The preparation of N-acetyl-Co(III)-microperoxidase-8 (NAcCoMP8) and its ligand substitution reactions: A comparison with aquacobalamin (vitamin B12a)

Probing the nature of the Co(III) ion in cobalamins: The reactions of aquacobalamin (vitamin B12a), aqua-10-chlorocobalamin and aqua-10-bromocobalamin with anionic and neutral ligands

“…If the ligand is an anion, however, binding of an anionic ligand will be favoured because of electrostatic interaction with the corrin, and, moreover, the charge donation can be accepted by the corrin and by delocalisation onto the C- 10 (Table 3). We have previously shown that a cobalamin will usually coordinate an ambident nucleophile through the softer of the two potential donor atoms, as in SeCN À , NO 2 À and S 2 O 3 2À [3].…”

“…We note ( Table 5) that DK = log K 10H À log K 10Z for imidazole and (11) 12.5 [59] a Interpolated from the activation parameters. b N-methylimidazole.…”

“…We have been exploring the nature of Co(III) in the cobalt corrins (derivatives of vitamin B 12 ) in an effort to elucidate the effect of the corrin ligand on the chemistry of the metal ion [1][2][3][4][5][6][7][8][9][10][11][12]. We have suggested that an important factor in modifying the properties of normally inert Co(III) and conferring on it the unusual lability found in the cobalt corrins is the delocalisation of electron density from the corrin equatorial ligand onto Co(III), making the metal softer and imparting on it some measure of labile Co(II) character.…”

“…Firstly, we have perturbed the electronic structure of the corrin by substituting the H atom at C-10 (see Fig. 1 for numbering) by either Cl (which is p electron-donating towards the corrin) [1,4] or NO (which is p electron-withdrawing) [2]; secondly, we have disrupted the p conjugated system by oxidising the C5-C6 double bond [6,7,9]; thirdly, we have prepared an aquacobalamin (vitamin B 12a , H 2 OCbl + ) analogue containing a porphyrin [10]; and more recently we have prepared a B 12a analogue containing a corrole [12]. In each case we have compared the physical properties and the thermodynamics (and in some cases the kinetics) of the substitution of the axial H 2 O by a series of neutral and anionic ligands to determine the effect that perturbing the electronic structure of the corrin, or exchanging a corrin for a porphyrin or a corrole, has on the chemistry of Co(III).…”

“…Briefly, we have demonstrated that there is indeed electronic communication between the axial and the equatorial ligands in the cobalt corrins [5] and that the C-10-Cl bond length in [X-(10-Cl)Cbl] depends on the nature of the axial ligand X [1]; that substituting the C-10 H by NO deactivates the metal ion [2]; that the ligand substitution reactions of [H 2 O-(10-Cl)Cbl] + are slower than those of vitamin B 12a , [H 2 OCbl] + , itself [4]; that interrupting the conjugation of the corrin makes the metal ion harder [7,9]; and that the difference in charge on the macrocyle (À3 in corroles, À2 in porphyrins and À1 in corrins), which modifies the net charge at the metal centre, plays an important role in controlling and modifying the chemistry of the metal ion [10,12].…”