6623-40-1Relevant academic research and scientific papers
Proton-in-flight mechanism for the spontaneous hydrolysis of N-methyl O-phenyl sulfamate: Implications for the design of steroid sulfatase inhibitors
Edwards, David R.,Wolfenden, Richard
experimental part, p. 4450 - 4453 (2012/06/30)
The hydrolysis of N-methyl O-phenyl sulfamate (1) has been studied as a model for steroid sulfatase inhibitors such as Coumate, 667 Coumate, and EMATE. At neutral pH, simulating physiological conditions, hydrolysis of 1 involves an intramolecular proton transfer from nitrogen to the bridging oxygen atom of the leaving group. Remarkably, this proton transfer is estimated to accelerate the decomposition of 1 by a factor of 1011. Examination of existing kinetic data reveals that the sulfatase PaAstA catalyzes the hydrolysis of sulfamate esters with catalytic rate accelerations of ～104, whereas the catalytic rate acceleration generated by the enzyme for its cognate substrate is on the order of ～1015. Rate constants for hydrolysis of a wide range of sulfuryl esters, ArOSO2X-, are shown to be correlated by a two-parameter equation based on pKa ArOH and pKaArOSO2XH.
