The nature and energy characteristics of intramolecular hydrogen bonds in crystals

The review concerns the results of systematic X-ray diffraction studies of the electron density distribution in the crystals of compounds with strong intramolecular hydrogen bonds N-H...O, O-H...O, O-H...N, and N-H...S. The advantages of the topological analysis of the electron density distribution function in the analysis of the nature and estimation of the H-bond energies directly from experimental data are discussed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 1–14, January, 2006.     

Role of steric factors in formation of O—H...M hydrogen bonds with metallocenes

Molecular mechanics calculations of geometric parameters and energies of molecular complexes with a O-H...M hydrogen bond have been performed for osmocene and decamethylosmocene with three proton donors. The results of calculations demonstrated that when rings are methylated, steric hindrances to formation of this hydrogen bond increase. This is the reason for anomalously low formation constants of H-bonded Cp ₂ ^* M molecular associates compared to CP₂M associates.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1925–1927, October, 1995.The work was supported by the Russian Foundation for Basic Research (Project No. 93-03-4610) and the International Science Foundation (Grant MP5 000).     

The orientation of N-H...O=C and N-H...N hydrogen bonds in biological systems: How good is a point charge as a model for a hydrogen bonding atom?

In order to design new ligands for protein-binding sites of unknownstructure, it would be useful to predict the likely sites of hydrogenbonding of an unknown protein fragment to a known molecule. The positions ofmaxima and minima in the electrostatic potential at appropriate distancesfrom the van der Waals surface were calculated for various small molecules,nucleic acid bases, peptide units and amino acid side chains containinggroups which can form the biologically important N-H...O=C andN-H...N hydrogen bonds. Their ability to predict the positions of H andO/N in hydrogen bonded complexes, as predicted by optimising theelectrostatic interactions of pairs of such molecules constrained by themolecular shapes, was assessed. It is shown that extrema in theelectrostatic potential around the isolated molecules give worthwhilepredictions for the locations of hydrogen bonding partners. For moleculesbound by a single N-H...O=C hydrogen bond, the electrostatic maximumassociated with the H is usually less than 1 Å from an acceptor atom,while a C=O electrostatic minimum is generally less than 1.5 Å fromthe hydrogen bond proton. However, a significant number of hydrogen bondsform to the opposite lone pair from the electrostatic minimum, in which casethe separation is up to 3.3 Å. This reflects the broad electrostaticpotential well around a carbonyl oxygen between the lone pair directions.The model predicts when neighbouring atoms drastically change the hydrogenbonding characteristics of an N-H or C=O group. Although the geometries ofhydrogen bonded complexes are influenced by the other van der Waals contactsbetween the molecules, particularly multiple hydrogen bonds, theseinfluences are constant when considering hydrogen bonding to a specificuncharacterised binding site. Hence, the consideration of stericallyaccessible electrostatic extrema will be useful in the design of newligands.     

Intramolecular C-H...Ccarbene hydrogen bonds and competing interactions in monoprotonated tripodal carbenes

The anionic tripodal N-heterocyclic carbene (C3N2H3)3BH- first prepared by Fehlhammer, together with three neutral variants, (C3N2H3)3CH, (C3N2H3)3P, and (C3N2H3)3SiH, have been studied using quantum chemical methods. Isodesmic reactions are used to deduce that the phosphine-bridgehead species in particular has a large-resonance stabilization energy. All the podands undergo substantial conformational change on excitation to the lowest triplet electronic state, with effective localization of the excitation on one of the heterocyclic rings, dearomatizing it. On monoprotonation of the ground states, three of these species display intramolecular C-H...Ccarbene hydrogen bonding: The nature and strength of these interactions is explored using model (intermolecularly hydrogen-bonded) complexes, isodesmic reactions, and GIAO calculations of chemical shifts. One surprising result is that C-H...Ccarbene hydrogen bonds involving ethenic hydrogens can be almost as strong as those involving the imidazolium proton (first identified by Arduengo). The case of the monoprotonated carbon bridgehead species is in particular intriguing. It is stabilized by a competitive Ccarbene...N interaction of sufficient strength to override the C-H...Ccarbene bonding motif observed in the other structures.     

Correlations between bond lengths and stretching frequencies in the O—D...O hydrogen bridge and their consequences

Based on modern neutron diffraction data and the known empirical correlations between the geometric and spectroscopic parameters of hydrogen bonds, the analytical expression describing the relation between the O—D covalent and D...O hydrogen bond lengths in the O—D...O hydrogen bridge was obtained. The distribution functions of the interatomic and nearest intermolecular distances in heavy water were calculated from the Raman band shapes in the 10 to 90 °C temperature interval in the framework of the fluctuation theory of hydrogen bonding.     

