Aqueous solubility of beryllium(II) at physiological pH: effects of buffer composition and counterions

Beryllium ion elicits p53-mediated cell cycle arrest in some types of human cancer cells, and it is a potent inhibitor of GSK3 kinase activity. Paradoxically, Be²⁺ is regarded to have almost negligible aqueous solubility at physiological pH, due to precipitation as Be(OH)₂. This study demonstrates that the interaction of Be²⁺ with serum proteins greatly increases its effective solubility. In typical serum-supplemented mammalian cell culture medium, Be²⁺ was soluble up to about 0.5 mM, which greatly exceeds the concentration needed for biological activity. Some biochemical studies require protein-free Be²⁺ solutions. In such cases, the inclusion of a specific inorganic counterion, sulfate, increased solubility considerably. The role of sulfate as a solubility-enhancing factor became evident during preparation of buffered solutions, as the apparent solubility of Be²⁺ depended on whether H₂SO₄ or a different strong acid was used for pH adjustment. The binding behavior of Be²⁺ observed via isothermal titration calorimetry was affected by the inclusion of sodium sulfate. The data reflect a "Diverse Ion Effect" consistent with ion pair formation between solvated Be²⁺ and sulfate. These insights into the solubility behavior of Be²⁺ at physiological and near-physiological pH will provide guidance to assist sample preparation for biochemical studies.