It is the purpose of this chapter to use the principles that have been described in previous chapters on metal complexes, chelates, and macro cyclic compounds to develop an understanding of the use of metal complexes or ligands for medical purposes. Previous chapters have emphasized the factors involved in designing metal complexes with maximum stability, and with a large degree of selectivity. Both of these factors are important in biological systems because of the fact that all metal ions are subject to interaction with the natural ligands that are present in body fluids for the purpose of storage, transport and the regulation of the activity of natural metal ions that are needed for various mctabolic purposes. Therefore, in order for a ligand to be effective in biological systems, or a metal complex to retain its integrity in competition with natural carriers, the thermodynamic stability of the complex in question must be maximized. When a ligand is designed to remove a certain metal ion because it has reached toxic levels, it must be as selective as possible for that metal ion so as not to disturb thc metals that are naturally present. However, high thermodynamic stability and selectivity are not the sole requirements of the ligand or of the metal complex being considered, because there are many other factors in biological systems which must be taken into consideration. Such factors include the method of administration (oral, sub-cutaneous, intravenous injection, etc.), bioavailability, membrane permeability, toxicity, and rapid elimination of the ligand and its metal chelate without spreading the undesired metal to other organs throughout the body. It will be the philosophy of this chapter that the thermodynamic stability of a metal chelate should be maximized, and the principles described in this book will be used for this purpose. While ligand design to achieve these purposes seems fairly straightforward, the other factors of importance in biological systems such as toxicity, bioavailability and membrane permeability are not as easily predicted. Therefore, many complexes that meet the stability requirements cannot be used in biological systems because they fail to meet the other biological requirements described above.A few examples of metal complexes will serve to illustrate this point. Macrocycles such as cyclam which form very stable copper complexes (with stability constants of the order of ~ 1028) were found to be considerably less effective in enhancing urinary excretion of copper than were the polyamines (with copper stability constants of ~ 1020-1024). This is possibly due to differences in bioavailability of the two types of complexing ligands, as well as the fact that the rate at which Cu(II) cyclam complexes form is very slow. Another example is the catechol group containing ligands such as the 149 A. E. Martell et al., Metal Complexes in Aqueous Solutions