48028-75-7Relevant academic research and scientific papers
Dephosphorylation reactions of mono-, Di-, and triesters of 2,4-dinitrophenyl phosphate with deferoxamine and benzohydroxamic acid
Medeiros, Michelle,Orth, Elisa S.,Manfredi, Alex M.,Pavez, Paulina,Micke, Gustavo A.,Kirby, Anthony J.,Nome, Faruk
, p. 10907 - 10913 (2013/02/22)
This work presents a detailed kinetic and mechanistic study of biologically interesting dephosphorylation reactions involving the exceptionally reactive nucleophilic group, hydroxamate. We compare results for hydroxamate groups anchored on the simple molecular backbone of benzohydroxamate (BHA) and on the more complex structure of the widely used drug, deferoxamine (DFO). BHA shows extraordinary reactivity toward the triester diethyl 2,4-dinitrophenyl phosphate (DEDNPP) and the diester ethyl 2,4-dinitrophenyl phosphate (EDNPP) but reacts very slowly with the monoester 2,4-dinitrophenyl phosphate (DNPP). Nucleophilic attack on phosphorus is confirmed by the detection of the phosphorylated intermediates formed. These undergo Lossen-type rearrangements, resulting in the decomposition of the nucleophile. DFO, which is used therapeutically for the treatment of acute iron intoxication, carries three hydroxamate groups and shows correspondingly high nucleophilic activity toward both triester DEDNPP and diester EDNPP. This result suggests a potential use for DFO in cases of acute poisoning with phosphorus pesticides.
Characterization of transition states in dichloro(1,4,7-triazacyclononane)copper(II)-catalyzed activated phosphate diester hydrolysis
Deal, Kim A.,Hengge, Alvan C.,Burstyn, Judith N.
, p. 1713 - 1718 (2007/10/03)
The reaction mechanism for Cu[9]aneN3CI2-catalyzed hydrolysis of ethyl 4-nitrophenyl phosphate was probed using kinetic isotope effects and isotope exchange experiments. The solvent deuterium isotope effect ((D)k = 1.14), combined with the absence of 18O incorporation into 4-nitrophenol, suggests that hydrolysis proceeds through intramolecular attack of the metal-coordinated hydroxide at the phosphorus center. The secondary 15N isotope effect (15k = 1.0013 ± 0.0002) implies that loss of the leaving group occurs at the rate-limiting step with approximately 50% bond cleavage in the transition state. This study is one of the first applications of the secondary 15N isotope effect to simple metal-promoted hydrolysis reactions, and the result is consistent with concerted bond formation and cleavage. A mechanism consistent with the isotope studies is presented.
