Effects of solvent and ionic medium on the kinetics of axial ligand substitution in vitamin B12. Part IV. The reaction between aquocobalamin and the thiocyanate ion in acetonitrile-water mixtures

The rate constants for the reaction of aquocobalamin with the thiocyanate ion were measured as a function of ionic strength and solvent composition in acetonitrile-water mixtures. The reaction is described by a two-step mechanism: the ligation reaction, where the most stable isomer (S-bonded) is formed and the isomerisation reaction (S-bonded to N-bonded thiocyanate). For the ligation reaction a full quantitative analysis of solvent effects could be performed, whereas for the isomerisation reaction only qualitative observations were made. The equilibrium constant for the isomerisation (S-bonded/N-bonded) is large and does not change with the solvent composition. It is found that the transfer Gibbs energies of activation for the ligation reaction are the same as found for the ligand thiourea. The absence of a solvent effect on the isomerisation reaction is a further example of the ability of vitamin B₁₂ to create its own micro environment.     

Effects of solvent and ionic medium on the kinetics of axial ligand substitution in vitamin B12. Part II. the reaction between aquocobalamin and thiourea in dioxane-water and acetonitrile-water mixtures

The rate constants for the reaction of aquocobalamin with thiourea were measured as a function of ionic strength, pH and solvent composition in dioxane-water and acetonitrile-water mixtures. With the help of solubility measurements a complete quantitative analysis of solvent effects on the reaction profile could be made. The transfer Gibbs energy of the initial state strongly depends on solvent composition. Because the transition state and the final state closely follow the initial state, this is not reflected in the rate constants.For the acetonitrile-water mixtures the transfer enthalpy and transfer entropy were determined and were found to exhibit the familiar compensation effect.It is concluded that, when the solvent changes, vitamin B₁₂ creates its own micro-environment around the active metal site, so that the reactivity is effectively solvent independent. The mechanism of activation is dissociative.     

Effects of solvent and ionic medium on the kinetics of axial ligand substitution in vitamin B12. Part VI. Partial molar volumes of some cobalamin derivates

Apparent molar volumesφ_v, were measured at 25 °C in 0.1 molal NaClO₄ for aquocobalamin chloride, methylcobalamin, 5′-deoxyadenosylcobalamin and aquanitrocobaloxime. For the organocobalamins the pH dependence of φ_v was studied, and for aquocobalamin and aquanitrocobaloxime the dependence on solvent composition was studied. The base-off forms of the organocobalamins have the same volumes as the base-on forms. The apparent molar volume of aquocobalamin chloride is almost independent of solvent composition in dioxane-water mixtures, but increases dramatically in acetonitrile-water mixtures.     

Axial pertubations on the electronic and magnetic properties of ferric porphyrins: II. Solvent effects on the proton NMR spectra of low-spin cyano complexes

The proton NMR spectra of a series of low-spin bis-cyano ferric complexes of tetraarylporphyrins and octaethylporphyrin in a variety of solvents have been recorded and analyzed. The hyperfine shifts are shown to be very sensitive to the solvent, experiencing an overall downfield bias as the solvent hydroge-bonding donor strength increased. The characteristic pattern of the contact and dipolar shifts for the meso-aryl group in tetraarylporphyrin complexes are shown to permit a quantitative separation of the dipolar and contact contributions to the hyperfine shift. The separated components indicate that increased solvent hydrogen bonding strength significantly decreases the magnetic anisotropy of the iron and diminishes porphyrin → iron π bonding. The changes in anisotropy with solvent are shown to be consistent with the coordinated cyanide acting as a proton acceptor. Although similar effects are found to be absent in bis-imidazole complexes, a downfield bias of half the magnitude of the bis-cyano complexes is observed in mixed cyano/imidazole complexes. Hence, the heme hyperfine shifts in cyano-metmyoglobins and -hemoglobins may serve as probes for the protonation of the distal histidyl imidazole.     

