Hydrophobic Vitamin B12 Derivatives Research Articles

Ligand-substitution reactions of hydrophobic vitamin B12 derivatives: reaction of cobyric acid heptamethyl ester with azoles

Hydrophobic cobyrinic acid heptamethyl ester corrinoids XCbs–Me (axial ligand X = CN−, , and vinyl) have been prepared from vitamin B12 by hydrolysis of the seven-amide chain and conversion to methyl ester. The solvents affect both the Soret band and the shape of the UV-Vis spectra of the hydrophobic corrinoids. The equilibrium constant, K, for the reactions of XCbs–Me (X = CN−, , and vinyl) with pyrazole (Pz) and imidazole (ImH) have been determined spectrophotometrically at 25°C. Value of K for Pz was less than that obtained for ImH in all the solvents used in the present study. The values of K increase as the solvent polarity increases, water > methanol > DMSO > DMF. The values of K for the two azoles decreases in the order X = CN− > > vinyl. This shows that the ligands coordinated at the trans position in the substitution site have a significant effect on the value of K.

Organic/inorganic hybrid nanomaterials with vitamin B12 functions

A hybrid nanomaterial was prepared by human serum albumin (HSA) and vitamin B12 derivatives. The incorporation of hydrophobic vitamin B12 derivatives, which have ester groups in place of the peripheral amide moieties of the natural cobalamin, into HSA is primarily controlled by the hydrophobicity of the peripheral ester groups. Microenvironmental property around the hydrophobic vitamin B12 in HSA was examined by fluorescence and fluorescence polarization measurements. The hydrophobic vitamin B12 itself in HSA is in a microenvironment equivalent in medium polarity to dichloromethane. The molecular motion of hydrophobic vitamin B12 in HSA was markedly suppressed under such microenvironmental conditions. Carbon-skeleton rearrangement reaction of an alkyl radical derived from an alkyl ligand bound to the hydrophobic vitamin B12 was markedly favored in HSA aqueous solution, relative to the reactions in methanol and benzene. The 1,2–migration of the electron-withdrawing group arises from both the suppression of molecular motion and desolvation effects on the alkylated hydrophobic vitamin B12 in HSA.

ビタミンＢ１２モデル錯体を触媒とした有機電解反応

Vitamin B12-dependent enzymes, involving the cobalt species as a catalytic center, mediate various isomerization reactions accompanied by carbon-skeleton rerragements. In order to simulate the catalytic functions of vitamin B12 as excerted in the hydrophobic active sites of enzymes concerned, we have been dealing with hydrophobic vitamin B12 derivatives which have ester groups in place of the peripheral amide moieties of the naturally occurring vitamin B12. In this work, the carbon-skeleton rearrangements as mediated by hydrophobic vitamin B12 derivatives were investigated under elec-trochemical conditions. The controlled-potential electrolyses of alkyl halides with various electronwithdrawing groups were carried out, and the electrochemical carbon-skeleton rearrangements proceeded effectively via formation of anionic intermediates. These reactions can be also applied to the ring-expansin reactins. We have carried out the electrolysis of an alkyl halide having two ester groups and one phenyl group on the β-carbon atom in the presence of a catalytic amount of the hydrophobic vitamin B12. The migration of the pheny group was observed under the conditions forming a radical intermediate. The ester-migrated product was detected under the conditions forming an anionic intermediate. This is the first successful example in selecting a migrating group by electroylsis potential. We have also prepared a strapped hydrophobic vitamin B12 in order to change the enantioselectivity. The controlled-potential electrolysis of a racemic alkyl halide having phenyl, methoxy, and carboxylic ester groups on the same carbon atom was carried out. The simple hydrophobic vitamin B12 tends to bind S-enantiomers more favorably. On the other hand, strapped hydrophobic vitamin B12 acts to bind R-enantiomers more favorably. These results suggested that the stability of alkylated complexes was dominated the enantioselectivity of reduction products.

