ABSTRACT
Our understanding of the fundamental chemistry of Fe-S clusters owes much to studies of small “analogue” compounds. Compounds have been prepared and characterized that are analogues of [2Fe-2S]2+/+ (i.e., [Fe2S2((S)2Ar)2]2−/3−), [4Fe-4S]2+/+ (i.e., [Fe4S4(SR)4]2−/3−), and [3Fe-4S] ([Fe3S4(SR)3]2−/3−); clusters of higher nuclearity, perhaps having some as-yet unrealized biological relevance, have also been synthesized, including [6Fe-6S] [1, 13]. Further efforts have led also to the synthesis of heterometal cubanes and ‘sub-site differentiated’ clusters such as the thiolate-bridged [4Fe-4S]−Feporphyrin active site of sulfite reductase [1, 13]. In all these studies, the practical emphasis has been on identifying and examining clusters that are sufficiently stable to allow their characterization as isolated species. However, we are certain that the protein plays a major role in determining the properties of Fe-S clusters; importantly, unstable, reactive intermediates such as fragments, weakly bound adducts, and species generated under extremes of electrochemical potential may be difficult to detect and characterize. Furthermore, clusters may vacillate between species differing in ligation or nuclearity, perhaps in rapid response to changes in external conditions that are so subtle as to give the impression of chaotic behavior. Consequently, the goal should be to study reactions of clusters in their natural protein environment. We must therefore be able to (a) generate and examine species formed at extremes of reduction potential, (b) keep track of ‘vacillatory’ cluster systems-those lacking sufficient stability in any single form to be easily studied, and (c) resolve the complex reactions that are coupled to electron transfer. These are each characteristics of the catalysts and sensors, mentioned above, that have become a major focus of interest.
