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.     

Theoretical study of the interaction between 5-methylcytosine and acrylamide

The hydrogen-bonded complexes between 5-methylcytosine and acrylamide have been investigated using the density function theory (DFT) method. Five stable complexes have been found with no imaginary frequencies. Complex C3 is the most stable one with interaction energies of -69.01?kJ?mol(-1) corrected for basis set superposition error (BSSE). The charge change in the process of these complexes formation has also been examined. The atoms in molecules (AIM) theory and natural bond orbital (NBO) method have been performed to investigate the hydrogen bonds involved in all the complexes. The electron density and its corresponding Laplacian at the bond and ring critical points have been analyzed. In C3 complex, there is the largest stabilization energy (18.17?kJ?mol(-1)) between N11-H12 antibonding orbital and lone electron pair of O17. It can be seen that the hydrogen bonds play a crucial role in the stability of all the complexes between 5-methylcytosine and acrylamide. The theoretical results could provide helpful information for other researchers in further work.     

Topological analysis of aromatic halogen/hydrogen bonds by electron charge density and electrostatic potentials

In this work, the intermolecular distribution of the electronic charge density in the aromatic hydrogen/halogen bonds is studied within the framework of the atoms in molecules (AIM) theory and the molecular electrostatic potentials (MEP) analysis. The study is carried out in nine complexes formed between benzene and simple lineal molecules, where hydrogen, fluorine and chlorine atoms act as bridge atoms. All the results are obtained at MP2 level theory using cc-pVTZ basis set. Attention is focused on topological features observed at the intermolecular region such as bond, ring and cage critical points of the electron density, as well as the bond path, the gradient of the density maps, molecular graphs and interatomic surfaces. The strength of the interaction increases in the following order: F⋅⋅⋅π < Cl⋅⋅⋅π < H⋅⋅⋅π. Our results show that the fluorine atom has the capability to interact with the π−cloud to form an aromatic halogen bond, as long as the donor group is highly electron withdrawing. The Laplacian topology allows us to state that the halogen atoms can act as nucleophiles as well as electrophiles, showing clearly their dual character.     

Polarization-induced σ-holes and hydrogen bonding

The strong collinear polarizability of the A-H bond in A-H···B hydrogen bonds is shown to lead to an enhanced σ-hole on the donor hydrogen atom and hence to stronger hydrogen bonding. This effect helps to explain the directionality of hydrogen bonds, the well known cooperative effect in hydrogen bonding, and the occurrence of blue-shifting. The latter results when significant additional electron density is shifted into the A-H bonding region by the polarization effect. The shift in the A-H stretching frequency is shown to depend essentially linearly on the calculated atomic charge on the donor hydrogen for all donors in which A belongs to the same row of the periodic table. A further result of the polarization effect, which is also expected for other σ-hole bonds, is that the strength of the non-covalent interaction depends strongly on external electric fields.     

Theoretical study of penta- and heteropentadienyl beryllium complexes coordinated to hydrogen molecules

A series of penta- and heteropentadienyl [CH₂CHCHCHXBe]⁺, (X?=?CH₂, O, NH, S) complexes has been theoretically studied. All calculated complexes show beryllium atoms with two, three, and five coordination numbers. The density functional theory (DFT) was used to determine the electron and structural behavior of those beryllium complexes. The nature of the ligands plays an important role in the form of binding to the beryllium atom. Beryllium structures 1–4 are able to coordinate only one hydrogen molecule. A molecular orbital analysis for all complexes was performed in order to know more about the nature of their bonding scheme.     

The computational study of the γ-Fe2O3 nanoparticle as Carmustine drug delivery system: DFT approach

In the present study, it is attempted to scrutinize the properties of the maghemite nanoparticle as a Carmustine drug delivery system by means of the density functional theory calculations regarding their geometries, adsorption energies, vibrational frequencies, and topological features of the electron density. Based on the density functional theory results, it is found that the interaction between Carmustine drug molecule and maghemite nanoparticle is weak; so that, the adsorption of the Carmustine drug is typically physisorption. It is also found that the intermolecular hydrogen bonds between the drug and the nanoparticle play the significant role in the stability of the physisorption configurations. The nature of the intermolecular interactions has been explored by calculation of the electron densities and their Laplacian at the bond critical points using Atoms-in-Molecule theory. Moreover, natural bond orbital analysis indicates that the Carmustine molecule can be adsorbed on the nanoparticle surface with a charge transfer from the Carmustine drug to the nanoparticle.     

