OC Hydrogen Bonds Research Articles

A hydrazone-linked covalent organic framework with abundant N and O atoms for detecting heavy metal ions

The bioaccumulation of heavy metal ions (HMIs), even at low concentrations, will lead to high toxicity. So, in this work, a hydrazone-linked covalent organic framework (COF) with abundant N and O atoms was prepared for sensitive HMIs detection. Under the room temperature, terephthaloyl dihydrazide (TD) and triformylphloroglucinol (TP) reacted to form the hydrazone bond, and a new hydrazone-linked TP-TD COF was prepared. During the reaction, enole-keto tautomerism occurred, and NH···OC hydrogen bond was formed, which improved the crystallinity and chemical stability of COF. Accordingly, the hydrazone-linked TP-TD COF presented three-dimensional network morphology. The porous channels could promote the migration of HMIs, and the affinity of N and O atoms to HMI was utilized. There were abundant O·N·O sites in each unit, so the hydrazone-linked TP-TD COF was applied to the sensing of HMIs. The electrochemical sensor constructed by TP-TD COF was used to detect Cd2+, Pb2+, Cu2+ and Hg2+ simultaneously. Under optimized conditions, the electrochemical sensor based on TP-TD COF showed fast response speed, sensitive detection ability and the potential for practical sample detection.

Demarcating Noncovalent and Covalent Bond Territories: Imine-CO2 Complexes and Cooperative CO2 Capture.

Chemical bond territory is rich with covalently bonded molecules wherein a strong bond is formed by equal or unequal sharing of a quantum of electrons. The noncovalent version of the bonding scenarios expands the chemical bonding territory to a weak domain wherein the interplay of electrostatic and π-effects, dipole-dipole, dipole-induced dipole, and induced dipole-induced dipole interactions, and hydrophobic effects occur. Here we study both the covalent and noncovalent interactive behavior of cyclic and acyclic imine-based functional molecules (XN) with CO2. All parent XN systems preferred the formation of noncovalent (nc) complex XN···CO2, while more saturated such systems (XN') produced both nc and covalent (c) complexes XN'+-(CO2)-. In all such cases, crossover from an nc to c complex is clearly demarcated with the identification of a transition state (ts). The complexes XN'···CO2 and XN'+-(CO2)- are bond stretch isomers, and they define the weak and strong bonding territories, respectively, while the ts appears as the demarcation point of the two territories. Cluster formation of XN with CO2 reinforces the interaction between them, and all become covalent clusters of general formula (XN+-(CO2)-)n. The positive cooperativity associated with the NH···OC hydrogen bond formation between any two XN'+-(CO2)- units strengthened the N-C coordinate covalent bond and led to massive stabilization of the cluster. For instance, the stabilizing interaction between the XN unit with CO2 is increased from 2-7 kcal/mol range in a monomer complex to 14-31 kcal/mol range for the octamer cluster (XN'+-(CO2)-)8. The cooperativity effect compensates for the large reduction in the entropy of cluster formation. Several imine systems showed the exergonic formation of the cluster and are predicted as potential candidates for CO2 capture and conversion.

The conformational landscape of α-aminoglycine

The conformational landscape of α-aminoglycine has been studied. A conformational search has been first done using a set of different low-cost computational methods. The conformers obtained have been finally optimized at MP2 and B3LYP-D3/6–311++G(2d,p) levels of theory. A conformational landscape of 15 conformers with relative energies lower than 2000 cm−1 has been obtained. For the global minimum (IIa) a cooperative network formed by an OH···NH, NH···N and NH···OC hydrogen bonds, closing a sequential cycle stabilizes the structure. The next conformer in energy (Ia) also has two NH···OC, and NH··N and NH···OH hydrogen bonds. The potential energy surfaces associated with different torsions have been investigated, to rationalize the stability of some conformers. The relative population ratio in a supersonic jet has been estimated to calculate the relative intensity of the rotational spectra of the predicted conformers.

Right- and left-handed PPI helices in cyclic dodecapeptoids.

Enantiomorphic right- and left-handed polyproline type I helices in four cyclic dodecapeptoids with methoxyethyl and propargyl side chains are observed for the first time by single crystal X-ray diffraction. The peculiar absence of NH⋯OC hydrogen bonds in peptoids unveils the role of intramolecular backbone-to-backbone CO⋯CO interactions and CH⋯OC hydrogen bonds in the stabilization of the macrocycle conformation. Moreover, intramolecular backbone-side chain C5 CH⋯OC hydrogen bonds emerge as a stabilizing factor.

