Gd(III)[15-Metallacrown-5] Recognition of Chiral α-Amino Acid Analogues

Abstract

Chiral Ln(III)[15-metallacrown-5] complexes with phenyl side chains have been shown to encapsulate aromatic carboxylates reversibly in their hydrophobic cavities. Given the importance of selective guest binding for applications of supramolecular containers in synthesis, separations, and materials design, the affinity of Gd(III)[15-metallacrown(Cu(II), L-pheHA)-5] hosts for a series of chiral carboxylate guests with varying substitutions on the α-carbon (phenylalanine, N-acetyl-phenylalanine, phenyllactate, mandelate, methoxyphenylacetate) has been investigated. Differential binding of S- and R-phenylalanine was revealed by X-ray crystallography, as the S-enantiomer exclusively forms associative hydrogen bonds with oxygen atoms in the metallacrown ring. Selective guest binding in solution was assessed with isothermal titration calorimetry, which measures the sequential guest binding in the hydrophobic cavity first and the hydrophilic face of the host, and a cyclic voltammetry assay, which quantifies guest binding strength in the hydrophobic cavity of the host exclusively. In solution, the Gd(III)[15-metallacrown(Cu(II), L-pheHA)-5] hydrophobic cavity exhibits modest chiral selectivity for enantiomers of phenylalanine (K(S)/K(R) = 2.4) and mandelate (K(S)/K(R) = 1.22). Weak binding constants of ∼100 M(-1) were measured for neutral and -1 charged carboxylates with hydrophilic functional groups (ammonium, N-acetyl, methyl ether). Weaker binding relative to the unsubstituted guests is attributed to unfavorable interactions between the hydrophilic functionalities of the guest and the hydrophobic cavity of the host. In contrast, binding constants greater than 2000 M(-1) were measured for α-hydroxy analogues phenyllactate and mandelate. The significantly increased affinity likely arises from the guests being bound as a -2 anion upon metal-assisted deprotonation in the Gd(III)[15-metallacrown(Cu(II), l-pheHA)-5] cavity. It is established that guest binding affinity in the hydrophobic cavity of the host follows the general trend of neutral zwitterion < monoanion < dianion, with hydrophilic functional groups decreasing the binding affinity. These results have broad implications for the development of metallacrowns as supramolecular catalysts or in chiral separations.

Fluorescent/luminescent detection of natural amino acids by organometallic systems

“…This is why the U.S. Food and Drug Administration (FDA) has laid down strict guidelines on the identification and quantification of chiral compounds [186][187][188][189]. Therefore, enantioselectivity is one of the most important goals for the sensing of organic substances [190][191][192][193][194][195][196][197][198], because biological activity is strictly correlated with stereochemistry. Although some enantioselective methods based on capillary electrophoresis [199][200], voltammetry [201], colorimetric methods [202][203][204] etc.…”

Enantioselective Inhibition of Human Papillomavirus L1 Pentamer Formation by Chiral‐Proline Modified Calix[4]arenes: Targeting the Protein Interface

“…Chirality is a prominent characteristic of biological molecules, and enantiomers of a chiral molecule often exhibit striking differences in terms of their physiological responses . Therefore, enantiomers have been widely applied to the various fields of science and technology, such as catalytic chemistry, biotechnology, and especially pharmaceutical science . Consequently, numerous efforts have been devoted to the synthesis and application of artificial chiral host and/or receptors .…”

Facile One‐Pot Route toward Water‐Soluble Lanthanide–Copper–Glycinehydrox­imate 15‐Metallacrown‐5 Complexes

“…[3] A large amount of systematic structural studies of Ln[15MC CuRha -5] complexes derived from α-aminohydroxamic acids with various organic anions have been performed, [4][5][6][7][8][9][10][11][12][13][14] and the affinity of the Ln III ion Scheme 1. It has been demonstrated that the anion affinity for the metallacrown is dependent on the R-substituted hydroximate ligands (Rha).…”