Hydrophobic vitamin B12. Part 12. Preparation, characterization and enantioselective alkylation of strapped hydrophobic-vitamin B12

Cyanocobalamin has been modified to afford a strapped hydrophobic vitamin B12 by introducing a 1,3-phenylenediacetyl moiety into the peripheral site of the corrin's B ring. The modified complex was characterized by various spectroscopic methods and cyclic voltammetry in comparison with the corresponding data for a simple hydrophobic vitamin B12 without a strapping moiety. The alkylation of hydrophobic vitamin B12 derivatives with racemic 3-bromo-2-methylpropionic esters at the β-axial site was carried out in methanol, and extents of the enantioselectivity were examined by 1H NMR spectroscopy. The strapped hydrophobic vitamin B12 and a simple hydrophobic vitamin B12 were found to react with (S)-3-bromo-2-methylpropionates more readily than the corresponding R-enantiomers; the highest S-selectivity (75% ee) was observed with the strapped hydrophobic vitamin B12. The S-enantioselectivity was discussed from a stereochemical viewpoint based on the conformational search for the alkylated hydrophobic vitamin B12 by means of molecular mechanics and dynamics calculations.

Photolysis of Hydrophobic Vitamin B12 Derivatives Covalently Bound to Lipid in Aqueous Media

Abstract An alkyl ligand coordinated to hydrophobic vitamin B12 derivatives covalently bound to N,N-dihexadecyl-Nα-[6-(trimethylammonio)hexanoyl]-l-aspartamide bromide underwent a novel bromination reaction along with its rearrangement in the single-walled vesicle of N,N-dihexadecyl-Nα-[6-(trimethylammonio)hexanoyl]-l-alaninamide bromide under photolysis conditions.

Hydrophobic Vitamin B12. XI. Preparation, Characterization, and Enantioselective Alkylation of Hydrophobic Vitamin B12 Bearing a Binaphthyl Moiety

Abstract Hydrophobic vitamin B12 derivatives bearing a chiral binaphthyl moiety, hexamethyl 71-decarboxy-71-[(R)-2′-methoxy-1,1′-binaphthyl-2-carboxymethyl]cobyrinate perchlorate [B12–BINAP(R)] and hexamethyl 71-decarboxy-71-[(S)-2′-methoxy-1,1′-binaphtyl-2-carboxymethyl]cobyrinate perchlorate [B12–BINAP(S)], were prepared from cyanocobalamin. These complexes were characterized by means of electronic and circular dichroism spectroscopy as well as by cyclic voltammetry in comparison with those data for a hydrophobic vitamin B12 without a binaphthyl moiety. The enantioselective alkylation of hydrophobic vitamin B12 derivatives at the β-axial site was examined in methanol with various 3-bromo-2-methylpropionic esters by means of 1H NMR spectroscopy. All the hydrophobic vitamin B12 derivatives used here, the one bearing methoxycarbonyl groups as peripheral substituents without a binaphthyl moiety, B12–BINAP(R), and B12-BINAP(S), were found to bind (S)-2-methylpropionates more favorably than the corresponding R-enantiomers; the highest S-selectivity was observed with the latter two derivatives, 65% e.e. The cause of such S-enantioselectivity was discussed with attention to stereochemical configurations of the peripheral substituents placed in the corrin ring.

Hydrogen Source in the Photochemical Cobalt–Carbon Cleavage of Hydrophobic Vitamin B12 Derivatives in Hydrophobic Microenvironments

Abstract The photolysis of a hydrophobia vitamin B12 with a benzyl moiety at the Coβ site was carried out in a D2O solution containing single-walled vesicles, and a major product was the non-deuterated toluene. A hydrogen atom was apparently abstracted from the hydrophobic vitamin B12 or a lipid molecule, and not from bulk water.

Effect of proteins on the response of anion‐selective electrodes based on vitamin B12 derivatives

AbstractThe potentiometric response of several polymer membrane based ion‐selective electrodes prepared with hydrophobic vitamin B12 derivatives is described. The effect of different proteins on the properties of these electrodes is discussed. It is suggested that the observed changes in potential upon addition of proteins are due mainly to nonspecific interactions between the proteins and the polymer membrane. Reduction of the nonspecific binding effect is possible by using a polymer matrix that contains free hydroxyl groups. The observed results agree with a theoretical model, which predicts that the nonspecific binding effect is more evident when membranes loaded with relatively small amounts of ionophore are used. The implications of these observations for the development of biosensors are discussed.

