Praekunatham 2020 Chem Res Toxicol: Difference between revisions
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Latest revision as of 13:43, 13 May 2020
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. |
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 โผ70% of the overall absorbance changes, representing the major process observed, with second-order rate constants of 29 (ยฑ4) M-1 s-1 at 25 ยฐC and 70 (ยฑ10) M-1 s-1 at 37 ยฐC. 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 (ยฑ4) min, compared to controls, 40 (ยฑ8) 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). โข Keywords: Azide antidote, Azide decorporation, Cobalt macrocycle, Cytochrome c oxidase โข Bioblast editor: Plangger M โข O2k-Network Lab: US PA Pittsburgh Peterson J
Labels: MiParea: Respiration, Pharmacology;toxicology
Pathology: Other
Organism: Mouse
HRR: Oxygraph-2k
2020-05