Hydrogen-bonded NH Research Articles

Pressure-Controlled Neutral–Ionic Transition and Disordering of NH···N Hydrogen Bonds in Pyrazole

Pyrazole exhibits exceptional effects of temperature and pressure for H-disorder in hydrogen bonds NH···N. Under normal conditions, α-pyrazole is polar (orthorhombic space group Pna21), but the structure is pseudo-centrosymmetric. Two symmetry-independent molecules differently favor the H-sites at their amine nitrogen atoms. The asymmetric disorder of protons in hydrogen bonds NH···N leads to the disproportionation favoring the cations at one site and anions at the other. High temperature increases distortions of the structure from the centrosymmetric symmetry, activates the disproportionation defects, and stabilizes the averaged ionic disparity of symmetry-independent molecules at the ±0.1 e level. Critical pressure Pc = 0.45 GPa induces a transition to centrosymmetric phase β, space group Pnab. This transition involves the 50:50 H-disordering in NH···N hydrogen bonds and eliminates molecular displacements as well as the favored H-sites. The NH···N bonds are hardly compressed at Pc in pyrazole, and they...

Folding and anion-binding properties of an indolocarbazole dimer with urea appendages

An indolocarbazole dimer with the urea functional group was prepared as an anion receptor which contained eight NH hydrogen bonds donors. Two indolocarbazole units were coupled through a butadiynyl linker to allow for helical folding of the resulting dimer by intramolecular hydrogen bonding and dipole–dipole attractions as proven in the 1H NMR spectroscopy. The dimer was found to bind anions (Cl− , Br− , N3 − , AcO− , and ) by multiple hydrogen bonds in 10% (v/v) MeOH–acetone, showing high selectivity for sulphate ion. The 1H NMR spectra clearly demonstrated that only indolocarbazole NH protons were involved in the hydrogen bonding with small anions such as chloride, but all of the existing indolocarbazole and urea NHs participated in the hydrogen bonding with sulphate ion. This difference in the binding mode might be responsible for the high affinity and selectivity towards sulphate ion.

Molecular structure and vibrational spectra of Bis(melaminium) terephthalate dihydrate: A DFT computational study

The experimental and theoretical vibrational spectra of Bis(melaminium) terephthalate dihydrate were studied. The Fourier transform infrared (FT-IR) spectra of the Bis(melaminium) terephthalate dihydrate and its deuterated analogue were recorded in the solid phase. The molecular geometry and vibrational frequencies of Bis(melaminium) terephthalate dihydrate in the ground state have been calculated by using the density functional method (B3LYP) with 6-31++G(d,p) basis set. The results of the optimized molecular structure are presented and compared with the experimental X-ray diffraction. The molecule contains the weak hydrogen bonds of NH⋯O, NH⋯N and OH⋯O types, and those bonds are calculated with DFT method. In addition, molecular electrostatic potential, frontier molecular orbitals and natural bond orbital analysis of the title compound were investigated by theoretical calculations. The lack of the second harmonic generation (SHG) confirms the presence of macroscopic center of inversion.

Solvation Effect on the NH Stretching Vibrations of Solvated Aminopyrazine, 2-Aminopyridine, and 3-Aminopyridine Clusters

The vibrational spectra of the hydrated and methanol-solvated aminopyrazine, 2-aminopyridine and 3-aminopyridine in supersonic jets have been measured in terms of IR-UV double-resonance spectroscopy. Comparing the IR spectrum of aminopyrazine with those of 2-aminopyridine and 3-aminopyridine clusters, we determine the solvation structure of aminopyrazine to be a similar cyclic structure as hydrated 2-aminopyridine clusters [Wu, et al., Phys. Chem. Chem. Phys. 2004, 6, 515]. In the case of monohydrated aminopyrazine cluster, one of the normal modes composed of the hydrogen-bonded OH and NH stretching local modes gives the anomalously weak IR intensity, which is ascribed to the cancellation of the dipole moment change between the OH and NH stretching local modes. The solvated 3-aminopyridine clusters forms the hydrogen-bond between the pyridyl nitrogen atom and the OH group, but the amino group is indirectly affected to induce slight blue shift of the NH(2) stretches. This phenomenon is explained by inductive effect where the electron withdrawing from the amino group upon the solvation results in a "quinoid-like" structure of the amino group.

