Department of Environmental and Occupational Health, Graduate School of Public Health , The University of Pittsburgh , Pittsburgh , Pennsylvania 15261 , United States.
Chem Res Toxicol. 2020 Feb 17;33(2):333-342. doi: 10.1021/acs.chemrestox.9b00229. Epub 2020 Jan 13.
There is presently no antidote available to treat azide poisoning. Here, the Schiff-base compound Co(II)-2,12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.1]heptadeca-1(17)2,11,13,15-pentaenyl dibromide (Co(II)N[11.3.1]) is investigated to determine if it has the capability to antagonize azide toxicity through a decorporation mechanism. The stopped-flow kinetics of azide binding to Co(II)N[11.3.1] in the absence of oxygen exhibited three experimentally observable phases: I (fast); II (intermediate); and III (slow). The intermediate phase II accounted for ∼70% of the overall absorbance changes, representing the major process observed, with second-order rate constants of 29 (±4) M s at 25 °C and 70 (±10) M s at 37 °C. The data demonstrated pH independence of the reaction around neutrality, suggesting the unprotonated azide anion to be the attacking species. The binding of azide to Co(II)N[11.3.1] appears to have a complicated mechanism leading to less than ideal antidotal capability; nonetheless, this cobalt complex does protect against azide intoxication. Administration of Co(II)N[11.3.1] at 5 min post sodium azide injection (ip) to mice resulted in a substantial decrease of righting-recovery times, 12 (±4) min, compared to controls, 40 (±8) min. In addition, only two out of seven mice "knocked down" when the antidote was administered compared to the controls given toxicant only (100% knockdown).
目前尚无解毒剂可用于治疗叠氮化物中毒。在这里，研究了席夫碱化合物 Co(II)-2,12-二甲基-3,7,11,17-四氮杂环十八烷-1(17)-2,11,13,15-戊烯二溴化物（Co(II)N[11.3.1]），以确定其是否具有通过脱金属机制拮抗叠氮化物毒性的能力。在没有氧气的情况下，叠氮化物与 Co(II)N[11.3.1]的停流动力学表现出三个可观察到的实验阶段：I（快速）；II（中间）；和 III（缓慢）。中间阶段 II 占总吸光度变化的∼70%，代表观察到的主要过程，在 25°C 时的二级速率常数为 29（±4）M s，在 37°C 时为 70（±10）M s。数据表明反应在中性附近的 pH 不依赖，表明未质子化的叠氮阴离子是攻击物种。叠氮化物与 Co(II)N[11.3.1]的结合似乎具有复杂的机制，导致解毒能力不理想；尽管如此，这种钴配合物确实能防止叠氮化物中毒。在注射（ip）NaN 3 后 5 分钟向小鼠给予 Co(II)N[11.3.1]，导致翻正恢复时间显著减少，为 12（±4）分钟，而对照组为 40（±8）分钟。此外，与仅给予毒物的对照组相比（100%击倒），给予解毒剂时只有两只小鼠“击倒”。
