A family of soluble, reduced iron-sulfur clusters with nuclearities 4, 8, and 16 having tertiary phosphine ligation and based on the Fe4S4 cubane-type structural motif has been synthesized. The results of this investigation substantially extend and improve the results of our original work on iron-sulfur-phosphine clusters (Goh, C.; Segal, B. M.; Huang, J.; Long, J. R.; Holm, R. H. J. Am. Chem. Soc. 1996, 118, 11844). A general property of this cluster family is facile phosphine substitution. The clusters [Fe4S4(PR3)(4)](+) are precursors to monosubstituted [Fe4S4(PR3)(3)X] (X = Cl-, RS-), homoleptic [Fe4S4(SR)(4)](3-), and all-ferrous monocubanes [Fe4S4(PR3)(4)] (R = Pr-i, Cy, Bu-t; generated in solution). In turn, [Fe4S4(PPr3i)(3)(SSiPh3)] and [Fe4S4(PPr3i)(4)] can be transformed into the dicubanes [Fe8S8-(PPr3i)(4)(SSiPh3)(2)] and [Fe8S8(PPr3i)(6)], respectively. Further, the tetracubanes [Fe16S16(PR3)(8)] are also accessible from [Fe4S4(PR3)(4)] under different conditions. X-ray structures are described for [Fe4S4(PCy3)(3)X] (X = Cl-, PhS-), [Fe8S8(PPr3i)(4)(SSiPh3)(2)], [Fe8S8(PPr3i)(6)], and [Fe16S16(PCy3)(8)]. The monosubstituted clusters show different distortions of the [Fe4S4](+) cores from idealized cubic symmetry. The dicubanes possess edge-bridged double cubane structures with an Fe-2(mu(4)-S)(2) bridge rhomb and idealized C-2h symmetry. The ready cleavage of these clusters into single cubanes is considered a probable consequence of strained bond angles at the mu(4)-S atoms. Tetracubanes contain four individual cubanes, each of which is implicated in two bridge rhombs so as to generate a cyclic structure of idealized D-4 symmetry. Redox properties and Mossbauer spectroscopic parameters are reported. The species [Fe4S4(PR3)(4)] (in solution), [Fe8S8(PR3)(6)], and [Fe16S16(PR3)(8)] are the only synthetic all-ferrous clusters with tetrahedral iron sites that have been isolated. Their utility as precursors to other highly reduced iron-sulfur clusters is under investigation.