitions of four isotopologues are split into two component lines due to the internal rotation of the water moiety around its C2 axis. In the HDO isotopologue, a small µc dipole moment component is generated which inverts upon internal rotation of water, allowing the experimental determination of the tunneling splitting (21.46(5) GHz). Such splitting can be reproduced with a one-dimensional flexible model when the barrier to internal rotation of water is 87.4(2) cm-1.

Tetrel bonds and conformational equilibria in the formamide-CO2 complex: a rotational study.

The rotational spectra of the complex formamide-CO2 have been measured and assigned by pulsed jet Fourier transform microwave spectroscopy. Two isomers of the complex have been detected where a CO tetrel bond dominates the interactions, and either N-HO or C-HO forms a secondary linkage. Bader's quantum theory of atoms in molecules and Johnson's non-covalent interaction analyses were applied to unveil the intermolecular binding sites and energetic properties in the complex. Relative intensity measurements on a set of µa-type transitions allowed estimating the relative population of the observed two isomers as NI/NII ≈ 18/1.

Molecular structure and non-covalent interaction of 2-thiophenecarboxaldehyde and its monohydrated complex.

The rotational spectrum of 2-thiophenecarboxaldehyde was investigated by using supersonic jet Fourier transform microwave spectroscopy. The measurements were extended to the 34S, 33S, 13C, and 18O isotopologs for the cis conformer, as well as to the 34S and 13C isotopologs for the trans conformer, leading to an accurately structural determination of the two observed conformers. The unchanged experimental Pcc values upon isotopic substitution indicate effective planar geometries of the two conformers. The ring structures of thiophene are slightly different between the cis and trans conformers. Two isomers of the monohydrated complex of 2-thiophenecarboxaldehyde, formed between a cis or trans monomer with water stabilized by an O-H⋯O hydrogen bond (HB) and an additional (C=O)CH⋯O(H2O) or (Cring)CH⋯O(H2O) HB, respectively, were observed in jet expansion. The noncovalent interactions attributed to the stabilization of the monomer and the monohydrated complex are revealed by quantum chemical methods. The interaction energy for trans-w-1 is 4 kJ mol-1 larger than that of cis-w-1, attributed to the relative stronger CH⋯O HB. The relative abundance of the two conformers of the 2-thiophenecarboxaldehyde monomer and the two isomers of the complex was estimated in the jet.

The Unexplored World of Cycloalkene-Water Complexes: Primary and Assisting Interactions Unraveled by Experimental and Computational Spectroscopy.

The intermolecular interactions in cycloalkene-water adducts were computationally characterized, thus demonstrating that the primary O-H⋅⋅⋅πC=C hydrogen bond is dominated by the electrostatic interaction. A deeper investigation by means of a joint rotational spectroscopy/state-of-the-art quantum chemistry approach also led to the determination of an accurate semi-experimental equilibrium structure for the cyclopentene adduct.