Charge-assisted bond and molecular self-assembly drive the gelation of lenvatinib mesylate

Lenvatinib mesylate (LM) is a first-line anticancer agent for the treatment of unresectable hepatocellular carcinoma, while it formed viscoelastic hydrogel when contacting with aqueous medium, which would significantly hinder its in vitro dissolution. The aim of this study was to systematicly explore the gelation mechanism and gel properties via thermal analysis, rheology, morphology and spectroscopy studies. The formed hydrogel was found to be composed of a new polymorph of crystalline LM, and its mechanical strength depended on the cross-linking degree of the fibrillar network structure. Spectroscopy analyses revealed that the intermolecular hydrogen bonds (the bifurcated hydrogen bond between the adjacent urea groups and the NH⋯OC hydrogen bond between the primary amide groups) as well as π-π stacking interactions (between the benzene ring and the quinoline ring) were suggested to be the driving forces for the self-assembly of LM during gelation process. Additionally, no gelation phenomenon was observed when suspending the base form lenvatinib in water, while it could form gel in various acidic solutions (e.g. hydrochloric acid, phosphoric acid and methanesulfonic acid) because the regenerated N+-H group increased the solubility of lenvatinib and promoted the balance between the dissolution or aggregation of LX (X: acid radical ion) molecules in solutions. In conclusion, the charge-assisted bond N+-H in LM molecule and intermolecular non-covalent interactions drived the hydrogel formation of LM in aqueous media. This study elucidates the gelation mechanism and gel properties of LM hydrogel, which would be helpful to figure out strategy to eliminate its gelation fundamentally and pave the way for its further formulation development in future.

The contribution of non-classical CHaxOC hydrogen bonds to the anomeric effect in fluoro and oxa-methoxycyclohexanes.

In this theory study we demonstrate the dominance of non-classical 1,3-diaxial CHaxOC hydrogen bonds (NCHBs) dictating a 'pseudo' anomeric effect in selectively fluorinated methoxycyclohexanes and also influencing the axial preference in the classical anomeric exhibitor 2-methoxytetrahydropyran, a phenomenon which is most often described as a consequence of hyperconjugation. Analogues of methoxycyclohexane where ring CH2's are replaced by CF2 can switch to an axial preference and theory methods (NBO, QTAIM, NCI) indicate the dominance of 1,3-CHaxOMe interactions over hyperconjugation. For 2-methoxytetrahydropyran, it is revealed that the global contribution to the anomeric effect is from electrostatic interactions including NCHBs, not hyperconjugation, although hyperconjugation (nO→σ*CO or nO→σ*CC) remains the main contributor to the exo-anomeric phenomenon. When two and three ether oxygens are introduced into the ring, then both the NCHB interactions and hyperconjugative contributions become weaker, not stronger as might have been anticipated, and the equatorial anomers progressively dominate.

Conformational and crystal structure of acyl thiourea compounds: The case of the simple (2,2-dimethyl-propionyl) thiourea derivative

A novel and simple compound from the family of 1-acyl thioureas, namely (2,2-dimethyl-propionyl) thiourea (also named as N-carbamothioyl pivalamide), has been prepared. It has been fully characterized by microelemental analysis, FTIR, multinuclear (1H and 13C) NMR and mass spectroscopy, and the crystal structure determined by using single crystal X-ray diffraction study. Intramolecular N–H⋯OC hydrogen bond occurs between the carbonyl (CO) and thioamide (–NH2) groups forming a S6 pseudo-ring that stabilize the conformation. The Natural Bond Orbital (NBO) population analysis demonstrates that the hyperconjugative remote interaction between the donor lone pairs located on the carbonyl oxygen and the N–H group, i.e. lpO → σ∗(N–H) is responsible for the preferred conformation. Intermolecular interactions in the crystal are characterized by hydrogen-bonding networks between the carbamide (NH2) groups and the thiocarbonyl bond (CS), including R22(8) dimer motifs promoted by the N–H⋯SC synthon. Hirshfeld surface analysis was performed for visualizing, exploring and quantifying intermolecular interactions present in the crystal structure.

