The progression of strong and weak hydrogen bonds in a series of ethylenediammonium dithiocyanate derivatives--a new bonding protocol for macromolecules?

The experimental charge densities for a series of sym-N-methyl-substituted ethylenediammonium dithiocyanate salts have been investigated based on low-temperature and high-resolution X-ray diffraction data. This series of organic dications provides both strong and weak hydrogen bonding networks that vary depending on the N-H : SCN(-) (donor/acceptor) ratios. The number of N-HN hydrogen bonds connected to each cation increases (linear to bifurcated) as the number of N-H donor groups increases. The bifurcated thiocyanate anions also form a less energetic N-HS hydrogen bond. The presence of more than one hydrogen bond acceptor on each thiocyanate anion results in a competition between the sulfur and nitrogen atoms in forming both strong and weak hydrogen bonds. The formation of a significant number of weak hydrogen bonds is shown to play a crucial role in stabilizing these organic ionic crystals. The progression of these organic dications (smaller to larger N-H : SCN(-) ratios) results in the weaker hydrogen bonds playing a smaller role in stabilizing the crystalline structures. In addition, the electron density along the saddle point has been shown to vary significantly from weak hydrogen bonds to van der Waals interactions. This has led to a better understanding of the progression of hydrogen bonding in the crystalline states of sym-N-methyl substituted ethylenediammonium dithiocyanate salts and provides insight into the relationship between strong and weak hydrogen bonds in organic ionic crystals.     

Interpretation of hydrogen bonding in the weak and strong regions using conceptual DFT descriptors

Hydrogen bonding is among the most fundamental interactions in biology and chemistry, providing an extra stabilization of 1-40 kcal/mol to the molecular systems involved. This wide range of stabilization energy underlines the need for a general and comprehensive theory that will explain the formation of hydrogen bonds. While a simple electrostatic model is adequate to describe the bonding patterns in the weak and moderate hydrogen bond regimes, strong hydrogen bonds, on the other hand, require a more complete theory due to the appearance of covalent interactions. In this study, conceptual DFT tools such as local hardness, eta(r) and local softness, s(r), have been used in order to get an alternative view on solving this hydrogen-bonding puzzle as described by Gilli et al. [J. Mol. Struct. 2000, 552, 1]. A series of both homonuclear and heteronuclear resonance-assisted hydrogen bonds of the types O-H...N, N-H...O, N-H...N, and O-H...O with strength varying from weak to very strong have been studied. First of all, DeltaPA and DeltapK(a) values were calculated and correlated to the hydrogen bond energy. Then the electrostatic effects were examined as hard-hard interactions accessible through molecular electrostatic potential, natural population analysis (NPA) charge, and local hardness calculations. Finally, secondary soft-soft interaction effects were entered into the picture described by the local softness values, providing insight into the covalent character of the strong hydrogen bonds.     

Weak Intermolecular Hydrogen Bonds with Fluorine: Detection and Implications for Enzymatic/Chemical Reactions,Chemical Properties,and Ligand/Protein Fluorine NMR Screening

It is known that strong hydrogen‐bonding interactions play an important role in many chemical and biological systems. However, weak or very weak hydrogen bonds, which are often difficult to detect and characterize, may also be relevant in many recognition and reaction processes. Fluorine serving as a hydrogen‐bond acceptor has been the subject of many controversial discussions and there are different opinions about it. It now appears that there is compelling experimental evidence for the involvement of fluorine in weak intramolecular or intermolecular hydrogen bonds. Using established NMR methods, we have previously characterized and measured the strengths of intermolecular hydrogen‐bond complexes involving the fluorine moieties CH₂F, CHF₂, and CF₃, and have compared them with the well‐known hydrogen‐bond complex formed between acetophenone and the strong hydrogen‐bond donor p‐fluorophenol. We now report evidence for the formation of hydrogen bonds involving fluorine with significantly weaker donors, namely 5‐fluoroindole and water. A simple NMR method is proposed for the simultaneous measurement of the strengths of hydrogen bonds between an acceptor and a donor or water. Important implications of these results for enzymatic/chemical reactions involving fluorine, for chemical and physical properties, and for ligand/protein ¹⁹F NMR screening are analyzed through experiments and theoretical simulations.     

