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.     

Interplay between halogen and chalcogen bonding in the XCl∙∙∙OCS∙∙∙NH3 (X = F,OH, NC,CN, and FCC) complex

The interplay between halogen and chalcogen bonding in the XCl???OCS and XCl???OCS???NH₃ (X = F, OH, NC, CN, and FCC) complex was studied at the MP2/6-311++G(d,p) computational level. Cooperative effect is observed when halogen and chalcogen bonding coexist in the same complex. The effect is studied by means of binding distance, interaction energy, and cooperative energy. Molecular electrostatic potential calculation reveals the electrostatic nature of the interactions. Cooperative effect is explained by the difference of the electron density. Second-order stabilization energy was calculated to study the orbital interaction in the complex. Atoms in molecules analysis was performed to analyze the enhancement of the electron density in the bond critical point.     

Dye–tissue interactions: mechanisms,quantification and bonding parameters for dyes used in biological staining

Staining of tissues by dyes is accomplished through various types of bonds, some of which have been poorly defined in traditional biological literature. Here, basic principles of bonding are reviewed to establish uniform terminology and definitions consistent with the field of chemistry. The concept of charge – its presence or absence, magnitude, extent of delocalization and potential for being displaced by outside forces – underlies all bonding phenomena. These same attributes influence solubility and resistance to extraction during dehydration of tissue sections. Covalent bonds involve shared electrons; they are very strong and essentially irreversible under conditions encountered during staining. Polar covalent bonds within dye molecules generate partial atomic charges that create the potential for hydrogen bonding. This is measured by the hydrogen bonding parameter (h), the number of groups bearing charges within the ranges ?0.15 to ?0.50 eV or +0.15 to +0.30 eV. The potential for ionic bonding is indicated by net charge (Z), while the strength of such bonds is a function of charge site geometry on both bonding partners. Charge delocalization owing to conjugation, electron influencing groups, and resonance creates soft charge sites in which the ionic charge is spread over a large volume. Poorly delocalized charges or point charges are hard (small in volume). Firm bonds result from hard-hard or soft-soft pairs. Hard-soft combinations are weak, readily displaced in competitive interactions, and disrupted by solvents. Coordinate bonds with certain metals are involved with mordant staining and metal chelation dyes. Three different van der Waals attractions comprise the remainder of bonding types, all involving dipoles: Keesom (dipole-dipole) forces, Debye (dipole-induced dipole) forces and London (induced dipole-induced dipole) forces. Potentials for engaging in any of these is quantified by measures of polarity (dipole moment, d), polarizability (crudely with π atoms describing the size of the conjugated system, or more directly with α), hydrophobicity (with the octanol-water partition coefficient, log P or the more convenient Hydrophobic Index, HI), and the number of halogen atoms (X). By using molecular modeling software, quantitative measures of bonding potential (bonding parameters) have been determined for over 400 dyes.     

The McClure and Weiss models of Fe–O2 bonding for oxyhemes, and the HbO2 + NO reaction

For the Fe–O₂(S = 0) linkages of oxyhemes, valence bond (VB) structures are re-presented for the McClure [Fe^II(S = 1) + O₂(S = 1)], Pauling–Coryell [Fe^II(S = 0) + O₂*(S = 0)], and Weiss [Fe^III(S = ½) + O₂ ^?(S = ½)] models of bonding. The VB structures for the McClure and Weiss models are of the increased-valence type, with more electrons participating in bonding than occur in their component Lewis structures. The Fe–O bond number and O–O bond order for the McClure structure are correlated with measured Fe–O and O–O bond lengths for oxymyoglobin. Back-bonding from O ₂ ^? to Fe^III of the Weiss structure gives a restricted form of the McClure structure. The McClure and Weiss increased-valence structures are used to provide VB formulations of mechanisms for the oxyhemoglobin + NO reaction. The products of these two formulations are Hb⁺ and NO₃ ^? (where Hb is hemoglobin) and Hb⁺ and OONO^?, respectively. Because Hb⁺ and NO₃ ^? are the observed products, they provide an experimental procedure for distinguishing the McClure and Weiss models. It is also shown that the same type of agreement between McClure-type theory and experiment occurs for oxycoboglobin + NO, cytochrome P450 monooxygenases, and related hydrogen atom transfer reactions. In the appendices, the results of density functional theory and multireference molecular orbital calculations for oxyhemes are related to one formulation of the increased-valence wavefunction for the McClure model, and theory is presented for the calculation of approximate weights for the Lewis structures that are components of the McClure increased-valence structure.     

