Hydrogen‐Bond Cooperativity in Formamide2–Water: A Model for Water‐Mediated Interactions

The rotational spectrum of formamide₂–H₂O formed in a supersonic jet has been characterized by Fourier‐transform microwave spectroscopy. This adduct provides a simple model of water‐mediated interaction involving the amide linkages, as occur in protein folding or amide‐association processes, showing the interplay between self‐association and solvation. Mono‐substituted ¹³C, ¹⁵N, ¹⁸O, and ²H isotopologues have been observed and their data used to investigate the structure. The adduct forms an almost planar three‐body sequential cycle. The two formamide molecules link on one side through an N?H???O hydrogen bond and on the other side through a water‐mediated interaction with the formation of C=O???H?O and O???H?N hydrogen bonds. The analysis of the quadrupole coupling effects of two ¹⁴N‐nuclei reveals the subtle inductive forces associated to cooperative hydrogen bonding. These forces are involved in the changes in the C=O and C?N bond lengths with respect to pure formamide.     

OH⋅⋅⋅N and CH⋅⋅⋅O Hydrogen Bonds Control Hydration of Pivotal Tropane Alkaloids: Tropinone⋅⋅⋅H2O Complex

The effect of monohydration in equatorial/axial isomerism of the common motif of tropane alkaloids is investigated in a supersonic expansion by using Fourier‐transform microwave spectroscopy. The rotational spectrum reveals the equatorial isomer as the dominant species in the tropinone???H₂O complex. The monohydrated complex is stabilized primarily by a moderate O?H???N hydrogen bond. In addition, two C?H???O weak hydrogen bonds also support this structure, blocking the water molecule and avoiding any molecular dynamics in the complex. The water molecule acts as proton donor and chooses the ternary amine group over the carbonyl group as a proton acceptor. The experimental work is supported by theoretical calculations; the accuracy of the B3LYP, M06‐2X, and MP2 methods is also discussed.     

Torsional and Electronic Factors Control the C−H⋅⋅⋅O Interaction

The precise role of non‐conventional hydrogen bonds such as the C?H???O interaction in influencing the conformation of small molecules remains unresolved. Here we survey a series of β‐turn mimetics using X‐ray crystallography and NMR spectroscopy in conjunction with quantum calculation, and conclude that favourable torsional and electronic effects are important for the population of states with conformationally influential C?H???O interactions. Our results also highlight the challenge in attempting to deconvolute a myriad of interdependent noncovalent interactions in order to focus on the contribution of a single one. Within a small molecule that is designed to resemble the complexity of the environment within peptides and proteins, the interplay of different steric burdens, hydrogen‐acceptor/‐donor properties and rotational profiles illustrate why unambiguous conclusions based solely on NMR chemical shift data are extremely challenging to rationalize.     

Self‐Complementary Dimers of Oxalamide‐Functionalized Resorcinarene Tetrabenzoxazines

Self‐complementarity is a useful concept in supramolecular chemistry, molecular biology and polymeric systems. Two resorcinarene tetrabenzoxazines decorated with four oxalamide groups were synthesized and characterized. The oxalamide groups possessed self‐complementary hydrogen bonding sites between the carbonyls and amide groups. The self‐complementary nature of the oxalamide groups resulted in self‐included dimeric assemblies. The hydrogen bonding interactions within the tetrabenzoxazines gave rise to the formation of dimers, which were confirmed by single‐crystal X‐ray diffractions analysis and supported by NMR spectroscopy and mass spectrometry. The self‐included dimers were connected by numerous and strong intermolecular N?H???O and C?H???O hydrogen bonds supplemented with C?H???π interactions, forming one‐dimensional polymers, which were then further linked into three‐dimensional networks.     

