SYNTHESIS AND HYDROLYSIS OF AN ESTER OF THE ONE RING OPEN HYDROLYSIS PRODUCT OF THE ANTICANCER DRUG 1,2-BIS(3,5-DIOXOPIPERAZIN-1-YL)PROPANE, RAZOXANE

The reaction between the anticancer drug Razoxane (I) and CuCl2 . 2H(2 )O in methanol causes opening of one imide ring giving Cu-(III)Cl-2 . 1 1/2H(2)O which contains the ligand III: resulting from methanolysis of one of the imide rings. The ester group in this complex undergoes a very rapid base promoted hydrolysis reaction to give the complex Cu-( II)Cl-2 . MeOH . H2O. The kinetics of this hydrolysis reaction at vari ous temperatures have been studied and the very rapid rate of reaction , which is estimated to be 7.3x10(6) times faster than for the free li gand, was found to be due to a lowering in Delta H-not equal and an in crease in delta S-not equal . The proposed reaction mechanism involves nucleophilic attack by OH- ion on the ester group activated by coordi nation.