A theoretical study on unusual intermolecular T-shaped X–H...π interactions between the singlet state HB=BH and HF, HCl, HCN or H2C2

The unusual T-shaped X–H...π hydrogen bonds are found between the B=B double bond of the singlet state HB=BH and the acid hydrogen of HF, HCl, HCN and H₂C₂ using MP2 and B3LYP methods at 6-311++G(2df,2p) and aug-cc-pVTZ levels. The binding energies follow the order of HB=BH...HF>HB=BH...HCl>HB=BH...HCN>HB=BH...H₂C₂. The hydrogen-bonded interactions in HB=BH...HX are found to be stronger than those in H₂C=CH₂...HX and OCB≡BCO...HX. The analyses of natural bond orbital (NBO) and the electron density shifts reveal that the nature of the T-shaped X–H...π hydrogen-bonded interaction is that much of the lost density from the π-orbital of B=B bond is shifted toward the hydrogen atom of the proton donor, leading to the electron density accumulation and the formation of the hydrogen bond. The atoms in molecules (AIM) theory have also been applied to characterize bond critical points and confirm that the B=B double bond can be a potential proton acceptor. The unusual T-shaped X–H...π hydrogen bonds are found between the B=B double bond of the singlet state HB=BH and the acid hydrogen of HF, HCl, HCN and H₂C₂     

Quantum chemical investigation of the intra- and intermolecular proton transfer reactions and hydrogen bonding interactions in 4-amino-5-(2-hydroxyphenyl)-2H-1,2,4-triazole-3(4H)-thione

The intramolecular thione-thiol tautomerism and intermolecular double proton transfer reaction of the hydrogen-bonded thione and thiol dimers in the title triazole compound were studied at the B3LYP level of theory using 6?311++G(d,p) basis function. The influence of the solvent on the single and double proton transfer reactions was examined in three solvents (chloroform, methanol and water) using the polarizable continuum model (PCM) approximation. The computational results show that the thione tautomer is the most stable isomer with a very high tautomeric energy barrier both in the gas phase and in solution phase, indicating a quite disfavored process. The solvent effect is found to be sizable with increasing polarity. In the double proton transfer reaction, the thione dimer is found to be more stable than thiol dimer both in the gas phase and in solution phase. The energetic and thermodynamic parameters of the double proton transfer process show that the double proton exchange from thione dimer to thiol dimer is thermodynamically unfavored. However, the exchange from thiol dimer to thione dimer for the gas phase and water phase seems to be feasible with a low barrier height and with a negative value in enthalpy and free energy changes. In addition, the hydrogen bonding interactions were analyzed in the gas phase regarding their geometries and energies. It is found that all complex formations are enthalpically favored, and the stability of the H-bonds comes in the order of S1—H2···N2 > N2—H2···S1 > N3—H3B···O1. Finally, non-linear optical properties were carried out at the same calculation level in the gas phase.

Theoretical investigations on the hydrogen bonding of nitrile isomers with H2O,HF, NH3 and H2S

The hydrogen bonds formed by the interaction of nitriles with water, hydrogen fluoride, ammonia and hydrogen sulphide have been studied using B3LYP and second-order Møller–Plesset perturbation (MP2) methods and 6-311+ + G(d,p) basis set. The energies and structures of 80 hydrogen-bonded complexes between nitriles and small molecules were examined systematically using B3LYP and MP2 procedure. Categorisation of the hydrogen bonds involved in the various complexes led to an ordering of hydrogen bond donor and acceptor abilities for some functional groups. The interaction energies have been corrected for the basis set superposition error using Boy's counterpoise correction method. The Morokuma energy decomposition analysis reveals that the strong interactions are due to the attractive contributions from the electrostatic (ES), polarisation (PL) and charge transfer (CT) components. The topological parameters, electron density and Laplacian of electron density show excellent correlation with the hydrogen bond length. Natural bond orbital (NBO) analysis has also been performed to study the CT from proton acceptor to the antibonding orbital of the H–Y bond in the proton donor part of complexes. The frequency analysis of C–H…Y bond in the complexes indicates the blue-shifting nature largely in case of sp² hybridised carbon atom.     

