Statistical Ligand Substitution

None of the ligand environments discussed in the previous sections has afforded isolation of a subsite-differentiated [4Fe-4S] cluster. The complex [Fe4S4(9-peptide) (S-r-Bu)] (13, Fig. 4) exhibits the correct ratio of peptide to t-butylthiolate by integration of the H NMR resonances (78), and therefore meets our criterion for a subsite-differentiated compound. Cluster 13 was not isolated, however, and a structure determination was not performed. 

The main barrier to isolation of a mixed-ligand cluster is its substitutional lability, which can lead to statistical disproportionation. Thus, site-differentiated clusters 29 and 30, which have been trapped as sparingly soluble Ph4P salts and structurally characterized in the solid state (102, 103), 

The problem of performing site-specific chemistry at one iron site in a [4Fe-4S] cluster requires interrelating the reactivity of three of the iron atoms such that the fourth site can react independently. This relationship has been achieved by the synthesis of a semirigid tridentate thiolate ligand that readily binds several types of cubane clusters. The details of the synthesis and reactivity of site-differentiated clusters will be provided in Section IV. We next turn to the topic of subsite-specific properties observed in biological systems. 

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Figure 17. Three ligand substitution reactions that afford essentially statistical product mixtures, together with certain dimensions of [Fe4S,L4] - clusters.

Other quantitative approaches to address selectivity rely on generating and consistently interpreting individual statistical models, which again provide very detailed information on desirable scaffold substitution pattern and spatial areas around superimposed ligands, which allow to selectively interact only with one binding site. There are multiple interesting applications of this concept in the literature (e.g., [109-112]). 

In fact, experimental results indicate that the statistical distribution is seldom followed. With trans reactants, both acid aquation and base substitution reactions result in a mixture of isomers the fractions of cis and trans depend on the retained ligand and range from 100% trans to 94% cis, as shown in Tables 12-8 and 12-9. Of course, any... 

Quite recently, Kruck 118) obtained 80% yields of tetrakistrifiuoro-phosphine nickel by reaction at 100° C. and 350 atm. Clark and co-worker 56) studied the reaction mixture of Ni(CO)4 and PF3 by gas chromatography and NMR, determining the physical constants (density, vapor pressure) of all the substitution products, and showing that in first approximation the equilibrium composition of the mixture can be calculated if there was a statistical equilibrium between the ligands CO and PF3. This means that the metal-to-ligand bonds are of the same strength. 

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