Substitution reactions at the nickel site of the cubane-type cluster [(Ph3P)NiFe3S4(LS3)](2-) (2) have been investigated in the course of a synthetic approach to the C-clusters of CODH. Reaction of 2 with RS- or toluene-3,4-dithiolate affords [(RS)NiFe3S4(LS3)](3-) (R = Et (5), H (6)) or [(tdt)NiFe3S4(LS3)](3-) (7), demonstrating that anionic sulfur ligands can be bound at the Ni-II site. Clusters 5 and 6 contain tetrahedral Ni(mu(3)-S)(3)(SR) sites. Cluster 7 is of particular interest because it includes a cubanoid NiFe3(mu(2)-S)(mu(3)-S)(3) core and an approximately planar Ni(tdt)(mu(3)-S)(2) unit. The cubanoid structure is found in all C-clusters, and an NiS4-type unit has been reported in C. hydrogenoformans CODH. Clusters 5/6 are formulated to contain the core [NiFe3S4](1+) equivalent to Ni2+ (S = 1) + [Fe3S4](1-) (S = 5/2) and 7 the core [NiFe3S4](2+) equivalent to Ni2+ (S = 0) + [Fe3S4](0) (S = 2) on the basis of structure, Fe-57 isomer shifts, and H-1 NMR isotropic shifts. Also reported are [(EtS)CuFe3S4(LS3)](3-) (9) and [Fe4S4(LS3)(tdt)](3-) (11). The structures of 5-7, 9, and 11 are presented. Cluster 11, with a five-coordinate Fe(tdt)(mu(3)-S)(3) site, provides a clear structural contrast with 7, which is currently the closest approach to a C-cluster but lacks the exo iron atom found in the NiFe4S4,5 cores of the native clusters. (CODH = carbon monoxide dehydrogenase, LS3 = 1,3,5-tris((4,6-dimethyl-3-mercaptophenyl)thio)-2,4,6-tris(p-tolylthio)b enzene(3-), tdt = toluene-3,4-dithiolate).