Difference between revisions of "Praekunatham 2020 Chem Res Toxicol"
(Created page with "{{Publication |title=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...") |
|||
(One intermediate revision by the same user not shown) | |||
Line 5: | Line 5: | ||
|year=2020 | |year=2020 | ||
|journal=Chem Res Toxicol | |journal=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) | |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)N<sub>4</sub>[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<sub>4</sub>[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<sup>-1</sup> s<sup>-1</sup> at 25 °C and 70 (±10) M<sup>-1</sup> s<sup>-1</sup> 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<sub>4</sub>[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<sub>4</sub>[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 | |keywords=Azide antidote, Azide decorporation, Cobalt macrocycle, Cytochrome c oxidase | ||
|editor=[[Plangger M]] | |editor=[[Plangger M]] | ||
|mipnetlab=US PA Pittsburgh Peterson J | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration, Pharmacology;toxicology | ||
|diseases=Other | |||
|organism=Mouse | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=2020-05 | |additional=2020-05 | ||
}} | }} |
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 ∼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