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A polymer bearing hydroxamic acid groups and having a high affinity for iron(III) was prepared through the following procedure. Acryloylalanine (III), prepared by the reaction of acryloyl chloride with alanine, was treated with N‐hydroxysuccinimide in the presence of dicyclohexylcarbodiimide to give the N‐hydroxysuccinimide ester (IV). The ester IV was polymerized by using AIBN in dioxane to give polymer V. Treatment of polymer V with methylhydroxylamine in DMF gave the hydroxamic acid polymer II. The water‐soluble polymer II was purified by dialysis or by gel‐permeation chromatography (GPC) on Sephadex G‐25. Analytical GPC on Sephadex G‐200 and Sepharose 4B indicate that the average molecular weight of the polymer is in the range of 5 × 105 to 1 × 106. The presence of hydroxamic acid groups is confirmed by the intense red‐brown color produced by the addition of iron(III) to a 50% aqueous DMF solution of the polymer under acidic conditions. In pure water the polymer‐iron complex precipitates as a tan solid. Iron‐binding studies of the polymer reveal that the iron(III) trihydroxamic acid complex FeA3 forms at low concentrations of iron. At higher iron levels a lower order of stability is apparent, which can be accounted for by the conversion of FeA3 to FeA2+. In contrast, the FeA3 complex of the trihydroxamic acid deferoxamine‐B is stable at all iron levels. These results are consistent with the polymer structure, which for steric reasons would favor a stable complex, FeA2+, between iron and two adjacent hydroxamic acid groups. An FeA3 complex would be expected to have a lower stability as a result of either bond angle strain and atomic compression, or a lower probability in bringing a third hydroxamic acid into position to form the octahedral complex.

SynopsisThe iron chelating ability of hydroxamic acid polymers was studied as a function of the atomic chain spacing separating neighboring hydroxamic acid units. Two polymers were prepared, one having the hydroxamic acid group separated by 11 atoms and the other by three atoms. The iron binding of these polymers was compared with the model compound desferrioxamine B (DFO) and with a previously prepared polymer having a nine-atom spacing. Mole ratio plots indicated the following order of stability: DFO = 11 atom > 9 atom > 3 atom. These results are in accordance with the picture derived from molecular models which shows that with a spacing of 11 atoms, three neighboring hydroxamic acids can fit the octahedral arrangement of the iron(II1) complex without appreciable strain. Some strain is introduced when the spacing becomes only nine atoms, and with three atoms, complex formation between three neighboring groups becomes virtually impossible.

The effect of structure on the ability of hydroxamic acid polymers to chelate iron(III) was examined. The polymers were derived from acryloyl or methacryloyl backbones that bore side chains terminated in hydroxamic acids. The side chain length, which establishes the atomic chain distances between hydroxamic acid groups, had the most pronounced effect on the stability constant of the iron chelate. It was this atomic chain distance that determined how easily the three neighboring hydroxamic acids could fit the octahedral sphere of the iron. Other structural changes such as the presence or absence of methyl groups on the backbone or on the hydroxamic acid nitrogen had little measurable effect. The stability of the iron complexes appeared to be optimum at an 11‐atom spacing between hydroxamic acids and decreased with shorter or longer spacing distances.

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