SONOLYSIS PROMOTES INDIRECT CO-C POND CLEAVAGE OF ALKYLCOB(III)ALAMINBIOCONJUGATES

Sonolysis of aqueous solutions produces H-. and HO. that lead to Co-C bond cleavage in methylcob-(III)alamin (CH3-Cbl(III)) and nyl]butyroxy ]ethylcob(III)alamin(Chl-HE-Cbl(III)). Under anaerobic conditions, H-. reduces CH3-Cbl(III) to the unstable 19 e(-) CH3-Cb-III that dissocia tes to the alkane and Cbl(II). Under aerobic conditions, O-2 scavenges H-. and Co-C bond cleavage occurs via a HO.-mediated process along wi th modification of the corrin ring by HO.. When H-. and HO. are scaven ged, there is no evidence of Co-C bond cleavage. This suggests no dire ct sonolysis of the Co-C bond occurs, in spite of the fact that the Co -C bond is 80 kcal/mol weaker than the H-OH bond. A bioconjugate of co b(III)alamin and the alkylating agent chlorambucil has been synthesize d cobalamin complex also undergoes Co-C bond cleavage in a manner simi lar to that of methylcob(III)alamin. Sonorelease of an active alkylati ng agent from the bioconjugate may provide a new method for the select ive release of anticancer drugs and thus potentially reduce systemic t oxicity.