Theoretical study of the triangular bonding complex formed by carbon tetrabromide, a halide, and a solvent molecule in the gas phase

MP2(full)/aug-cc-pVDZ(-PP) computations predict that new triangular bonding complexes (where X^? is a halide and H–C refers to a protic solvent molecule) consist of one halogen bond and two hydrogen bonds in the gas phase. Carbon tetrabromide acts as the donor in the halogen bond, while it acts as an acceptor in the hydrogen bond. The halide (which commonly acts as an acceptor) can interact with both carbon tetrabromide and solvent molecule (CH₃CN, CH₂Cl₂, CHCl₃) to form a halogen bond and a hydrogen bond, respectively. The strength of the halogen bond obeys the order CBr₄???Cl^? > CBr₄???Br^? > CBr₄???I^?. For the hydrogen bonds formed between various halides and the same solvent molecule, the strength of the hydrogen bond obeys the order C-H???Cl^? > C-H???Br^? > C-H???I^?. For the hydrogen bonds formed between the same halide and various solvent molecules, the interaction strength is proportional to the acidity of the hydrogen in the solvent molecule. The diminutive effect is present between the hydrogen bonds and the halogen bond in chlorine and bromine triangular bonding complexes. Complexes containing iodide ion show weak cooperative effects.

AllerTOP v.2—a server for in silico prediction of allergens

The microcosmic mechanism of the Menshutkin reaction between DABCO and benzyl fluoride/fluorodiphenylmethane has been investigated in both the gas and solvent phase by performing DFT calculations at B3LYP/6-31G(d,p) level of theory. The Gibbs free energy profiles to reach the possible transition states, i.e., five-membered ring transition state and S_N2 transition state show that the reaction between DABCO and benzyl fluoride proceeds through S_N2 transition state in accordance with previously reported studies, while the reaction between DABCO and fluorodiphenylmethane proceeds through five-membered ring transition state contrary to earlier literature. The role of solvent has been elucidated by reoptimizing the structures using SMD model of solvation. Hydrogen bonding and steric hinderance have been identified as the key factors in guiding the reaction pathway of commercially important Menshutkin reaction.     

An NMR investigation of the conformational equilibria of 2-(2'-pyridyl)ethylphosphonic acid in several solvents

Vicinal proton-proton NMR couplings have been used to investigate whether the position of conformational equilibria is determined by intramolecular N-H hydrogen bonding for 2-(2'-pyridyl)ethylphosphonic acid 1 in its various possible ionization states in water, methanol, ethanol, and dimethyl sulfoxide (DMSO). With 1 in the form of its monoanion and dianion, the trans is favored, with the dianion being more trans than the monoanion for a given solvent, probably as the result of steric effects, possibly enhanced by repulsive electrostatic effects between the negatively charged phosphonic group and the lone pair on the pyridine nitrogen. For 1 and its conjugate acid, the gauche amounts, respectively, to 43% and 45% in water, 66% and 51% in methanol, 66% and 64% in ethanol, and 29% and 49% in DMSO. For these latter two species, electrostatic, steric, and hydrogen bonding-effects are all likely to play a role in determining the conformational equilibria.     

Kinetics and activation parameters of the reaction of cyanide with free aquocobalamin and aquocobalamin bound to a haptocorrin from chicken serum

The kinetics of the reaction of cyanide with free aquocobalamin (H2OCbl) and with aquocobalamin bound to a vitamin B12-binding protein (haptocorrin) from chicken serum (HC-H2OCbl) have been investigated as a function of temperature and pH. The mechanism of replacement of H2O from protein-bound and free H2OCbl is apparently the same and involves attack of both CN- (k1) and HCN (k2). The reactions with HC-H2OCbl are somewhat slower than those with free H2OCbl, k1 being 22-fold smaller and k2 7-fold smaller at 25 degrees C. The relatively small effect of the protein on the rate constants supports the view that the metal in HC-H2OCbl is readily accessible to solvent. Activation parameters suggest that the transition states for ligand substitution are stabilized by nucleophilic participation (at least by CN-) and that ligand substitution on the protein-bound cobalamin proceeds through more ordered, concerted transition states. The latter effect suggests that the Co-O bond of H2OCbl is strengthened upon binding to the haptocorrin.     

Cobalt(III) complexes of some aromatic thiohydrazides - Synthesis, characterization and structure

[Co(NH₃)₅Cl]Cl₂ forms neutral 1:3 complex by reaction with aromatic thiohydrazides, i.e. thiobenzhydrazide, o-hydroxythiobenzhydrazide, thiophen-2-thiohydrazide and furan-2-thiohydrazide. All these complexes are diamagnetic and have been characterized by elemental analysis and combination of spectroscopic methods. Cyclic voltammometry of the complexes shows irreversible metal centered and ligand centered electron transfer reactions. One complex, tris-o-hydroxythiobenzhydrazidocobalt(III), has been crystallized from DMSO solution to produce solvated crystals and its structure has been established by X-ray crystallography. Cobalt(III) ion is linked through three hydrazinic nitrogen and three sulfur atoms of three identical deprotonated ligand molecules in a distorted octahedral environment. Involvement of -OH group in intramolecular and intermolecular hydrogen bonding is crucial for crystal formation.     

