Sonolysis promotes indirect Co-C bond cleavage of alkylcob(III)alamin bioconjugates.
Sonolysis promotes indirect Co-C bond cleavage of alkylcob(III)alamin bioconjugates.
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Sonolysis 促进烷基钴 (III) 胺生物共轭物的间接 Co-C 键裂解。
DOI：
10.1021/bc970077l
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
West,FG
中科院分区：
文献类型：
--
作者：
HowardJr,WA;Bayomi,A;Natarajan,E;Aziza,MA;el-Ahmady,O;Grissom,CB;West,FG
水溶液的声波分解产生H·和HO·，导致甲基cob(III)alamin （CH3-CblIII）和2-[4-[4 ' -[双（2-氯乙基）氨基]苯基]丁基]乙基cob(III)alamin （Chl-HE-CblIII）中的Co−C键断裂。在厌氧条件下，H·将ch3 -CblII还原为不稳定的19 e- ch3 -CblII，并解离成烷烃和CblII。在有氧条件下，o2清除H·和Co - C键的裂解是通过HO·介导的过程以及HO·对corrin环的修饰发生的。当H·和HO·被清除时，没有Co−C键断裂的证据。这表明，尽管Co - C键比H - OH键弱80千卡/摩尔，但Co - C键没有发生直接的声波溶解。合成了一种cob(III)alamin与烷基化剂chlorambucil的生物偶联物，得到了2-[4-[4 ' -[双（2-氯乙基）氨基]苯基]丁基]乙基cob(III)alamin。氯苯-钴胺素复合物也经历Co - C键的裂解，其方式类似于甲基cob（III）钴胺素。从生物偶联物中快速释放活性烷基化剂可能为抗癌药物的选择性释放提供一种新的方法，从而潜在地降低全身毒性。
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-CblIIIto the unstable 19 e-CH3-CblIIthat dissociates to the alkane and CblII. Under aerobic conditions, O2scavenges 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(III)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.