Effect of Ascorbate on the Cyanide-Scavenging Capability of Cobalt(III) meso-Tetra(4-N-methylpyridyl)porphine Pentaiodide: Deactivation by Reduction?
Effect of Ascorbate on the Cyanide-Scavenging Capability of Cobalt(III) meso-Tetra(4-N-methylpyridyl)porphine Pentaiodide: Deactivation by Reduction?
复制标题
抗坏血酸对钴(III)内消旋四(4-N-甲基吡啶基)卟啉五碘化物清除氰化物能力的影响：还原失活？
DOI：
10.1021/acs.chemrestox.5b00447
复制
发表时间：
2016
影响因子：
4.1
通讯作者：
Pearce,LindaL
中科院分区：
文献类型：
--
作者：
Benz,OscarS;Yuan,Quan;Cronican,AndreaA;Peterson,Jim;Pearce,LindaL
含钴(Ⅲ)的水溶性金属卟啉cobalt(III)meso-tetra(4-N-methylpyridyl)porphine五碘化合物(CoIIITMPyP)是一种潜在的除氰剂。抗坏血酸还原CoIIITMPyP的速度足够容易，在还原剂的活度范围内，几分钟内就可以转化为含Co(II)的CoIITMPyP。因此，金属卟啉的任何氰化物脱孔能力应更多地取决于CoIITMPyP的氰化物结合特性，而不是给药形式CoIIITMPyP的氰化物结合特性。将氰化物加入到CoIITMPyP(pH 7.4，25-37℃)的缓冲水溶液中，可以相当迅速地(K2=∼103m-1s-1)结合/取代两个可用轴向位置上的氰离子(K‘β=1010~1011)。电子顺磁共振光谱和循环伏安测试表明，氰化物诱导氧化生成含Co(III)的二氰基物种。讨论了这些观察结果对CoIITMPyP与氰化物反应的可能机理的限制。将CoIIITMPyP和氰化物添加到新鲜提取的小鼠血液中的实验表明，发生了相同的反应序列(金属卟啉还原→氰化物结合/取代→再氧化)。因此，在用这种金属卟啉清除氰化物的应用中，我们应该既利用Co(II)上比Co(III)上的配体取代速度更快的优点，也利用Co(III)对阴离子配体的亲和力比Co(II)的更高的优点。最后，使用已建立的氰化物中毒亚致死小鼠模型，CoIIITMPyP在中毒前5分钟(预防)或中毒后1分钟给药，被证明具有非常显著的解毒能力。对先前一项相互矛盾的研究的结果进行了可能的解释，该研究未能发现CoIIITMPyP对氰化物中毒的任何预防作用。
The Co(III)-containing water-soluble metalloporphyrin cobalt(III)meso-tetra(4-N-methylpyridyl)porphine pentaiodide (CoIIITMPyP) is a potential cyanide-scavenging agent. The rate of reduction of CoIIITMPyP by ascorbate is facile enough that conversion to the Co(II)-containing CoIITMPyP should occur within minutes at prevailingin vivolevels of the reductant. It follows that any cyanide-decorporating capability of the metalloporphyrin should depend more on the cyanide-binding characteristics of CoIITMPyP than those of the administered form, CoIIITMPyP. Addition of cyanide to buffered aqueous solutions of CoIITMPyP (pH 7.4, 25–37 °C) results in quite rapid (k2= ∼103M–1s–1) binding/substitution of cyanide anion in the two available axial positions with high affinity (K′β= 1010to 1011). Electron paramagnetic resonance spectroscopic measurements and cyclic voltammetry indicate that cyanide induces oxidation to the Co(III)-containing dicyano species. The constraints that these observations put on plausible mechanisms for the reaction of CoIITMPyP with cyanide are discussed. Experiments in which CoIIITMPyP and cyanide were added to freshly drawn mouse blood showed the same sequence of reactions (metalloporphyrin reduction → cyanide binding/substitution → reoxidation) to occur. Therefore, in cyanide-scavenging applications with this metalloporphyrin, we should be taking advantage of both the improved rate of ligand substitution at Co(II) compared to that at Co(III) and the increased affinity of Co(III) for anionic ligands compared to that of Co(II). Finally, using an established sublethal mouse model for cyanide intoxication, CoIIITMPyP, administered either 5 min before (prophylaxis) or 1 min after the toxicant, is shown to have very significant antidotal capability. Possible explanations for the results of a previous contradictory study, which failed to find any prophylactic effect of CoIIITMPyP toward cyanide intoxication, are considered.