Heteronuclear NMR studies of cobalamins. 31P NMR observations of cobalamins bound to a haptocorrin from chicken serum

A vitamin B12-binding protein (haptocorrin) from chicken serum has been purified to homogeneity by photodissociative affinity chromatography and characterized by gel electrophoresis and UV-visible spectrophotometry of its aquocobalamin, hydroxocobalamin, and cyanocobalamin complexes. The haptocorrin is a glycoprotein with a molecular mass of about 70 kDa and a protein moiety of about 40 kDa. 31P NMR resonances of the haptocorrin-cobalamin complexes are relatively broad singlets (with or without proton decoupling) shifted downfield by 0.7-1.0 ppm from the position of the free cobalamin resonances. From the line width data, the relaxation of the phosphorus nucleus is found to be dominated by chemical shift anisotropy with a very minor (13%) component from dipolar interaction with the two nearest neighbor protons. The rotational correlation time of the haptocorrin at 25 degrees C is estimated to be 85 ns and the activation energy for rotational correlation 3.9 +/- 0.3 kcal mol-1. The downfield shift of the 31P resonances of cobalamins upon binding to the haptocorrin cannot be due to hydrogen bonding phosphodiester moiety or displacement of the axial base by a group on the protein. Calculations also show that the downfield shift is very unlikely to be due to dipolar deshielding of the phosphorus nucleus by the ring current of an aromatic residue of the protein. It is concluded that the downfield shift of the 31P resonance must be due to sterically induced changes in phosphodiester conformation which may, or may not, involve steric compression of the axial Co-N bond.     

The diffusion-controlled reaction kinetics of the binding of CO and O2 to myoglobin in glycerol-water mixtures of high viscosity

The kinetics of the reaction of myoglobin (Mb) with CO and O₂ have been studied as a function of temperature by flash photolysis in mixtures of glycerol and water of high viscosities. This was done in order to examine the importance of diffusion-controlled kinetics on protein-ligand reactions. The apparent activation enthalpies of the binding reaction show changes with temperature consistent with a change from chemical activation control of the reaction at higher temperatures to diffusion control at the lower temperatures and higher viscosities. The activation enthalpies for ligand binding in the diffusion-controlled temperature region are similar in value to the viscosity activation energies of the particular solvent mixture as might be expected for a diffusion-controlled reaction. Curve fitting of the rate-temperature data yields factors by which the diffusion-controlled reaction departs from that predicted for reaction between spherically symmetric, uniformly reactive molecules of equal radii. This factor is between 0.1 and 6, depending both upon the solvent mixture and the ligand. Various models for diffusion-controlled reaction with steric requirements are examined in order to rationalize these results. The existence of a linear correlation between ΔH3 and ΔS3 for the chemica activation-controlled portions of reaction yield isokinetic temperatures of 305 and 288 °K for the CO and O₂ reactions, respectively.     

Computer graphics presentations and analysis of hydrogen bonds from molecular dynamics simulation

To obtain better insights into the dynamic nature of hydrogen bonding, computer graphics representations were introduced as an aid for the analysis of molecular dynamics trajectories. A schematic representation of hydrogen bonding patterns is generated to reflect the frequency and the type of hydrogen bonding occurring during the simulation period. Various trajectory plots for monitoring geometrical parameters and for analyzing three-center hydrogen bonding were also generated. The methods proposed are applicable to a variety of biopolymers. In this study, hydrogen bonding in the d(G) · d(C)₆ system was examined. For the nucleic acid fragments examined, three-center hydrogen bonds can be classified as in-plane and major or minor groove types. The in-plane three-center hydrogen bond represents a stable state in which both bonds simultaneously satisfy the relaxed hydrogen bonding criteria for a measurable period. On the other hand, groove three-center hydrogen bonds behave as a transient intermediate state in a flip-flop hydrogen bonding system.     