Hydrogen bonding analysis of phosphoric acid–N,N-dimethylformamide mixtures

Crizotinib is the most effective and the only drug that has been approved for the treatment of anaplastic lymphoma kinase (ALK)-positive lung cancer. Reports suggest that there is a development of an acquired resistance against crizotinib action due to the emergence of several mutations in the ALK gene and F1174L is one such mutation. In this study, we used molecular docking and molecular dynamics (MD) approach to decipher the effect of F1174L mutation in drug–target binding. Docking results suggest that crizotinib was found to adopt the most promising conformations to the native-type ALK by identifying the M1199 residue as a prospective partner for making a hydrogen bond as compared to the mutant-type ALK. MD results showed that the average atom, especially atoms of the native-type ALK-crizotinib complex, movements were less, displayed less fluctuation, fast convergence of energy, and changes in geometry. This shows the stable binding of crizotinib with the native-type ALK in comparison to the mutant-type ALK. We believe that this study could be useful for the logical design of stronger, more selective, and more consistent ALK inhibitor against drug-resistant F1174L mutation.     

Mother–young bonding in prolific D’man and Romanov sheep

The effect of prolificacy on mother–young mutual recognition is still largely unknown in sheep. The aim of the present study was to investigate the ability of prolific ewes to develop an exclusive bond with their neonate and to recognize each other from alien subjects. Observations were performed on 11 D’man and 16 Romanov ewes with, respectively, 19 and 37 of their lambs. Maternal selectivity was tested at 24 h postpartum during two consecutive periods of 3 min. All mothers accepted their own lambs at suckling, while 21 out of 27 (78%) rejected the alien, thus displaying mostly selective nursing. To assess mother–young recognition, a two-choice test was performed at 36 h postpartum. Ewes clearly preferred their own lambs to an alien lamb and behavioral differences were not found between mothers of small (singletons and twins) and large litters (triplets and quadruplets). Romanov ewes reached their own lambsmore rapidly and spent more time near them than D’man ewes. Lambs from small litters, in particular light lambs, clearly preferred their mothers to an alien dam; however, both light and heavy lambs in large litters did not discriminate between the two stimulus ewes. D’man lambs clearly preferred their mothers to an alien dam; in contrast, such a preference was not as clearly demonstrated in Romanov lambs.     

The interplay of O-H?O hydrogen bonding in the generation of three new supramolecular complexes of Cu, Ni and Co: Syntheses, characterization and structural aspects

Three new coordination complexes, [Cu(L¹)(H₂O)] (1), [Ni(L²)₂]·CH₃CN (2) and [Co(HL³)(L³)] (3) [where H₂L¹, N,N′-bis(3-methoxysalicylidenimino)-1,3-diamino-propane; HL², 2-((E)-(1,3-dihydroxy-2-methylpropan-2-ylimino)methyl)phenol; H₂L³, 2-((E)-(2-hydroxyethylimino)methyl)-4-bromophenol] have been synthesized and systematically characterized by elemental analyses, FT-IR, electronic spectroscopy, cyclic voltammetry and thermogravimetric analyses. Single crystal X-ray diffraction studies confirm that the metal center in complex 1 has distorted square-pyramidal geometry while it is distorted octahedral in the other two complexes. In all the complexes O-H?O hydrogen bondings assemble the molecular units leading to ordered supramolecular architectures. While both complexes 1 and 2 form infinite one-dimensional arrays through the self organisation of hydrogen bonded ring motifs, complex 3 is a unique star-shaped cyclic hexamer generated through intermolecular hydrogen bonding.     

