Organometallics Targeted to Specific Biological Sites the Development of New Therapies

Organometallics Targeted to Specific Biological Sites the Development of New Therapies 

Medicinal inorganic chemistry s current position has been the subject ofa number of recent reviews and books [1-10]. Until now, this field has generally focused on coordination complexes. 

Althotigh dsplatin itself 1 is a purely inorganic compound, with an imfortunately high level of general toxicity, its structural analogy to metaUocene-type complexes of other metals, Ti, Fe, V, Mo, Re, Nb, Hf [17-28] soon became apparent. Dichlorotitanocene 2 has been the subject of a number of studies but clinical testing was recently discontinued due principally to difficulties of formulation [29, 30], 

This chapter will outline another approach to the treatment of specific diseases, whether infectious, cancerous or parasitic, using organometaHic moieties that are accurately targeted in order to reduce the problems of general toxicity. The approach is to use a known vector as a Trojan horse to transport the organometaHic function into the target cell. 

When the ferrocenyl group is situated too dose sterically to the p-lactam nudeus, where R = FcC(O)-, no antibiotic activity is observed for the modified penicillins and cephalosporins. However, the addition of a methylene spacer to distance the ferrocenyl moiety from the p-lactam nudeus restores the antibiotic activity to the same high levd as that of the controls (Penicillin G and methidUin). Replacement of the methylene by CMe2 increases p-lactamase inhibition and decreases the antibiotic activity. For a recent and exhaustive review of metallic antibiotics in general, see Ming [10]. 

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