Synthesis and structural characterization of organic co-crystals 4,4′-bipyridine-bis(N-phenylanthranilic acid) and 4,4′-bipyridinium bis(3-carboxypyridine-2-carboxylate)

Two organic co-crystals namely, 4,4′-bipyridine-bis(N-phenylanthranilic acid) (1) and 4,4′-bipyridinium bis(3-carboxypyridine-2-carboxylate) (2) have been synthesized and studied by FT-IR, TGA/DTA, and single crystal XRD studies. The crystal system of co-crystal 1 is triclinic with space group P1 and Z=4 and that of co-crystal 2 is monoclinic with space group P21/n and Z=2. Intermolecular hydrogen bonds, OH⋯N, with graph set designator D22 (10) play a vital role in the formation of the co-crystal 1. Intramolecular hydrogen bond S(6) is also present in 1 and there is no π–π interaction. Whereas in co-crystal 2, the intermolecular hydrogen bonds NH⋯N with graph set designator D22 (12), OH⋯O with graph set designator D, and the π–π interactions together play a major role in stabilizing the structure.

Negative linear compression and expanding NH⋯N bonds in an imidazoline compound

The 3-dimensional network of NH⋯N hydrogen bonds and Cl⋯Cl hydrogen contacts in the crystal structure of 2-(3′-chlorophenyl)imidazoline exhibits an anomalous hydrostatic compression. The lengthening of hydrogen bonds NH⋯N and some CH⋯N contacts as well as their supramolecular architecture lead to anomalous expansion of the crystal along [x] and [y] on increasing pressure to 0.1 GPa. The mechanism of this phenomenon is due to the ‘stiffness’ of the NH⋯N and Cl⋯Cl interactions and ‘softness’ of other van der Waals contacts. Above 0.1 GPa all crystal directions become compressed. However, up to 1.20 GPa, the crystal remains in the same orthorhombic phase of polar space group Fdd2.

Synthesis and recognition properties of higher order tetrathiafulvalene (TTF) calix[n]pyrroles (n = 4–6)

Two new benzoTTF-annulated calix[n]pyrroles (n = 5 and 6) were synthesized via a one-step acid catalyzed condensation reaction and fully characterized via single crystallographic analyses. As compared to the known tetra-TTF annulated calix[4]pyrrole, which is also produced under the conditions of the condensation reaction, the expanded calix[n]pyrroles (n = 5 and 6) are characterized by a larger cavity size and a higher number of TTF units (albeit the same empirical formula). Analysis of the binding isotherms obtained from UV-Vis spectroscopic titrations carried out in CHCl3 in the presence of both anionic (Cl−, Br−, I−, CH3COO−, H2PO4−, and HSO4−) and neutral (1,3,5-trinitrobenzene (TNB) and 2,4,6-trinitrotoluene (TNT)) substrates revealed that as a general rule the calix[6]pyrrole derivative proved to be the most efficient molecular receptor for anions, while the calix[4]pyrrole congener proves most effective for the recognition of TNB and TNT. These findings are rationalized in terms of the number of electron rich TTF subunits and NH hydrogen bond donor groups within the series, as well as an ability to adopt conformations suitable for substrate recognition, and are supported by solid state structural analyses.

Solution-state NMR spectroscopy of famotidine revisited: spectral assignment, protonation sites, and their structural consequences

Multinuclear one (1D-) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopic investigations of famotidine, the most potent and widely used histamine H(2)-receptor antagonist, were carried out in dimethyl sulfoxide-d(6) (DMSO-d(6)) and water. Previous NMR assignments were either incomplete or full assignment was based only on 1D spectra and quantum-chemical calculations. Our work revealed several literature misassignments of the (1)H, (13)C, and (15)N NMR signals and clarified the acid-base properties of the compound at the site-specific level. The erroneous assignment of Baranska et al. (J. Mol. Struct. 2001, 563) probably originates from an incorrect hypothesis about the major conformation of famotidine in DMSO-d(6). A folded conformation similar to that observed in the solid-state was also assumed in solution, stabilized by an intramolecular hydrogen bond involving one of the sulphonamide NH(2) protons and the thiazole nitrogen. Our detailed 1D and 2D NMR experiments enabled complete ab initio (1)H, (13)C, and (15)N assignments and disproved the existence of the sulphonamide NH hydrogen bond in the major conformer. Rather, the molecule is predominantly present in an extended conformation in DMSO-d(6). The aqueous acid-base properties of famotidine were studied by 1D (1)H- and 2D (1)H/(13)C heteronuclear multiple-bond correlation (HMBC) NMR-pH titrations. The experiments identified its basic centers including a new protonation step at highly acidic conditions, which was also confirmed by titrations and quantum-chemical calculations on a model compound, 2-[4-(sulfanylmethyl)-1,3-thiazol-2-yl]guanidine. Famotidine is now proved to have four protonation steps in the following basicity order: the sulfonamidate anion protonates at pH = 11.3, followed by the protonation of the guanidine group at pH = 6.8, whereas, in strong acidic solutions, two overlapping protonation processes occur involving the amidine and thiazole moieties.

