Ferric ion sequestering agents. 15. Synthesis, solution chemistry, and electrochemistry of a new cationic analog of enterobactin

Abstract

A new ferric ion sequestering tricatecholate, TRENCAM, has been synthesized from @$',@''-triaminotriethylamine (TREN) in high yield. The solution coordination chemistry of the ligand and its iron(3+,2+) complexes have been studied by means of pH potentiometric, spectrophotometric, and voltammetric methods. The last five stepwise protonation constants (log K ) to (H,TRENCAM)Br are 11.26, 8.75, 8.61, 6.71, and 5.88 (from least-squares refinement of the potentiometric data from pH 3.5 to 10.7). The potentiometric data of the ferric complex have shown that the last three protonation constants are positioned close to one another between pH 5 and 5.6. These are resolved by spectrophotometric data from pH 8 to 5.6, which show that the first protonation constant (log K ) of ferric(TRENCAM) is 5.59. From the reduction potential vs. pH curve of the iron(3+,2+) complexes the corresponding protonation constant (log K ) of the ferrous complex has been determined to be 11.2. The specific affinity of TRENCAM for ferric ion relative to ferrous ion results in a highly negative reduction potential of the iron(3+,2+) center: -1.04 V vs. (NHE). From competition experiments with EDTA, the formation constant (log K ) of ferric(TRENCAM) has been estimated to be 43.6. At pH 7.4, [ligand],, = 10 pM, and [Fe3+],,, = 1 pM, p[Fe3+] = 27.8. Implications of the results for in vivo iron removal are presented.