Aspartic and Glutamic Acid as Ligands to Alkali and Alkaline‐Earth Metals: Structural Chemistry as Related to Magnesium Therapy

Magnesium and other alkaline‐earth and alkali metals play an important role in the biochemistry of virtually all living organisms. In contrast to “trace elements” these “common metals” are distributed in most cells and tissues, often in considerable concentrations, and a constant supply is indispensable for unrestricted performance of biological functions. In contemporary medicine, various forms of magnesium therapy are recommended in order to compensate for magnesium deficiency due to certain dysfunctions as well as to loss from excessive transpiration. In addition, there are numerous indications for prophylaxis. Magnesium is usually administered orally in the form of “complexes” with “natural” anions derived from I‐aspartic, L‐glutamic, L‐pyroglutamic (pidolic), citric, and orotic acid. Analytical, electrochemical, and spectroscopic investigations of aqueous solutions of these Pharmaceuticals, together with X‐ray diffraction studies of crystalline samples, have given a detailed knowledge of these coordination compounds. Only certain combinations can be addressed as magnesium complexes, whereas others are only present as aquo complexes both in aqueous solutions and in the solid state. Thus, a delicate balance of metal complexation and hydrogen bonding exists for the components of the drugs, which is relevant for the metal carrier functions of the organic ligands. Compared with the more flexible stereochemistry of Ca, Sr, Ba, Mn^II, Zn, Li, Na, and K complexes, which have coordination numbers between 4 and 9, octahedral hexacoordination is found exclusively for magnesium, the most stereoselective of these metals.