On the evolutionary conservation of hydrogen bonds made by buried polar amino acids: the hidden joists,braces and trusses of protein architecture

Background  

The hydrogen bond patterns between mainchain atoms in protein structures not only give rise to regular secondary structures but also satisfy mainchain hydrogen bond potential. However, not all mainchain atoms can be satisfied through hydrogen bond interactions that arise in regular secondary structures; in some locations sidechain-to-mainchain hydrogen bonds are required to provide polar group satisfaction. Buried polar residues that are hydrogen-bonded to mainchain amide atoms tend to be highly conserved within protein families, confirming that mainchain architecture is a critical restraint on the evolution of proteins. We have investigated the stabilizing roles of buried polar sidechains on the backbones of protein structures by performing an analysis of solvent inaccessible residues that are entirely conserved within protein families and superfamilies and hydrogen bonded to an equivalent mainchain atom in each family member.     

Mechanism of proton transfer. II. Transfers to and from imidazole

A CNDO/2 calculation of an imidazole plus a proton in the plane perpendicular to the imidaxole plane has shown that the proton is lost most easilu in the direction defined by the N---H bond regardless of whether the hydrogen bond is bent or is not bent. However, bent hydrogen bonds transfer protons much easier than unstrained hydrogen bonds in agreement with the chymotrypsin mechanism of Wang.     

Association studies of N-acetyl-amino acid N,N-dimethylamides in carbon tetrachloride

The self-association of N-acetylglycine N,N-dimethylamide, N-acetyl-L -valine N,N-dimethylamide, and N-acetyl-L -phenylalanine N,N-dimethylamide in carbon tetrachloride was investigated by using ir and ¹H-nmr methods. It was concluded from ir measurements that the associated species is the dimer formed as a result of the simultaneous formation of two intermolecular hydrogen bonds. This is supported by the results of ¹H-nmr measurements. Thermodynamic quantities for the association were determined from the temperature and concentration dependence of the NH proton chemical shifts of the sample solutions. Compared with the Gly derivative, L -Val and L -Phe derivatives have larger values of ?ΔH for association, which shows good correlation with Δv_NH values, the difference between the maxima of the monomer and dimer bands, obtained from ir spectra. This is due to the less stable monomer conformation and to the stronger intermolecular hydrogen bonding of the dimers in L -Val and L -Phe derivatives. The line shapes of both methyl proton resonances of L -Val residue and methylene proton resonances of L -Phe residue were found to vary with concentration and temperature of the sample solutions. These data indicate that the rotation about the C^α—C^β bond is restricted by the steric hindrance present in the associated dimers. All these experimental results can be related to the fact that L -Val and L -Phe derivatives have a warped framework because of the bulky side chains, whereas the Gly derivative has a planar framework.     

Computational study of the intramolecular proton transfer reactions of 3-hydroxytropolone (2,7-dihydroxycyclohepta-2,4,6-trien-1-one) and its dimers

The proton transfer reaction and dimerization processes of 3-hydroxytropolone (3-OHTRN) have been investigated using density functional theory (DFT) at the B3LYP/6–31+G** level. The influence of the solvent on the proton transfer reaction of 3-OHTRN was examined using the self-consistent isodensity polarized continuum model (SCI-PCM) with different dielectric constants (ε?=?4.9, CHCI₃; ε?=?32.63, CH₃OH; ε?=?78.39, H₂O). The intramolecular proton transfer reaction occurs more readily in the gas phase than in solution. Results also show that the stability of 3-OHTRN dimers in the gas phase is directly affected by the hydrogen bond length in the dimer structure.     

Dissecting non-canonical interactions in frameshift-stimulating mRNA pseudoknots

A variety of powerful NMR experiments have been introduced over the last few years that allow for the direct identification of different combinations of donor and acceptor atoms involved in hydrogen bonds in biomolecules. This ability to directly observe tertiary structural hydrogen bonds in solution tremendously facilitates structural studies of nucleic acids. We show here that an adiabatic HNN-COSY pulse scheme permits observation and measurement of J(N,N) couplings for nitrogen sites that are separated by up to 140 ppm in a single experiment at a proton resonance frequency of 500 MHz. Crucial hydrogen bond acceptor sites in nucleic acids, such as cytidine N3 nitrogens, can be unambiguously identified even in the absence of detectable H41 and H42 amino protons using a novel triple-resonance two-dimensional experiment, denoted H5(C5C4)N3. The unambiguous identification of amino nitrogen donor and aromatic nitrogen acceptor sites associated with both major groove as well as minor groove triple base pairs reveal the details of hydrogen bonding networks that stabilize the complex architecture of frameshift-stimulating mRNA pseudoknots. Another key tertiary interaction involving a 2′-OH hydroxyl proton that donates a hydrogen bond to an aromatic nitrogen acceptor in a cis Watson–Crick/sugar edge interaction can also be directly detected using a quantitative J(H,N) ¹H,¹⁵N-HSQC experiment.     