Theoretical analysis of the electronic properties of the sex pheromone and its analogue derivatives in the female processionary moth Thaumetopoea pytiocampa

In the present work, the distribution of the electronic charge density of the natural sex pheromone, the (Z)-13-hexadecen-11-ynyl acetate, in the female processionary moth, Thaumetopoea pytiocampa, and its nine analogue derivatives was studied within the framework of the Density Functional Theory and the Atoms in Molecules (AIM) Theory at B3LYP/6-31G *//B3LYP/6-31++G * * level. Additionally, molecular electrostatic potential (MEP) maps of the previously mentioned compounds were computed and compared. Furthermore, the substitution of hydrogen atoms from the methyl group in the acetate group by electron withdrawing substituents (i.e., halogen atoms) as well as the replacement effect of hydrogen by electron donor substituents (+I effect) as methyl group, were explored. The key feature of the topological distribution of the charge density in analogue compounds, such as the variations of the topological properties encountered in the region formed by neighbouring atoms from the substitution site were presented and discussed. Using topological parameters, such as electronic charge density, Laplacian, kinetic energy density, and potential energy density evaluated at bond critical points (BCP), we provide here a detailed analysis of the nature of the chemical bonding of these molecules. In addition, the atomic properties (population, charge, energy, volume, and dipole moment) were determined on selected atoms. These properties were analyzed at the substitution site (with respect to the natural sex pheromone) and related to the biological activity and to the possible binding site with the pheromone binding protein, (PBP). Moreover, the Laplacian function of the electronic density was used to locate electrophilic regions susceptible to be attacked (by deficient electron atoms or donor hydrogen). Our results indicate that the change in the atomic properties, such as electronic population and atomic volume, are sensitive indicators of the loss of the biological activity in the analogues studied here. The crucial interaction between the acetate group of the natural sex pheromone and the PBP is most likely to be a hydrogen bonding and the substitution of hydrogen atoms by electronegative atoms in the pheromone molecule reduces the hydrogen acceptor capacity. This situation is mirrored by the diminish of the electronic population on carbon and oxygen atoms at the carbonylic group in the halo-acetate group. Additionally, the modified acetate group (with electronegative atoms) shows new charge concentration critical points or regions of concentration of charge density in which an electrophilic attack can also occur. Finally, the use of the topological analysis based in the charge density distribution and its Laplacian function, in conjunction with MEP maps provides valuable information about the steric volume and electronic requirement of the sex pheromone for binding to the PBP.     

Modulating weak intramolecular interactions through the formation of beryllium bonds: complexes between squaric acid and BeH2

The electronic structure of the two most stable isomers of squaric acid and their complexes with BeH₂ were investigated at the B3LYP/6-311?+?G(3df,2p)// B3LYP/6-31?+?G(d,p) level of theory. Squaric acid forms rather strong beryllium bonds with BeH₂, with binding energies of the order of 60 kJ?mol^?1. The preferential sites for BeH₂ attachment are the carbonyl oxygen atoms, but the global minima of the potential energy surfaces of both EZ and ZZ isomers are extra-stabilized through the formation of a BeH···HO dihydrogen bond. More importantly, analysis of the electron density of these complexes shows the existence of significant cooperative effects between the beryllium bond and the dihydrogen bond, with both becoming significantly reinforced. The charge transfer involved in the formation of the beryllium bond induces a significant electron density redistribution within the squaric acid subunit, affecting not only the carbonyl group interacting with the BeH₂ moiety but significantly increasing the electron delocalization within the four membered ring. Accordingly the intrinsic properties of squaric acid become perturbed, as reflected in its ability to self-associate.

Conformational analysis and intramolecular hydrogen bonding of cis-3-aminoindan-1-ol: a quantum chemical study

In the present work, we carried out a conformational analysis of cis-3-aminoindan-1-ol and evaluated the role of the intramolecular hydrogen bond in the stabilization of various conformers using quantum mechanical DFT (B3LYP) and MP2 methods. On the basis of relative energies, we have found nine conformational minima, which can interchange through the ring-puckering and the internal rotation of the OH and NH₂ groups on the five-membered ring. The intramolecular hydrogen bonds such as OH????π, NH????π, NH????OH and HN????HO are expected to be of critical importance for the conformational stabilities. The intramolecular interactions of the minima have been analyzed by calculation of electron density (ρ) and Laplacian (ρ) at the bond critical points (BCPs) using atoms-in-molecule (AIM) theory. The existence or absence of OH????π and NH????π in cis-3-aminoindan-1-ol remains unclear since the geometrical investigation has not been confirmed by topological criteria. The results of theoretical calculations demonstrate that this compound exists predominantly in one ring-puckering form stabilized by strong hydrogen bond HN????HO Interaction.     

