Alkylcobalamins

Reactions of alkylcobalamins with platinum complexes. Y. T. Fanchiang, Coord. Chem. Rev., 1985, 68,131 (76). 

The reductive cleavage of the alkylcobalamine is facilitated by light irradiation and can then proceed at a much more positive potential. A demonstration photoelec-trochemical reactor for the Bij-catalyzed photoelectrochemical synthesis of Michael adduct 17, the alarm pheromone of the ant atta texana (Scheme 9) has been constructed where the complete device is driven solely by solar energy . Hopefully, mediated photoelectrochemical reactions of this type will also be realized at chemically modified electrodes. 

The nitroxalkylcorrinoids are easy to characterize since they are basically alkyl corrinoids. The u.v.-visible absorption spectra of the nitroxalkylcorrinoids are quite similar to other alkylcorrinoids. The nitroxalkyl cobalamin has a spectrum with Amax at 525,357, and 329nm with relative extinctions of 1.1, 1.2, and 0.65 respectively. Spectra for a number of typical alkylcobalamins have been reported by Firth et al. (121). The corresponding cobinamide has absorption maxima at 455, 428, 360, and 325 nm with relative extinctions of 1.4, 1.0, 0.61, and 0.62 respectively. Aerobic photolysis of these compounds leaves the corresponding aquocobalamin or aquocobinamide. Likewise, addition of cyanide to the nitroxalkylcobinamide in base leaves dicyano cobinamide. 

It is possible to synthesize alkylcobalamins containing halogenated alkyl groups. Of these, the compounds studied most extensively are the halo-methylcobalamins (745). For the various fluorine containing derivatives which have been prepared, 19F NMR spectra have been obtained and the results are shown in Table 6. Chemical shifts of a number of fluorome-thanes are included for comparison. 

Mechanism (1), first suggested almost three decades ago [150], continues to be the most invoked explanation of the role of the enzyme in promoting homolysis. Cleavage of the C—Co bond of sterically hindered alkylcobalamins (e.g., neopentylcobalamin) was markedly increased by diol dehydrase [72], Such cobal-amins do not function as coenzymes but convert to enzyme-bound hydroxocobal-amin in stoichiometric first-order reactions. The strong competitive inhibition by AdoB 12 indicates that labilization occurs at the active site of the enzyme and is suggested to be caused by a steric distortion of the corrin ring. 

Although the transient spectrum of a radical-ion pair was recorded in a picosecond-nanosecond time domain in the flash photolysis of Co(III) alkylcobalamins,123 there has been no direct spectroscopic observation of the LMCT excited states. The observed photochemical behavior may be simply described by the following sequence of events (1) absorption of radiation produces a Franck-Condon excited state, which (2) rapidly loses its excess vibrational energy (k > 10ns ) to form the thermalized excited state, followed by (3) product formation and internal conversion to the ground state. The existence of LMCT excited states with a finite lifetime in the... 

Radical additions of primary, secondary, and tertiary alkyl bromides 249 to diethyl mesaconate 248 catalyzed by 5 mol% vitamin B12a 247 (X=OH2) proceeded in yields of 63-90% [301]. Deuteration experiments and comparison to similar addition processes support that 247 is initially reduced to cobalt complex 253A. This reacts with 249 giving an alkylcobalamin(III) intermediate... 

A troublesome feature of this mechanistic interpretation is the absence of direct supporting evidence that the Co-C bond in coenzyme B12 (whose dissociation energy has not yet been determined) is sufficiently weak that facile homolysis under the mild conditions of the enzymic reactions is a plausible process. In fact, alkylcobalamins, including coenzyme B12, exhibit considerable thermal stability and typically do not decompose at measurable rates, in the absence of light or reagents such as 02, until fairly elevated temperatures ( 200°C for methylcobalamin) (4). Among the possible interpretations of this behavior are ... 

In this case, decomposition should be induced by appropriate radical traps such as 02. The results of numerous studies on the thermal and photochemical stabilities of alkylcobalamins as well as of model compounds are consistent with this.) (5, 6, 7, 8). 

Lott WB, Chagovetz AM, Grissom CB. Alkyl radical geometry controls geminate cage recombination in alkylcobalamins../ Am Chem Soc 1995 117 12194-201. 

Schrauzer GN, Lee LP, Sibert JW. Alkylcobalamins and alkylcobaloximes. Electronic structure, spectra, and mechanism of photodealkylation. J Am Chem Soc 1970 92 2997-3005. 

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... 

Most alkylcobalamin derivatives are thermally stable but are photosensitive. When irradiated in the presence of O2, methylcobalamin gives formation of formaldehyde and a cobalt (III) aquo complex [Eq. (102)]. 

ESR studies 112,114-118a) are also consistent with the formation of free radicals upon photolysis of alkylcobalamin and coenzyme Bi2- For example, Lappert and co-workers 116) demonstrated that homolysis of the cobalt-alkyl bond occurs upon photolysis of coenzyme B12 and ethylcobalamin by trapping the S -deoxyadenosyl and ethyl radicals produced with (CH3)3CN0. They were able to detect the spin-trapped (CH3)3CN(0)R radicals by ESR spectroscopy. Homolysis of the cobalt-methyl bond was also shown to occur upon anaerobic photolysis of methylcobalamin 117). However, the presence of traces of oxygen in the methanol solvent was shown to affect signiflcantly the photochemistry of methylcobalamin 118). Indeed, under those conditions, the 5,S-dimethyl-1-pyrroline iV-oxide (DMPO) spin adducts of both the methyl and hydrogen radicals, 113 and 114, respectively, were detected by ESR spectro-... 

This property of alkylcobaloximes and alkylcobalamins has been used to model the conversion of 1,2-diols to aldehydes catalyzed by the adenosyl-cobalamin-dependent enzyme diol dehydratase. For example, both organo-cobalamins (726, 126a) and alkylcobaloximes 126a, b) were shown to convert 1,2-diols to aldehydes under photolytic conditions. Lappert et al. 

Methylcobalamin can methylate many compounds, including metals. The reactions of alkylcobalamins depend on cleavage of the alkyl — cobalt bond, which can result in Co(l) and an alkyl cation, Co(II) and an alkyl radical, or Co(III) and an alkyl anion, with the radical mechanism being the most common. The alkyl products can then react in a number of ways. Some of the reactions include the following ... 

Reaction of alkyl Grignard and other organometallic reagents with Co(III) species was originally used for formation of the Co—C bond , in particular for the preparation of alkylcobalamin analogues . 

The reaction of alkylcobalamins with metal electrophiles, such as Hg(II), has been studied extensively since MeBjj may be responsible for formation of highly toxic meth-ylmercury(II) compounds under environmental conditions ". The reaction mechanism has been studied for both alkylcobaloximes and alkylcobalamins " . Reaction of alkylcobaloximes with Hg(II) salts can be described as a bimolecular electrophilic substitution (Se2), which takes place with inversion of configuration . 

The reaction of alkylcobalamins is more complicated, since Hg( I) coordinates to... 

Similar reactions are observed with Tl(III) and Pd(II) Pd(II) also coordinates 5,6-dimethylbenzimidazole but kinetic studies show that the base-on complex is the only reactive species . Platinum(IV) also reacts with alkylcobalamins but Ft(II) is required as catalyst suggesting a redox mechanism . 

Dealkylation of alkyl cobalt species by thiolate was suggested as a reductive cleavage process, involving reduction of alkylcobalamin with thiol to form a trans axial thiol complex . This accounts for the low yield of thioether . Carbon-13 and P studies... 

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