Microbial aldolases as C–C bonding enzymes—unknown treasures and new developments

Aldolases are a specific group of lyases that catalyze the reversible stereoselective addition of a donor compound (nucleophile) onto an acceptor compound (electrophile). Whereas most aldolases are specific for their donor compound in the aldolization reaction, they often tolerate a wide range of aldehydes as acceptor compounds. C–C bonding by aldolases creates stereocenters in the resulting aldol products. This makes aldolases interesting tools for asymmetric syntheses of rare sugars or sugar-derived compounds as iminocyclitols, statins, epothilones, and sialic acids. Besides the well-known fructose 1,6-bisphosphate aldolase, other aldolases of microbial origin have attracted the interest of synthetic bio-organic chemists in recent years. These are either other dihydroxyacetone phosphate aldolases or aldolases depending on pyruvate/phosphoenolpyruvate, glycine, or acetaldehyde as donor substrate. Recently, an aldolase that accepts dihydroxyacetone or hydroxyacetone as a donor was described. A further enlargement of the arsenal of available chemoenzymatic tools can be achieved through screening for novel aldolase activities and directed evolution of existing aldolases to alter their substrate- or stereospecifities. We give an update of work on aldolases, with an emphasis on microbial aldolases.     

Metal–metal bonding in 1st, 2nd and 3rd row transition metal complexes: a topological analysis

A topological analysis based on density functional electronic and spin densities of the bonding characteristics in a series of Fe, Ru, Os, Tc and Rh dimers and trimers bridged, respectively, by μ-1,8-naphthyridine (nap) and μ-2,2′-dipyridylamine (dpa) is presented. By this simple qualitative analysis, we were able to determine the electronic ground state and correlated bonding order for a number of complexes potentially involved in extended metal atom chains (EMAC). Furthermore, we showed in the Ru dimer that it was possible to control the spin state simply by changing the bonded counter-anion.

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Graphical Abstract Electron localization analysis of the bonding properties in [M₂(nap)₄Cl₂]²⁺ and [M₃(dpa)₄(Cl₂] complexes

     

Halogen bonding: the σ-hole

Halogen bonding refers to the non-covalent interactions of halogen atoms X in some molecules, RX, with negative sites on others. It can be explained by the presence of a region of positive electrostatic potential, the σ-hole, on the outermost portion of the halogen’s surface, centered on the R–X axis. We have carried out a natural bond order B3LYP analysis of the molecules CF₃X, with X = F, Cl, Br and I. It shows that the Cl, Br and I atoms in these molecules closely approximate the configuration, where the z-axis is along the R–X bond. The three unshared pairs of electrons produce a belt of negative electrostatic potential around the central part of X, leaving the outermost region positive, the σ-hole. This is not found in the case of fluorine, for which the combination of its high electronegativity plus significant sp-hybridization causes an influx of electronic charge that neutralizes the σ-hole. These factors become progressively less important in proceeding to Cl, Br and I, and their effects are also counteracted by the presence of electron-withdrawing substituents in the remainder of the molecule. Thus a σ-hole is observed for the Cl in CF₃Cl, but not in CH₃Cl. Figure Schematic representation of the atomic charge generation. The molecular electrostatic potential (MEP) is calculated using the AM1* Hamiltonian. The semiempirical MEP is then scaled to DFT or ab initio level and atomic charges are generated from it by the restrained electrostatic potential (RESP) fit method.     

ETS-NOCV description of σ-hole bonding

The ETS-NOCV analysis was applied to describe the σ-hole in a systematic way in a series of halogen compounds, CF₃-X (X?=?I, Br, Cl, F), CH₃I, and C(CH3)_nH_3-n-I (n?=?1,2,3), as well as for the example germanium-based systems. GeXH₃, X?=?F, Cl, H. Further, the ETS-NOCV analysis was used to characterize bonding with ammonia for these systems. The results show that the dominating contribution to the deformation density, Δρ ₁ , exhibits the negative-value area with a minimum, corresponding to σ-hole. The “size” (spatial extension of negative value) and “depth” (minium value) of the σ-hole varies for different X in CF₃-X, and is influenced by the carbon substituents (fluorine atoms, hydrogen atoms, methyl groups). The size and depth of σ-hole decreases in the order: I, Br, Cl, F in CF₃-X. In CH₃-I and C(CH3)_nH_3-n-I, compared to CF₃-I, introduction of hydrogen atoms and their subsequent replacements by methyl groups lead to the systematic decrease in the σ-hole size and depth. The ETS-NOCV σ-hole picture is consistent with the existence the positive MEP area at the extension of σ-hole generating bond. Finally, the NOCV deformation density contours as well as by the ETS orbital-interaction energy indicate that the σ-hole-based bond with ammonia contains a degree of covalent contribution. In all analyzed systems, it was found that the electrostatic energy is approximately two times larger than the orbital-interaction term, confirming the indisputable role of the electrostatic stabilization in halogen bonding and σ-hole bonding.

