The fundamental solution chemistry of the copper(II) complexes of 1, 4, 7-- triazacyclononane-N,N',N"""""""" triacetate (NOTA) was studied in aqueous media. The prime goal was to determine the speciation of CU(II) in NOTA solutions and to measure the chemical reactivities of the CU(II)NOTA complexes. This information may be used to describe the chemical factors which influence the stability of 67CuNOTA antibody conjugates in vivo. 1 . Speciation of Cu(II)NOTA. Using the method of potentiometric titration, we determined the protonation constants (log K) of H3NOTA to be 11.33, 5.73, and 3.28 in 0.1 M NaClO(4). In addition, the conditional protonation constant for the CuNOTA- complex was measured by conventional spectrophotometry, log K= 2.50. The later result indicates that the CU(II) complex of NOTA undergoes a single-step protonation at pH ca. 2.5; the anion Cu(NOTA)- is the predominate CU(II) species in solution above PH 4.0. 2. Kinetics of CU(II)NOTA Isotopic Exchange. The rate parameters for the isotopic exchange of CU(II)NOTA and 67Cu(ii) were measured until isotopic equilibrium was attained. The empirical form of the rate law showed both acid dependent and acid-independent pathways for exchange, the net rate being dependent on the concentration of CuNOTA.