The oxidation of some polysaccharides by the hydroxyl radical: an e.s.r. investigation

E.s.r. Experiments employing a flow system in conjunction with the TiIII-H2O2 couple show that dextrans react with the hydroxyl radical (HO.) via indiscriminate attack (except that abstraction of hydrogen atoms from carbons which are both linked by glycosidic bonds and included in the pyranose ring may be inhibited, possibly for steric reasons). Acid- and base-catalysed transformations of first-formed radicals have been demonstrated; the suggestion that such reactions can lead to glycosidic cleavage is supported by viscosity studies which confirm the pH-dependence of radical-initiated degradation. For galacturonan and related compounds, e.s.r. results indicate that reaction with HO. proceeds preferentially via abstraction of the hydrogen on the carbon adjacent to the carboxyl group. The crucial step in the subsequent degradation pathway probably involves a pH-independent rearrangement.     

Control of redox reactivity of flavin and pterin coenzymes by metal ion coordination and hydrogen bonding

The electron-transfer activities of flavin and pterin coenzymes can be fine-tuned by coordination of metal ions, protonation and hydrogen bonding. Formation of hydrogen bonds with a hydrogen-bond receptor in metal–flavin complexes is made possible depending on the type of coordination bond that can leave the hydrogen-bonding sites. The electron-transfer catalytic functions of flavin and pterin coenzymes are described by showing a number of examples of both thermal and photochemical redox reactions, which proceed by controlling the electron-transfer reactivity of coenzymes with metal ion binding, protonation and hydrogen bonding.     

Replication of non-hydrogen bonded bases by DNA polymerases: A mechanism for steric matching

Recent experiments have presented evidence that Watson–Crick hydrogen bonds in a base pair are not absolute requirements for efficient synthesis of that pair by DNA polymerase enzymes. Here we examine quantitative steady-state kinetic data from several published studies involving poorly hydrogen-bonding DNA base analogues and adducts, and analyze the results in terms of solvation, hydrogen bonding, and steric effects. We propose a mechanism that can explain the surprising lack of hydrogen-bonding requirement accompanied by significant selectivity in pairing. This hypothesis makes use of steric matching, enforced both by the tightly confined polymerase active site and by the DNA backbone, as a chief factor determining nucleotide selection during DNA synthesis. The results also suggest that hydrogen bonds from bases to water (solvation) may be important in increasing the effective size of DNA bases, which may help prevent misinsertion of small bases opposite each other. © 1998 John Wiley & Sons, Inc. Biopoly 48: 3–17, 1998     

Effect of Macromolecular Crowding on Reaction Rates: A Computational and Theoretical Study

The effect of macromolecular crowding on the rates of association reactions are investigated using theory and computer simulations. Reactants and crowding agents are both hard spheres, and when two reactants collide they form product with a reaction probability, p_rxn. A value of p_rxn < 1 crudely mimics the fact that proteins must be oriented properly for an association reaction to occur. The simulations show that the dependence of the reaction rate on the volume fraction of crowding agents varies with the reaction probability. For reaction probabilities close to unity where most of encounters between reactants lead to a reaction, the reaction rate always decreases as the volume fraction of crowding agents is increased due to the reduced diffusion coefficient of reactants. On the other hand, for very small reaction probabilities where, in most of encounters, the reaction does not occur, the reaction rate increases with the volume fraction of crowding agents—in this case, due to the increase probability of a recollision. The Smoluchowski theory refined with the radiation boundary condition and the radial distribution function at contact is in quantitative agreement with simulations for the reaction rate constant and allows the quantitative analysis of both effects separately.     

Effects of non-aqueous solvents on CO2 absorption in monoethanolamine: Ab initio calculations

