Lariat Ether Carboxylic Acids as Ionizable Hosts in the Second Coordination Sphere of the Siderophore Ferrioxamine B in Chloroform

Abstract

A new series of lariat ether carboxylic acids (LnCOOH) was synthesized with different lengths of side arm (6, 9, and 12 atom spacers between the benzo-18-crown-6 crown ether ring and the carboxylic acid functional group). These lariat ethers were used as neutral and anionic hosts for the molecular recognition of the cationic siderophore, ferrioxamine B. Lariat ether pKa values were determined by potentiometric titration in 50% methanol (v/v) to be in the range 5.23−5.32. Molecular recognition of ferrioxamine B occurs through second-sphere complexation of the pendant protonated amine (−(CH2)5NH3+) by the lariat ether cavity, utilizing an ion−dipole host−guest interaction to form a supramolecular assembly in wet chloroform. At conditions where the pendant carboxylic acid side arm is not ionized (pH = 3.2), the lariat ethers behave as the parent unsubstituted crown ether structure, benzo-18-crown-6 (B18C6). At pH conditions well above their pKa values, the lariat ether carboxylic acids function both as a host and as an internal counterion. The stability of this binary assembly, {FeHDFB+,LnCOO-}, is significantly increased (log Kapp = 4.85 for L12COO-) compared with that of the ternary assembly involving the protonated lariat ether, {FeHDFB+,LnCOOH,ClO4-} (log K = 3.26 for L12COOH), or the parent crown ether, {FeHDFB+,B18C6,ClO4-} (log K = 3.21). Stability was also observed to increase with the length of the side arm from 6 (log Kapp = 4.29) to 12 atom spacers (log Kapp = 4.85). We attribute this effect to the increased conformational freedom of the longer arm, which facilitates interaction between the protonated amine site and the carboxylate moiety.