Optimization of the lariat ether carboxylic acid host structure for ferrioxamine B: Demonstration of a second coordination shell chelate effect

Host-guest supramolecular assembly formation constants involving the second -sphere complexation of the siderophore ferrioxamine B (FeHDFB+) by a laria t ether carboxylic acid host (Ln+2COOH) in wet chloroform were obtained fro m liquid-liquid extractions at pH values above and below the host pK(a) (si milar to5.3). The host-guest formation constants, K-a, determined at pH = 3 .2 for the assemblies (FeHDFB+, Ln+2COOH,ClO4-) (n = 4, 7, 10, 15) in wet c hloroform 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 sta ble assembly, (FeHDFB+,Ln+2COO-), as measured by the host-guest formation c onstant, K-app. This enhanced stability is shown to be a function of the la riat ether sidearm chain length (n = 4, 7, 10, 15) and is corroborated by m olecular modeling calculations. Additionally, molecular modeling and extrac tion data demonstrate that there is an optimum lariat ether sidearm chain l ength with respect to host-guest assembly stability as measured by Kapp. We attribute the enhanced stability effect of the ionized lariat ether in the host-guest assembly (FeHDFB+,Ln+2COO-), relative to (FeHDFB+,Ln+2COOH,ClO4 -) or to (FeHDFB+,B18C6,ClO4-), to a second coordination shell chelate effe ct.