Corrin Macrocycle Research Articles

Modulation of polyaniline memristive device switching voltage by nucleotide-free analogue of vitamin B12

Memristive devices offer essential properties to become a part of the next-generation computing systems based on neuromorphic principles. Organic memristive devices exhibit a unique set of properties which makes them an indispensable choice for specific applications, such as interfacing with biological systems. While the switching rate of organic devices can be easily adjusted over a wide range through various methods, controlling the switching potential is often more challenging, as this parameter is intricately tied to the materials used. Given the limited options in the selection conductive polymers and the complexity of polymer chemical engineering, the most straightforward and accessible approach to modulate switching potentials is by introducing specific molecules into the electrolyte solution. In our study, we show polyaniline (PANI)-based device switching potential control by adding nucleotide-free analogue of vitamin B12, aquacyanocobinamide, to the electrolyte solution. The employed concentrations of this molecule, ranging from 0.2 to 2 mM, enabled organic memristive devices to achieve switching potential decrease for up to 100 mV, thus providing a way to control device properties. This effect is attributed to strong aromatic interactions between PANI phenyl groups and corrin macrocycle of the aquacyanocobinamide molecule, which was supported by ultraviolet-visible spectra analysis.

Aquacobalamin Accelerates Orange II Destruction by Peroxymonosulfate via the Transient Formation of Secocorrinoid: A Mechanistic Study.

Besides its use in medicine, vitamin B12 (cobalamin) and its derivatives have found in numerous applications as catalysts. However, studies related to the activation of oxidants via cobalamin are scant. In this work, we showed how the addition of aquacobalamin (H2OCbl) accelerates the destruction of azo-dye Orange II by peroxymonosulfate (HSO5−) in aqueous solutions. In neutral and weakly alkaline media, the process is initiated by the modification of the corrin macrocycle with HSO5−, which requires the preliminary deprotonation of the aqua-ligand in H2OCbl to give hydroxocobalamin, producing 5,6-dioxo-5,6-secocobalamin or its isomer (14,15-dioxo-14,15-secocobalamin). In acidic solutions, where the concentration of hydroxocobalamin is negligible, the formation of dioxo-seco-species is not observed, and the reaction between H2OCbl and HSO5− results in slow chromophore bleaching. Using terephthalic acid, we demonstrated the formation of hydroxyl radicals in the mixture of H2OCbl with HSO5−, whereas the generation of sulfate radicals was proved by comparing the effects of ethanol and nitrobenzene on Orange II destruction using the H2OCbl/HSO5− system. The reaction mechanism includes the binding of HSO5− to the Co(III) ion of dioxo-secocobalamin, which results in its deprotonation and the labilization of the O-O bond, leading to the formation of sulfate and hydroxyl radicals which further react with Orange II.

Experimental and Computational Observations of Immunogenic Cobalt Porphyrin Lipid Bilayers: Nanodomain-Enhanced Antigen Association.

Cobalt porphyrin phospholipid (CoPoP) can incorporate within bilayers to enable non-covalent surface-display of antigens on liposomes by mixing with proteins bearing a polyhistidine tag (his-tag); however, the mechanisms for how this occurs are poorly understood. These were investigated using the his-tagged model antigen Pfs25, a protein antigen candidate for malaria transmission-blocking vaccines. Pfs25 was found to associate with the small molecule aquocobalamin, a form of vitamin B12 and a cobalt-containing corrin macrocycle, but without particle formation, enabling comparative assessment. Relative to CoPoP liposomes, binding and serum stability studies indicated a weaker association of Pfs25 to aquocobalamin or cobalt nitrilotriacetic acid (Co-NTA) liposomes, which have cobalt displayed in the aqueous phase on lipid headgroups. Antigen internalization by macrophages was enhanced with Pfs25 bound to CoPoP liposomes. Immunization in mice with Pfs25 bound to CoPoP liposomes elicited antibodies that recognized ookinetes and showed transmission-reducing activity. To explore the physical mechanisms involved, we employed molecular dynamics (MD) simulations of bilayers containing phospholipid, cholesterol, as well as either CoPoP or NTA-functionalized lipids. The results show that the CoPoP-containing bilayer creates nanodomains that allow access for a limited but sufficient amount of water molecules that could be replaced by his-tags due to their favorable free energy properties allowing for stabilization. The position of the metal center within the NTA liposomes was much more exposed to the aqueous environment, which could explain its limited capacity for stabilizing Pfs25. This study illustrates the impact of CoPoP-induced antigen particleization in enhancing vaccine efficacy, and provides molecular insights into the CoPoP bilayer properties that enable this.