Hydrogen bonding interactions in E- or Z-2-phenyl-3-( X'-pyridyl)propenoic acid ( X=2, 3 or 4) assemblies--a molecular modeling study

The agglomeration properties of stereoisomeric 2-phenyl-3-(X-pyridyl)propenoic acids (X=2, 3 or 4) were studied by the PM3 semiempirical quantum chemical method. Calculations revealed that dimers kept together by the intermolecular hydrogen bonding interactions of the carboxylic groups could be built from both stereoisomers irrespective of the position of the nitrogen heteroatom. The dimers of the Z-isomers could also be built through (aromatic)C–H...N hydrogen bonds between the dimer units. The longest agglomerate was the pentamer of the dimers when the nitrogen was in the 2 position. Longer hydrogen-bonded agglomerates than dimers could only be constructed from the E-isomer with the nitrogen in position 4. Here, the trimer of the dimers proved to be the longest hydrogen-bonded entity and similarly to the Z-isomers, the dimer units are kept together by (aromatic)C–H...N intermolecular hydrogen bonds.Figure The helical structure of the pentamer of dimers for the Z-2-phenyl-3-(2-pyridyl)propenoic acid molecule, when in the initial geometry (aromatic)C(4)–H...N close contact was enforced.     

Structure of prealbumin: secondary, tertiary and quaternary interactions determined by Fourier refinement at 1.8 A

The principal elements of the secondary, tertiary and quaternary structure of the tetrameric human plasma prealbumin molecule have been determined by Fourier refinement of X-ray diffraction data at 1.8 Å resolution. The subunit has an extensive β-structure composed of eight strands organised into two four-stranded sheets. There is also one short α-helix. The tertiary structure is largely determined by the association of the two β-sheets. Important contributions to the tertiary structure are made by three tyrosines and one aspartic acid involved in side-chain-main-chain interactions; a buried histidine associated with a group of internal water molecules; and a compact cluster of seven aromatic residues. Quaternary interactions occur at two sets of interfaces closely organised around two of the three molecular 2-fold axes. The exclusive monomer-monomer interface is chiefly concerned with antiparallel hydrogen bond interactions which extend the two four-stranded sheets in the monomers to eight-stranded sheets in the dimer. One of the sheet interactions includes water molecules and tyrosine hydroxyls in the hydrogen bond pattern. The dimers associate through both hydrophilic and hydrophobic interactions at interfaces that involve all four monomers.     

Theoretical investigations of the H···π and X (X = F,Cl, Br,I)···π complexes between hypohalous acids and benzene

The H···π and X (X = F, Cl, Br, I)···π interactions between hypohalous acids and benzene are investigated at the MP2/6-311++G(2d,2p) level. Four hydrogen-bonded and three halogen-bonded complexes were obtained. Ab initio calculations indicate that the X···π interaction between HOX and C₆H₆ is mainly electrostatically driven, and there is nearly an equal contribution from both electrostatic and dispersive energies in the case of XOH–C₆H₆ complexes. Natural bond orbital (NBO) analysis reveals that there exists charge transfer from benzene to hypohalous acids. Atom in molecules (AIM) analysis locates bond critical points (BCP) linking the hydrogen or halogen atom and carbon atom in benzene.     

Structure and dynamics of a proton wire: a theoretical study of H+ translocation along the single-file water chain in the gramicidin A channel.

The rapid translocation of H+ along a chain of hydrogen-bonded water molecules, or proton wire, is thought to be an important mechanism for proton permeation through transmembrane channels. Computer simulations are used to study the properties of the proton wire formed by the single-file waters in the gramicidin A channel. The model includes the polypeptidic dimer, with 22 water molecules and one excess proton. The dissociation of the water molecules is taken into account by the "polarization model" of Stillinger and co-workers. The importance of quantum effects due to the light mass of the hydrogen nuclei is examined with the use of discretized Feynman path integral molecular dynamics simulations. Results show that the presence of an excess proton in the pore orients the single-file water molecules and affects the geometry of water-water hydrogen bonding interactions. Rather than a well-defined hydronium ion OH3+ in the single-file region, the protonated species is characterized by a strong hydrogen bond resembling that of O2H5+. The quantum dispersion of protons has a small but significant effect on the equilibrium structure of the hydrogen-bonded water chain. During classical trajectories, proton transfer between consecutive water molecules is a very fast spontaneous process that takes place in the subpicosecond time scale. The translocation along extended regions of the chain takes place neither via a totally concerted mechanism in which the donor-acceptor pattern would flip over the entire chain in a single step, nor via a succession of incoherent hops between well-defined intermediates. Rather, proton transfer in the wire is a semicollective process that results from the subtle interplay of rapid hydrogen-bond length fluctuations along the water chain. These rapid structural fluctuations of the protonated single file of waters around an average position and the slow movements of the average position of the excess proton along the channel axis occur on two very different time scales. Ultimately, it is the slow reorganization of hydrogen bonds between single-file water molecules and channel backbone carbonyl groups that, by affecting the connectivity and the dynamics of the single-file water chain, also limits the translocation of the proton across the pore.     