Homochiral vs. heterochiral sodium core dimers of tartaric acid esters: A mass spectrometry and vibrational spectroscopy study

The mixed sodium core dimers of dimethyl-l-tartrate (Lmt) and the two enantiomers of diisopropyl tartrate (Lipt and Dipt) are studied by mass spectrometry coupled with laser vibrational spectroscopy. Infra-Red Multiple Photon Dissociation (IRMPD) spectra of the two diastereomer sodium-core dimers, namely, LmtLiptNa+ and LmtDiptNa+, are identical in the fingerprint region but show a slight difference in the OH stretch region. Comparison to ab initio calculations indicates that the formed complexes probably reflect the structures pre-existing in solution. The difference between LmtLiptNa+ and LmtDiptNa+ arises from the presence of an additional Na+ … O interactions in the homochiral complex. The two complexes also differ in the strength and nature of the OH…OC hydrogen bond.

Sub-picomolar Inhibition of HIV-1 Protease with a Boronic Acid.

Boronic acids have been typecast as moieties for covalent complexation and are employed only rarely as agents for non-covalent recognition. By exploiting the profuse ability of a boronic acid group to form hydrogen bonds, we have developed an inhibitor of HIV-1 protease with extraordinary affinity. Specifically, we find that replacing an aniline moiety in darunavir with a phenylboronic acid leads to 20-fold greater affinity for the protease. X-ray crystallography demonstrates that the boronic acid group participates in three hydrogen bonds, more than the amino group of darunavir or any other analog. Importantly, the boronic acid maintains its hydrogen bonds and its affinity for the drug-resistant D30N variant of HIV-1 protease. The BOH···OC hydrogen bonds between the boronic acid hydroxy group and Asp30 (or Asn30) of the protease are short ( rO···O = 2.2 Å), and density functional theory analysis reveals a high degree of covalency. These data highlight the utility of boronic acids as versatile functional groups in the design of small-molecule ligands.

One-pot synthesis, quantum chemical calculations and X-ray diffraction studies of thiazolyl-coumarin hybrid compounds

Two closely related hybrid species containing both, thiazolyl and coumarin groups, were synthesized by using two different one-pot procedures from a common precursor. The reaction of α-bromoacetylcoumarin with thioacetamide in methanol furnished 3‑(2‑methylthiazol‑4‑yl)‑2H‑chromen‑2‑one (2), whereas refluxing α‑bromoacetylcoumarin with potassium thiocyanate in ethanol afforded 3‑(2‑ethoxythiazol‑4‑yl)‑2H‑chromen‑2‑one (3). Both derivatives were fully characterized by spectroscopic methods, elemental analysis and X-ray diffraction studies. Intramolecular C4H⋯N and C5′H⋯OC hydrogen bonds between the heterocycles determine the conformational behavior. The co-planarity of the coumarin and thiazolyl rings favors the occurrence of two remote orbital interactions involving the oxygen and nitrogen lone pairs and the corresponding σ*CH electron acceptor, as demonstrated by Natural Bond Orbital population analysis. The 2-substitution of the thiazol‑4‑yl group has little effect on the molecular structures but causes significant differences in the crystal packing of the two compounds.

FTIR study of hydrogen bonding interaction between fluorinated alcohol and unsaturated esters

The 1:1 complexes of two unsaturated esters with 2,2,2-trifluoroethanol (TFE) were investigated experimentally and computationally. The experimental observations of the spectral shifts of the OH-stretching vibrational transitions were obtained at 113cm−1 for TFE–methyl acrylate (MA) and 92cm−1 for TFE–vinyl acetate (VA). There are three docking sites in the two unsaturated esters for the incoming TFE. The predicted red shifts of the OH-stretching vibrational transitions were found to be larger for the OH⋯OC hydrogen bonded conformer than those for the OH⋯π and OH⋯O ones. The binding energies further prove that the OH⋯OC hydrogen bonded conformers are the most stable ones. On the basis of the DFT calculations as well as previous works, the carbonyl group is the best docking site for TFE. Furthermore, the thermodynamic equilibrium constants of TFE–MA and TFE–VA were obtained at 0.28 and 0.15 by combining the experimental spectra data and the DFT calculations. Consequently, the Gibbs free energies of formation were determined to be 3.2 and 4.8kJmol−1 for TFE–MA and TFE–VA, respectively. The quantum theory of atoms in molecules (AIM) and generalized Kohn−Sham energy decomposition analysis (GKS-EDA) were carried out for further characterization of the hydrogen bonding interactions. GKS-EDA shows an “electrostatic” dominated hydrogen bonding character for the OH⋯OC hydrogen bonds.

