Mechanism of the hydrolysis of the sulfamate EMATE—an irreversible steroid sulfatase inhibitor

The kinetics of hydrolysis of the medicinally important sulfamate ester EMATE have been probed over a wide pH range and into moderately strong base (H_ region). Analysis of the pH/H_-rate profile, measurements of pKas, solvent-reactivity, kinetic isotope effects and determination of activation data reveal that in the pH range from ∼1 to ∼8 an SN2 (S) solvolytic mechanism is followed and after the pKa of EMATE (pKa ∼9) is passed, a second pathway showing a first-order dependence on base operates and an E1cB mechanism is supported.