Studies on reaction of glutathionylcobalamin with hypochlorite. Evidence of protective action of glutathionyl-ligand against corrin modification by hypochlorite.

Glutathionylcobalamin (GSCbl), a tight complex of glutathione (GSH) with cobalamin(III), is readily oxidized to aquacobalamin by hypochlorite. Corrin macrocycle remains unmodified in the presence of threefold excess of hypochlorite, whereas aqua- and cyanocobalamins are partially transformed to chlorinated species under the same conditions. The suggested mechanism of reaction between GSCbl and hypochlorite involves subsequent oxidation of thiol and amino groups and dissociation of oxidized glutathione from Co(III)-ion.

Kinetic studies on the reaction of cob(II)alamin with hypochlorous acid: Evidence for one electron oxidation of the metal center and corrin ring destruction

Kinetic and mechanistic studies on the reaction of a major intracellular vitamin B12 form, cob(II)alamin (Cbl(II)), with hypochlorous acid/hypochlorite (HOCl/OCl−) have been carried out. Cbl(II) (Co(II)) is rapidly oxidized by HOCl to predominately aquacobalamin/hydroxycobalamin (Cbl(III), Co(III)) with a second-order rate constant of 2.4×107M−1s−1 (25.0°C). The stoichiometry of the reaction is 1:1. UHPLC/HRMS analysis of the product mixture of the reaction of Cbl(II) with 0.9mol equiv. HOCl provides support for HOCl being initially reduced to Cl and subsequent H atom abstraction from the corrin macrocycle occurring, resulting in small amounts of corrinoid species with two or four H atoms fewer than the parent cobalamin. Upon the addition of excess (H)OCl further slower reactions are observed. Finally, SDS-PAGE experiments show that HOCl-induced damage to bovine serum albumin does not occur in the presence of Cbl(II), providing support for Cbl(II) being an efficient HOCl trapping agent.

Axial Ligation and Redox Changes at the Cobalt Ion in Cobalamin Bound to Corrinoid Iron-Sulfur Protein (CoFeSP) or in Solution Characterized by XAS and DFT.

A cobalamin (Cbl) cofactor in corrinoid iron-sulfur protein (CoFeSP) is the primary methyl group donor and acceptor in biological carbon oxide conversion along the reductive acetyl-CoA pathway. Changes of the axial coordination of the cobalt ion within the corrin macrocycle upon redox transitions in aqua-, methyl-, and cyano-Cbl bound to CoFeSP or in solution were studied using X-ray absorption spectroscopy (XAS) at the Co K-edge in combination with density functional theory (DFT) calculations, supported by metal content and cobalt redox level quantification with further spectroscopic methods. Calculation of the highly variable pre-edge X-ray absorption features due to core-to-valence (ctv) electronic transitions, XANES shape analysis, and cobalt-ligand bond lengths determination from EXAFS has yielded models for the molecular and electronic structures of the cobalt sites. This suggested the absence of a ligand at cobalt in CoFeSP in α-position where the dimethylbenzimidazole (dmb) base of the cofactor is bound in Cbl in solution. As main species, (dmb)CoIII(OH2), (dmb)CoII(OH2), and (dmb)CoIII(CH3) sites for solution Cbl and CoIII(OH2), CoII(OH2), and CoIII(CH3) sites in CoFeSP-Cbl were identified. Our data support binding of a serine residue from the reductive-activator protein (RACo) of CoFeSP to the cobalt ion in the CoFeSP-RACo protein complex that stabilizes Co(II). The absence of an α-ligand at cobalt not only tunes the redox potential of the cobalamin cofactor into the physiological range, but is also important for CoFeSP reactivation.

Pulse radiolysis and ultra-high-performance liquid chromatography/high-resolution mass spectrometry studies on the reactions of the carbonate radical with vitamin B12 derivatives.