Estimating the energy of intramolecular bifurcated (three-centered) hydrogen bond by X-ray, IR and 1H NMR spectroscopy, and QTAIM calculations

The structure of a series of the 2-substituted pyrroles containing the intramolecular NH⋯OC hydrogen bond and the 2,5-disubstituted pyrroles having the three-centered intramolecular CO⋯H(N)⋯OC hydrogen bond was studied by X-ray, IR, NMR spectroscopy, and quantum chemical calculations, including calculations in terms of Quantum Theory of Atoms in Molecules (QTAIM). The X-ray diffraction data show that the intramolecular rH … O and RN … O distances increase upon conversion from a two-centered hydrogen bond to a three-centered hydrogen bond, indicating a weakening of the last interaction. The topological parameters of the hydrogen bond obtained from the QTAIM calculations (electron density ρBCP and potential energy density V at the critical point of the hydrogen bond) made it possible to quantify the hydrogen bond energy in the studied compounds. The energy of intramolecular NH⋯OC hydrogen bond in the 2-substituted pyrroles is in the range from 5.5 to 6.0 kcal mol−1 (moderate hydrogen bond), whereas the energy of the components of the three-centered intramolecular CO⋯H(N)⋯OC hydrogen bond in the 2,5-disubstituted pyrroles is reduced to 2.5–3.5 kcal mol−1 (weak hydrogen bond). For weak components of the three-centered hydrogen bond, the principle of the additivity of effects on the spectral parameters influenced by the hydrogen bond (change in the vibration frequency of the NH bond, ΔνN‒H, and the chemical shift of bridge proton, ΔδNH) was proposed. For this reason, the ½ΔνN-H and ½ΔδNH values also were used for estimating the energy of the two-centered components of the three-centered CO⋯H(N)⋯OC hydrogen bond. These estimates are in good agreement with those obtained from the ρBCP and V parameters. Consequently, the ½ΔνN-H and ½ΔδNH parameters can be used as an energy descriptor for two-centered components in the case of a symmetric intramolecular three-centered hydrogen bond.

Study of the Cys-His bridge electron transfer pathway in a copper-containing nitrite reductase by site-directed mutagenesis, spectroscopic, and computational methods

The Cys-His bridge as electron transfer conduit in the enzymatic catalysis of nitrite to nitric oxide by nitrite reductase from Sinorhizobium meliloti 2011 (SmNir) was evaluated by site-directed mutagenesis, steady state kinetic studies, UV–vis and EPR spectroscopic measurements as well as computational calculations. The kinetic, structural and spectroscopic properties of the His171Asp (H171D) and Cys172Asp (C172D) SmNir variants were compared with the wild type enzyme. Molecular properties of H171D and C172D indicate that these point mutations have not visible effects on the quaternary structure of SmNir. Both variants are catalytically incompetent using the physiological electron donor pseudoazurin, though C172D presents catalytic activity with the artificial electron donor methyl viologen (kcat=3.9(4) s−1) lower than that of wt SmNir (kcat=240(50) s−1). QM/MM calculations indicate that the lack of activity of H171D may be ascribed to the Nδ1H…OC hydrogen bond that partially shortcuts the T1–T2 bridging Cys-His covalent pathway. The role of the Nδ1H…OC hydrogen bond in the pH-dependent catalytic activity of wt SmNir is also analyzed by monitoring the T1 and T2 oxidation states at the end of the catalytic reaction of wt SmNir at pH6 and 10 by UV–vis and EPR spectroscopies. These data provide insight into how changes in Cys-His bridge interrupts the electron transfer between T1 and T2 and how the pH-dependent catalytic activity of the enzyme are related to pH-dependent structural modifications of the T1–T2 bridging chemical pathway.