Carbon-13 and nitrogen-15 nuclear-magnetic-resonance investigation on Desulfovibrio vulgaris flavodoxin

Desulfovibrio vulgaris apoflavodoxin has been reconstituted with 15N and 13C-enriched riboflavin 5'-phosphate. For the first time all carbon atoms of the isoalloxazine ring of the protein-bound prosthetic group have been investigated. The reconstituted protein was studied in the oxidized and in the two-electron-reduced state. The results are interpreted in terms of specific interactions between the apoprotein and the prosthetic group, and the chemical structure of protein-bound FMN. In the oxidized state weak hydrogen bonds exist between the apoprotein and the N(5), N(3) and O(4 alpha) atoms of FMN. The N(1) and O(2 alpha) atoms of FMN form strong hydrogen bonds. The isoalloxazine ring of FMN is strongly polarized and the N(10) atom shows an increased sp2 hybridisation compared to that of free FMN in aqueous solution. The N(3)-H group is not accessible to bulk solvent, as deduced from the coupling constant of the N(3)-H group. In the reduced state the hydrogen bond pattern is similar to that in the oxidized state and in addition a strong hydrogen bond is observed between the N(5)-H group of FMN and the apoprotein. The reduced prosthetic group possesses a coplanar structure and is ionized. The N(3)-H and N(5)-H groups are not accessible to solvent water. Two-electron reduction of the protein leads to a large electron density increase in the benzene subnucleus of bound FMN compared to that in free FMN. The results are discussed in relation to the published crystallographic data on the protein.     

Relationship between the oxidation potential of the bacteriochlorophyll dimer and electron transfer in photosynthetic reaction centers

The primary electron donor in the photosynthetic reaction center from purple bacteria is a bacteriochlorophyll dimer containing four conjugated carbonyl groups that may form hydrogen bonds with amino acid residues. Spectroscopic analyses of a set of mutant reaction centers confirm that hydrogen bonds can be formed between each of these carbonyl groups and histidine residues in the reaction center subunits. The addition of each hydrogen bond is correlated with an increase in the oxidation potential of the dimer, resulting in a 355-mV range in the midpoint potential. The resulting changes in the free-energy differences for several reactions involving the dimer are related to the electron transfer rates using the Marcus theory. These reactions include electron transfer from cytochrome c₂ to the oxidized dimer, charge recombination from the primary electron acceptor quinone, and the initial forward electron transfer.     

Molecular dynamics study of deformation mechanisms of poly(vinyl alcohol) hydrogel

Molecular dynamics (MD) simulations have been performed on the physically crosslinking poly(vinyl alcohol) (PVA) hydrogel to study the deformation mechanisms under uniaxial tensile conditions. The distributions of hydroxyl oxygens and dihedral angle and the number of hydrogen bonds have been analysed to study the structure of the hydrogel. The water content and temperature dependency of mechanical properties have been investigated. The energy contributions from the partially united atom potential have been calculated as a function of strain. It is found that the stress–strain curve comprises toe region, linear region and yield and failure region which is close to most biomaterials. In the toe and yield region, all the contributions to the internal energy change a little. However, in the linear region, the bond stretching and angle bending energy increase rapidly and mainly dominate the region, and the energy increases more rapidly with the increasing water content but the decreasing temperature. The degree of crosslinking decreases with the increasing deformation. The polymer chains occur significant torsional activity in the toe region. Hydrogen bonds are stable in the toe and yield region, but the hydrogen bonds between hydroxyl groups and waters decrease in the linear region.     