The reactions of the carbonate radical anion (CO3 (.) (-) ) with vitamin B12 derivatives were studied by pulse radiolysis. The carbonate radical anion directly oxidizes the metal center of cob(II)alamin quantitively to give hydroxycobalamin, with a bimolecular rate constant of 2.0×10(9) M(-1) s(-1) . The reaction of CO3 (.) (-) with hydroxycobalamin proceeds in two steps. The second-order rate constant for the first reaction is 4.3×10(8) M(-1) s(-1) . The rate of the second reaction is independent of the hydroxycobalamin concentration and is approximately 3.0×10(3) s(-1) . Evidence for formation of corrinoid complexes differing from cobalamin by the abstraction of two or four hydrogen atoms from the corrin macrocycle and lactone ring formation has been obtained by ultra-high-performance liquid chromatography/high-resolution mass spectrometry (UHPLC/HRMS). A mechanism is proposed in which abstraction of a hydrogen atom by CO3 (.) (-) from a carbon atom not involved in the π conjugation system of the corrin occurs in the first step, resulting in formation of a Co(III) C-centered radical that undergoes rapid intramolecular electron transfer to form the corresponding Co(II) carbocation complex for about 50 % of these complexes. Subsequent competing pathways lead to formation of corrinoid complexes with two fewer hydrogen atoms and lactone derivatives of B12 . Our results demonstrate the potential of UHPLC combined with HRMS in the separation and identification of tetrapyrrole macrocycles with minor modifications from their parent molecule.

Controlling Binding Dynamics of Corrin-Based Chemosensors for Cyanide

This paper describes a strategy to control the binding dynamics between cyanide and aquacyanocorrinoids on the molecular level. Aquacyanocorrinoids represent an important class of chemosensors and convert upon cyanide coordination to the corresponding dicyano derivatives. Structure-reactivity relationships were investigated for the first time by synthesizing and studying three diastereomerically pure aquacyanocorrinoids differing either in the configuration of the axially bound ligands or in the nature of remote side chains located at the periphery of the corrin macrocycle. Substitution of cobalt-coordinated water with cyanide was investigated using stopped-flow measurements between 5 and 30 °C, and second order rate constants and activation parameters were determined. In particular, it is demonstrated that the binding kinetics depend not only on (i) the configuration at the central metal center but also on (ii) the remote structural modifications of the macrocycle.

7-Decarboxymethyl-cobyrinates: Vitamin B12-Derivatives that Lack the c-Side Chain

The synthesis of cobyrinic acid derivatives by reduction of dehydrocobyrinates is largely unexplored. It is, however, a rational path to B(12) analogues that lack specific substituents of the corrin moiety of natural B(12) derivatives. The partial syntheses of four epimeric 7-decarboxymethyl-cobyrinates is described, which is achieved by reduction of Δ7-dehydro-7-de[carboxymethyl]-cobyrinate with zinc or with the 'prebiotic' reducing agent formic acid. A direct and remarkably efficient route was found to 7-decarboxymethyl-cobyrinates, which are cobyrinic acid derivatives in which the c-side chain at ring B of vitamin B(12) is missing. The structures of the hexamethyl-7-decarboxymethyl-cobyrinates were characterized and the stereochemical and conformational properties at their newly saturated ring B were analyzed. The stereochemical outcome of the reduction was found to depend strongly on the reaction conditions. In 7-decarboxymethyl-cobyrinates, both peripheral carbon centres of ring B carry a hydrogen atom, and the characteristic quaternary carbon centre at C7 of the cobyrinic acid moiety of vitamin B(12) is lacking. The still highly substituted 7-decarboxymethyl-cobyrinates are readily dehydrogenated in the presence of dioxygen, furnishing 7-de[carboxymethyl]-Δ(7)-dehydro-cobyrinate as the common, unsaturated oxidation product. The noted stability of vitamin B(12) and of other Co(III)-cobyrinates in the presence of air is a consequence of their highly substituted corrin macrocycle, a finding of interest in the context of chemical rationalizations of the B(12) structure.

Reconstitution of the B12Macrocycle by Radical Ring Closure of a Blue Secocorrin

A radical B12 synthesis: A recently described blue 7,8-secocorrinoid, a degradation product of vitamin B12, has a remarkable structural predisposition for ring closure. Reductive reconstitution of the corrin macrocycle by means of a stereospecific radical reaction leads to a 7-epicobalamin. Human B12-binding proteins bind this vitamin B12 analogue significantly less strongly than natural cobalamins.