Synthesis, structure, computational and in-silico anticancer studies of N,N-diethyl-N′-palmitoylthiourea

A new potential ONS donor ligand N,N-diethyl-N′-palmitoylthiourea (PACDEA) with the molecular formular C21H42N2OS has been synthesized and characterized by ESI-MS, UV, FTIR 1H and 13C NMR spectroscopy and single X-ray crystallography. The asymmetric molecules crystallized in the centrosymmetric structure of monoclinic crystal system with space group P21/c. In the crystal structure of the compound, molecules are linked in a continuous chain by intermolecular NH⋯OC hydrogen bonds, which stabilized the crystal structure. The palmitoyl moiety and N (2)-ethyl group lie on a plane, while the thiocarbonyl moiety is twisted and lying othorgonal to the plane. Non-covalent interaction (NCI) analysis on the hydrogen bonded solid state structure of the molecule revealed the presence of a significant number of non-covalent interactions including intermolecular hydrogen bonding interactions, CH--lone pair interactions, weak Van der Waals interactions, and steric/ring closure interactions. The NCI analysis also showed the presence of intramolecular stabilizing CH⋯OC and CH⋯SC interactions. Docking simulation revealed that the compound interacted favourably with ten selected validated anticancer drug targets, which is an indication that the compound could possess some anticancer properties.

Hydrogen bonds in the blends of polybenzoxazines and N,N′-(pyridine-2,6-diyl)diacetamide: Inter- or intra-molecular hydrogen bonds?

This work aims at probing the formation of hydrogen bonds in the blends of polybenzoxazines and additional hydrogen-bond donor moieties-containing compounds. Based on experimental study and computer simulations, we found that the dominant hydrogen bonds of p-cresol-aniline-based dimer (pC-a-D) and polybenzoxazines (PpC-a) were OH⋯N while N,N′-(pyridine-2,6-diyl)diacetamide (DAA) was NH⋯OC hydrogen bond. After blending pC-a-D or PpC-a with DAA, additional hydrogen bonds formed, i.e., OH⋯OC and OH⋯NH. Moreover, the total quantity of hydrogen bonds of the blends increased. These results suggested that hydrogen bonds formed between polybenzoxazines and the additional hydrogen-bond donor moieties-containing polymers or compounds, and furthermore would be desirable to foster the promoted performance. This novel insight about polybenzoxazine blends is anticipated to help researchers explore more blends of polybenzoxazines with excellent properties.

Synthesis, crystallization, X-ray structural characterization and solid-state assembly of a cyclic hexapeptoid with propargyl and methoxyethyl side chains.

The synthesis and the structural characterization of a cyclic hexapeptoid with four methoxyethyl and two propargyl side chains have disclosed the presence of a hydrate crystal form [form (I)] and an anhydrous crystal form [form (II)]. The relative amounts of form (I) and form (II) in the as-purified product were determined by Rietveld refinement and depend on the purification procedures. In crystal form (I), peptoid molecules assemble in a columnar arrangement by means of side-chain-to-backbone C=CH...OC hydrogen bonds. In the anhydrous crystal form (II), cyclopeptoid molecules form ribbons by means of backbone-to-backbone CH2...OC hydrogen bonds, thus mimicking β-sheet secondary structures in proteins. In both crystal forms side chains act as joints among the columns or the ribbons and contribute to the stability of the whole solid-state assembly. Water molecules in the hydrate crystal form (I) bridge columns of cyclic peptoid molecules, providing a more efficient packing.

The Born-Oppenheimer molecular simulations of infrared spectra of crystalline poly-(R)-3-hydroxybutyrate with analysis of weak C[sbnd]H⋯O[dbnd]C hydrogen bonds

In this letter we present results of study of weak CH⋯OC hydrogen bonds of crystalline poly-(R)-3-hydroxybutyrate (PHB) by using Born-Oppenheimer molecular dynamics. The polymeric structure and IR spectra of PHB result from the presence of the weak hydrogen bonds. We applied the post-molecular dynamics analysis to consider a CO motion as indirectly involved in the hydrogen bonds. Quantization of the nuclear motion of the oxygens was done to perform detailed analysis of the strength and properties of the CO bands involved in the weak hydrogen bonds. We have also shown the dynamic character of the weak hydrogen bond interactions.

