Designer Ligands for Beryllium

Abstract

We report the rational design of ligands that selectively bind beryllium. We selected two ligands to design Be based on binding polynulear species with a Be-O-Be motif: 2-hydroxyisophthalic acid (HIPA) and 2,3-dihydroxybenzoic acid (DHBA). All previous work has focused on BeL or BeL2 species. The HIPA and DHBA have extremely high binding constants of 17.5 and 18.4, respectively. These ligands outcompete chromotropic acid, which has one the highest binding constants for Be reported in the literature for a simple BeL species. The binding of the second Be to form the Be-O-Be motif is so strong that polynuclear species predominates in solution down to micromolar concentrations. Both ligands show a fluorescence response in the presence of beryllium, making them promising candidates for fluorescence-based sensors. In the case of HIPA, there is a fluorescence shift, and in the case of DHBA, the presence of beryllium turns on the fluorescence by removing two OH bonds that otherwise lead to nonradiative decay. The most dramatic result is that DHBA selectively binds Be in the presence of a metal cocktail containing a 50-fold excess of Al, Fe, Cr, Cu, Zn, Cd, and Pb. This is the first time that such selectivity for beryllium has been demonstrated.

The bioinorganic chemistry and associated immunology of chronic beryllium disease

“…4). 30 HIPA has two sixmembered ring binding pockets with carboxylate groups on either side of the phenoxide functionality, and DHBA has one six-membered and one five-membered ring binding pocket made from the two phenol groups and the carboxylic acid. Absorbance and fluorescence changes in the aromatic ligands were used to determine the binding constants directly.…”

Stable, Soluble Beryllium Aluminum Citrate Complexes Inspired by the Emerald Mineral Structure

“…A few citrate-type aqueous complexes containing CÀO units bridging two beryllium atoms are known [10,11] and very stable complexes with Be-O-Be linkages with phenolic species acting as bridging oxygen atoms have been recently reported. [12] We report here on the synthesis of a new stable citrate complex containing beryllium and aluminum atoms with a Be-O-Al linkage similar to that of beryl and a related aluminum beryllium citrate structure with bridging phosphate units that is highly soluble (1m) in aqueous phosphate solution (0.5 m). The mixed-metal citrate complex in both cases is the single dominant species in solution with no evidence of dissociation or rearrangement to Al citrate and Be citrate species.…”

“…The deprotonation of the ahydroxy group of citric acid is unusual but has been previously reported for Al citrate complexes. [11,14] The bridging hydroxy group has been shown to be vital for the stability of beryllium citrate type complexes [10,12] but has not been characterized by X-ray diffraction studies to date. Aluminum citrate complexes have been shown to bridge through the a-hydroxy group; however, bridging hydroxy groups or water molecules were also bound to the Al atom in all but one of these cases.…”

Beryllium binding at neutral pH: The importance of the motif

“…Dimethylcitric acid (DMCA) was prepared from trimethylcitrate (Aldrich) by a previously reported method [16]. NMR data ( 1 H, 9 Be, 13 C) were obtained on Bunker 400 MHz instruments. T 1 experiments followed literature precedent [17].…”

“…Despite the strong evidence for cluster formation in water, most aqueous research has focused on monomeric BeL or BeL 2 complexes at low pH. A recent report has shown that a Be O Be motif is highly stable and selective for Be with the bridging O coming from a phenolate [9]. Also another recent report showing a Al/Be motif (A1 O Be) utilizing CA [10].…”