Homochirality and long-range transfer in biological systems.

It has been shown that the chiral purity of biomacromolecules has important biological significance not only from the standpoint of lock-and-key stereocomplementarity, but also as a basis for long-range communication in biosystems. An explicit demonstration is given for the case of proton transfer along the hydrogen-bonded chain that is formed by amino acids containing OH groups. It is found that the replacement of the L-amino acid residue by the D-isomer in a peptide chain suppresses proton transport through the hydrogen bond network.     

Hydrogen bonds determine the structures of the ternary heterocyclic complexes C₂H₄O···2HF, C₂H₅N···2HF and C₂H₄S···2HF: density functional theory and topological calculations

A theoretical study of structural, electronic, topological and vibrational parameters of the ternary hydrogen-bonded complexes C₂H₄O···2HF, C₂H₅N···2HF and C₂H₄S···2HF is presented here. Different from binary systems with a single proton donor, the tricomplexes have the property of forming multiple hydrogen bonds, which are analyzed from a structural and vibrational point of view, but verified only by means of the quantum theory of atoms in molecules (QTAIM). As traditionally done in the hydrogen bond theory, the charge transfer between proton donors and acceptors was computed using the CHELPG calculations, which also revealed agreement with dipole moment variation and a cooperative effect on the tricomplexes. Furthermore, redshift events on proton donor bonds were satisfactorily identified, although, in this case, an absence of experimental data led to the use of a theoretical argument to interpret these spectroscopic shifts. It was therefore the use of the QTAIM parameters that enabled all intermolecular vibrational modes to be validated. The most stable tricomplex in terms of energy was identified via the strength of the hydrogen bonds, which were modeled as directional and bifurcated.     

Abundance and arrangement of single,double and bifurcated hydrogen bonds in protein α-helices: Statistical analysis of PDB-select

Statistics are collected and analyzed for the possibility of hydrogen bonding in the secondary structures of globular proteins, based on geometric criteria. Double and bifurcated bonds are considered as pairs of admissible H-bonds with two proton donors or two proton acceptors, respectively. Most of such bonds belong to peptide groups in α-helices, with O _i …N _{i + 3} nearly as frequent as O _i …N _{i + 4}; in contrast, most of the 3/10-helical segments are too short to have any. Alternating double and bifurcated bonds in α-helices form an apparently cooperative network structure. A typical α-helical segment perhaps carries two stretches of the H-bond network broken in the middle. The constituent H-bonds are nonlinear: the hydrogen atom is off the straight line connecting the proton donor and proton acceptor atoms. This deflection is larger for H _{i + 3} vs. bond line O _i −N _{i + 3} than for H _{i + 4} vs. O _i −N _{i + 4}, and though the two kinds of bond have about the same length (exceeding those typical of low-molecular compounds), O _i …N _{i + 4} must be stronger than O _i …N _{i + 3}. Double/bifurcated bonds are also not coplanar, i.e., hydrogen atoms are beyond the N…O…N (or O…N…O) plane. The text was submitted by the authors in English.     

Proton transfer in and polarizability of hydrogen bonds coupled with conformational changes in proteins. II. IR investigation of polyhistidine with various carboxylic acids

