Praekunatham 2020 Chem Res Toxicol

Praekunatham H, Garrett KK, Bae Y, Cronican AA, Frawley KL, Pearce LL, Peterson J (2020) A cobalt Schiff-base complex as a putative therapeutic for azide poisoning. Chem Res Toxicol 33:333-42.

» PMID: 31599574

Praekunatham H, Garrett KK, Bae Y, Cronican AA, Frawley KL, Pearce LL, Peterson J (2020) Chem Res Toxicol

Abstract: 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^-1 s^-1 at 25 °C and 70 (±10) M^-1 s^-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; 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 two out of seven mice "knocked down" when the antidote was administered compared to the controls given toxicant only (100% knockdown). • Keywords: Azide antidote, Azide decorporation, Cobalt macrocycle, Cytochrome c oxidase • Bioblast editor: Plangger M • O2k-Network Lab: US PA Pittsburgh Peterson J

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Other 

Organism: Mouse 

HRR: Oxygraph-2k 

2020-05