Competition and interplay between the lithium bonding and hydrogen bonding: R3C···HY···LiY and R3C···LiY···HY triads as a working model (R=H, CH3; Y=CN, NC)

UMP2 calculations with aug-cc-pVDZ basis set were used to analyze intermolecular interactions in R₃C···HY···LiY and R₃C···LiY···HY triads (R=H, CH₃; Y=CN, NC), which are connected via lithium and hydrogen bonds. To better understand the properties of these systems, the corresponding dyads were also studied. Molecular geometries and binding energies of dyads, and triads were investigated at the UMP2/aug-cc-pVDZ computational level. Particular attention was paid to parameters such as cooperative energies, and many-body interaction energies. All studied complexes, with the simultaneous presence of a lithium bond and a hydrogen bond, showed cooperativity with energy values ranging between ?1.71 and ?9.03 kJ mol^?1. The electronic properties of the complexes were analyzed using parameters derived from atoms in molecules (AIM) methodology. Energy decomposition analysis revealed that the electrostatic interactions are the major source of the attraction in the title complexes.     

Membrane adsorption and binding, cellular uptake and cytotoxicity of cell-penetrating peptidomimetics with α-peptide/β-peptoid backbone: effects of hydrogen bonding and α-chirality in the β-peptoid residues

Cell-penetrating peptides (CPPs) provide a promising approach for enhancing intracellular delivery of therapeutic biomacromolecules by increasing transport through membrane barriers. Here, proteolytically stable cell-penetrating peptidomimetics with α-peptide/β-peptoid backbone were studied to evaluate the effect of α-chirality in the β-peptoid residues and the presence of guanidinium groups in the α-amino acid residues on membrane interaction. The molecular properties of the peptidomimetics in solution (surface and intramolecular hydrogen bonding, aqueous diffusion rate and molecular size) were studied along with their adsorption to lipid bilayers, cellular uptake, and toxicity. The surface hydrogen bonding ability of the peptidomimetics reflected their adsorbed amounts onto lipid bilayers as well as with their cellular uptake, indicating the importance of hydrogen bonding for their membrane interaction and cellular uptake. Ellipsometry studies further demonstrated that the presence of chiral centers in the β-peptoid residues promotes a higher adsorption to anionic lipid bilayers, whereas circular dichroism results showed that α-chirality influences their overall mean residue ellipticity. The presence of guanidinium groups and α-chiral β-peptoid residues was also found to have a significant positive effect on uptake in living cells. Together, the findings provide an improved understanding on the behavior of cell-penetrating peptidomimetics in the presence of lipid bilayers and live cells.     

Two μ1,5-dicyanamide bridged 2D and 3D metal complexes formed by covalent bonding and weak interactions

One 2D and one 3D dicyanamide bridged complexes, [Cu(dca)₂(et₂-en)]_n (1) and [Mn(dca)₂(im)₂]_n (2) [dca=dicyanamide, et₂-en=N,N-diethyl-ethylenediamine, im=imidazole], have been synthesized. Both the complexes are 1D by covalent bonding but interchain H-bonding promotes dimensionality. Moreover, π-π interaction among the imidazole ligands also plays an important role to have an interlocked 3D structure for 2. Magnetic study of both the complexes shows weak antiferromagnetic interaction between the metal centers. The magnetic data have been fitted with appropriate equations yielding best fit parameters for 1: J=−0.58±0.02 cm⁻¹, g=2.11±0.01 with R=3.2×10⁻⁶ and for 2, J=−0.21 cm⁻¹, g=2.00 and R=5.6×10⁻⁴.     