Structural study of a novel acetylide-thiourea derivative and its evaluation as a detector of benzene

The new derivative 1-hexanoyl-3-(4-p-tolylethynyl-phenyl)-thiourea (APHX) was synthesised by the addition reaction between 4[4-aminophenyl] ethynyltoluene and hexanoyl isothiocyanate in acetone. The acetylide group was incorporated by using Sonogashira cross-coupling reaction allowing for the preparation of acetylide-thiourea compound. APHX was then elucidated via single crystal X-ray crystallography analysis, spectroscopic and elemental analysis by Fourier Transform Infrared (FT-IR) spectroscopy, 1H and 13C Nuclear Magnetic Resonance (NMR), UV–visible analysis, CHNS-elemental analysis. APHX was also evaluated theoretically via density functional theory (DFT) approach. APHX was fabricated onto glass substrate via drop-cast technique prior to act as optical thin-film and its performance as volatile organic compounds (VOCs) sensor was investigated through the difference in UV–vis profile before and after exposure towards benzene. Preliminary findings revealed that APHX showed interaction towards benzene with about 48% sensitivity. According to thermogravimetric studies, APHX showed good thermal stability, without decomposition up to ca. 190 °C. Whilst, crystal structure of APHX consists in a nearly planar acylthiourea moiety with the CO and CS bonds utilizing trans position, favoring by an intramolecular NH⋯OC hydrogen bonds. The alkyl chain is oriented 90° with respect to acylthiourea group. The phenyls group in the 1-methyl-4-(phenylethynyl)benzene moieties are mutually planar and slightly twisted with respect to the acylthiourea plane. Centrosymmetric dimers generated by intermolecular NH⋯SC and CH⋯SC hydrogen bonds forming R22 (8) and R21(6) motifs are present in the crystals. The interaction between APHX with benzene has been modelled and calculated using density functional theory (DFT) via Gaussian 09 software package and the preferred sites of binding are located at the acylthiourea group.

Raman spectra of crystalline secondary amides

We present a Raman-spectroscopic study of secondary amides (acetanilide, methacetin, phenacetine, orthorhombic and monoclinic polymorphs of paracetamol) as well as simple amides formanilide and benzanilide. The study was carried out on single crystals and in the temperature range of 5–300K. The series of compounds with the same molecular fragment - acetamide group – can serve as a model system to study the interrelation between this group and the properties of the intermolecular “peptide-type” NH⋯OC hydrogen bonds. For all of the “acetamide family” of the compounds, similar changes in the Raman spectra were observed upon cooling of the samples: emergence of new Amide I(−) and Amide I(+) bands, which are red and blue shifted, respectively, from the conventional Amide-I band by around of 5–10cm−1. Corresponding changes in the same temperature range were observed for the NH out-of-plane bending (Amide V) and NH stretching vibrations of the NH⋯OC hydrogen bond. All of the spectral changes observed upon cooling of the samples can be presumed to result from a delocalization of the Amide-I and NH modes and appearance of dynamical (Davydov's) splitting at low temperature.

Toward an ab initio potential energy surface for paclitaxel: A C-13 isoserine side chain conformational study

(S)-3-Methyl-3-butenyl-(2R,3S)-N-benzoyl-3-phenylisoserinate is used as a model of the C-13 side chain, an essential subunit for the cytotoxicity of the diterpenoid paclitaxel, a chemotherapeutic drug used in the treatment of cancer. The potential energy surface (PES), calculated using a density functional theory method (DFT) and refined with MP2 single-point energy calculations, based on B3LYP geometries, was evaluated. Twelve intramolecular hydrogen bond patterns were identified for 103 in vacuo conformers. The most stable subset of these structures was found to have cooperative NH ⋯ OH ⋯ OC(O) motifs and six minima of importance that lie within 1.2kcal/mol of each other. The oxygen atoms of the ester groups effectively compete with the 2′-oxygen as a proton acceptor of NH to form stable internal hydrogen bonded structures. Additionally, the conventional OH ⋯ OC(N) hydrogen bond, which is represented by almost one third of the located minima, donates a number of stable conformers. However, the PES of the conformationally flexible model is highly dependent on the polarity of the environment. For example, the OH ⋯ OC(N) feature dominates over the cooperative motif in water. The side chain of the experimental T-taxol shaped structure agrees nicely with the respective theoretical lowest energy minimum. The π-π interactions of the phenyl rings and ethylene moiety of this structure are also discussed.