Observation of O-H...N scalar coupling across a hydrogen bond in nocathiacin I

We report here the observation of O-H...N hydrogen-bond (1h)J(N,OH) scalar coupling in a biologically active natural product. The intramolecular hydrogen bond between the threonine hydroxyl (Thr-OH) group and the thiazolyl nitrogen at the second thiazole ring (Thz-2) in nocathiacin I was directly detected by a 1H-15N HMBC NMR experiment. The magnitude of the scalar coupling constant (1h)J(N,OH) was accurately measured to be 1.8 +/- 0.1 Hz by a J-resolved 1H-15N HMBC experiment. By adding the O-H...N distance restraint, the 3D solution structure of nocathiacin I was refined. The structure refinement indicated that the distance between the Thr-3 hydroxyl hydrogen and the Thz-2 nitrogen is or= 0.23 A. The presence of an intramolecular hydrogen bond in nocathiacin I is further supported by a number of NMR parameters and additional NMR experiments. This observation provides valuable information for characterizing molecular conformations, and for studying structure-activity relationships.     

Improper hydrogen C-H...O bonds cause self-association of alpha, beta-enaminoketones containing fluorosubstituted alkyl groups.

Concentration- and temperature-dependent IR, NMR and dipole-moment studies on 4-N,N-dimethylamino-1,1,1-trifluoro-3-buten-2-one and two of its higher homologues showed that these compounds undergo reversible dimerization in nonpolar solvents. Antiparallel "closed" dimers are formed with a network of improper intermolecular C-H...O hydrogen bonds. Quantitative analysis of the 1H NMR data yielded delta H0 = -17.6 kJ mol-1 and delta S0 = -46.9 J deg-1 mol-1. The interactions observed are the strongest among those involving a C-H group reported so far. The complex described here is the first example of a cyclic complex stabilized by two improper C-H...O hydrogen bonds. The conclusions drawn from the solution and solid-state data were confirmed by ab initio calculations.     

Statistical theory for hydrogen bonding fluid system of A_aD_d type (I): The geometrical phase transition

The influence of hydrogen bonds on the physical and chemical properties of hydrogen bonding fluid system of AaDd type is investigated from two viewpoints by the principle of statistical mechanics. In detail, we proposed two new ways that can be used to obtain the equilibrium size distribution of the hydrogen bonding clusters, and derived the analytical expression of a relationship between the hydrogen bonding free energy and hydrogen bonding degree. For the nonlinear hydrogen bonding systems, it is shown that the sol-gel phase transition can take place under proper conditions, which is further proven to be a kind of geometrical phase transition rather than a thermodynamic one. Moreover, several problems associated with the geometrical phase transition and liquid-solid phase transition in nonlinear hydrogen bonding systems are discussed.     

NMR parameters and geometries of OHN and ODN hydrogen bonds of pyridine-acid complexes

In this paper, equations are proposed which relate various NMR parameters of OHN hydrogen-bonded pyridine-acid complexes to their bond valences which are in turn correlated with their hydrogen-bond geometries. As the valence bond model is strictly valid only for weak hydrogen bonds appropriate empirical correction factors are proposed which take into account anharmonic zero-point energy vibrations. The correction factors are different for OHN and ODN hydrogen bonds and depend on whether a double or a single well potential is realized in the strong hydrogen-bond regime. One correction factor was determined from the known experimental structure of a very strong OHN hydrogen bond between pentachlorophenol and 4-methylpyridine, determined by the neutron diffraction method. The remaining correction factors which allow one also to describe H/D isotope effects on the NMR parameters and geometries of OHN hydrogen bond were determined by analysing the NMR parameters of the series of protonated and deuterated pyridine- and collidine-acid complexes. The method may be used in the future to establish hydrogen-bond geometries in biologically relevant functional OHN hydrogen bonds.     

Nature of weak inter-and intramolecular interactions in crystals 8. Influence of intermolecular contacts on the strength of intramolecular O-H...N bonds in crystals of 3-(2-hydroxyphenyl)-1,2,4-triazoles

The nature and energy of the intramolecular H-bond in 3-(2-hydroxyphenyl)-1,2,4-triazoles was studied by X-ray diffraction and quantum chemical methods. In this system, the conjugation does not additionally contribute to the enhancement of the H-bond energy. The cooperative effects lead to a strengthening of the intramolecular H-bond. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 396–402, March, 2006.     

