Biological implications of the interaction (via silanol groups) of silicon with metal ions.

Since the demonstration, in 1972, of the essentiality of silicon in higher animals, bio-inorganic chemists have speculated about the site and mechanism of action of silicon. Bone and connective tissue have been identified as tissues that are altered in the absence of silicon. Si-C bonds are foreign to biochemistry so organic bonding must be via Si-O-C, but the instability of the ester bond in aqueous solution at pH 7.4 has prompted us to investigate the interactions of silicic acid. Silicic acid could, by hydrogen bonding, alter the conformation of organic macromolecules, since hydrogen bond association can inhibit silanol condensation. However, silanols are also able to interact with metal ions that are basic at physiological pH, e.g. Fe3+ or Al3+ but not Ca2+, and such interactions are known in geochemistry. The observed effects of Si on hard and soft tissue could therefore result from interactions of Si(OH)4 with Fe3+, which is involved in connective tissue synthesis (via enzymes, e.g. prolyl hydroxylase) and damage (via iron-catalysed radical generation), or with Al3+ which exerts toxic effects at sites (bone and brain) at which Si has also been observed. Although we have demonstrated several Fe3+/Si interactions, we have not been able to show their relevance in a biochemical context. Al3+ interacts with Si(OH)4 in aqueous solution and preliminary experiments have suggested that silicic acid can counteract deleterious effects of aluminium, for example the activity of prolyl hydroxylase, an observation with implications not only in osteogenesis but also in Alzheimer's disease and aluminium toxicity in acidified waters.