Corrin ring-induced redox tuning

The density functional calculations suggest that the expansion of the corrin macrocycle's N(4) core by 0.06-0.10 Å leads to an appreciable lowering of 100-150 mV vs. saturated calomel electrode in the reduction potentials of two biologically important B(12) cofactors namely methylcobalamin and adenosylcobalamin respectively. This redox tuning of B(12) cofactors may encourage the electron transfer-based activation mechanism for B(12)-dependent enzymes.

A Blue Corrinoid from Partial Degradation of Vitamin B12in Aqueous Bicarbonate: Spectra, Structure, and Interaction with Proteins of B12Transport

Cobalamin (Cbl) is a complex cofactor produced only by bacteria but used by all animals and humans. Cyanocobalamin (vitamin B(12), CNCbl) is one commonly isolated form of cobalamin. B(12) belongs to a large group of corrinoids, which are characterized by a distinct red color conferred by the system of conjugated double bonds of the corrin ring retaining a Co(III) ion. A unique blue Cbl derivative was produced by hydrolysis of CNCbl in a weakly alkaline aqueous solution of bicarbonate. This corrinoid was purified and isolated as dark blue crystals. Its spectroscopic analysis and X-ray crystallography revealed B-ring opening with formation of 7,8-seco-cyanocobalamin (7,8-sCNCbl). The unprecedented structural change was caused by cleavage of the peripheral C-C bond between saturated carbons 7 and 8 of the corrin macrocycle accompanied by formation of a C═C bond at C7 and a carbonyl group at C8. Additionally, the C-amide was hydrolyzed to a carboxylic acid. The extended conjugation of the π-system caused a considerable red shift of the absorbance spectrum. Formation and degradation of 7,8-sCNCbl were analyzed qualitatively. Its interaction with the proteins of mammalian Cbl transport revealed both a slow binding kinetics and a low overall affinity. The binding data were compared to those of other monocarboxylic derivatives and agreed with the earlier proposed scheme for two-step ligand recognition. The obtained results are consistent with the structural models of 7,8-sCNCbl and the transport proteins intrinsic factor and transcobalamin. Potential applications of the novel derivative for drug conjugation are discussed.

TiO2-assisted Photocatalytic Degradation of Vitamin B12 in Aqueous Solution:Influencing Factors, Kinetics, and Reaction Investigations

The photodegradation (λ=365 nm) of the biomolecule vitamin B12, catalyzed by the photocatalyst TiO2 nanoparticles (NPs), has been investigated in aqueous suspension. The photodegradation process of vitamin B12 has been monitored by means of electronic absorption (Abs), Fourier-transform infrared (FT-IR), and resonance Raman (RR) spectroscopies, respectively. The results show that only under UV illumination in the presence of TiO2 is there effective degradation, and the photocatalytic degradation of vitamin B12 is strongly influenced by the amount of TiO2 NPs, the pH, and the initial concentration of vitamin B12. The photocatalytic reaction kinetics of vitamin B12 conforms to a Langmuir-Hinshelwood isotherm model. Changes involving the three structural units of the carbon-metal bond C–Co, the organic corrin macrocycle combined with the benzimidazole nucleotide, and the inorganic CN in the vitamin B12 molecule during the photocatalytic degradation are also discussed.

Trifluoracetic Acid-Assisted Crystallization of Vitamin B12 Results in Protonation of the Phosphate Group of the Nucleotide Loop: Insight into the Influence of Crystal Packing Forces on Vitamin B12 Structures

