Optimization of the lariat ether carboxylic acid host structure for ferrioxamine B: demonstration of a second...

Host-guest supramolecular assembly formation constants involving the second-sphere complexation of the siderophore ferrioxamine B (FeHDFB(+)) by a lariat ether carboxylic acid host (L(n+2)COOH) in wet chloroform were obtained from liquid-liquid extractions at pH values above and below the host pK(a) (approximately 5.3). The host-guest formation constants, K(a), determined at pH = 3.2 for the assemblies [FeHDFB(+),L(n+2)COOH,ClO(4)(-)] (n = 4, 7, 10, 15) in wet chloroform are similar to those of the parent crown ether, benzo-18-crown-6. At pH = 9.3, the lariat ethers are ionized, and this results in a more stable assembly, [FeHDFB(+),L(n+2)COO(-)], as measured by the host-guest formation constant, K(app). This enhanced stability is shown to be a function of the lariat ether sidearm chain length (n = 4, 7, 10, 15) and is corroborated by molecular modeling calculations. Additionally, molecular modeling and extraction data demonstrate that there is an optimum lariat ether sidearm chain length with respect to host-guest assembly stability as measured by K(app). We attribute the enhanced stability effect of the ionized lariat ether in the host-guest assembly [FeHDFB(+),L(n+2)COO(-)], relative to [FeHDFB(+),L(n)+2)COOH,ClO(4)(-)] or to [FeHDFB(+),B18C6,ClO(4)(-)], to a second coordination shell chelate effect.