Helical structure of β(1–3) xylan and the water mediated hydrogen bonding schemes

A six-fold intertwined triple helical structure for the polysaccharide β(1–3) xylan was generated with the axial advance of 0·306 nm per residue. A stereochemically possible site for the water molecule has been determined and water mediated intrachain and interchain hydrogen bond schemes are possible for the right-handed triple helical structure, whereas only interchain hydrogen bonding appears plausible in the left-handed triple helical structure. The water mediated hydrogen bond is almost linear. X-ray refinement using a Linked-Atom Least-Squares (LALS) procedure has enabled us to determine the orientation of the molecule in the hexagonal unit cell, locate the position of the water molecules and yield a reliability index, R, of 0·35. The refined model in this present study confirms the original chirality of an earlier model but differs in the water mediated hydrogen bonding scheme.     

Sex, Death, and Evolution in Proto- and Metazoa, 1876–1913

In the period 1875–1920, a debate about the generality and applicability of evolutionary theory to all organisms was motivated by work on unicellular ciliates like Paramecium because of their peculiar nuclear dualism and life cycles. The French cytologist Emile Maupas and the German zoologist August Weismann argued in the 1880s about the evolutionary origins and functions of sex (which in the ciliates is not linked to reproduction), and death (which appeared to be the inevitable fate of lineages denied sexual conjugation), an argument rooted in the question of whether the ciliates and their processes where homologous to other cellular organisms. In the beginning of the twentieth century, this question of homology came to be less important as the ciliates were used by the British protozoologist Clifford Dobell and the American zoologist Herbert Spencer Jennings to study evolutionary processes in general rather than problems of development and cytology. For them, homology mattered less than analogy. This story illustrates two partially distinct problems in evolutionary biology: first, the question of whether all living things have common features and origins; and second, whether their history and current nature can be described by identical mechanisms. Where Maupas (contra Weismann) made the ciliates qualitatively the same as all other organisms in order to create a cohesive evolutionary theory for biology, Jennings and Dobell made them qualitatively different in order to achieve the same end. This revised version was published online in July 2006 with corrections to the Cover Date.     

Rates of entry and oxidation of acetate,glucose, d(?)-β-hydroxybutyrate,palmitate, oleate and stearate,and rates of production and oxidation of propionate and butyrate in fed and starved sheep

1. Rates of entry and oxidation of a range of metabolites have been measured in tracheostomized sheep (diet, 800g. of lucerne chaff and 100g. of maize/day) by combining isotope-dilution techniques with the continuous measurement of total respiratory gas exchange, and ¹⁴CO₂ production during the intravenous or intraruminal infusion of ¹⁴C-labelled substrates. 2. Mean entry rates in fed and starved (24hr.) sheep respectively, expressed as mg./min./kg. body wt.^0·75, were: glucose, 5·0 (range 4·8–5·1, 2 observations) and 3·8 (3·2–4·2, 4); acetate, 10·8 (9·1–13·5, 4) and 5·8 (1); d(−)-β-hydroxybutyrate, 1·4 (1) and 1·5 (0·8–2·4, 4); palmitate, oleate and stearate (starved sheep only) 1·0 (0·6–1·9, 7), 0·9 (0·2–1·6, 10) and 0·9 (0·5–1·1, 11) respectively. 3. Production rates of propionate and butyrate in continuously feeding sheep were 6·4 (4·7–8·3, 4) and 4·3 (3·4–6·1, 4) mg./min./kg.^0·75 respectively, and in starved (24hr.) sheep were 2·5 (2·2–2·9, 2) and 1·0 (0·8–1·2, 2) mg./min./kg.^0·75 respectively. 4. Calculated terminal values for the specific radioactivity of respiratory ¹⁴CO₂ during measurements of entry rates and production rates were used to calculate the contributions of individual substrates to overall oxidative metabolism. Mean values for fed and starved sheep respectively were: glucose, 9·1 (8·6–9·6, 2) and 11·2 (5·9–15·1, 4)%; acetate, 31·6 (26·8–38·1, 4) and 22·1 (1)%; d(−)-β-hydroxybutyrate, 10·4 (1) and 4·8 (1·9–7·7, 4)%; propionate, 23·0 (13·8–29·9, 4) and 7·1 (6·8–7·4, 2)%; butyrate, 16·5 (13·7–20·5, 4) and 5·3 (5·2–5·3, 2)%; palmitate, oleate and stearate (starved sheep only), 4·7 (2·0–7·7, 7), 4·0 (1·2–6·6, 10) and 4·4 (3·8–5·8, 9)% respectively. The sum of these values for individual substrates in fed and starved sheep, excluding that of β-hydroxybutyrate and after correction of the glucose value for the known interrelations of this substrate with propionate, accounted for 76% and 58% respectively of total production of carbon dioxide. 5. Calculations based on the proportion of substrate entry directly oxidized indicated that the substrates studied accounted for 63% (fed sheep) and 43% (starved sheep) of total energy expenditure measured by oxygen uptake. The contribution of β-hydroxybutyrate was excluded, and corrections were made for glucose–propionate interrelations, and for the different rates of oxidation of the methyl and carboxyl fragments of acetate. 6. The present results have been combined with those obtained earlier in this Laboratory to examine the relationships between rates of substrate entry and oxidation, and concentrations of substrate in blood. Rates of entry of acetate, glucose, d(−)-β-hydroxybutyrate, palmitate and oleate (but not stearate) were well correlated with concentration in blood, and substrate contribution to production of carbon dioxide showed a similar correlation to blood concentration, except with glucose. 7. It was concluded that the general technique is of potential value in providing valid quantitative parameters of animal metabolism.     