The hydrogen bond in the solid state

The hydrogen bond is the most important of all directional intermolecular interactions. It is operative in determining molecular conformation, molecular aggregation, and the function of a vast number of chemical systems ranging from inorganic to biological. Research into hydrogen bonds experienced a stagnant period in the 1980s, but re-opened around 1990, and has been in rapid development since then. In terms of modern concepts, the hydrogen bond is understood as a very broad phenomenon, and it is accepted that there are open borders to other effects. There are dozens of different types of X-H.A hydrogen bonds that occur commonly in the condensed phases, and in addition there are innumerable less common ones. Dissociation energies span more than two orders of magnitude (about 0.2-40 kcal mol(-1)). Within this range, the nature of the interaction is not constant, but its electrostatic, covalent, and dispersion contributions vary in their relative weights. The hydrogen bond has broad transition regions that merge continuously with the covalent bond, the van der Waals interaction, the ionic interaction, and also the cation-pi interaction. All hydrogen bonds can be considered as incipient proton transfer reactions, and for strong hydrogen bonds, this reaction can be in a very advanced state. In this review, a coherent survey is given on all these matters.     

Nature and physical origin of CH/pi interaction: significant difference from conventional hydrogen bonds

Recently reported high-level ab initio calculations and gas phase spectroscopic measurements show that the nature of CH/pi interactions is considerably different from conventional hydrogen bonds, although the CH/pi interactions were often regarded as the weakest class of hydrogen bonds. The major source of attraction in the CH/pi interaction is the dispersion interaction and the electrostatic contribution is small, while the electrostatic interaction is mainly responsible for the attraction in the conventional hydrogen bonds. The nature of the "typical" CH/pi interactions is similar to that of van der Waals interactions, if some exceptional "activated" CH/pi interactions of highly acidic C-H bonds are excluded. Shifts of C-H vibrational frequencies and electronic spectra also support the similarity. The hydrogen bond is important in controlling structures of molecular assemblies, since the hydrogen bond is sufficiently strong and directional due to the large electrostatic contribution. On the other hand, the directionality of the "typical" CH/pi interaction is very weak. Although the "typical" CH/pi interaction is often regarded as an important interaction in controlling the structures of molecular assemblies as in the cases of conventional hydrogen bonds, the importance of the "typical" CH/pi interactions is questionable.     

Ab initio investigation of the complexes between bromobenzene and several electron donors: some insights into the magnitude and nature of halogen bonding interactions

Halogen bonding, a specific intermolecular noncovalent interaction, plays crucial roles in fields as diverse as molecular recognition, crystal engineering, and biological systems. This paper presents an ab initio investigation of a series of dimeric complexes formed between bromobenzene and several electron donors. Such small model systems are selected to mimic halogen bonding interactions found within crystal structures as well as within biological molecules. In all cases, the intermolecular distances are shown to be equal to or below sums of van der Waals radii of the atoms involved. Halogen bonding energies, calculated at the MP2/aug-cc-pVDZ level, span over a wide range, from -1.52 to -15.53 kcal/mol. The interactions become comparable to, or even prevail over, classical hydrogen bonding. For charge-assisted halogen bonds, calculations have shown that the strength decreases in the order OH- > F- > HCO2- > Cl- > Br-, while for neutral systems, their relative strengths attenuate in the order H2CS > H2CO > NH3 > H2S > H2O. These results agree with those of the quantum theory of atoms in molecules (QTAIM) since bond critical points (BCPs) are identified for these halogen bonds. The QTAIM analysis also suggests that strong halogen bonds are more covalent in nature, while weak ones are mostly electrostatic interactions. The electron densities at the BCPs are recommended as a good measure of the halogen bond strength. Finally, natural bond orbital (NBO) analysis has been applied to gain more insights into the origin of halogen bonding interactions.     

Hydrogen bonding in selected vanadates: a Raman and infrared spectroscopy study

Water plays an important role in the stability of minerals containing the deca and hexavanadates ions. A selection of minerals including pascoite, huemulite, barnesite, hewettite, metahewettite, hummerite has been analysed. Infrared spectroscopy combined with Raman spectroscopy has enabled the spectra of the water HOH stretching bands to be determined. The use of the Libowitsky type function allows for the estimation of hydrogen bond distances to be determined. The strength of the hydrogen bonds can be assessed by these hydrogen bond distances. An arbitrary value of 2.74A was used to separate the hydrogen bonds into two categories such that bond distances less than this value are considered as strong hydrogen bonds whereas hydrogen bond distances greater than this value are considered relatively weaker. Importantly infrared spectroscopy enables the estimation of hydrogen bond distances using an empirical function.     