Dynamic and electrooptical properties of FH…F and FH…N hydrogen bridges

The dynamic and electrooptical parameters of the hydrogen bridges in (HF)₂, FH…FCD₃, FH…NCH, and FH…NCCH₃ complexes were calculated by the MINDO/3 method. Relationships between these parameters have been found. These parameters for the F−H…Y bridges mainly coincide with the relationships previously established for the hydrogen O−H…Y bridges. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1067–1069, May, 1997.     

Comparison of the effects of the intra- and intermolecular hydrogen bonds C-H...X (X = O,N) in1H and13C NMR spectra

A similarity between manifestations of the effects of the intra- and intermolecular hydrogen bonds C-H...X (X = O, N) in¹H and¹³C NMR spectra has been shown. A correlated increase in the direct spin-spin coupling constant¹³C—¹H and the chemical shifts of the proton participating in the interaction has been observed.Translated fromIzvestiya Akademii Nauk. Seriyo Khimicheskaya, No. 5, pp. 1205–1207, May, 1996.     

Remarkable metal counterion effect on the internucleotide J-couplings and chemical shifts of the N-H...N hydrogen bonds in the W-C base pairs

The effects of metal ion binding on the (2h) J(NN)-coupling and delta( (1)H)/Deltadelta( (15)N) chemical shifts of N-H...N H-bond units in internucleotide base pairs were explored by a combination of density functional theory calculations and molecular dynamics (MD) simulations. Results indicate that the NMR parameters vary considerably upon cation binding to the natural GC or AT base pairs, and thus can be used to identify the status of the base pairs, if cation-perturbed. The basic trend is that cation perturbation causes (2h) J(NN) to increase, Deltadelta( (15)N) to decrease, and delta( (1)H) to shift upfield for GC, and in the opposite directions for AT. The magnitudes of variation are closely related to the Lewis acidity of the metal ions. For both base pair series (M(z+)GC and M(z+)AT), these NMR parameters are linearly correlated among themselves. Their values depend strongly on the energy gaps (Delta(ELP-->sigma*)) and the second-order interaction energies ( E(2)) between the donor N lone pair (LP(N)) and the acceptor sigma* N-H localized NBO orbitals. In addition, the (2h) J NN changes are also sensitive to the amount of sigma charge transfer from LP(N) to sigma*(N-H) NBOs or from the purine to the pyrimidine moieties. The different trends are a consequence of the different H-bond patterns combined with the polarization effect of the metal ions in the cationized M(z+)AT series, M(z+) <-- A --> T, and the cationized GC series, M(z+) <-- G <-- C. The predicted cation-induced systematic trends of (2h) J(NN) and delta( (15)N, (1)H) in N-H...N H-bond units may provide a new approach to the determination of H-bond structure and strength in Watson-Crick base pairs, and provide an alternative probe of the heterogeneity of DNA sequences.     

Structure and stability of hydrogen fluoride complexes with N,N-dimethylformamide

The structure, stability, and paths of formation of 11 (HF)_m(DMF)_n heterocomplexes (m = 1–4, n = 1, 2) were studied in terms of the B3LYP/6-31++G(d, p) density functional calculation. The results of this calculation suggest that: a) addition of hydrogen fluoride molecules to the (HF)_mDMF cyclic fragment is the basic tendency in complex formation in the HF-DMF system; b) data about the structure and properties of stable molecular forms that prevail in N,N-dimethylformamide solutions of hydrogen fluoride can be obtained by quantum chemical calculations for (HF)_mDMF complexes (m = 5–10).     

An analytic potential energy function for the amide–amide and amide–water intermolecular hydrogen bonds in peptides

An analytic potential energy function is proposed and applied to evaluate the amide–amide and amide–water hydrogen‐bonding interaction energies in peptides. The parameters in the analytic function are derived from fitting to the potential energy curves of 10 hydrogen‐bonded training dimers. The analytic potential energy function is then employed to calculate the N? H…O?C, C? H…O?C, N? H…OH₂, and C?O…HOH hydrogen‐bonding interaction energies in amide–amide and amide–water dimers containing N‐methylacetamide, acetamide, glycine dipeptide, alanine dipeptide, N‐methylformamide, N‐methylpropanamide, N‐ethylacetamide and/or water molecules. The potential energy curves of these systems are therefore obtained, including the equilibrium hydrogen bond distances R(O…H) and the hydrogen‐bonding energies. The function is also applied to calculate the binding energies in models of β‐sheets. The calculation results show that the potential energy curves obtained from the analytic function are in good agreement with those obtained from MP2/6‐31+G** calculations by including the BSSE correction, which demonstrate that the analytic function proposed in this work can be used to predict the hydrogen‐bonding interaction energies in peptides quickly and accurately. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009     