The Intermolecular S?H⋅⋅⋅Y (Y=S,O) Hydrogen Bond in the H2S Dimer and the H2S–MeOH Complex

The nature of the S? H???S hydrogen‐bonding interaction in the H₂S dimer and its structure has been the focus of several theoretical studies. This is partly due to its structural similarity and close relationship with the well‐studied water dimer and partly because it represents the simplest prototypical example of hydrogen bonding involving a sulfur atom. Although there is some IR data on the H₂S dimer and higher homomers from cold matrix experiments, there are no IR spectroscopic reports on S? H???S hydrogen bonding in the gas phase to‐date. We present experimental evidence using VUV ionization‐detected IR‐predissociation spectroscopy (VUV‐ID‐IRPDS) for this weak hydrogen‐bonding interaction in the H₂S dimer. The proton‐donating S? H bond is found to be red‐shifted by 31 cm^?1. We were also able to observe and assign the symmetric (ν₁) stretch of the acceptor and an unresolved feature owing to the free S? H of the donor and the antisymmetric (ν₃) SH stretch of the acceptor. In addition we show that the heteromolecular H₂S–MeOH complex, for which both S? H???O and O? H???S interactions are possible, is S‐H???O bound.     

Pairing of Isolated Nucleobases: Double Resonance Laser Spectroscopy of Adenine–Thymine

The vibronic spectrum of the adenine–thymine (A–T) base pair was obtained by one‐color resonant two‐photon ionization (R2PI) spectroscopy in a free jet of thermally evaporated A and T under conditions favorable for formation of small clusters. The onset of the spectrum at 35 064 cm^?1 exhibits a large red shift relative to the π–π* origin of 9H‐adenine at 36 105 cm^?1. The IR–UV spectrum was assigned to cluster structures with HNH???O?C/N???HN hydrogen bonding by comparison with the IR spectra of A and T monomers and with ab initio calculated vibrational spectra of the most stable A–T isomers. The Watson–Crick A–T base pair is not the most stable base‐pair structure at different levels of ab initio theory, and its vibrational spectrum is not in agreement with the observed experimental spectrum. Experiments with methylated A and T were performed to further support the structural assignment.     

Hydrogen‐Bond Dynamics of C?H⋅⋅⋅O Interactions: The Chloroform⋅⋅⋅Acetone Case

Spectroscopic evidence for C? H ??? O hydrogen bonding in chloroform ??? acetone [Cl₃CH ??? O?C(CH₃)₂] mixtures was obtained from vibrational inelastic neutron scattering (INS) spectra. Comparison between the INS spectra of pure samples and their binary mixtures reveals the presence of new bands at about 82, 130 and 170 cm^?1. Assignment of the 82 cm^?1 band to the νO ??? H anti‐translational mode is considered and discussed. In addition, the βC? H mode of CHCl₃ at 1242 cm^?1 is split in the spectra of the mixtures, and the high‐wavenumber component is assigned to the hydrogen‐bonded complex. The plot of the integrated intensity of this component shows a maximum for x=0.5, in agreement with the 1:1 stoichiometry of the chloroform ??? acetone complex, with a calculated complexation constant of 0.15 dm³ mol^?1. Results also show that the complex behaves as an independent entity, that is, despite being weak, such interactions play a key role in supramolecular chemistry.     

How Water Interacts with Halogenated Anesthetics: The Rotational Spectrum of Isoflurane–Water

The rotational spectra of several isotopologues of the 1:1 complex between the inhaled anesthetic isoflurane and water have been recorded and analyzed by using Fourier transform microwave spectroscopy. The rotational spectrum showed a single rotamer, corresponding to the configuration in which the most stable conformer of isolated isoflurane is linked to the water molecule through an almost linear C?H???O weak hydrogen bond. All transitions display a hyperfine structure due to the ³⁵Cl (or ³⁷Cl) nuclear quadrupole effects.     