Monoethanolamine (MEA) is the most typical alkanolamine and its aqueous solutions are widely used for CO₂ absorption with mature technology, but the regeneration process is energy consuming. To reduce the energy demand, non-aqueous solvents, such as methanol and ethanol are proposed to substitute water in amine solutions. To understand the influence of the aqueous and non-aqueous solvents on CO₂ capture process, the chemical reactions of MEA absorbing CO₂ were conducted via ab initio calculations. The non-aqueous solvents discussed in this paper are methanol, ethanol, 1-propanol and 2-propanol. The reaction patterns were investigated and energy barriers were observed. The results show that zwitterion formation and the followed intermolecular hydrogen transfer are proven to be the most possible reaction pattern in both aqueous and non-aqueous solvents. The energy analysis shows that the forward reaction energy barriers increase while the backward barriers decrease as the solvent changes from water to methanol, ethanol, 1-propanol and 2-propanol in turn. The decreases of the energy barriers for backward processes are much higher than the corresponding increases for forward processes. These results indicate that lower energies are required in non-aqueous solvents than in water during the desorption reactions and the non-aqueous solvents are very promising to reduce the regeneration energy consumption in MEA capturing CO₂ process. Moreover, the reaction energy gaps between different solvation effects were found to have linear relationship with the logarithm of the dielectric constant difference, which could provide an easy way to theoretically predict the reaction energies of monoethanolamine absorbing CO₂ in other solvation effect and can be used to screen appropriate CO₂ capture solvent.     

Configurational effects on conformational properties of cyclic nucleotides. I. Theoretical calculations of conformer preferences in α-nucleoside 3′,5′ cyclic monophosphates

A comparative study has been made of the configurational effects on the conformational properties of α- and β-anomers of purine and pyrimidine nucleoside 3′,5′,-cyclic monophosphates and their 2′-arabino epimers. Correlation between orientation of the base and the 2′-hydroxyl group have been studied theoretically using the PCILO (Perturbative Configuration Interaction using Localized Orbitals) method. The effect of change in ribose puckering on the base-hydroxyl interaction has also been studied. The result show that steric repulsions and stabilizing effects of intramolecular hydrogen bonding between the base and the 2′-hydroxyl (OH) group are of major importance in determining configurations of α-anomers and 2′-arabino-β-epimers. For example, hydrogen bonding between the 2′-hydroxyl group and polar centers on the base ring is clearly implicated as a determinant of syn-anti preferences of the purine (adenine) or pyrimidine (uracil) bases in α-nucleoside 3′,5′-cyclic monophosphates. Moreover, barrier heights for interconversion between conformers are sensitive to ribose pucker and 2′-OH orientations. The result clearly show that a change in ribose-ring pucker plays an essential role in relieving repulsive interaction between the base and the 2′-hydroxyl group. Thus a C2′-exo-C3′-endo (₂T³) pucker is favored for α-anomers in contrast with the C4′-exo-C3′-endo (₄T³) from found in β-compounds.     

Biomimetic asymmetric hydrogenation.

Enzymes and synthetic organometallic catalysts utilize different approaches for the creation of chiral centers in prochiral substrates. While chiral organometallic catalysts realize the transfer of chirality mainly by repulsive interactions, several enzymes use preferentially stereodiscriminating hydrogen bonding. To investigate if hydrogen bonding within the catalyst-substrate assembly can also have a benefit on the rhodium diphosphine-catalyzed asymmetric hydrogenation, some model metal complexes and substrates were investigated. As 'biomimetically acting' functionalities, hydroxy groups were incorporated in the chiral ligand. Three secondary interactions could be identified by different analytical methods which influence rate and enantioselectivity of the catalytic reaction: 1) HO/Rh-interactions, 2) HO/HO-interactions within the backbone of the ligand, and 3) hydrogen bonding between HO-groups of the ligand and functional groups of an appropriate substrate. Due to the effect of the additional hydroxy groups, enantioselectivities by up to 99% ee could be induced in the hydrogenation product even with water as solvent.     

Unusual silver coordination by mono-carboxylate utilization of a poly-carboxylate anion, solid-state structures of silver-tetrachlorophthalate with phthalazine and amine ligands

Silver carboxylate coordination with the tetrachlorophthalate anion, in combination with neutral donor ligands, has been found to deviate from other known poly-carboxylate complexes. Both complexes reported here, bis-[tetrachlorophthalato-silver phthalazine] and bis-[ammino-tetrachlorophthato-silver di-ammino-silver], utilize mixed carboxylate bonding types for silver coordination. In the case of the phthalazine ligand, both chelating and monodentate carboxylates form the framework for the oligomeric structure. In the case of the ammine ligand, one carboxylate forms a monodentate connection to a silver-ammine group, while the other is simply involved with hydrogen bonding to lock in a [(Ag-NH₃)₂-Ag-NH₃] substructure with an adjacent tetrachlorophthalato-silver unit. Both structures exhibit supramolecular connections via hydrogen bonding and π-π interactions.