Secondary interactions involving zinc-bound ligands: Roles in structural stabilization and macromolecular interactions

A large number of proteins contain bound zinc ions. These zinc ions are frequently coordinated by a combination of histidine and cysteine residues. In addition to atoms that coordinate directly to the zinc ions, these side chains have groups that can donate or accept hydrogen bonds from other groups. These secondary interactions can help stabilize the zinc-binding sites, can contribute to protein folding and stability, and, on occasion, can participate in interactions with other macromolecules. Five examples of these secondary interactions are discussed: carbonic anhydrase (where secondary interactions involving histidine residues stabilize the zinc-binding site thermodynamically and kinetically), retroviral nucleocapsid proteins and TRAF proteins (where cysteinate sulfur to peptide NH hydrogen bonds contribute to the structural relationships between adjacent domains), and nucleic acid binding proteins, Zif268 and TIS11 where secondary interactions participate in protein–nucleic acid interactions.

Do Rhodium Bis(σ‐amine‐borane) Complexes Play a Role as Intermediates in Dehydrocoupling Reactions of Amine‐boranes?

The recently synthesized rhodium complex [Rh{P(C(5)H(9))(2)(η(2)-C(5)H(7))}(Me(2)HNBH(3))(2)]BAr(F)(4) (2), which incorporates two amine-boranes coordinated to the rhodium center with two different binding modes, namely η(1) and η(2), has been used to probe whether bis(σ-amine-borane) motifs are important in determining the general course of amine-boranes dehydrocoupling reactions. DFT calculations have been carried out to explore mechanistic alternatives that ultimately lead to the formation of the amine-borane cyclic dimer [BH(2)NMe(2)](2) (A) by hydrogen elimination. Sequential concerted, on- or off-metal, intramolecular dehydrogenations provide two coordinated amine-borane molecules. Subsequent dimerization is likely to occur off the metal in solution. In spite of the computationally confirmed presence of a BH⋅⋅⋅NH hydrogen bond between amine-borane ligands, neither a simple intermolecular route for dehydrocoupling of complex 2 is operating, nor seems [Rh{P(C(5)H(9))(2)(η(2)-C(5)H(7))}B](+) to be important for the whole dehydrocoupling process.

Ion-orbital coupling in Car-Parrinello calculations of hydrogen-bond vibrational dynamics: Case study with the NH3–HCl dimer

We have performed Car-Parrinello molecular dynamics (CPMD) calculations of the hydrogen-bonded NH(3)-HCl dimer. Our main aim is to establish how ionic-orbital coupling in CPMD affects the vibrational dynamics in hydrogen-bonded systems by characterizing the dependence of the calculated vibrational frequencies upon the orbital mass in the adiabatic limit of Car-Parrinello calculations. We use the example of the NH(3)-HCl dimer because of interest in its vibrational spectrum, in particular the magnitude of the frequency shift of the H-Cl stretch due to the anharmonic interactions when the hydrogen bond is formed. We find that an orbital mass of about 100 a.u. or smaller is required in order for the ion-orbital coupling to be linear in orbital mass, and the results for which can be accurately extrapolated to the adiabatic limit of zero orbital mass. We argue that this is general for hydrogen-bonded systems, suggesting that typical orbital mass values used in CPMD are too high to accurately describe vibrational dynamics in hydrogen-bonded systems. Our results also show that the usual application of a scaling factor to the CPMD frequencies to correct for the effects of orbital mass is not valid. For the dynamics of the dimer, we find that the H-Cl stretch and the N-H-Cl bend are significantly coupled, suggesting that it is important to include the latter degree of freedom in quantum dynamical calculations. Results from our calculations with deuterium-substitution show that both these degrees of freedom have significant anharmonic interactions. Our calculated frequency for the H-Cl stretch using the Becke-exchange Lee-Yang-Parr correlation functional compares reasonably well with a previous second-order Møller-Plesset calculation with anharmonic corrections, although it is low compared to the experimental value for the dimer trapped in a neon-matrix.

