Rapid, biomimetic degradation in water of the persistent drug sertraline by TAML catalysts and hydrogen peroxide.
2011
Iron TAML activators (oxidation catalysts based upon tetraamido macrocyclic ligands) at nanomolar concentrations in water activate hydrogen peroxide to rapidly degrade sertraline, the persistent, active pharmaceutical ingredient (API) in the widely used drug Zoloft. Although all the API is readily consumed, degradation slows significantly at one intermediate, sertraline ketone. The process occurs from neutral to basic pH. The pathway has been characterized through four early intermediates which reflect the metabolism of sertraline, providing further evidence that TAML activator/peroxide reactive intermediates mimic those of cytochrome P450 enzymes. TAML catalysts have been designed to exhibit considerable variability in reactivity and this provides an excellent tool for observing degradation intermediates of widely differing stabilities. Two elusive, hydrolytically sensitive intermediates and likely human metabolites, sertraline imine and N-desmethylsertraline imine, could be identified only by using a fa...
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
32
References
45
Citations
NaN
KQI