Solid‐State Form Screen of Cardiosulfa and Its Analogues

Cardiosulfa is a biologically active sulfonamide molecule that was recently shown to induce abnormal heart development in zebrafish embryos through activation of the aryl hydrocarbon receptor (AhR). The present report is a systematic study of solid‐state forms of cardiosulfa and its biologically active analogues that belong to the N‐(9‐ethyl‐9H‐carbazol‐3‐yl)benzene sulfonamide skeleton. Cardiosulfa (molecule 1 ; R¹=NO₂, R²=H, R³=CF₃), molecule 2 (H, H, CF₃), molecule 3 (CF₃, H, H), molecule 4 (NO₂, H, H), molecule 5 (H, CF₃, H), and molecule 6 (H, H, H) were synthesized and subjected to a polymorph search and solid‐state form characterization by X‐ray diffraction, differential scanning calorimetry (DSC), variable‐temperature powder X‐ray diffraction (VT‐PXRD), FTIR, and solid‐state (ss) NMR spectroscopy. Molecule 1 was obtained in a single‐crystalline modification that is sustained by N? H???π and C? H???O interactions but devoid of strong intermolecular N? H???O hydrogen bonds. Molecule 2 displayed a N? H???O catemer C(4) chain in form I, whereas a second polymorph was characterized by PXRD. The dimorphs of molecule 3 contain N? H???π and C? H???O interactions but no N? H???O bonds. Molecule 4 is trimorphic with N? H???O catemer in form I, and N? H???π and C? H???O interactions in form II, and a third polymorph was characterized by PXRD. Both polymorphs of molecule 5 contain the N? H???O catemer C(4) chain, whereas the sulfonamide N? H???O dimer synthon R₂²(8) was observed in polymorphs of 6 . Differences in the strong and weak hydrogen‐bond motifs were correlated with the substituent groups, and the solubility and dissolution rates were correlated with the conformation in the crystal structure of 1 , 2 , 3 , 4 , 5 , 6 . Higher solubility compounds, such as 2 (10.5 mg mL^?1) and 5 (4.4 mg mL^?1), adopt a twisted confirmation, whereas less‐soluble 1 (0.9 mg mL^?1) is nearly planar. This study provides practical guides for functional‐group modification of drug lead compounds for solubility optimization.     

Structure of Amido Pyridinium Betaines: Persistent Intermolecular C−H⋅⋅⋅N Hydrogen Bonding in Solution

A hydrogen bond of the type C?H???X (X=O or N) is known to influence the structure and function of chemical and biological systems in solution. C?H???O hydrogen bonding in solution has been extensively studied, both experimentally and computationally, whereas the equivalent thermodynamic parameters have not been enumerated experimentally for C?H???N hydrogen bonds. This is, in part, due to the lack of systems that exhibit persistent C?H???N hydrogen bonds in solution. Herein, a class of molecule based on a biologically active norharman motif that exhibits unsupported intermolecular C?H???N hydrogen bonds in solution has been described. A pairwise interaction leads to dimerisation to give bond strengths of about 7 kJ mol^?1 per hydrogen bond, which is similar to chemically and biologically relevant C?H???O hydrogen bonding. The experimental data is supported by computational work, which provides additional insight into the hydrogen bonding by consideration of electrostatic and orbital interactions and allowed a comparison between calculated and extrapolated NMR chemical shifts.     

A Combined Experimental and Theoretical Electron Density Study of Intra‐ and Intermolecular Interactions in Thiourea S,S‐Dioxide

The thiourea S,S‐dioxide molecule is recognized as a zwitterion with a high dipole moment and an unusually long C? S bond. The molecule has a most interesting set of intermolecular interactions in the crystalline state—a relatively strong O???H? N hydrogen bond and very weak intermolecular C???S and N???O interactions. The molecule has C_s symmetry, and each oxygen atom is hydrogen‐bonded to two hydrogen atoms with O???H? N distances of 2.837 and 2.826 Å and angles of 176.61 and 158.38°. The electron density distribution is obtained both from Xray diffraction data at 110 K and from a periodic density functional theory (DFT) calculation. Bond characterization is made in terms of the analysis of topological properties. The covalent characters of the C? N, N? H, C? S, and S? O bonds are apparent, and the agreement on the topological properties between experiment and theory is adequate. The features of the Laplacian distributions, bond paths, and atomic domains are comparable. In a systematic approach, DFT calculations are performed based on a monomer, a dimer, a heptamer, and a crystal to see the effect on the electron density distribution due to the intermolecular interactions. The dipole moment of the molecule is enhanced in the solid state. The typical values of ρ_b and H_b of the hydrogen bonds and weak intermolecular C???S and N???O interactions are given. All the interactions are verified by the location of the bond critical point and its associated topological properties. The isovalue surface of Laplacian charge density and the detailed atomic graph around each atomic site reveal the shape of the valence‐shell charge concentration and provide a reasonable interpretation of the bonding of each atom.     