Factors Controlling the Reactivity of Zinc Finger Cores

Although the Zn(2+) cation in Zn·Cys(4), Zn·Cys(3)His, Zn·Cys(2)His(2), and Zn(2)Cys(6) cores of zinc finger (Zf) proteins typically plays a structural role, the Zn-bound thiolates in some Zf cores are reactive. Such labile Zf cores can serve as drug targets for retroviral or cancer therapies. Previous studies showed that the reactivity of a Zn-bound thiolate toward electrophiles is significantly reduced if it forms S---NH hydrogen bonds with the backbone amide. However, we found several well-known inactive Zf cores containing Cys ligands with no H-bonding interactions. Here, we show that H bonds from the peptide backbone or bonds from a second Zn cation to Zn-bound S atoms suppress the reactivity not only of these S atoms, but also of Zn-bound S* atoms with no interactions. Indeed, two or more indirect NH---S hydrogen bonds raise the free energy barrier for methylation of a Zn-bound S* in a Cys(4) core more than a direct NH---S* hydrogen bond. These findings help to elucidate why several well-known Zf cores have Cys ligands with no H bonds, but are unreactive. They also help to provide guidelines for distinguishing labile Cys-rich Zn sites from structural ones, which in turn help to identify novel potential Zf drug targets.

Molecular Dynamics Simulations of a Binding Intermediate between FKBP12 and a High-Affinity Ligand.

We characterized a binding intermediate between the protein FKBP12 and one of its high-affinity ligands by means of molecular dynamics simulations. In such an intermediate, which is expected to form at the end-point of the bimolecular diffusional search, short-range interactions between the molecular partners may play a role in the specificity of recognition as well as in the association rate. Langevin dynamics simulations were carried out to generate the intermediate by applying an external biasing force to unbind the ligand from the protein. The intermediate was then refined by seven independent molecular dynamics simulations performed with an explicit solvent model. We found consistent results both for the structure of the protein and for the position of the ligand in the intermediate. The two carbonyl oxygens O2 and O3 of the ligand core region act as two main anchors, making permanent contacts in the intermediate. The transient contacts with the protein are made by the ligand noncore moieties whose structures and mobilities enable many alternative contacts of different types to be formed: π-π molecular overlap and weak hydrogen bonds NH···π, CH···π, and CH···O. Hence, the stability of the ligand at the entrance of the protein binding pocket offers the possibility of fine-tuning a variety of short-range contacts that involve the ligand noncore moieties. Under the hypothesis that the stability of this intermediate is related to the affinity of the ligand, this binding intermediate model comes closest to explaining the role played by the noncore moieties in the affinity of this ligand. Moreover, this model also provides a plausible explanation for how structurally diverse core motifs that all share the carbonyl atoms O2 and O3 bind to FKBP12.

Dynamics and Couplings of N−H Stretching Excitations of Guanosine−Cytidine Base Pairs in Solution

N-H stretching vibrations of hydrogen-bonded guanosine-cytidine (G·C) base pairs in chloroform solution are studied with linear and ultrafast nonlinear infrared (IR) spectroscopy. Assignment of the IR-active bands in the linear spectrum is made possible by combining structural information on the hydrogen bonds in G·C base pairs with literature results of density functional theory calculations, and empirical relations connecting frequency shifts and intensity of the IR-active vibrations. A local mode representation of N-H stretching vibrations is adopted, consisting of ν(G)(NH(2))(f) and ν(C)(NH(2))(f) modes for free NH groups of G and C, and of ν(G)(NH(2))(b), ν(G)(NH), and ν(C)(NH(2))(b) modes associated with N-H stretching motions of hydrogen-bonded NH groups. The couplings and relaxation dynamics of the N-H stretching excitations are studied with femtosecond mid-infrared two-dimensional (2D) and pump-probe spectroscopy. The N-H stretching vibrations of the free NH groups of G and C have an average population lifetime of 2.4 ps. Besides a vibrational population lifetime shortening to subpicosecond values observed for the hydrogen-bonded N-H stretching vibrations, the 2D spectra reveal vibrational excitation transfer from the ν(G)(NH(2))(b) mode to the ν(G)(NH) and/or ν(C)(NH(2))(b) modes. The underlying intermode vibrational couplings are on the order of 10 cm(-1).

Mechanism in Brill transition of polyamide 66 studied by two-dimensional correlation infrared spectroscopy

The Brill transition of polyamide 66 was investigated by temperature-dependent infrared spectroscopy combined with moving-window two-dimensional (MW2D) correlation spectroscopy. The temperature range of the Brill transition determined by MW2D correlation spectroscopy was 90–170 °C. We employed generalized 2D correlation spectroscopy to study the sequential order of polyamide 66 chains with linear increment of temperature. The movement of the methylene segments near to NH is earlier than those on the C O sides. At the same time, the methylene which is close to NH varies before the inner methylene. Three kinds of NH groups in polyamide 66 were found. The sequential order of their motions is as follows. The free hydrogen-bonded NH groups change first, and then the disordered hydrogen-bonded NH groups. Finally, the ordered hydrogen-bonded NH groups start to change. We also found that the changes of the ordered hydrogen-bonded NH groups follow with the methylene groups.

