The 7Fe ferredoxin from Desulfovibrio africanus contains a reactive 3Fe cluster which incorporates Fe and other metals to form cubanes [M3Fe-4S] having non-cysteine ligation to the added metal (M). These reactions are addressed at controlled potentials in protein molecules adsorbed on a graphite electrode, thereby facilitating an appraisal of factors that control cluster interconversions. Electrochemical and spectroscopic methods have been used to establish connectivities among interconversions with different M, explore the influence of pH, and determine reactivities of specific cluster oxidation levels. Formation of clusters with M = Fe, Zn, and Co depends on ionization of a group with pK = 5.5 + 0.3, thus supporting congruence among products and suggesting common involvement of aspartate-14 which replaces a cysteine normally present in [4Fe-4S] binding motifs. The influence of potential is complex: rapid and reversible interconversion (M = Fe, Zn) occurs only between the states [M3Fe-4S](2+) and [3Fe-4S](0), with [3Fe-4S](1+) having little affinity for M. The [M3Fe-4S](1+) cubanes and hyperreduced [3Fe-4S](2-) are relatively unreactive. Uptake and release are significantly more rapid for M = Zn compared to Fe. Among potentially intrusive metals, Pb has a particularly high affinity for the [3Fe-4S] cluster, but the product undergoes subsequent irreversible reactions. The studies provide complementary perspectives on factors influencing cluster stability or reactivity and on the feasibility and consequences of metal substitutions.