Preorganization of ferric alcaligin, Fe(2)L(3). The first structure of a ferric dihydroxamate siderophore

Siderophores are microbial iron transport agents that are produced when the organism is iron deficient. Most siderophores are hexadentate, completely encapsulating octahedral Fe(III). In order to encapsulate completely the metal ion, a dihydroxamate siderophore (represented by L) must form minimally a binuclear metal complex with a stoichiometry of Fe2L3. An early example is provided by rhodotorulic acid (RA), the linear dihydroxamate siderophore of Rhodotorula pilimanae, which forms a complex of stoichiometry Fe2L3. We report here the first example of the alternative mono-bridged structure as found in the Fe2L3 complex of alcaligin. The crystal structure provides a ready explanation for the differences seen in the stability constants for alcaligin and rhodotorulic acid. The preorganization of the alcaligin ring puts both chelate rings in the correct position for the metal complex. This results in a 100-fold increase in the stability of the complex compared to the flexible rhodotorulic acid. Alcaligin is a siderophore whose geometry is optimized for initial complexation of iron, a key to its role as a pathogen growth factor.