Polyhistidine-carboxylic acid systems are studied by ir spectroscopy. It is shown that OH ?N ? O^?…H⁺N bonds formed between carboxylic groups and histidine residues are easily polarizable proton-transfer hydrogen bonds when the pK_a of the protonated histidine residues is about 2.8 units larger than that of the carboxylic groups. From these results it bis concluded that OH ?N ? O^? ?H⁺N bonds between glutamic or aspartic acid histidine residues in proteins may be easily polarizable proton-transfer bonds. Furthermore, it is demonstrated that water molecules shift the proton-transfer equilibria in these hydrogen bonds in favor of the polar structure, i.e., due to water or polar environments OH ?N ? O^? ?H⁺N bonds with smaller ΔpK_a values become easily polarizable proton-transfer hydrogen bonds. A consideration of the amide bands of polyhistidine shows that it can be present in five different conformations. It is shown that these conformational changes are strongly related to the degree of proton transfer. Hence, the degree of proton transfer, the degree of hydration, and conformation are not independent of each other, but are strongly coupled. Further proof for the interdependence of proton transfer and conformational changes are hysteresis effects, which are observed with studies of polyhistidine dependent on carboxylic acid, adsorption and desorption. OH ?N ? O^? ?H⁺N bonds between aspartic and glutamic acid and histidine residues are present in hemoglobin, in ribonucleases, and in proteases, whereby this type of bond is preferentially found in the active centers of these enzymes. It is pointed out that hydrogen bonds with such interaction properties should be of great significance for structure and especially functions of proteins in which they are present.     

Assignment of the histidine 12-threonine 45 hydrogen-bonded proton in the NMR spectrum of ribonuclease A in H2O.

Described herein are proton nmr experiments on chemically modified derivatives of ribonuclease A designed to elucidate the origin of an exchangeable resonance, assigned previously to a histidine ring N proton that titrates between 11 to 13 ppm with a pK_a of 6.1 in H₂O solution. Histidines 48 and 105, which are distant from the active site, are eliminated as candidates for this resonance from inhibitor binding studies on the enzyme in acetate–water solutions. This exchangeable resonance titrates with modified pK_a's and constant area over the above pH range in His-119-N₁-carboxymethylated-RNase A and des-(121–124)-RNase A, thus eliminating the imidazole N₃ proton in the His 119-Asp 121 hydrogen bond. In His-12-N₁-carboxymethylated-RNase A, this resonance is also observable, but broadens on raising the pH above 7 and at elevated temperatures above neutrality. It exhibits a pH-independent chemical shift characteristic of the protonated state of histidine. On the basis of these findings, this exchangeable resonance, designated a, is assigned to the imidazole N₁ proton of His 12, which is hydrogen-bonded to the carbonyl oxygen of Thr 45 in the crystal.     

The influence of hydrogen bonds on electron transfer rate in photosynthetic RCs

Hydrogen bonds formed between photosynthetic reaction centers (RCs) and their cofactors were shown to affect the efficacy of electron transfer. The mechanism of such influence is determined by sensitivity of hydrogen bonds to electron density rearrangements, which alter hydrogen bonds potential energy surface. Quantum chemistry calculations were carried out on a system consisting of a primary quinone Q_A, non-heme Fe²⁺ ion and neighboring residues_. The primary quinone forms two hydrogen bonds with its environment, one of which was shown to be highly sensitive to the Q_A state. In the case of the reduced primary quinone two stable hydrogen bond proton positions were shown to exist on [Q_A-His^M219] hydrogen bond line, while there is only one stable proton position in the case of the oxidized primary quinone. Taking into account this fact and also the ability of proton to transfer between potential energy wells along a hydrogen bond, theoretical study of temperature dependence of hydrogen bond polarization was carried out. Current theory was successfully applied to interpret dark P⁺/Q_A⁻ recombination rate temperature dependence.     

Crystal Structure of Bovine Heart Cytochrome c Oxidase at 2.8 Å Resolution

Thirteen different polypeptide subunits, each in one copy, five phosphatidyl ethanolamines and three phosphatidyl glycerols, two hemes A, three Cu ions, one Mg ion, and one Zn ion are detectable in the crystal structure of bovine heart cytochrome c oxidase in the fully oxidized form at 2.8 Å resolution. A propionate of hems a, a peptide unit (–CO–NH–), and an imidazole bound to Cu_A are hydrogen-bonded sequentially, giving a facile electron transfer path from Cu_A to heme a. The O₂ binding and reduction site, heme a ₃, is 4.7 Å apart from Cu_B. Two possible proton transfer paths from the matrix side to the cytosolic side are located in subunit I, including hydrogen bonds and internal cavities likely to contain randomly oriented water molecules. Neither path includes the O₂ reduction site. The O₂ reduction site has a proton transfer path from the matrix side possibly for protons for producing water. The coordination geometry of Cu_B and the location of Tyr²⁴⁴ in subunit I at the end of the scalar proton path suggests a hydroperoxo species as the two electron reduced intermediate in the O₂ reduction process.