Desmotropy, polymorphism, and solid-state proton transfer: four solid forms of an aromatic o-hydroxy Schiff base

The Schiff base derived from salicylaldehyde and 2-amino-3-hydroxypyridine affords a diversity of solid forms, two polymorphic pairs of the enol-imino (D1?a and D1?b) and keto-amino (D2?a and D2?b) desmotropes. The isolated phases, identified by IR spectroscopy, X-ray crystallography, and (13)C cross-polarization/magnetic angle spinning (CP/MAS) NMR spectroscopy, display essentially planar molecular conformations characterized by strong intramolecular hydrogen bonds of the O-H???N (D1) or N-H???O (D2) type. A change in the position of the proton within this O???H???N system is accompanied by substantially different molecular conformations and, subsequently, by divergent supramolecular architectures. The appearance and interconversion conditions for each of the four phases have been established on the basis of a number of solution and solvent-free experiments, and evaluated against the results of computational studies. Solid phases readily convert into the most stable form (D1?a) upon exposure to methanol vapor, heating, or by mechanical treatment, and these transformations are accompanied by a change in the color of the sample. The course of thermally induced transformations has been monitored in detail by means of temperature-resolved powder X-ray diffraction and infrared spectroscopy. Upon dissolution, all forms equilibrate immediately, as confirmed by NMR and UV/Vis spectroscopy in several solvents, with the equilibrium shifted far towards the enol tautomer. This study reveals the significance of peripheral groups in the stabilization of metastable tautomers in the solid state.     

CsTe2O(6-x): novel mixed-valence tellurium oxides with framework-deficient pyrochlore-related structure

Structures of CsTe?O(6-x) phases were investigated by single-crystal X-ray diffraction and neutron powder diffraction. Stoichiometric CsTe?O? is a mixed-valence Cs?Te??Te???O?? compound with a rhombohedral pyrochlore-type structure where there is complete order of Te?? and Te??. On heating, this compound develops significant electrical conductivity. As CsTe?O? becomes oxygen deficient above 600 °C, the rhombohedral pyrochlore-type structure is replaced by a cubic pyrochlore-type structure with disordered Te??/Te?? and oxygen vacancies. However, for CsTe?O(6-x) phases prepared at 500 °C, the observed pyrochlore-type structure has symmetry. The Te?? and O vacancies are all on chains running along the b axis, and the maximum value of x observed is about 0.3. At still higher values of x a new compound was discovered with a structure related to that reported for Rb?Te???Te???O??.     

