Alkyl cobalamin complexes

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]. 

Other pubKcations dealing with the catalytic ability of electrogenerated cobalt(I) species have appeared. Cob(I)alamin reacts with 1,4-dibromobutane to yield a tet-ramethylene-1,4-di-Co -cobalamin complex [138]. Alkyl radicals (which arise from the oxidative addition of cobalt(I) tetraphenyl porphyrin to an alkyl halide) have been found to migrate from the cobalt center to a nitrogen of a pyrrole ring [139]. 

The suspected 5-coordinate complexes, Co(saloph)R and base-off al-kylcobalamins, share the behavior that Co—C bond homolysis is less facile than in the counterpart 6-coordinate complexes, LCo(saloph)R and base-on alkyl-cobalamins [93,141,145], Base-off cobalamins (made by adding acid to hy-dronate the benzimidazole ring) and cobinamides (which are derived from cobalamins but lack 5,6-dimethylbenzimidazole) are believed to be 5-coordinate when R is a strong electron donor, but the evidence is primarily spectroscopic [141], However, 5-coordinate species are generally more thermally stable than their 6-coordinate counterparts. 

Finally, the apparent thermal stabilities of alkyl-cobalamins, as well as of some of the other transition-metal-alkyl compounds that have been examined in the course of these studies, generally are higher than would correspond to their metal-C bond-dissociation energies. The most probable explanation for this is that, in the absence of effective radical scavengers, homolytic dissociation of metal-alkyl bonds occurs reversibly because of selective recombination of the initially produced radicals and metal complexes. 

Many short-lived small inorganic radicals and unusual transition metal centers have been generated by photolysis or radiolysis methods in matrices [22], (The matrix can be a glassy frozen solvent or a solid, e.g. zeolite or other oxide). This method is, however, also suitable for investigation of rather complex systems such as alkyl cobalamins and related B12 species [29, 30]. Irradiation with visible light is even sufficient to cleave the crucial Co-Caikyi bond in these macrocyclic compounds to yield Co products and the less persistent alkyl radical intermediates both can be detected by ESR in low-temperature matrices (Eq. 2) [30]. 

Strong bases (pKa > 11) also convert alkyl cobaloximes and alkyl cobalamins into -complexes such as 73. This is usually followed by further decomposition to olefins and alkanes. The stability of complexes such as 73 depends very much upon X and the nature of the axial ligand in the cobalt chelate.98-218-227 230 Strong nucleophiles such as RS or CN can cause decomposition of LCo—R as well.98-231 Under the normal conditions of radical polymerization, Markovnikov organocobaloxime should form whenever the hydride, LCoH, appears in the polymerization mixture. If 1,2-vinylidene monomers are being polymerized, then thermally unstable tert-alkyl-cobaloximes are obtained. These species are expected to undergo homolytic Co—C cleavage to yield tertiary radicals. 

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... 

Complexes of the composition RCo (dioximeH)2L (R = alkyl, L = neutral ligand) and their parent complexes with BR2 bridges RCo(dioxime-BR2)2L 127 (Fig. 33) are known as organocobaloximes [173-178] and have received attention being models for vitamin B12 (cobalamines) [183]. A series of related complexes of the composition Fe (dioxime-BR2)LL 128 (Fig. 33) without the metal-carbon bond is also known [179, 180]. 

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). 

The CoIII-alkyl bond was established some time ago with the characterization of simple complexes with Co—CH3 or other Co—R groups. Incorporation of R as an axial ligand in Co111 porphyrins, Schiff base and bis(dimethylgloximato) compounds were early types defined, and examples continue to appear. This is a key feature of cobalamin (B12) model complexes and a review of this area appears in Section 6.1.3.1.1. The deceptively simple isoelectronic alkyl homologs of [Co(NH3)6]3+ and [Co(en)3]3+, (122)531 and (123), have appeared since the first edition of... 

Zinc is the active metal in the largest group of metalloproteins found in the nature. Recently a new class of zinc enzymes with a sulfur-rich environment has emerged the thiolate-alkylating enzimes, the most prominent of which is the cobalamine-independent methionine synthase.126 For these reasons several monothiolate zinc complexes have been prepared for the modelling of these enzymes with different N2S as (13),127 130 N20,13° 132 N3,132,133 S3,134 tripod ligands, or with Cd because of the favourable spectroscopic properties with an S3 tripod ligand.135... 

Cobalt complexes with square planar tetradentate ligands, including salen, cor-rin, and porphyrin types, all catalyse the reduction of alkyl bromides and iodides. Most preparative and mechanistic work with these reactions has used cobalamines, including vitamin-B,. A generalised catalytic cycle is depicted in Scheme 4.10 [219]. At potentials around -0.9 V vs. see, the parent ligated Co(lll) compound un-... 

In these compounds the cobalt atom is enclosed in a highly conjugated cobalamin structure and linked to an alkyl group via a metal-carbon bond. The B12 coenzymes are diamagnetic and can be regarded as complexes of cobalt(III) with a carbanion as a ligand (2). As this review will be limited to cases of direct metal-protein interactions the corrinoids will not be discussed further. 

Other cobalt(III) complexes showing soft behaviour with preference for cyanide, iodide and alkyl ligands are the cobalamine group of vitamin B 1260 and the bis (di-methylglyoximates) involving four nitrogen atoms bound in the equatorial plane in both cases, as is true for porphyrin and chlorophyll complexes. 

As a model study of methyl cobalamine (methyl transfer) in living bodies, a methyl radical, generated by the reduction of the /s(dimethylglyoximato)(pyridine)Co3+ complex to its Co1+ complex, reacts on the sulfur atom of thiolester via SH2 to generate an acyl radical and methyl sulfide. The formed methyl radical can be trapped by TEMPO or activated olefins [8-13]. As a radical character of real vitamin B12, the addition of zinc to a mixture of alkyl bromide (5) and dimethyl fumarate in the presence of real vitamin B12 at room temperature provides a C-C bonded product (6), through the initial reduction of Co3+ to Co1+ by zinc, reaction of Co1+ with alkyl bromide to form R-Co bond, its homolytic bond cleavage to form an alkyl radical, and finally the addition of the alkyl radical to diethyl fumarate, as shown in eq. 11.4 [14]. 

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. 

A perspective report emphasised the key role of the application of pressure in kinetic studies in bringing clarity to understanding the mechanism of substitution reactions of cobalamins.193 The effect of various alkyl substituents in the trans position on the kinetic, thermodynamic and ground-state properties has been studied. Cobalamins featuring in these studies were cyanocobalamin (vitamin Bi2), aquacobalamin and the complex formed when the cyano or water ligand is replaced... 

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