In the course of experiments concerning our ongoing project on the synthesis of vitamin B(12) (cyanocobalamin, CNCbl) bioconjugates for drug-delivery purposes, we observed the formation of well-shaped red parallelepipeds from a concentrated aqueous solution of the HPLC-purified vitamin. The X-ray structural investigation (MoK(α)) at 98 K on these crystals revealed a CNCbl-TFA salt of formula [CNCbl(H)](TFAc)·14H(2)O (1, where TFA = trifluoracetic acid; TFAc(-) = trifluoracetate anion), in which a proton transfer from the trifluoracetic acid to the phosphate-O4P oxygen atoms is observed. 1 crystallizes in the standard orthorhombic P2(1)2(1)2(1) space group, a = 16.069(2) Å, b = 20.818(2) Å, c = 24.081(2) Å, Z = 4. The final full-matrix least-squares refinements on F(2) converged with R(1) = 4.1% for the 18957 significant reflections, a very low crystallographic residual for cobalamins, which facilitated the analysis of the extensive network of hydrogen bonds within the lattice. To the best of our knowledge, this is the first cobalamin structure to show protonation of the phosphate group of the cobalamin nucleotide loop. In this work, the crystal structure of 1 is analyzed and compared to other CNCbls reported in the literature, namely, CNCbl·3PrOH·12H(2)O (2, PrOH = propyl alcohol), CNCbl·acetone·20H(2)O (3), CNCbl·2LiCl·10.2H(2)O (4), and CNCbl·2KCl·10.6H(2)O (5). The analysis confirmed that protonation of the phosphate leaves the major CNCbl structural parameters unaffected, so that 1 can be considered an "unmodified" Cbl solvate. However, comparison between 1-5 led to interesting findings. In fact, although the cobalt(III) coordination sphere in 1-5 is similar, significant differences could be noted in the upward fold angle of the corrin macrocycle, a parameter commonly related to the steric hindrance of the axial lower "α" nucleotide-base and the electronic trans influence of the upper "β" substituent. This suggests that crystal-packing forces may influence the corrin deformation as well. Herein we explore, on the basis of the newly acquired structure and reported crystallographic data, whether the incongruities among 1-5 have to be attributed to random crystal packing effects or if it is possible to associate them with specific crystal packing (clusters).

Electron Densities of Three B12 Vitamins

The electron densities of the three natural B(12)-vitamins, two of them being essential cofactors for animal life, were determined in a procedure combining high-order X-ray data collection at low to very low temperatures with high-level density functional calculations. In a series of extensive experimental attempts, a high-order data set of adenosylcobalamin (AdoCbl) could be collected to a resolution of sin theta/lambda = 1.00 A(-1) at 25 K. This modification contains only minor disorder at the solvent bulk. For methylcobalamin (MeCbl), only a severely disordered modification was found (sin theta/lambda = 1.00 A(-1), 100 K, measured with synchrotron radiation). The already published data set of cyanocobalamin (CNCbl) (sin theta/lambda = 1.25 A(-1), 100 K) was reintegrated to guarantee similar treatment of the three compounds and cut to sin theta/lambda = 1.11 A(-1) to obtain a higher degree of completeness and redundancy. On the basis of these accurate experimental geometries of AdoCbl, MeCbl, and CNCbl, state-of-the-art density functional calculations, single-point calculations, and geometry optimizations were performed on model compounds at the BP86/TZVP level of theory to evaluate the electronic differences of the three compounds. AdoCbl and MeCbl are known to undergo different reaction paths in the body. Thus, the focus was directed toward the characterization of the dative Co-C(ax) and Co-N(ax) bonds, which were quantifed by topological parameters, including energy densities; the source function including local source; and the electron localizability indicator (ELI-D), respectively. The source function reveals the existence of delocalized interactions between the corrin macrocycle and the axial ligands. The ELI-D indicates unsaturated Co-C(ax) bonding basins for the two biochemically active cofactors, but not for CNCbl, where a population of 2.2e is found. This may be related to significant pi-backbonding, which is supported by the delocalization index, delta, of 0.15 between the Co atom and the N atom of the cyano ligand. Considering all results, the inherent electronic differences between AdoCbl and MeCbl are found to be small thus, supporting earlier findings that the interaction with the protein site mainly controls the type of Co-C(ax) bond cleavage.

Structural insights into methyltransfer reactions of a corrinoid iron–sulfur protein involved in acetyl-CoA synthesis

