Unveiling the underappreciated: The bonding features of C-H⋯S-S interactions observed from rotational spectroscopy.

The C-H⋯S-S interactions are fundamentally important to understand the stability of biomacromolecules and their binding with small molecules, but they are still underappreciated. Herein, we characterized the C-H⋯S-S interactions in model molecular complexes. The rotational spectra of the complexes of diethyl disulfide with CH2CH2 and CH2CHF were measured and analyzed. All the detected structures are mainly stabilized by a C-H⋯S-S hydrogen bond, providing stabilization energies of 2.3-7.2 kJ mol-1. Incidental C-H⋯π or C-H⋯F interactions enhance the stabilization of the complexes. London dispersion, which accounts for 54%-68% of the total attractions, is the main driving force of stabilization. The provided bonding features of C-H⋯S-S are crucial for understanding the stabilizing role of this type of interaction in diverse processes such as supramolecular recognition, protein stability, and enzyme activity.

Noncovalent interactions of aromatic heterocycles: rotational spectroscopy and theoretical calculations of the thiazole-CF4 and thiazole-SF6 complexes.

The complexes of thiazole with CF4 and SF6 have been investigated by Fourier transform microwave spectroscopy and quantum chemical calculations. One rotational spectrum was observed for the thiazole-CF4 complex. Experiments and theoretical computations confirmed that the observed structure of thiazole-CF4 is primarily formed due to N⋯CCF4 interaction with the C atom of CF4 located in the plane of the thiazole ring. The rotational transitions of thiazole-CF4 exhibit A/E torsional splitting induced by the internal rotation of the -CF3 top. The potential barrier of the -CF3 internal rotation is 0.2411(1) kJ mol-1, consistent with the calculated value (∼0.3 kJ mol-1). For the thiazole-SF6 complex, one conformer with SF6 located above the thiazole ring is detected. The observed structure of thiazole-SF6 is mainly stabilized by van der Waals interactions. The energy decomposition analysis reveals that the electrostatics and dispersion are the dominant attractive contributions to the formation of thiazole-CF4 and thiazole-SF6 dimers, whereas the weight of the dispersion term becomes more significant in the thiazole-SF6 complex compared to that of the thiazole-CF4 complex.

Strategy of Choosing Templates in Molecular Imprinting to Expand the Recognition Width for Family-Selectivity.

The class-selective molecular-imprinted polymers (MIPs) have shown the recognition ability to multiple targeted molecules through using one or multiple templates. However, choosing the right templates, the core problem, still lacks a systemic guide and decision-making. In this work, we propose a strategy of selecting templates through expanding the recognition width for the improvement of class-selectivity. First, three families of genotoxic impurity (GTI) were selected as model objects, and the spatial size and binding energy of each GTI-monomer complexes were obtained and compared by computational simulation. The two indexes of energy width (WE) and size width (WL) were introduced to compare the similarity and differences on the two recognition factors, binding strength and spatial size, among these GTIs in each family. Through shortening the width to increase similarity on binding energy and size, the dual templates in the aromatic amines (AI) family and sulfonic acid esters (SI) family were successfully selected. Correspondingly, the prepared dual-template MIPs in the two GTI families can simultaneously recognize all the GTIs comparing with that of single template MIP, respectively. Meanwhile, through comparing the adsorption capacity of the selected template and its analogues in one GTI family, the recognition efficiency of the dual-template MIPs was higher than that of the single-template MIP. This indicates that though using the selected right templates, the higher class-selectivity and the larger recognition width can be realized. Thus, this work can solve the problem of blind template selection, and provide the useful theoretical guidance for designing family-selective molecular imprinting.

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.

Conformations and non-covalent interactions of cyclohexyl isothiocyanate and its water complex.

The conformational equilibria of cyclohexyl isothiocyanate and its complex with water were studied by microwave spectroscopy combined with theoretical calculations. For the bare cyclohexyl isothiocyanate, the rotational spectra of the two conformers, namely a-trans and e-trans, were measured and analyzed. Additional mono-substituted isotopologues of two 13C and one 34S of a-trans and e-trans were also measured, which result in an accurate structural determination of the two conformers. For the binary complex with water, the rotational spectra were measured for the monohydrates of both a-trans and e-trans conformers. Water isotopologues were also detected for the monohydrates. All the measured rotational spectra show 14N quadrupole coupling hyperfine structures. Water molecule prefers linking to the isothiocyanate group through a OwH⋯S hydrogen bond and forming two CH⋯Ow hydrogen bonds with the oxygen atom of water acting as a proton acceptor. The non-covalent bonding features of the monohydrates were revealed by natural bond orbital analysis and symmetry-adapted perturbation theory analysis.

