Almost half of all known to date proteins contain metal co-factors. Over the course of 3–4 billion years of organism evolution, several metal species of different oxidation state (Na+, K+, Mg2+, Ca2+, Zn2+, Mn2+, Fe2+/3+, Co2+/3+, Ni2+ and Cu+/2+) have been chosen to participate in key biological processes. They are known as “native”, or “biogenic” metals. On the other end stand toxins like mercury and lead, which poison the recipient by competing with the natural co-factors for binding the essential proteins. As a third example, however, should be outlined some abiogenic metal species, which exert a curative effect on the host organism, and are, therefore, applied in medicine as novel drugs. Such are silver (Ag+), strontium (Sr2+), and gallium (Ga3+). The current study investigates their ability to compete with the native cuprous (Cu+), calcium (Ca2+), and ferric (Fe3+) cations, respectively, by exploiting the methods of the computational chemistry. Nowadays, silver finds broad application in many areas of medicinal use, e.g. being added to dressings of burn wounds as a concomitant therapy of skin ulcers, as a potential water disinfectant, or even in ophthalmology as an active component in eye drops. Strontium prevents the destruction of bones and contributes to their restoration. Sr2+ salt of ranelic acid is a medication (under the names Protelos, Protos, Strontium ranelate Aristo) used for treatment of osteoporosis in postmenopausal women and very elderly patients. Gallium, in its cationic form (Ga3+), is well known for its anticancer activity. Nonetheless, recent experimental studies have considered the employment of gallium as a promising “Trojan horse” strategy against pathogenic microorganisms. Herewith, we set on a quest for deciphering the most acclaimed mechanisms of therapeutic action of the aforementioned metal cations at atomic level. The obtained results shed light on the intimate echanisms of metal recognition, thus revealing key factors governing the processes of native/abiogenic metal rivalry. This approach serves not only for explaining already existing experimental findings, but also as a first step in designing/engineering novel drug molecules of potential therapeutic value.
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