Toward assessing the position-dependent contributions of backbone hydrogen bonding to beta-sheet folding thermodynamics employing amide-to-ester perturbations

An amide-to-ester backbone substitution in a protein is accomplished by replacing an alpha-amino acid residue with the corresponding alpha-hydroxy acid, preserving stereochemistry, and conformation of the backbone and the structure of the side chain. This substitution replaces the amide NH (a hydrogen bond donor) with an ester O (which is not a hydrogen bond donor) and the amide carbonyl (a strong hydrogen bond acceptor) with an ester carbonyl (a weaker hydrogen bond acceptor), thus perturbing folding energetics. Amide-to-ester perturbations were used to evaluate the thermodynamic contribution of each hydrogen bond in the PIN WW domain, a three-stranded beta-sheet protein. Our results reveal that removing a hydrogen bond donor destabilizes the native state more than weakening a hydrogen bond acceptor and that the degree of destabilization is strongly dependent on the location of the amide bond replaced. Hydrogen bonds near turns or at the ends of beta-strands are less influential than hydrogen bonds that are protected within a hydrophobic core. Beta-sheet destabilization caused by an amide-to-ester substitution cannot be directly related to hydrogen bond strength because of differences in the solvation and electrostatic interactions of amides and esters. We propose corrections for these differences to obtain approximate hydrogen bond strengths from destabilization energies. These corrections, however, do not alter the trends noted above, indicating that the destabilization energy of an amide-to-ester mutation is a good first-order approximation of the free energy of formation of a backbone amide hydrogen bond.     

Spectroscopic and semiempirical studies of new Schiff base of gossypol with allylamine in solution

The Schiff base of racemic gossypol with allylamine (GSBAL) has been studied by FT-IR, ¹H and ¹³C NMR spectroscopy as well as by the PM5 semiempirical method. The spectroscopic methods have shown that GSBAL Schiff base exists in chloroform solution as enamine–enamine tautomer. The structure of GSBAL and the hydrogen bonds within this structure have been calculated to show that the allyl groups are out-of-planes of naphthalene rings. The strongest intramolecular hydrogen bond within the structure of GSBAL is formed between O₇H–N₁₆ atoms and it belongs to the medium strong bonds. The other hydrogen bonds, although very weak, play a very important role in stabilising the GSBAL enamine–enamine structure.     

Electron correlations in molecules. III. Strength of electron correlations in localized and aromatic bonds of main-group atoms

We investigate electron correlations within a minimal basis of various chemical bonds formed by second- and third-row atoms and hydrogen. The effects of correlations are characterized by two quantities: (i) intrabond correlation energy ϵ_corr and (ii) the correlation strength parameter Σ. The latter describes the relative suppression of the charge fluctuations within a bond. The quantities ϵ_corr and Σ can be associated with chemical bonds due to the local nature of the correlation phenomenon. It is found that one may distinguish between different classes of chemical bonds which are characterized by similar values of Σ parameter within each class. For instance, all considered bonds between hydrogen and main-group atoms fall into one class. The homopolar bonds formed by the atoms of the third row are characterized by a weaker σ but stronger π correlation strength than the respective bonds of the second row. The strongest correlations are found in homopolar single π bonds of third-row atoms. A particular detailed discussion is given of heteropolar bonds. The electron correlations of aromatic π electrons are found to be considerably weaker than those within the corresponding localized bonds. For the SCF input of the correlation calculation a semi-empirical method is used. The bond orbital approximation allows for a transparent interpretation of the computational results.     

Energetics of protein backbone hydrogen bonds and their local electrostatic environment

MD simulation study of several peptides including a polyalanine,a helix(pdb:2I9M),and a leucine zipper were carried out to investigate hydrogen bond energetics using dynamic polarized protein-specific charge(DPPC)to account for the polarization effect in protein dynamics.Results show that the backbone hydrogen-bond strength is generally correlated with its specific local electrostatic environment,measured by the number of water molecules near the hydrogen bond in the first solvation shell.The correlation coefficient is found to be 0.89,0.78,and 0.80,respectively,for polyalanine,2I9M protein,and leucine zipper.In the polyalanine,the energies of the backbone hydrogen bonds are very similar to each other due to their similar local electrostatic environment.The current study helps demonstrate and support the understanding that hydrogen bonds are stronger in a hydrophobic surrounding than in a hydrophilic one.For comparison,the result from simulation using standard force field shows a much weaker correlation between hydrogen bond energy and local electrostatic environment due to the lack of polarization effect in the force field.     