Hydrophobic vitamin B12. Part 9. An artificial holoenzyme composed of hydrophobic vitamin B12 and synthetic bilayer membrane for carbon-skeleton rearrangements

The incorporation of hydrophobic vitamin B12 derivatives, which have ester groups in place of the peripheral amide moieties of the naturally occurring vitamin B12, into single-compartment vesicles composed of synthetic lipids having an alanyl residue in the single-chain segment, is primarily controlled by the hydrophobicity of the peripheral ester groups. Such incorporation into vesicles of another synthetic lipid, having a histidyl residue in place of an alanyl residue, was much enhanced when coordination was allowed to take place between the nuclear cobalt of the hydrophobic vitamin B12 and the imidazolyl moiety of the lipid. Microenvironmental properties around heptapropyl cobyrinate derivatives placed in single-compartment vesicles of the former lipid were examined by electronic, fluorescence and fluorescence polarization measurements as well as by differential scanning calorimetry. The hydrophobic vitamin B12 was incorporated into the intramembrane domain composed of assembly of the single-chain segment of each lipid molecule, and its molecular motion was markedly suppressed under such microenvironmental conditions. Carbon-skeleton rearrange-ment reactions of alkyl ligands bound to heptapropyl cobyrinate were markedly favoured in the single-compartment vesicle, relative to the reactions in methanol and benzene, under anaerobic photolysis conditions at ordinary temperatures. The 1,2-migration of electron-withdrawing groups, such as acetyl, cyano, carboxylic ester and thioester, apparently arises both from suppression of molecular motion and desolvation effects operating on the alkylated hydrophobic vitamin B12 in the vesicle. Finally, the catalytic mediator, constituted with heptapropyl cobyrinate perchlorate and the single-compartment vesicle in aqueous media, was coupled with a substrate-activation system, composed of atmospheric oxygen and vanadium(III) ions, to establish a real artifical holoenzyme. 2-Acetyl-2-ethoxycarbonylpropane, 2-cyano-2-ethoxycarbonylpropane and 1-acetyl-1-ethoxy-carbonylethane were converted catalytically into the corresponding rearrangement products under aerobic photolysis conditions at 20 °C. A plausible reaction mechanism for the catalytic reaction is discussed.

ChemInform Abstract: Hydrophobic Vitamin B12. Part 6. Carbon‐Skeleton Rearrangement via Formation of Host‐Guest Complexes Derived from an “Octopus” Azaparacyclophane and Hydrophobic Vitamin B12 Derivatives: A Novel Holoenzyme Model System.

The alkylation reaction of a hydrophobic vitamin B12 derivative with alkyl bromides in an ‘octopus’ azaparacyclophane having eight hydrocarbon chains have been investigated. Molecular discrimination has been shown to originate from electrostatic interaction between the octopus cyclophane and the alkyl bromides. Alkylation was enhanced by desolvation and proximity effects operating on the reacting species via formation of a ternary complex composed of the octopus cyclophane, the hydrophobic vitamin B12 derivative, and an alkyl halide. Carbon-skeleton rearrangements reactions of alkyl ligands bound to the hydrophobic vitamin B12 were found to be markedly favoured in the hydrophobic cavity provided by the octopus cyclophane, relative to the reactions in methanol and benzene, under anaerobic photolysis conditions at ordinary temperatures. The same reactions took place readily in solid benzene below 4°C under similar conditions. The central cobalt atom of the hydrophobic vitamin B12 participates in the rearrangements reaction via formation of a tight pair with an alkyl radical species. Non-enzymic rearrangement reactions have been shown here to proceed quite efficiently by employing a relevant apoenzyme model.

Novel catalytic functions of hydrophobic vitamin B12 in electrochemical carbon-skeleton rearrangements

Abstract

CATALYTIC FUNCTION OF A HOST–GUEST COMPLEX DERIVED FROM OCTOPUS AZAPARACYCLOPHANE AND HYDROPHOBIC VITAMIN B12 AS A HOLOENZYME MODEL

Abstract The isomerization reaction accompanied with carbon-skeleton rearrangement, as typically catalyzed by the vitamin B12-dependent methylmalonyl-CoA mutase, was simulated by employing the host–guest complexes formed with an octopus azaparacyclophane having eight hydrocarbon chains and hydrophobic vitamin B12 derivatives.