Synthetic and Structural Studies of 1,8‐Chalcogen Naphthalene Derivatives

Four novel 1,8‐disubstituted naphthalene derivatives 4 – 7 that contain chalcogen atoms occupying the peri positions have been prepared and fully characterised by using X‐ray crystallography, multinuclear NMR spectroscopy, IR spectroscopy and MS. Molecular distortion due to noncovalent substituent interactions was studied as a function of the bulk of the interacting chalcogen atoms and the size and nature of the alkyl group attached to them. X‐ray data for 4 – 7 was compared to the series of known 1,8‐bis(phenylchalcogeno)naphthalenes 1 – 3 , which were themselves prepared from novel synthetic routes. A general increase in the E???E′ distance was observed for molecules containing bulkier atoms at the peri positions. The decreased S???S distance from phenyl‐ 1 and ethyl‐ 4 analogues is ascribed to a weaker chalcogen lone pair–lone pair repulsion acting in the ethyl analogue due to the presence of two equatorial S(naphthyl) ring conformations. Two novel peri‐substituted naphthalene sulfoxides of 1 , Nap(O?SPh)(SPh) 8 and Nap(O?SPh)₂ 9 , which contain different valence states of sulfur, were prepared and fully characterised by using X‐ray crystallography and multinuclear NMR spectroscopy, IR spectroscopy and MS. Molecular structures were analysed by using naphthalene ring torsions, peri‐atom displacement, splay angle magnitude, S???S interactions, aromatic ring orientations and quasi‐linear O?S???S arrangements. The axial S(naphthyl) rings in 8 and 9 are unfavourable for S???S contacts due to stronger chalcogen lone pair–lone pair repulsion. Although quasi‐linear O?S???S alignments suggest attractive interaction is conceivable, analysis of the B3LYP wavefunctions affords no evidence for direct bonding interactions between the S atoms.     

Desmotropy,Polymorphism, and Solid‐State Proton Transfer: Four Solid Forms of an Aromatic o‐Hydroxy Schiff Base

The Schiff base derived from salicylaldehyde and 2‐amino‐3‐hydroxypyridine affords a diversity of solid forms, two polymorphic pairs of the enol‐imino ( D1 a and D1 b ) and keto‐amino ( D2 a and D2 b ) desmotropes. The isolated phases, identified by IR spectroscopy, X‐ray crystallography, and ¹³C cross‐polarization/magnetic angle spinning (CP/MAS) NMR spectroscopy, display essentially planar molecular conformations characterized by strong intramolecular hydrogen bonds of the O? H???N ( D1 ) or N? H???O ( D2 ) type. A change in the position of the proton within this O???H???N system is accompanied by substantially different molecular conformations and, subsequently, by divergent supramolecular architectures. The appearance and interconversion conditions for each of the four phases have been established on the basis of a number of solution and solvent‐free experiments, and evaluated against the results of computational studies. Solid phases readily convert into the most stable form ( D1 a ) upon exposure to methanol vapor, heating, or by mechanical treatment, and these transformations are accompanied by a change in the color of the sample. The course of thermally induced transformations has been monitored in detail by means of temperature‐resolved powder X‐ray diffraction and infrared spectroscopy. Upon dissolution, all forms equilibrate immediately, as confirmed by NMR and UV/Vis spectroscopy in several solvents, with the equilibrium shifted far towards the enol tautomer. This study reveals the significance of peripheral groups in the stabilization of metastable tautomers in the solid state.     

Sol–gel template synthesis and characterization of VO2 nanotube arrays

In this paper, we report on the obtention of highly ordered VO₂ nanotube arrays synthesized by the simple sol?Cgel template method. Techniques of transmission electron microscopy, X-ray powder diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy were used to characterize the morphology and structure of the as-synthesized nanotube arrays. It is found that the size of the as-obtained nanotubes has the dimension of 180?C220?nm in outer diameter, 110?C140?nm in inner diameter and up to 10???m in length. The results show that as-synthesized sample is assigned to VO₂ (B) phase in expected V/O ratio with V existing in the +4 oxidation state.     

Intramolecular Hydrogen Bonds in Low‐Molecular‐Weight Polyethylene Glycol

We used static DFT calculations to analyze, in detail, the intramolecular hydrogen bonds formed in low‐molecular‐weight polyethylene glycol (PEG) with two to five repeat subunits. Both red‐shifted O?H???O and blue‐shifting C?H???O hydrogen bonds, which control the structural flexibility of PEG, were detected. To estimate the strength of these hydrogen bonds, the quantum theory of atoms in molecules was used. Car–Parrinello molecular dynamics simulations were used to mimic the structural rearrangements and hydrogen‐bond breaking/formation in the PEG molecule at 300 K. The time evolution of the H???O bond length and valence angles of the formed hydrogen bonds were fully analyzed. The characteristic hydrogen‐bonding patterns of low‐molecular‐weight PEG were described with an estimation of their lifetime. The theoretical results obtained, in particular the presence of weak C?H???O hydrogen bonds, could serve as an explanation of the PEG structural stability in the experimental investigation.     

