Beryllium and strong hydrogen bonds.

We compare beryllium to H+ and show that beryllium can displace H+ in many "strong hydrogen bonds" where Be as a "tetrahedral proton" (O-Be-O angle is tetrahedral as opposed to the nearly linear O-H-O angle) is thermodynamically preferred. The strong hydrogen bond provides two advantages. First, the O-X distance in a strong hydrogen bond is in the range 2.4-2.8 A, which brings two oxygen atoms into a predefined chelating binding site for beryllium. Second, the strong hydrogen bond provides a low barrier pathway to displace the proton without breaking a strong covalent O-H bond by shifting the proton to the more acidic site as Be interacts with the basic oxygen. The low barrier to proton transfer associated with a strong hydrogen bond provides a kinetic pathway for Be binding, and the binding strength increases with the increasing basicity of the site as indicated by the pKa. The physiological importance of this type of interaction is demonstrated with the solubility of a variety of Be complexes at pH 7. Based on this concept, new ligands have been designed for Be binding that solubilize Be in phosphate media and can be used as fluorescent imaging agents. Finally, the binding of Be to the iron transport protein transferrin is discussed as it relates to the same type of binding.