The cobalt- and iron-containing corrinoid iron-sulfur protein (CoFeSP) is functional in the acetyl-CoA (Ljungdahl-Wood) pathway of autotrophic carbon fixation in various bacteria and archaea, where it is essential for the biosynthesis of acetyl-CoA. CoFeSP acts in two methylation reactions: the transfer of a methyl group from methyltransferase (MeTr)-bound methyltetrahydrofolate to the cob(I)amide of CoFeSP and the transfer of the methyl group of methyl-cob(III)amide to the reduced Ni-Ni-[4Fe-4S] active site cluster A of acetyl-CoA synthase (ACS). We have solved the crystal structure of as-isolated CoFeSP(Ch) from the CO-oxidizing hydrogenogenic bacterium Carboxydothermus hydrogenoformans at 1.9-A resolution. The heterodimeric protein consists of two tightly interacting subunits with pseudo-twofold symmetry. The large CfsA subunit comprises three domains, of which the N-terminal domain binds the [4Fe-4S] cluster, the middle domain is a (betaalpha)(8)-barrel, and the C-terminal domain shows an open fold and binds Cobeta-aqua-(5,6-dimethylbenzimidazolylcobamide) in a "base-off" state without a protein ligand at the cobalt ion. The small CfsB subunit also displays a (betaalpha)(8)-barrel fold and interacts with the upper side of the corrin macrocycle. Structure-based alignments show that both (betaalpha)(8)-barrel domains are related to the MeTr in the acetyl-CoA pathway and to the folate domain of methionine synthase. We suggest that the C-terminal domain of the large subunit is the mobile element that allows the necessary interaction of CoFeSP(Ch) with the active site of ACS(Ch) and the methyltetrahydrofolate carrying MeTr. The conformation in the crystal structure shields the two open coordinations of cobalt and likely represents a resting state.

Spectroscopic and Computational Studies of Co1+Cobalamin: Spectral and Electronic Properties of the “Superreduced” B12 Cofactor

The 4-coordinate, low-spin cob(I)alamin (Co1+Cbl) species, which can be obtained by heterolytic cleavage of the Co-C bond in methylcobalamin or the two-electron reduction of vitamin B12, is one of the most powerful nucleophiles known to date. The supernucleophilicity of Co1+Cbl has been harnessed by a number of cobalamin-dependent enzymes, such as the B12-dependent methionine synthase, and by enzymes involved in the biosynthesis of B12, including the human adenosyltransferase. The nontoxic nature of the Co1+Cbl supernucleophile also makes it an attractive target for the in situ bioremediation of halogenated waste. To gain insight into the geometric, electronic, and vibrational properties of this highly reactive species, electronic absorption, circular dichroism (CD), magnetic CD, and resonance Raman (rR) spectroscopies have been employed in conjunction with density functional theory (DFT), time-dependent DFT, and combined quantum mechanics/molecular mechanics computations. Collectively, our results indicate that the supernucleophilicity of Co1+Cbl can be attributed to the large destabilization of the Co 3dz2-based HOMO and its favorable orientation with respect to the corrin macrocycle, which minimizes steric repulsion during nucleophilic attack. An intense feature in the CD spectrum and a prominent peak in the rR spectra of Co1+Cbl have been identified that may serve as excellent probes of the nucleophilic character, and thus the reactivity, of Co1+Cbl in altered environments, including enzyme active sites. The implications of our results with respect to the enzymatic formation and reactivity of Co1+Cbl are discussed, and spectroscopic trends along the series from Co3+Cbls to Co2+Cbl and Co1+Cbl are explored.

Probing the nature of the Co(iii) ion in cobalamins: a comparison of the reaction of aquacobalamin (vitamin B12a) and aqua-10-chlorocobalamin with some anionic and N-donor ligands

To probe the cis effect of the corrin macrocycle in vitamin B12 derivatives, equilibrium constants for the substitution of coordinated H2O in aquacobalamin (vitamin B12a, H2OCbl+) and in aqua-10-chlorocobalamin, H2O-10-ClCbl+, (in which Cl has replaced the C10 H) by an exogenous ligand, L (L = an anion, NO2-, SCN-, N3-, OCN-, S2O3(2-), NCSe- or a neutral N-donor, CH3NH2, pyridine, imidazole) have been determined. The cis influence reported in the electronic spectra of the cobalamins is observed in the spectra of L-10-ClCbls as well. Anionic ligands bind more strongly to H2O-10-ClCbl+ than to H2OCbl+ with log K values between 0.10 and 0.63 (average 0.26) larger; the converse is true for the neutral N-donor ligands, where log K is between 0.17 and 0.3 (average 0.25) smaller. Semi-empirical molecular orbital (SEMO) calculations using the ZINDO/1 model on the hydroxo complexes show that charge density is delocalised from the axial donor atom to the metal and Cl. This explains why coordinated OH- is a poorer base in HO-10-ClCbl than in HOCbl and the pK(a) of H2O-10-ClCbl+ is lower than that of H2OCbl+. It further explains why, because of the ability of the metal in concert with the C10 Cl to accept charge density from the ligand, an anionic ligand will bind more strongly to Co(III) in H2O-10-ClCbl+ than in H2OCbl+. The kinetics of the replacement of coordinated H2O by two probe ligand, pyridine and azide, were determined. The rate constants for substitution of H2O in H2O-10-ClCbl+ by pyridine show saturation, whilst those for substitution by N3- do not; this is inconsistent with a purely dissociative mechanism and the reactions proceed through an interchange mechanism. The values of the activation parameters are more positive for the reaction between these ligands and H2OCbl+, than for their reaction with H2O-10-ClCbl+. This is interpreted to mean that the transition state in the reaction of H2O-10-ClCbl+ occurs earlier along the reaction coordinate. In the temperature range studied, H2O-10-ClCbl+ reacts more slowly with py and N3- than does H2OCbl+. SEMO calculations indicate that as the Co-O bond to the departing H(2)O molecule is stretched, the charge density on Co in H2OCbl+ is always lower than on Co in H2O-10-ClCbl+. This suggests that the former is a better electrophile towards the incoming ligand, and offers an explanation for the kinetics observations.

