Understanding the localization of berylliosis; interaction of Be2+ with carbohydrates and related biomimetic ligands.

Here we present a detailed study on the interaction of Be2+ ions with fructose and glucose as well as simpler biomimetic ligands, which emulate binding motives of saccharides. Through NMR and IR spectroscopy as well as single crystal X-ray diffraction, complemented by competition reactions we were able to determine a distinctive trend in the binding affinity of these ligands. This suggests that under physiological conditions beryllium ions are only bound irreversibly in glycoproteins or polysaccharides if a quasi ideal tetrahedral environment and k4-coordination is provided by the respective biomolecule. Furthermore, Lewis acid induced conversions of the ligands and an extreme increase in the Brønstedt acidity of the present OH-groups imply that upon enclosure of Be2+, alterations may be induced by the metal ion in glycoproteins or polysaccharides. In addition the frequent formation of Be-O-heterocycles indicates that multinuclear beryllium compounds might be the actual trigger of berylliosis. This investigation on beryllium coordination chemistry was supplemented by binding studies of selected biomimetic ligands with Al3+, Zn2+, Mg2+ and Li+, which revealed that non of these beryllium related ions was tetrahedrally coordinated under the give conditions. Therefore, studies on the metabolization of beryllium compounds can not be performed with other hard cations as substitute for the hazardous Be2+.