Presenter: Kimberly Garrett
Paper: A Cobalt Schiff-base Complex as a Putative Therapeutic for Azide Poisoning
Authors: Hirunwut Praekunatham, Kimberly K Garrett, Yookyung Bae, Andrea A. Cronican, Kristin L. Frawley, Linda Lorraine Pearce, Jim Peterson
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)N4[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)N4[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-1s-1 at 25°C and 70 (±10) M-1s-1 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)N4[11.3.1] appears to have a complicated mechanism leading to less than ideal antidotal capability; but nonetheless, this cobalt complex does protect against azide intoxication. Administration of Co(II)N4[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 2 out of 7 mice “knocked down” when the antidote was administered compared to the controls given toxicant only (100% knockdown).
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