Sonolysis promotes indirect Co-C bond cleavage of alkylcob(III)alamin bioconjugates.
Sonolysis of aqueous solutions produces H. and HO. that lead to Co-C bond cleavage in methylcob-(III)alamin (CH3-CblIII) and 2-[4-[4'-[bis(2-chloroethyl)amino]phenyl]butyroxy]ethylcob (III)alamin (Chl-HE-CblIII). Under anaerobic conditions, H. reduces CH3-CblIII to the unstable 19 e-CH3-CblII that dissociates to the alkane and CblII. Under aerobic conditions, O2 scavenges H. and Co-C bond cleavage occurs via a HO.-mediated process along with modification of the corrin ring by HO.. When H. and HO. are scavenged, there is no evidence of Co-C bond cleavage. This suggests no direct 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 cob(III)alamin and the alkylating agent chlorambucil has been synthesized to give 2-[4-[4'-[bis(2-chloroethyl)amino]phenyl]butyroxy]ethylcob(I II)alamin. The chlorambucil-cobalamin complex also undergoes Co-C bond cleavage in a manner similar to that of methylcob-(III)alamin. Sonorelease of an active alkylating agent from the bioconjugate may provide a new method for the selective release of anticancer drugs and thus potentially reduce systemic toxicity.
Howard
W A
WA
Department of Chemistry, University of Utah, Salt Lake City 84112, USA.
Bayomi
A
A
Natarajan
E
E
Aziza
M A
MA
el-Ahmady
O
O
Grissom
C B
CB
West
F G
FG
D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet; D014805:Vitamin B 12 / Q000031:analogs & derivatives / Q000737:chemistry*
D014805:Vitamin B 12