The [1:3] site-differentiated cubane-type clusters [F2(4)Q(4)(LS3))Cl](2-)(Q=S,Se;LS3=1,3,5-tris((4,6-dimethyl-3-mercaptophenyl)thio)-2,4,6-tris(p-tolylthio)benzenate(3-)) undergo substitution reactions at the unique iron site with a variety of ligands including thiolates, phenolates, cyclic triamines and a trisulfide, imidazoles, and tertiary phosphines. Reactions are readily followed because of the extreme sensitivity of isotropically shifted resonances to the nature of ligand L' in the product dusters [Fe(4)Q(4)(LS3)L'](2-,-), Isotropic shifts and redox potentials are reported for over 40 clusters, including many cluster pairs differing only in the core chalcogenide atom. In this way, comparative properties of sulfide and selenide clusters can be elicited. It is shown that the larger isotropic shifts consistently observed for selenide clusters and dominantly contact in nature arise from larger magnetic susceptibilities, which indicate a lesser extent of antiferromagnetic coupling. It is further demonstrated that, without exception, redox potentials of selenide clusters are more positive than those of sulfide clusters, usually by 20-60 mV, at parity of ligation. The difference in potentials of ca. 300 mV between the [Fe4S4](2+,+) couples of [Fe4S4(LS3)(SEt)](2-) and [Fe4S4(LS3)(Im)](-) (Im=imidazole) clusters is the best available estimate of the intrinsic potential difference between protein-bound [Fe4S4(Cys-S)(4)] and [Fe4S4(Cys-S)(3)(His-N)] clusters. The ligand LS3 undergoes spontaneous transfer between [Fe4S4](2+), [Fe4Se4](2+), and [MoFe3S4](3+) cores in reactions whose equilibrium constants are near the statistical value. The ligand binding affinity order PhS- > PhO- > CN- much greater than Cl- for [Fe(4)Q(4)](2+) cores was established. When taken together with earlier results from this laboratory,a comprehensive picture of ligand binding to single iron sires in [Fe(4)Q(4)](2+) dusters emerges.