FERRIC ION SEQUESTERING AGENTS .3. SPECTROPHOTOMETRIC AND POTENTIOMETRIC EVALUATION OF 2 NEW ENTEROBACTIN ANALOGS - 1,5,9-N,N',N''-TRIS(2,3-DIHYDROXYBENZOYL)-CYCLOTRIAZATRIDECANE AND 1,3,5-N,N',N''-TRIS(2,3-DIHYDROXYBENZOYL)TRIAMINOMETHYLBENZENE

The complexation and protonation equilibria of the ferric complexes of 1,5,9-N,N',N”-tris(2,3-dihydroxybenzoyl)-cyclotriazatridecane (3,3,4-CYCAM) and 1,3,5-N,N',N”-tris(2,3-dihydroxybenzoyl)triaminomethylbenzene (MECAM) have been investigated by potentiometric and spectrophotometric techniques. Proton dependent metal-ligand equilibrium constants [K* = ([ML][H]3)/([M][H3L])] have been determined to be log K* = 9.5 and 3.4 for the ferric complexes of MECAM and CYCAM, respectively. These results have been used to estimate the normal formation constants as 1046 for ferric MECAM and 1040 for ferric CYCAM. The MECAM value is the largest formation constant of any synthetic iron chelator. Both complexes undergo a series of protonations which shift the mode of bonding from one involving coordination through the two phenolic oxygens of the dihydroxybenzoyl group (catecholate mode) to one in which the iron is coordinated to the carbonyl oxygen and the ortho phenolate group (salicylate mode). The results are discussed in relation to the chelation therapy of chronic iron overload, as occurs in the treatment of Cooley's anemia. © 1979, American Chemical Society. All rights reserved.