Question 9: Quantum Self-Assembly and Photoinduced Electron Tunneling in Photosynthetic Systems of Artificial Minimal Living Cells

Natural and artificial living cells and their substructures are self-assembling, due to electron correlation interactions among biological and water molecules, which lead to attractive dispersion forces and hydrogen bonds. Dispersion forces are weak intermolecular forces that arise from the attractive force between quantum multipoles. A hydrogen bond is a special type of quantum attractive interaction that exists between an electronegative atom and a hydrogen atom bonded to another electronegative atom; and this hydrogen atom exist in two quantum states. The best method to simulate these dispersion forces and hydrogen bonds is to perform quantum mechanical non-local density functional potential calculations of artificial minimal living cells consisting of around 1,000 atoms. The cell systems studied are based on peptide nucleic acid and are 3.0–4.2 nm in diameter. The electron tunneling and associated light absorption of the most intense transitions, as calculated by the time dependent density functional theory method, differs from spectroscopic experiments by only 0.2–0.3 nm, which is within the value of experiment errors. This agreement implies that the quantum mechanically self-assembled structures of artificial minimal living cells very closely approximate realistic ones.     

Density functional theory studies of the adsorption of hydrogen sulfide on aluminum doped silicane

First principles total energy calculations have been performed to study the hydrogen sulfide (H₂S) adsorption on silicane, an unusual one monolayer of Si(111) surface hydrogenated on both sides. The H₂S adsorption may take place in dissociative or non-dissociative forms. Silicane has been considered as: (A) non-doped with a hydrogen vacancy, and doped in two main configurations; (B) with an aluminum replacing a hydrogen atom and (C-n; n?=?1, 2, 3) with an aluminum replacing a silicon atom at a lattice site. In addition, three supercells; 4x4, 3x3 and 2x2 have been explored for both non-doped and doped silicane. The non-dissociative adsorption takes place in geometries (A), (C-1), (C-2) and (C-3) while the dissociative in (B). Adsorption energies of the dissociative case are larger than those corresponding to the non-dissociated cases. In the dissociative adsorption, the molecule is fragmented in a HS structure and a H atom which are bonded to the aluminum to form a H-S-Al-H structure. The presence of the doping produces some electronic changes as the periodicity varies. Calculations of the total density of states (DOS) indicate that in most cases the energy gap decreases as the periodicity changes from 4x4 to 2x2. The features of the total DOS are explained in terms of the partial DOS. The reported charge density plots explain quite well the chemisorptions and physisorptions of the molecule on silicane in agreement with adsorption energies.     

Catalase-peroxidase KatG of Burkholderia pseudomallei at 1.7A resolution

The catalase-peroxidase encoded by katG of Burkholderia pseudomallei (BpKatG) is 65% identical with KatG of Mycobacterium tuberculosis, the enzyme responsible for the activation of isoniazid as an antibiotic. The structure of a complex of BpKatG with an unidentified ligand, has been solved and refined at 1.7A resolution using X-ray synchrotron data collected from crystals flash-cooled with liquid nitrogen. The crystallographic agreement factors R and R(free) are 15.3% and 18.6%, respectively. The crystallized enzyme is a dimer with one modified heme group and one metal ion, likely sodium, per subunit. The modification on the heme group involves the covalent addition of two or three atoms, likely a perhydroxy group, to the secondary carbon atom of the vinyl group on ring I. The added group can form hydrogen bonds with two water molecules that are also in contact with the active-site residues Trp111 and His112, suggesting that the modification may have a catalytic role. The heme modification is in close proximity to an unusual covalent adduct among the side-chains of Trp111, Tyr238 and Met264. In addition, Trp111 appears to be oxidized on C(delta1) of the indole ring. The main channel, providing access of substrate hydrogen peroxide to the heme, contains a region of unassigned electron density consistent with the binding of a pyridine nucleotide-like molecule. An interior cavity, containing the sodium ion and an additional region of unassigned density, is evident adjacent to the adduct and is accessible to the outside through a second funnel-shaped channel. A large cleft in the side of the subunit is evident and may be a potential substrate-binding site with a clear pathway for electron transfer to the active-site heme group through the adduct.     