HIV and HCV： from Co-infection to Epidemiology, Transmission, Pathogenesis, and Treatment

Human immunodeficiency virus (HIV) is the infectious agent causing acquired immu-nodeficiency syndrome (AIDS),a deadliest scourge of human society. Hepatitis C virus (HCV) is a major causative agent of chronic liver disease and infects an estimated 170 million people worldwide,resulting in a serious public health burden. Due to shared routes of transmission,co-infection with HIV and HCV has become common among individuals who had high risks of blood exposures. Among hemophiliacs the co-infection rate accounts for 85%; while among injection drug users (IDU) the rate can be as high as 90%. HIV can accelerate the progression of HCV-related liver disease,particularly when immunodeficiency has developed. Although the effect of HCV on HIV infection is controversial,most studies showed an increase in mortality due to liver disease. HCV may act as a direct cofactor to fasten the progression of AIDS and decrease the tolerance of highly active antiretroviral therapy (HARRT). Conversely,HAART-related hepatotoxicity may enhance the progression of liver fibrosis. Due to above complications,co-infection with HCV and HIV-1 has imposed a critical challenge in the management of these patients. In this review,we focus on the epidemiology and transmission of HIV and HCV,the impact of the two viruses on each other,and their treatment.     

The Cell and Protoplasm as Container,Object, and Substance, 1835–1861

This article revisits the development of the protoplasm concept as it originally arose from critiques of the cell theory, and examines how the term “protoplasm” transformed from a botanical term of art in the 1840s to the so-called “living substance” and “the physical basis of life” two decades later. I show that there were two major shifts in biological materialism that needed to occur before protoplasm theory could be elevated to have equal status with cell theory in the nineteenth century. First, I argue that biologists had to accept that life could inhere in matter alone, regardless of form. Second, I argue that in the 1840s, ideas of what formless, biological matter was capable of dramatically changed: going from a “coagulation paradigm” (Pickstone, 1973) that had existed since Theophrastus, to a more robust conception of matter that was itself capable of movement and self-maintenance. In addition to revisiting Schleiden and Schwann’s original writings on cell theory, this article looks especially closely at Hugo von Mohl’s definition of the protoplasm concept in 1846, how it differed from his primordial utricle theory of cell structure two years earlier. This article draws on Lakoff and Johnson’s theory of “ontological metaphors” to show that the cell, primordial utricle, and protoplasm can be understood as material container, object, and substance, and that these overlapping distinctions help explain the chaotic and confusing early history of cell theory.