Cooperative hydrogen bonding in thiazole⋯(H2O)2 revealed by microwave spectroscopy.

Two isomers of a complex formed between thiazole and two water molecules, thi⋯(H2O)2, have been identified through Fourier transform microwave spectroscopy between 7.0 and 18.5 GHz. The complex was generated by the co-expansion of a gas sample containing trace amounts of thiazole and water in an inert buffer gas. For each isomer, rotational constants, A0, B0, and C0; centrifugal distortion constants, DJ, DJK, d1, and d2; and nuclear quadrupole coupling constants, χaa(N) and [χbb(N) - χcc(N)], have been determined through fitting of a rotational Hamiltonian to the frequencies of observed transitions. The molecular geometry, energy, and components of the dipole moment of each isomer have been calculated using Density Functional Theory (DFT). The experimental results for four isotopologues of isomer I allow for accurate determinations of atomic coordinates of oxygen atoms by r0 and rs methods. Isomer II has been assigned as the carrier of an observed spectrum on the basis of very good agreement between DFT-calculated results and a set of spectroscopic parameters (including A0, B0, and C0 rotational constants) determined by fitting to measured transition frequencies. Non-covalent interaction and natural bond orbital analyses reveal that two strong hydrogen bonding interactions are present within each of the identified isomers of thi⋯(H2O)2. The first of these binds H2O to the nitrogen of thiazole (OH⋯N), and the second binds the two water molecules (OH⋯O). A third, weaker interaction binds the H2O sub-unit to the hydrogen atom that is attached to C2 (for isomer I) or C4 (for isomer II) of the thiazole ring (CH⋯O).

Three non-bonding interaction topologies of the thiazole-formaldehyde complex observed by rotational spectroscopy.

When an aldehyde molecule interacts with a nitrogen atom inserted in an aromatic ring, they form a number of non-bonding topologies. We measured the rotational spectra of three different isomers of the thiazole-formaldehyde adduct. In all of them, formaldehyde interacts specifically with thiazole through an n → π* interaction (along the Bürgi-Dunitz trajectory) and a C-H⋯O (acting as a proton acceptor) weak hydrogen bond, or through C-H⋯N (acting as a proton donor) and C-H⋯O (acting as a proton acceptor) weak hydrogen bonds. The spectra of isotopic substituted species were also measured to draw the molecular structures. Two n → π* stabilized isomers show a vertical structure in which the two molecular planes are perpendicular to each other, and the hydrogen bonded isomers feature a co-planar architecture. The competition between these non-bonding interactions was unveiled from experiments and theoretical calculations.

Hydrogen bond interactions between thioethers and amides: A joint rotational spectroscopic and theoretical study of the formamide⋯dimethyl sulfide adduct.

The rotational spectrum of the binary adduct of formamide (HCONH2) with dimethyl sulfide (DMS) has been investigated employing cavity-based Fourier transform microwave spectroscopy combined with theoretical computations. Experimentally, only one isomer of the adduct was unambiguously observed and assigned according to the theoretically predicted spectroscopic parameters, and its rotational spectrum displays the hyperfine splittings associated with the 14N nuclear quadrupole coupling effect. The observed isomer exhibits Cs symmetry, such that the ∠CSC angle of the DMS subunit is bisected by the ab-plane of the HCONH2 moiety. The two moieties in the detected isomer are connected via one primary NH···S and two secondary CH···O hydrogen bonds. Quantum theory of atoms in molecules (QTAIM), non-covalent interaction (NCI), natural bond orbital (NBO) and symmetry-adapted perturbation theory (SAPT) approaches were utilized for characterizing the intermolecular interactions occurring in the titled adduct. Additionally, the adduct of HCONH2 with dimethyl ether (DME) was also theoretically investigated to compare the difference in structure and energy characteristics between the NH···S and NH···O hydrogen bonds.

Intermolecular amide and aldehyde interactions: rotational spectroscopy of the complexes of formaldehyde with 2-azetidinone and formamide.