Density functional calculated spin densities and hyperfine couplings for hydrogen bonded 1,4-naphthosemiquinone and phyllosemiquinone anion radicals: a model for the A1 free radical formed in photosystem I

The B3LYP hybrid density functional method is used to calculate spin densities and hyperfine couplings for the 1,4-naphthosemiquinone anion radical and a model of the phyllosemiquinone anion radical. The effect of hydrogen bonding on the spin density distribution is shown to lead to a redistribution of pi spin density from the semiquinone carbonyl oxygens to the carbonyl carbon atoms. The effect of in plane and out of plane hydrogen bonding is examined. Out of plane hydrogen bonding is shown to give rise to a significant delocalisation of spin density on to the hydrogen bond donor heavy atom. Excellent agreement is observed between calculated and experimental hyperfine couplings. Comparison of calculated hyperfine couplings with experimental determinations for the A1 phyllosemiquinone anion radical present in Photosystem I (PS I) of higher plant photosynthesis indicates that the in vivo radical may have a hydrogen bond to the O4 atom only as opposed to hydrogen bonds to each oxygen atom in alcohol solvents. The hydrogen bonding situation appears to be the reverse of that observed for QA in the bacterial type II reaction centres where the strong hydrogen bond occurs to the quinone O1 oxygen atom. For different types of reaction centre the presence or absence of the non-heme Fe(II) atom may well determine which type of hydrogen bonding situation prevails at the primary quinone site which in turn may influence the direction of subsequent electron transfer.     

Five atomic resolution structures of endothiapepsin inhibitor complexes: implications for the aspartic proteinase mechanism

Endothiapepsin is derived from the fungus Endothia parasitica and is a member of the aspartic proteinase class of enzymes. This class of enzyme is comprised of two structurally similar lobes, each lobe contributing an aspartic acid residue to form a catalytic dyad that acts to cleave the substrate peptide bond. The three-dimensional structures of endothiapepsin bound to five transition state analogue inhibitors (H189, H256, CP-80,794, PD-129,541 and PD-130,328) have been solved at atomic resolution allowing full anisotropic modelling of each complex. The active sites of the five structures have been studied with a view to studying the catalytic mechanism of the aspartic proteinases by locating the active site protons by carboxyl bond length differences and electron density analysis. In the CP-80,794 structure there is excellent electron density for the hydrogen on the inhibitory statine hydroxyl group which forms a hydrogen bond with the inner oxygen of Asp32. The location of this proton has implications for the catalytic mechanism of the aspartic proteinases as it is consistent with the proposed mechanism in which Asp32 is the negatively charged aspartate. A number of short hydrogen bonds (approximately 2.6 A) with ESD values of around 0.01 A that may have a role in catalysis have been identified within the active site of each structure; the lengths of these bonds have been confirmed using NMR techniques. The possibility and implications of low barrier hydrogen bonds in the active site are considered.     

Hydratation of the rubredoxin polypeptide chain from data on the spatial structure

The hydration water distribution around the main chain protein rubredoxin has been analysed using the crystal data at high resolution obtained earlier. The analysis was based on the consideration of all nearest neighbour atoms around the N and O atoms of peptide groups. The atoms which can form hydrogen binds were the subject of final analysis. The nitrogen atom of a peptide NH group has only one vacancy for neighbours. The oxygen atom of a peptide CO group has one, two or more neighbours, some of them are oxygen-water atoms. About 27% of NH and 53% of CO peptide groups are hydrated, that corresponds to 0.12 H2O per gram of protein. A detailed analysis shows that NH and CO groups of the main chain are hydrated according to the principle of maximum possible in situ saturation of hydrogen bonds. Thus the peptide groups incorporated in the peptide hydrogen bond network were not hydrated as a rule. Consequently, for rubredoxin a pleated sheet region, some regions for the large and small main chain loops, and Fe-containing pocket are not hydrated. A method for evaluation of the main chain hydration is proposed when the coordinates of protein atoms are available.     

Experimental charge density from electron microscopic maps

The charge density (CD) distribution of an atom is the difference per unit volume between the positive charge of its nucleus and the distribution of the negative charges carried by the electrons that are associated with it. The CDs of the atoms in macromolecules are responsible for their electrostatic potential (ESP) distributions, which can now be visualized using cryo‐electron microscopy at high resolution. CD maps can be recovered from experimental ESP density maps using the negative Laplacian operation. CD maps are easier to interpret than ESP maps because they are less sensitive to long‐range electrostatic effects. An ESP‐to‐CD conversion involves multiplication of amplitudes of structure factors as Fourier transforms of these maps in reciprocal space by 1/d², where d is the resolution of reflections. In principle, it should be possible to determine the charges carried by the individual atoms in macromolecules by comparing experimental CD maps with experimental ESP maps.