LARIAT ETHER CARBOXYLIC-ACIDS AS IONIZABLE HOSTS IN THE 2ND COORDINATION SPHERE OF THE SIDEROPHORE FERRIOXAMINE-B IN CHLOROFORM

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 functio nal group). These lariat ethers were used as neutral and anionic hosts for the molecular recognition of the cationic siderophore, ferrioxami ne B. Lariat ether pK(a) values were determined by potentiometric titr ation in 50% methanol (v/v) to be in the range 5.23-5.32. Molecular re cognition of ferrioxamine B occurs through second-sphere complexation of the pendant protonated amine (-(CH2)(5)NH3+) by the lariat ether ca vity, utilizing an ion-dipole host-guest interaction to form a supramo lecular assembly in wet chloroform. At conditions where the pendant ca rboxylic acid side arm is not ionized (pH = 3.2), the lariat ethers be have as the parent unsubstituted crown ether structure, benzo-18-crown -6 (B18C6). At pH conditions well above their pK(a) values, the lariat ether carboxylic acids function both as a host and as an internal cou nterion. The stability of this binary assembly, {FeHDFB+,LnCOO-}, is s ignificantly increased (log K-app = 4.85 for L12COO-) compared with th at of the ternary assembly involving the protonated lariat ether, (FeH DFB+,LnCOOH,ClO4-) (log K = 3.26 for L12COOH), or the parent crown eth er, (FeHDFB+,B18C6,ClO4-) (log K = 3.21). Stability was also observed to increase with the length of the side arm from 6 (log K-app = 4.29) to 12 atom spacers (log K-app = 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 moi ety.