Inorganic Chemistry, Vol.40, No.27, 7079-7086, 2001
Fe(III) coordination properties of two new saccharide-based enterobactin analogues: Methyl 2,3,4-tris-O-{N-[2,3-di(hydroxy)benzoyl-glycyl]-aminopropyl}-alpha-D-glucopyranoside and methyl 2,3,4-tris-O-{N-[2,3-di-(hydroxy)-benzoyl]-aminopropyl}-alpha-D-glucopyranoside
The synthesis of two saccharide-based enterobactin analogues, methyl 2,3,4-tris-O-{N-[2,3-di(hydroxy)benzoyl-glycyl]-aminopropyl}-alpha -D-glucopyranoside (H6LA) and methyl 2,3,4-tris-O-{N-[2,3-di (hydroxy)benzoyl]-aminopropyl]-alpha -D-glucopyranoside (H6LB), are reported along with their pK(a) values, Fe(III) binding constants, and aqueous solution speciation as determined by spectrophotometric and potentiometric titration techniques, Use of a saccharide platform to synthesize a hexadentate triscatechol chelator provides some advantages over other approaches to enterobactin models, including significant water solubility, resistance to hydrolysis, and back-bone chirality which may provide favorable recognition and availability to cells. The protonation constants for the catechol ligand hydroxyl moieties were determined for both ligands and found to be significantly different, which is attributed to the differences in the spacer chain of the two triscatechols. Proton dependent Fe(III)-ligand equilibrium constants were determined using a model involving the sequential protonation of the Fe(Ill)-ligand complex. These results were used to calculate the formation constants, log beta (110) = 41.38 for Fe(III)-H6LA and log beta (110) = 46.38 for Fe(III)-H6LB. The calculated pM values of 28.6 for H6LA and 28.3 for H6LB indicate that these ligands possess Fe(III) affinities comparable to or greater than other enterobactin models and are thermodynamically capable of removing Fe(Ill) from transferrin.