Lasalocid anion

Outer-sphere complexes of lasalocid A (LAS) anion with [Co(NH3)6], [Co(en)3], and [Co(sep)] + cations were isolated as reported in Ref 321. The X-ray data for these complexes demonstrated that three lasalocid anions (in cyclic conformation) surround the cobalt complexes so that the overall shape is approximately spherical. In consequence of its hydrophobic outer surface, the adduct is soluble in nonpolar solvents such as chloroform. Lasalocid anion was showed to act as an ionophore for selective enantiomeric transport of the [Co(sep)]- + cation through a chloroform membrane. 

X-ray structural analysis of a 2 2 2 adduct between lasalocid, Na, and water obtained from 95 % ethanol solution In this complex, each of the sodium ions is mainly associated with a single lasalocid anion in a manner reminiscent of the aforementioned monomeric Na complex. Coordination of the metal ions is completed by two water molecules which are accommodated between the antibiotic molecules. The dimer is held together by hydrogen bonds via these water molecules. This suggests that the adduct might be a result of the initial association of two Na -lasalocid monomers, thus representing an intermediate in the complexation process. 

Fig. 5. The absorption and CD spectra of protonated lasalocid -----) and lasalocid anion...

Fig. 7. [0Ji and [0]n of lasalocid anion as a function of solvent Et value. Ef values are elfective parameters for correlating solvent properties such as the ability to donate an electron pair or to hydrogen bond with ionophore solution conformation ... 

Fig. 8. Deccmvoluted peak II of lasalocid anion generated in acetonitrile with l.S equivalents of tri-n-butylamine. Peak Ila arises from the n- n transition...

Complex formation between lasalocid anion and alkali cations results in large, solvent dependent increases in [0]i and [0], (Table 2). [0] values are consistently larger for the potassium complexes (Fig. 9). As the solvent value drops the magnitudes of peaks I and II increase for both complexes. 

Table 1. Resolution of Lasalocid Anion CD Peak II into Component Peaks Ila and lib...

Table 2. Effects of Alkali Cation Inclusion on the CD Spectrum of Lasalocid Anion in a Solvent Series of Decreasing Polarity...

Fig. 10. The acyclic quasilinear conformer of lasalocid anion which predominates under high polarity conditions. This conformer has the lowest intrinsic molecular strain energy as calculated using a QCFF energy minimization program - . Solvent effects on the conformation were modeled using an empirical specific site approach ...

Fig. 13. Lasalocid anions generated with (n-BuXi. NOH in 80% dioxane/water are initially ion paired to (n-Bu)4 N. Addition of another ion, DMPC, sets up an ion exchange equilibrium which is detected by changes in peaks I and II a of the CD spectrum...

As expected, system 13 did in fact bind and transport zwitterionic a-amino acids through a model membrane barrier with good selectivity under conditions where the porphyrin-derived control system (14), lacking the carboxylate anion chelation ability inherent in 13, would not. Specifically, it was found that at neutral pH compound 13 acts as a very efficient carrier for the through model membrane (H2O-CH2CI2-H2O) transport of phenylalanine and tryptophan. Further, in direct competition experiments, L-phenylalanine was found to be transported four times faster than L-tryptophan and 1000 times faster than L-tyrosine. As implied above, little or no transport was observed when a porphyrin control (14) was used. Nor was significant transport observed when a mixture of sapphyrin and lasalocid was used. 

An arrangement of this type was first shown by X-ray crystallography to exist in the barium complex of lasalocid In this complex, two antibiotic anions... 

In the crystalline state, the synthetic a-carboxy-(0-amino ligand forms a 2 2 dimer by formation of hydrogen bonds with the CIO anions (see Fig. 48). This arrangement is somewhat similar to that found in the 2 2 lasalocid complex with Na" " if one neglects the presence of the perchlorate anions. 

Since carboxylic ionophores transport ions by an electrically silent exchange diffusion mechanism, it is the anionic form of the ionophore which interacts with cations at membrane interfaces Therefore, the lasalocid species most germane for ion complexation within membranes is the free anion Deprotonation of the C25 carboxyl with base results in substantial changes in the absorption and CD spectra from that of the protonated form stabilized by 0.5 equivalents of HCl (cf Fig. 5). The 245 nm absorption band observed for protonated lasalocid intensifies and shifts to 240 nm upon deprotonation while the 317 nm absorption band shifts to 310 nm with little change in intensity. In the CD spectrum, peak I shifts hypso-chromically to 240 nm and intensifies upon deprotonation while peak II shifts bathochromically and diminishes in intensity. 

Figure 7.7 Selectivity coefficients, logi °j, as determined with the SSM for oNPOE-PVC (2 1, w/w) membranes based on lasalocid (Sr +-1) and ionic sites. Selectivity coefficients of the membranes with 50 mol% anionic sites are also hsted in Table 7.3. From reference (34). Copyright 2000 American Chemical Society.

Selected relevant examples (a) Gal, A., Andreu, D., Echavarren, A. M., Prados, P. and de Mendoza, J. (1992) A Receptor for the Enantioselective Recognition of Phenylalanine and Tryptophan under Neutral Conditions, J. Am. Chem. Soc. 114, 1511-1512 (b) Konishi, K., Yahara, K., Toshishige, H., Aida, T. and Inoue, S. (1994) A Novel Anion-Binding Chiral Receptor Based on a Metalloporphyrin with Molecular A mmetry. Highly Enantioselective Recognition of Amino Acid Derivatives, J. Am. Chem. Soc. 116, 1337-1344 (c) Sessler, J. L. and Andrievsky, A. (1998) Efficient transport of aromatic amino acids by sapphyrin-lasalocid conjugates, Chem. Eur. J. 4,159-167. 

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