Intermolecular-medium and intramolecular-weak hydrogen bonding chains in the crystals of chiral trifluoromethylated amino alcohols

A structural feature of hydrogen bonding chains found in the crystals of trifluoromethylated amino alcohols is reported. Hydrogen bondings of 3-(N,N-dialkylamino)-1,1,1-trifluoro-2-propanols construct chiral spiral hydrogen bonding chains. Lone pairs on the nitrogen atoms of the amino alcohols participate in two hydrogen bondings. Detailed structural analysis of the hydrogen bonds of the 3-(N,N-dimethylamino)-1,1,1-trifluoro-2-propanol suggested that the chain built up with alternating intermolecular-medium and intramolecular-weak hydrogen bonds. The medium intermolecular hydrogen bond, which transfers a proton from the hydroxy group to the amino nitrogen, would make a tentative zwitterionic form of the molecule. Then, electrostatic attraction between the charges in the zwitterion centers induced a weak intramolecular hydrogen bond.     

The coordination chemistry of the proton

It is well known that an acidic hydrogen atom can form hydrogen bonds to a hydrogen bond acceptor, a Lewis base. It is considerably less known that the proton can coordinate two or more atoms conveniently in bonding modes that cannot be described as hydrogen bonding. Agostic interactions, bridging hydrides, 3-centre-2-electron bonds in boranes, bifurcated hydrogen atoms, they are all elements of the coordination chemistry of the proton and, of course, the hydrogen bond comes in more than one facette as well.     

Quantum mechanical studies on the existence of a trigonal bipyramidal phosphorane intermediate in enzymatic phosphate ester hydrolysis

Phosphate ester hydrolysis is a key step in several enzymatic processes, which follow either a dissociative or an associative mechanism. While in the aqueous phase both pathways are favoured to about the same extent, the associative mechanism is relatively rarely observed. In this paper we report on quantum mechanical calculations for three enzymes HIV integrase, β-phosphoglucomutase and dUTPase, and try to find an explanation for the preference of the associative mechanism in a given enzyme. It is reasonable to suppose that the stabilisation of the pentacovalent, trigonal bipyramidal phosphorane moiety by formation of a covalent bond, one or more hydrogen bonds, or by co-ordination of a divalent metal cation with the equatorial oxygen atoms is the key factor. In all three enzymes studied one of the equatorial oxygen atoms is co-ordinated to a magnesium dication, while a second one is involved in a covalent bond. While in HIV integrase the third oxygen atom may only form a weak hydrogen bond with a solvent water molecule, in β-phosphoglucomutase this atom is stabilised by two strong hydrogen bonds with adjacent protein side chains and in dUTPase it is involved in a covalent bond. Contribution to the Fernando Bernardi Memorial Issue.     

Synthesis,Crystal and Molecular Structure of Mono- and Diaquadi(acetato-O)-Bis(2,4′-Bipyridyl) Copper(II)

The title compound has been synthesized and characterized by elemental analysis and conductivity studies. The crystal and molecular structure has been determined. There are two different types of molecules in the crystal: mono- and diaquadi(acetato-O)-bis(2,4'-bipyridyl) copper (II). Both copper atoms occupy special positions. The copper atoms show almost ideal square pyramidal (4 + 1) and square bipyramidal (4 + 2) coordination. Due to the Jahn-Teller effect, the axial Cu-O(water) bond distances are longer than respective equatorial Cu-O(acetate) bond distances. The bond valences of the copper were computed. An intramolecular strong hydrogen bond linking O(water) and O(acetate) atoms exists in the molecule. The differences of geometrical environment for copper in mono- and diaquadi(acetato-O)-bis(2,4'-bipyridyl) copper(II) are imposed by strong intermolecular hydrogen bonds creating a linear infinite chain structure along crystallographic x axis. Also weak intramolecular hydrogen bonds are present in the molecule.     