Statistical theory for hydrogen bonding fluid system of AaDd type (I): The geometrical phase transition

The influence of hydrogen bonds on the physical and chemical properties of hydrogen bonding fluid system of A _a D _d type is investigated from two viewpoints by the principle of statistical mechanics. In detail, we proposed two new ways that can be used to obtain the equilibrium size distribution of the hydrogen bonding clusters, and derived the analytical expression of a relationship between the hydrogen bonding free energy and hydrogen bonding degree. For the nonlinear hydrogen bonding systems, it is shown that the sol-gel phase transition can take place under proper conditions, which is further proven to be a kind of geometrical phase transition rather than a thermodynamic one. Moreover, several problems associated with the geometrical phase transition and liquid-solid phase transition in nonlinear hydrogen bonding systems are discussed.     

Evaluation of coarse grained models for hydrogen bonds in proteins

Backbone hydrogen bonds contribute very importantly to the stability of proteins and therefore they must be appropriately represented in protein folding simulations. Simple models are frequently used in theoretical approaches to this process, but their simplifications are often confronted with the need to be true to the physics of the interactions. Here we study the effects of different levels of coarse graining in the modeling of backbone hydrogen bonds. We study three different models taken from the bibliography in a twofold fashion. First, we calculate the hydrogen bonds in 2gb1, an (alpha + beta)-protein, and see how different backbone representations and potentials can mimic the effects of real hydrogen bonds both in helices and sheets. Second, we use an evolutionary method for protein fragment assembly to locate the global energy minimum for a set of small beta-proteins with these models. This way, we assess the effects of coarse graining in hydrogen bonding models and show what can be expected from them when used in simulation experiments.     

An FT-IR demonstration of the occurrence of satellite bands in the spectra of hydrogen bonds in crystals

OH stretching fundamentals in the spectra of hydrogen-bonded crystals are accompanied by satellite bands due to sum and difference transitions involving one quantum of the OH stretching vibration and one or more quanta of the low-frequency vibration of the hydrogen bond. Such satellites were detected in the FT-IR spectra of two hydrogen-bonded crystals, ice and methanol.NRCC No. 29006     

Weak C—H...X (X = O,N) hydrogen bonds in the crystal structure of dihydroberberine

Dihydroberberine (systematic name: 9,10‐dimethoxy‐6,8‐dihydro‐5H‐1,3‐dioxolo[4,5‐g]isoquinolino[3,2‐a]isoquinoline), C₂₀H₁₉NO₄, a reduced form of pharmacologically important berberine, crystallizes from ethanol without interstitial solvent. The molecule shows a dihedral angle of 27.94 (5)° between the two arene rings at the ends of the molecule, owing to the partial saturation of the inner quinolizine ring system. Although lacking classical O—H or N—H donors, the packing in the crystalline state is clearly governed by C—H...N and C—H...O hydrogen bonds involving the two acetal‐type C—H bonds of the 1,3‐dioxole ring. Each dihydroberberine molecule is engaged in four hydrogen bonds with neighbouring molecules, twice as donor and twice as acceptor, thus forming a two‐dimensional sheet network that lies parallel to the (100) plane.     

Unusual hydrogen bonding in L‐cysteine hydrogen fluoride

L‐Cysteine hydrogen fluoride, or bis(L‐cysteinium) difluoride–L‐cysteine–hydrogen fluoride (1/1/1), 2C₃H₈NO₂S⁺·2F⁻·C₃H₇NO₂S·HF or L‐Cys⁺(L‐Cys...L‐Cys⁺)F⁻(F⁻...H—F), provides the first example of a structure with cations of the `triglycine sulfate' type, i.e.A⁺(A...A⁺) (where A and A⁺ are the zwitterionic and cationic states of an amino acid, respectively), without a doubly charged counter‐ion. The salt crystallizes in the monoclinic system with the space group P2₁. The dimeric (L‐Cys...L‐Cys⁺) cation and the dimeric (F⁻...H—F) anion are formed via strong O—H...O or F—H...F hydrogen bonds, respectively, with very short O...O [2.4438 (19) Å] and F...F distances [2.2676 (17) Å]. The F...F distance is significantly shorter than in solid hydrogen fluoride. Additionally, there is another very short hydrogen bond, of O—H...F type, formed by a L‐cysteinium cation and a fluoride ion. The corresponding O...F distance of 2.3412 (19) Å seems to be the shortest among O—H...F and F—H...O hydrogen bonds known to date. The single‐crystal X‐ray diffraction study was complemented by IR spectroscopy. Of special interest was the spectral region of vibrations related to the above‐mentioned hydrogen bonds.