Dephosphorylation Reactions of Mono?, Di?, and Triesters of 2,4- Dinitrophenyl Phosphate with Deferoxamine and Benzohydroxamic Acid

摘要

This work presents a detailed kinetic andnmechanistic study of biologically interesting dephosphorylationnreactions involving the exceptionally reactive nucleophilicngroup, hydroxamate. We compare results for hydroxamatengroups anchored on the simple molecular backbone ofnbenzohydroxamate (BHA) and on the more complex structurenof the widely used drug, deferoxamine (DFO). BHA showsnextraordinary reactivity toward the triester diethyl 2,4-ndinitrophenyl phosphate (DEDNPP) and the diester ethyln2,4-dinitrophenyl phosphate (EDNPP) but reacts very slowlynwith the monoester 2,4-dinitrophenyl phosphate (DNPP). Nucleophilic attack on phosphorus is confirmed by the detection ofnthe phosphorylated intermediates formed. These undergo Lossen-type rearrangements, resulting in the decomposition of thennucleophile. DFO, which is used therapeutically for the treatment of acute iron intoxication, carries three hydroxamate groupsnand shows correspondingly high nucleophilic activity toward both triester DEDNPP and diester EDNPP. This result suggests anpotential use for DFO in cases of acute poisoning with phosphorus pesticides.