Alkyl cobalamins formation

Thermochemical. Application to the estimation of the enthalpy of a process such as that depicted by Equation 15 requires determination of the heats of formation of LnM—R, R , and LnM . The latter usually is not accessible to measurement although it is in the case of alkyl-cobalamins (where LnM- corresponds to vitamin B12r, a stable and accessible compound). Thus, thermochemical approaches, in principle, are potentially applicable to the estimation of the Co-C bond dissociation energy in coenzyme B12. However, the practical difficulties are considerable and the probable accuracy of the result is questionable. 

Recrystallization from water/acetone (even at a basic pH) causes some hydrolysis of the acetal. (2,2-Diethoxyethyl)cobalamin, like all alkyl cobalamins, is light sensitive in solution in addition, and unlike most other alkylcobalamins, it is add sensitive, decomposing to both (formylmethyl)cobalamin and aqua-cobalamin.2 The formation of other alkylcobalamins and cobaloximes by reaction with enol ethers has been described.2... 

A series of related reports have appeared on the equilibria between five- and six-coordinate species and possible adduct formation in Co(iii) corrinoids, on the thermodynamic and kinetic properties for what is termed the base-on/ base-off equilibration of alkyl cobalamins, " and on the kinetics and thermodynamics of parallel equilibria of alkyl-13-epicobalamins. In the first report, the pressure dependence of the UV/visible spectra of the five-coordinate (yellow)/six-coordinate (red) equilibrium for both methylcobalamin and vinylcobinamide was obtained. Water is the ligand that converts the five- to a six-coordinate species. The reaction volumes were obtained from the pressure dependence of the equilibrium constant. The values of AF of —12.5 1.2 and —12.5 l.Ocm moF for the methyl and vinyl complexes are close to the values 13cm moF advocated and accepted for the displacement or... 

Another use of cob(I)alamin (40 ) as a tool in toxicology is for the analysis of DNA-phosphate adducts. Utilizing the nucleophilicity of 40", alkyl groups from the phosphotriester configuration in DNA were transferred with the formation of alkyl-cobalamin complexes [251]. 

Schrauzer and co-workers have studied the kinetics of alkylation of Co(I) complexes by organic halides (RX) and have examined the effect of changing R, X, the equatorial, and axial ligands 148, 147). Some of their rate constants are given in Table II. They show that the rates vary with X in the order Cl < Br < I and with R in the order methyl > other primary alkyls > secondary alkyls. Moreover, the rate can be enhanced by substituents such as Ph, CN, and OMe. tert-Butyl chloride will also react slowly with [Co (DMG)2py] to give isobutylene and the Co(II) complex, presumably via the intermediate formation of the unstable (ert-butyl complex. In the case of Co(I) cobalamin, the Co(II) complex is formed in the reaction with isopropyl iodide as well as tert-butyl chloride. Solvent has only a slight effect on the rate, e.g., the rate of reaction of Co(I) cobalamin... 

Catalytic hydrogenation with platinum liberates the hydrocarbon from methylcobalamin (57) and from alkyl-Co-DMG complexes (161), but not from pentacyanides with primary alkyl, vinyl, or benzyl ligands, though the cr-allyl complex yields propylene (109). Sodium sand gives mixtures of hydrocarbons with the alkyl-Co-salen complexes (64). Dithioerythritol will liberate methane from a variety of methyl complexes [cobalamin, DMG, DMG-BF2, G, DPG, CHD, salen, and (DO)(DOH)pn] (156), as will 1,4-butanedithiol from the DMG complex (157), and certain unspecified thiols will reduce DMG complexes with substituted alkyl ligands (e.g., C0-CH2COOH ->CH3C00H) (163, 164). Reaction with thiols can also lead to the formation of thioethers (see Section C,3). 

Cobalamin catalysed reduction of alkyl halides has found use in organic synthesis because, like square planar Ni(o), it allows formation of alkyl radicals in the bulk of the solution away from the electi ode surface. Alkyl radical addition to activated alkenes is achieved in high yields. In the cases of primary alkyl halides,... 

However, some indirect indication of the strength of alkyl-Co bonds in organo-cobalamin, relative to those in other alkyl-cobalt compounds, is provided by observations concerning the stability of ben-zylcobalamin. Attempts to prepare benzylcobalamin by either the Bi2s route (Reaction 31) (32) or the Bi2r route (Reactions 32-34) (15) have yielded spectroscopic evidence for its initial formation in solution. However, benzylcobalamin proved to be too unstable for isolation and... 

Other uses of cobalt(I) catalysts include the reductive intramolecular cyclization of bromocyclohexenones to form bicyclic ketones [391] and the radical cyclization of bro-moacetals [392,393]. Krautler and coworkers [394] found that 1,4-dibromobutane interacts with electrogenerated cob(I)alamin to afford a tetramethylene-l,4-di = Co -cobalamin species. In a recent study of the reactions of cobalt(I) tetraphenyl porphyrin with benzyl chloride or 1-chlorobutane, Zheng and coworkers [395] reported that alkyl radicals are transferred from the cobalt center to a nitrogen of a pyrrole ring, leading to formation of an A-alkyl cobalt porphyrin complex. 

Simple alkylcobalt complexes (i.e. those without heteroatomic substituents on the alkyl ligand) are also known to undergo eliminations of cobalt(I) species. Thus Grate and Schrauzer [42] have studied the decomposition of unstable, sterically strained secondary alkyl- and cycloalkyl-cobalamins to form olefins and hydridocobalamin in neutral and acidic solution. In this case the formation of hydridocobalamin was inferred from the observation of monodeuteriohydrogen gas when undeuterated alkylcobalamins were decomposed in DCl/DjO, presumably via Eqns. 42 and 43. 

Dioximato-complexes. Studies of dioximato-complexes continue to be extensive probably because of their close similarity to the cobalamins and vitamin B12. Dissociative (often Z>) mechanisms are most commonly observed for the aquation reactions as well as for formations and for ligand exchange. Since these reactions are so similar most of the results will be collected together in this section. References to kinetic studies of aquation,ligand-exchange, and anation reactionsof neutral and anionic complexes of the type /ra 5-[Co(dioxime)2AX] dioxime = [HON=C(R )C(R )=NO] where R and R are alkyl groups are collected in Table 7. 

Weissbach et al., 1965). Higher alkyl-Bi2 compounds (e.g., propyl-, butyl-, and butyrate-Bi2) do not form holoenzyme, but combine with the enzyme, yielding an inhibited form which can be activated by light, a treatment known to cleave die carbon—cobalt bond of alkyl-Bi2 compounds (Weissbach et al., 1965). These results are all consistent with the possibility that a reduced cobalamin may be the active prosthetic group of the enzyme. Deoxyadenosyl-Bi2, the derivative active as coenzyme for most known Bi2-dependent reactions (Weissbach and Dickerman, 1965 Barker, 1967 Hogenkamp, 1968), supports holoenzyme formation only in the presence of a reducing system and a second protein fraction (holoenzyme synthetase) (Brot and Weissbach, 1966). 

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