Metalloporphyrin Co(III)TMPyP ameliorates acute, sublethal cyanide toxicity in mice.
Metalloporphyrin Co(III)TMPyP ameliorates acute, sublethal cyanide toxicity in mice.
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Metalloporphyrin Co(III)TMPyP 可改善小鼠的急性亚致死氰化物毒性。
DOI：
10.1021/tx300327v
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发表时间：
2012
影响因子：
4.1
通讯作者：
Peterson,Jim
中科院分区：
文献类型：
--
作者：
Benz,OscarS;Yuan,Quan;Amoscato,AndrewA;Pearce,LindaL;Peterson,Jim
在pH7.4时，Co Ⅲ ITMPyP（CN）2的形成是完全协同的（αH= 2），缔合常数为2.1（±0.2）× 10 ~（11）。停流分光光度法的动力学进行了研究，并揭示了一个复杂的净反应，在pH值为7.4的条件下，氰化物是在过量的表现出4个阶段。数据表明分子HCN（而不是CN-）是中性附近的攻击亲核试剂。当氰化物不过量时，两个较慢的相似乎不存在，并且另外两个相的速率与对已知有效的氰化物清除剂钴胺素观察到的速率相当。牛血清白蛋白（BSA）的加入不影响氰化物与CoIIITMPyP结合的协同性，仅使平衡常数略降至1.2（±0.2）× 10 ~（11），对观察速率无明显影响。使用亚致死小鼠模型评估CoIIITMPyP作为潜在氰化物解毒剂的有效性。向氰化钠中毒的小鼠施用CoIIITMPyP导致存活小鼠从仰卧位直立所需的时间（9 ± 2 min）与对照组（33 ± 2 min）相比显著减少。所有观察结果都与证明的CoIIITMPyP通过氰化物结合（即，清除）机制。
The formation of CoIIITMPyP(CN)2at pH 7.4 has been shown to be completely cooperative (αH= 2) with an association constant of 2.1 (±0.2) × 1011. The kinetics were investigated by stopped-flow spectrophotometry and revealed a complicated net reaction exhibiting 4 phases at pH 7.4 under conditions where cyanide was in excess. The data suggest molecular HCN (rather than CN–) to be the attacking nucleophile around neutrality. The two slower phases do not seem to be present when cyanide is not in excess, and the other two phases have rates comparable to that observed for cobalamin, a known effective cyanide scavenger. Addition of bovine serum albumin (BSA) did not affect the cooperativity of cyanide binding to CoIIITMPyP, only lowered the equilibrium constant slightly to 1.2 (±0.2) × 1011and had an insignificant effect on the observed rate. A sublethal mouse model was used to assess the effectiveness of CoIIITMPyP as a potential cyanide antidote. The administration of CoIIITMPyP to sodium cyanide intoxicated mice resulted in the time required for the surviving mice to right themselves from a supine position being significantly decreased (9 ± 2 min) compared to that of the controls (33 ± 2 min). All observations were consistent with the demonstrated antidotal activity of CoIIITMPyP operating through a cyanide-binding (i.e., scavenging) mechanism.