A Pyrrolyl-Based Triazolophane: A Macrocyclic Receptor With CH and NH Donor Groups That Exhibits a Preference for Pyrophosphate Anions

A pyrrolyl-based triazolophane, incorporating CH and NH donor groups, acts as a receptor for the pyrophosphate anion in chloroform solution. It shows selectivity for this trianion, followed by HSO(4)(-) > H(2)PO(4)(-) > Cl(-) > Br(-) (all as the corresponding tetrabutylammonium salts), with NH-anion interactions being more important than CH-anion interactions. In the solid state, the receptor binds the pyrophosphate anion in a clip-like slot via NH and CH hydrogen bonds.

Bis(2-alkyl-4-thiocarbamoyl-4-pyridinium) hexafluorosilicates

The reaction of 45% silicahydrofluoric acid with 2-ethyl-4-thiocarbamoyl-4-pyridine (L1) and 2-propyl-4-thiocarbamoyl-4-pyridine (L2) yields (L1H)2SiF6 and (L2H)2SiF6 hexafluorosilicates. These hexafluorosilicates are characterized by the data of IR spectroscopy, mass spectrometry, potentiometry, and solubility. The structure of (L1H)2SiF6 is determined by X-ray diffraction. In the ionic structure of the complex, the L1H+ cations (the protonation center is the pyridinic N atom) and SiF 6 2− anions (Si-F 1.657(2)–1.699(2) A) are joined by a system of interionic hydrogen bonds NH⋯F. Correlation between the characteristics of the interionic hydrogen bonds and the solubility of the hexafluorosilicates is discussed.

Supramolecular chemistry with uranyl tetrahalide ([UO2X4]2−) anions

Abstract Five compounds containing the uranyl tetrabromide anion ([UO2Br4]2−) have been synthesized through room temperature reactions of uranium (VI) oxyacetate with several pyridinium cations in highly acidic solutions containing Br− anions. The resulting compounds have been characterized via single-crystal X-ray diffraction and fluorescence spectroscopy. Three of these compounds exhibit both a bifurcated hydrogen bond NH ⋯ B r 2 U and an extended “ribbon motif” of alternating organic and inorganic species.

Caste-specific tyramides from Myrmicine ants.

Analysis of the extracts of male ants of Monomorium minimum and Monomorium ebeninum by GC-MS and GC-FTIR revealed the presence of tyramides 2 and 4c, for which the structures were established by comparison with synthetic samples. These compounds and their analogues 1 and 3 were also found in males of other Monomorium species, males of Myrmicaria opaciventris, and males of several Solenopsis (Diplorhoptrum) species. Vapor-phase FTIR spectra revealed critically important structural clues to two of the tyramides, which had methyl branching in the tyramide acyl moiety. Tyramide 4c exhibited a strong intramolecular amide NH hydrogen bond where an alpha-keto group was deduced to be present in the acyl moiety and also showed the overlap of this ketone group frequency with that of the amide nu(C horizontal lineO). The biological function of these compounds is uncertain; however, their role in ant-mating behavior may be suggested by a large body of evidence.

Tris(2-hydroxyethyl)ammonium salts: 2,8,9-Trihydroprotatranes

New method of synthesis of tris(2-hydroxyethyl)ammonium salts, 2,8,9-trihydroprotatranes X-[HN(CH2CH2OH)3]+, based on the reaction of tris(2-hydroxyethyl)amine (triethanolamine) with ammonium salts NH4X (X = F, Cl, Br, I, NO3, ClO4) was developed. 1H, 13C, 15N NMR and IR spectra of these protatranes were investigated, as well as those of their analogs with X = RCH2COO (R = H; 2-MeC6H4O; 2-Me-4ClC6H3O; 2-MeC6H4S; 4-ClC6H4S; 4-ClC6H4SO2; 3-IndS; 3-(PhCH2-IndS) prepared from the corresponding acids RCH2COOH and triethanolamine. The parameters of IR and NMR spectra of the studied protatranes were governed by the nature of substituent X, which also determined the character of the intra and intermolecular hydrogen bonds NH⋯O and OH⋯O in the protatrane framework.