A DFT-based study of the hydrogen-bonding interactions between epicatechin and methanol/water

Tea polyphenols are essential components that give tea its medicinal properties. Methanol and water are frequently used as solvents in the extraction of polyphenols. Hydrogen-bonding interactions are significant in the extraction reaction. Density functional theory (DFT) techniques were used to conduct a theoretical investigation on the hydrogen-bonding interactions between methanol or water and epicatechin, an abundant polyphenol found in tea. After first analyzing the epicatechin monomer's molecular geometry and charge characteristics, nine stable epicatechin (EC) H₂O/CH₂OH complex geometries were discovered. The presence of hydrogen bonding in these improved structures has been proven. The calculated hydrogen bond structures are very stable, among which the hydrogen bond bonded with a hydroxyl group has higher stability. The nine complex structures’ hydrogen bonds were thought to represent closed-shell-type interactions. The interaction energy with 30O-31H on the epicatechin benzene ring is the strongest in the hydrogen bond structure. While the other hydrogen bonds were weak in strength and mostly had an electrostatic nature, the hydrogen bonds between the oxygen atoms in H₂O or CH₂OH and the hydrogen atoms of the hydroxyl groups in epicatechin were of moderate strength and had a covalent character. Comparing the changes in the hydrogen bond structure vibration peak, the main change in concentration peak is the hydrogen bond vibration peak in the complex. Improved the study on the hydrogen bond properties of CH₂OH and H₂O of EC.     

Can We Merge the Weak and Strong Tetrel Bonds? Electronic Features of Tetrahedral Molecules Interacted with Halide Anions

Using the orbital-free quantum crystallography approach, we have disclosed the quantitative trends in electronic features for bonds of different strengths formed by tetrel (Tt) atoms in stable molecular complexes consisting of electrically neutral tetrahedral molecules and halide anions. We have revealed the role of the electrostatic and exchange-correlation components of the total one-electron static potential that are determined by the equilibrium atomic structure and by kinetic Pauli potential, which reflects the spin-dependent electron motion features of the weak and strong bonds. The gap between the extreme positions in the electrostatic and total static potentials along the line linking the Tt atom and halide anion is wide for weak bonds and narrow for strong ones. It is in very good agreement with the number of minima in the Pauli potential between the bounded atoms. This gap exponentially correlates with the exchange-correlation potential in various series with a fixed nucleophilic fragment. A criterion for categorizing the noncovalent tetrel bonds (TtB) based on the potential features is suggested.     

Quantitative information about the hydrogen bond strength in dilute aqueous solutions of methanol from the temperature dependence of the Raman spectra of the decoupled OD stretch

We have obtained quantitative information about the hydrogen bond strength in pure water and in dilute aqueous solutions of methanol by analyzing the temperature dependence of Raman spectra of the decoupled OD stretch from 21 to 160 degrees C with the hydrogen bond energy dispersion method. A minimum at 2440 cm(-1) assigned to strong icelike hydrogen bonds and a maximum at 2650 cm(-1) due to maximally (but not completely) broken hydrogen bonds result in all cases. The energy of the minimum decreases upon addition of methanol due to formation of stronger water-methanol hydrogen bonds, whereas the energy of the maximum increases because water hydrogen atoms in the vicinity of the methyl group might participate in "more broken" hydrogen bonds than in bulk water.     

Binding of genistein to the estrogen receptor based on an experimental electron density study

In a continuing effort to determine a relationship between the biological function and the electronic properties of steroidal and nonsteroidal estrogens by analysis of the submolecular properties, an experimental charge density study has been pursued on the nonsteroidal phytoestrogen, genistein. X-ray diffraction data were obtained using a Rigaku R-Axis Rapid high-power rotating anode diffractometer with a curved image plate detector at 20(1) K. The total electron density was modeled using the Hansen-Coppens multipole model. Genistein packs in puckered sheets characterized by intra- and intermolecular hydrogen bonds while weaker intermolecular hydrogen bonds (O...H-C) exist between the sheets. A topological analysis of the electron density of genistein was then completed to characterize all covalent bonds, three O...H-O and four O...H-C intermolecular hydrogen bonds. Two O...H-O hydrogen bonds are incipient (partially covalent) type bonds, while the other O...H-O hydrogen bond and O...H-C hydrogen bonds are of the pure closed-shell interaction type. In addition, two intermolecular H...H interactions have also been characterized from the topology of the electron density. The binding of genistein to the estrogen receptor is discussed in terms of the electrostatic potential derived from the electron density distribution.