The binary intermolecular complexes of amides and formaldehyde can be taken as suitable models to investigate the non-covalent interactions of a peptide with the carbonyl group. We herein studied the rotational spectra of the model complexes of 2-azetidinone-H2CO and formamide-H2CO generated in a helium supersonic jet. For each complex, one rotational spectra featuring hyperfine structures caused by the 14N quadrupole coupling effect was observed and assigned to its global minimum conformation. The detected isomers of both studied complexes are stabilized by a dominant amide hydrogen bond N-H⋯OC and a weaker C-H⋯O interaction, preferring the Cs symmetry. NBO and SAPT analyses provide quantitative estimation of the non-covalent interactions stabilizing the complexes.

Noncovalent Interactions between Aromatic Heterocycles and Carboxylic Acids: Rotational Spectroscopy of the Furan-Formic Acid and Thiophene-Formic Acid Complexes.

The binary molecular complexes formed between the aromatic heterocycles furan and thiophene with formic acid were investigated using pulsed-jet Fourier transform microwave spectroscopy and quantum chemical computations. For both of the complexes, rotational spectra of the lowest energy isomer were detected and assigned. Rotational spectroscopic results and density functional theory calculations support that the preferred conformation of the furan-formic acid complex is characterized by a relatively strong O-H···O and a weak C-H···O hydrogen bonds while the O-H···π and C-H···O hydrogen bonds stabilize the thiophene-formic acid complex. Natural bond orbital analysis further proves the experimental observation, suggesting that the strength of the O-H···O(furan) interaction is about two times stronger than that of O-H···π(thiophene). The symmetry adapted perturbation theory analysis reveals that electrostatic interaction is dominant in stabilizing the two complexes and that dispersion becomes significant in the thiophene-formic acid complex compared to furan-formic acid.

Conformations and structures of 1,4-pentadien-3-ol and its water complex characterized by rotational spectroscopy.

The 1,4-pentadien-3-ol and its monohydrate have been characterized by microwave spectroscopy in combination with theoretical computations. Experiments and ab initio calculations revealed that the 1,4-pentadien-3-ol monomer prefers a configuration with one vinyl being syn to the hydroxyl oxygen and the hydroxyl hydrogen toward the skew arranged vinyl, which therefore makes possible simultaneous CH···O and OH···π interactions. The observed monohydrate corresponds to the global minimum predicted theoretically, which is stabilized through a primary OH···Ow hydrogen bond together with a much weaker OwH···π hydrogen bond. The NCI analyses, NBO calculation and SAPT method were applied to further elucidate the characteristics of hydrogen bonds in the 1,4-pentadien-3-ol···water complex.

Structures and hydrogen bonding of 1,7-dioxaspiro[5.5]undecane and its hydrates.

The conformations of 1,7DSU and its stepwise solvation by up to 5 water molecules were explored using supersonic-jet Fourier transform microwave spectroscopy with the supplement of theoretical calculations. Experimentally, the rotational spectra of the most stable structures of the monomer, monohydrate and dihydrate were observed and assigned. The characteristics of the stability and intermolecular interaction topologies of the 1,7DSU monomer and its hydrated clusters were obtained by CREST conformational sampling followed by B3LYP-D3(BJ)/def2-TZVP geometrical optimizations and MP2/aug-cc-pVTZ single-point energy calculations. The first water molecule links to the 1,7DSU monomer through an OwH⋯O hydrogen bond. The water molecules tend to aggregate with each other and form cyclic structures for the n = 2-5 clusters. The interactions between water and the 1,7DSU monomer as well as those between water and water were revealed. The analyses of non-covalent interactions and the natural bond orbital suggest that the OwH⋯O1,7DSU, OwH⋯Ow, and CH⋯Ow hydrogen bonds play a prominent role in structural stability.

Unveiling the structural and energetic properties of thiazole-water complex by microwave spectroscopy and theoretical calculations.

The structure and non-covalent bonding features of the complex of thiazole and water were studied by using supersonic jet Fourier transform microwave spectroscopy and theoretical calculations. One isomer was observed which corresponds to the global minimum of the complex predicted theoretically. The rotational spectra of 9 additional isotopologues, including 5 mono-substituted heavy atoms of thiazole (34S, 13C and 15N), and 4 water isotopic species (H218O, DOH, HOD and D2O), were also measured and analyzed. The experimental spectroscopic parameters were used to determine the structural parameters of the observed isomer. Theoretical analyses based on quantum theory of atoms in molecules and natural bond orbital revealed that the two moieties are linked by a N···H-O hydrogen bond. The total interaction energy of the complex is calculated to be -25.1 kJmol-1 with electrostatics being the major term according to energy decomposition analysis.