CARBON-SKELETON REARRANGEMENT OF ALKYL LIGANDS COORDINATED TO HYDROPHOBIC VITAMIN B12 DERIVATIVES IN MOLECULAR AGGREGATES

Abstract The carbon-skeleton rearrangement of alkyl ligands coordinated to hydrophobic vitamin B12 derivatives took place in molecular a aggregates formed with CTAB, Triton X-100, or N,N-didodecyl-Nα-[6-(trimethylammonio)hexanoyl]-l-alaninamide bromide more favorably than the reaction in methanol or benzene under anaerobic conditions in the dark.

PHOTOLYSIS OF HYDROPHOBIC VITAMIN B12 DERIVATIVES WITH ALKYL LIGANDS IN NONAQUEOUS MEDIA

Abstract Aerobic photolysis of hydrophobic vitamin B12 derivatives having alkyl ligands was enhanced as the solvent polarity was reduced and by the coordination of a proximal base placed within the hydro-phobic complexes. The quantum yield remained constant regardless of the irradiation wavelength.

Hydrophobic Vitamin B12. IV. Addition Reactions of Alcohols to Olefins as Catalyzed by Hydrophobic Vitamin B12 Derivatives

Abstract Addition reactions of alcohols to olefins were catalyzed by hydrophobic vitamin B12 derivatives under aerobic irradiation conditions at the room temperature range. Ethyl vinyl ether, 1-pentene, and cyclohexene were adopted as olefins, while heptamethyl methylaquacobyrinate perchlorate and heptamethyl cyanoaquacobyrinate perchlorate were used as the starting complexes. Heptamethyl cobyrinate, which was generated from heptamethyl methylaquacobyrinate perchlorate by aerobic photolysis, is an appropriate catalyst for investigation of the reaction mechanism because the alkylated complex having the cobalt–carbon σ-bond, the reaction intermediate, has a long lifetime sufficient for its identification in the dark. On the other hand, heptamethyl cyanocobyrinate, which was derived from heptamethyl cyanoaquacobyrinate, is superior to heptamethyl cobyrinate as the catalyst for the addition reaction. The reaction proceeds via light-promoted decomposition of the alkylated complex, and the catalyst is regenerated upon autoxidation by air. These hydrophobic vitamin B12 derivatives are particularly effective homogeneous catalysts for the addition of an alcohol to an electron-rich olefin. Plausible reaction schemes for the catalytic cycle have been presented on the basis of experimental findings.

Hydrophobic Vitamin B12. III. Incorporation of Hydrophobic Vitamin B12 Derivatives into Single-Compartment Vesicles and Their Alkylation in Various Molecular Aggregates

Abstract The incorporation of hydrophobic vitamin B12 derivatives into the single-compartment vesicles of N,N-didodecyl-Nα-[6-(tyimethylammonio)hexanoyl]-l-alaninamide bromide (N+C5Ala2C12) was found to be primarily concerned with the extent of insolubility of the cobalt complexes in the aqueous bulk phase, while such incorporation into the single-walled vesicles of N,N-ditetradecyl-Nα-[6-(trimethylammonio)hexanoyl]-l-histidinamide bromide (N+C5His2C14) was enhanced by the coordination interaction between the cobalt complex and the imidazolyl group of the lipid. In molecular aggregates formed with hexadecyltrimethylammonium bromide, α-[4-(1,1,3,3-tetramethylbutyl)phenyl]-ω-hydroxypoly(oxyethylene), or N+C5Ala2C12, the alkylation rates of a hydrophobic vitamin B12 with 1-bromo-2-methylpropane and methyl 2-methyl-3-bromopropanoate were much enhanced relative to those in methanol. In the N+C5Ala2C12 vesicle, a two-step mechanism was observed for the alkylation with the latter reagent. The possible origin of such rate enhancement was discussed.