Probing the Nature of the CoIIIIon in Cobalamins − Spectroscopic and Structural Investigations of the Reactions of Aquacobalamin (Vitamin B12a) with Ambident Nucleophiles

AbstractThe rate of substitution of the H2O β‐ligand in aquacobalamin (vitamin B12a) is surprisingly fast for CoIII. This may arise as a result of transfer of electron density to CoIIIby the corrin, conferring on the metal atom a softer and more labile character, and would require electronic communication between the equatorial ligand and the axial coordination sites of the metal atom. We have substituted H2O in B12awith the ambidentate nucleophiles SCN−, SeCN−, NO2−and S2O32−, examined the UV/Vis spectra of the resultant complexes, crystallised them, and determined their structures by X‐ray diffraction methods. The UV/Vis spectra of these complexes, as well as those of H2OCbl+, SO3Cbl−and MeCbl, were fitted by Gaussian functions. The principal bands move to lower energy in response to an increase in donation of electron density from the axial ligand, demonstrating direct electronic communication between the axial and the equatorial ligands. In the solid state, the thiocyanato ligand in SCNCbl is coordinated through N, although13C NMR spectroscopy shows that the complex exists as a mixture of two linkage isomers in solution. SeCN−, NO2−and S2O32−are coordinated through the softer available donor in each case (Se, N and S, respectively). There is a regular ground‐statetranseffect such that as the donor power of the β‐ligand increases, thetransCo−Naxbond length increases. A survey of the structures available in the CSD shows that this preference for the softer donor atom in ambidentate nucleophiles is not unusual in CoIIIcomplexes. The Co−N bond length in SCNCbl is marginally long for coordination to CoIII, but the axial bond lengths of the other complexes are as expected. Hence, whereas the corrin macrocycle clearly imparts lability on CoIII, presumably by transfer of electron density onto the metal atom, this is insufficient to have a major effect on the ground‐state structures of its complexes. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Electronic Properties of the Axial Co−C and Co−S Bonds in B12 Systems − A Density Functional Study

The numerous accurate structural data of cobalamins now available allows us to optimize the geometry of these systems, based on a simplified model by using density functional theory (DFT) calculations. This approach, which reproduces the trend of the experimental distances derived from EXAFS and X-ray crystal structures in the corrin macrocycle, permit us to interpret the electronic properties in the NB3−Co−X axial system. In particular, the results are analyzed for cobalamins containing a sulfur ligand which exhibits a “regular” trans influence, i.e., when the Co−S bond shortens, the trans Co−NB3 bond lengthens. This feature appears in contrast with an anomalous effect (“inverse” trans influence) postulated a few years ago by analyzing the structural data of several alkylcobaloximes, LCo(DH)2R, a simple B12 model, and attributed principally to the electronic properties of the alkyl group R. The present study on the NB3−Co−S fragment does not indicate that the “inverse” trans influence is a general rule in cobalamins. The accurate crystal structures of the [(SO3)Cbl](NH4) and [(thiourea)Cbl](PF6) cobalamins based on synchrotron diffraction data at 100 K are also reported for comparison with the theoretical study. The former crystal structure, including one co-crystallized glycerol molecule, presents “for the first time” an ordered hydrogen-bonding pattern for the solvent molecules.