The Structure of N1‐Hydroxylophine N3‐Oxide (=1‐Hydroxy‐2,4,5‐ triphenyl‐1H‐imidazole 3‐Oxide) in the Solid State

The crystal structure of 1‐hydroxy‐2,4,5‐triphenyl‐1H‐imidazole 3‐oxide ( 1 ) has been determined from laboratory X‐ray powder‐diffraction data. The two independent molecules in the asymmetric unit form chains via O? H???O hydrogen bonds related by a twofold screw axis. One of the O???O distances is extremely short (2.32(1) and 2.43(1) Å). Solid‐state NMR spectroscopy (CPMAS) combined with calculation of absolute shieldings (GIAO/B3LYP/6‐31G*) allowed us to determine that the compound behaves as if the O? H???O hydrogen bond has the proton in the middle (single‐well potential), resulting in the near identity of both ¹⁵N‐NMR signals.     

Stereochemistry of Molecular Figures-of-Eight

A trans isomer of a figure-of-eight (Fo8) compound was prepared from an electron-withdrawing cyclobis(paraquat-p-phenylene) derivative carrying trans-disposed azide functions between its two phenylene rings. Copper(I)-catalyzed azide-alkyne cycloadditions with a bispropargyl derivative of a polyether chain, interrupted in its midriff by an electron-donating 1,5-dioxynaphthalene unit acting as the template to organize the reactants prior to the onset of two click reactions, afforded the Fo8 compound with C(i) symmetry. Exactly the same chemistry is performed on the cis-bisazide of the tetracationic cyclophane to give a Fo8 compound with C(2) symmetry. Both of these Fo8 compounds exist as major and very minor conformational isomers in solution. The major conformation in the trans series, which has been characterized by X-ray crystallography, adopts a geometry which maximizes its C?H???O interactions, while maintaining its π???π stacking and C?H???π interactions. Ab initio calculations at the M06L level support the conformational assignments to the major and minor isomers in the trans series. Dynamic (1) H?NMR spectroscopy, supported by 2D (1) H?NMR experiments, indicates that the major and minor isomers in both the cis and trans series equilibrate in solution on the (1) H?NMR timescale rapidly above and slowly below room temperature.     

Molecular Self‐Recognition: Rotational Spectra of the Dimeric 2‐Fluoroethanol Conformers

Fluoroalcohols show competitive formation of intra‐ and intermolecular hydrogen bonds, a property that may be crucial for the protein‐altering process in a fluoroalcohol/water solution. In this study, we examine the intra‐ and intermolecular interactions of 2‐fluoroethanol (FE) in its dimeric conformers by using rotational spectroscopy and ab initio calculations. Three pairs of homo‐ and heterochiral dimeric FE conformers are predicted to be local minima at the MP2/6‐311++G(d,p) level of theory. They are solely made of the slightly distorted most stable G+g?/G?g+ FE monomer units. Jet‐cooled rotational spectra of four out of the six predicted dimeric conformers were observed and unambiguously assigned for the first time. All four observed dimeric conformers have compact geometries in which the fluoromethyl group of the acceptor tilts towards the donor and ensures a large contact area. Experimentally, the insertion of the O? H group of one FE subunit into the intramolecular O? H???F bond of the other was found to lead to a higher stabilisation than the pure association through an intermolecular O? H???O? H link. The hetero‐ and homochiral combinations were observed to be preferred in the inserted and the associated dimeric conformers, respectively. The experimental rotational constants and the stability ordering are compared with the ab initio calculations at the MP2 level with the 6‐311++G(d,p) and aug‐cc‐pVTZ basis sets. The effects of fluorination and the competing inter‐ and intramolecular hydrogen bonds on the stability of the dimeric FE conformers are discussed.