Synthetic models for the zinc sites in the methionine synthases

The syntheses and molecular structures of a series of tetrahedral zinc complexes designed to model the active sites in Escherichia coli methionine synthases are reported. [PhTt(tBu)]ZnBr (PhTt(tBu) = phenyltris((tert-butylthio)methyl)borate) was prepared and characterized crystallographically to provide entry into [S-3]ZnX complexes. Metathesis with KSPh yielded the phenylthiolato complex, [PhTt(tBU)]Zn(SPh), which represents a structural mimic of the homocysteine ligated form of the enzyme. Alternatively, [S2N]ZnX (X = Br, CH3, SPh) species were prepared using the new mixed-donor ligands, [Ph(pz)Bt(tBu)] (phenyl(pyrazolyl)bis((tert-butylthio)met and [Ph(pz(tBu))Bt(tBu)] (phenyl(3-tert-butylpyrazolyl)bis((tert-butylthio. Protonolysis of [Ph(pz(tBu))Bt(tBu)]Zn(CH3) by PhSH in toluene yielded [Ph(pz(tBu))Bt(tBu)] Zn(SPh), a synthetic analogue of the homocysteine ligated form of cobalamin-independent methionine synthase (Met E). The average Zn-S bond distance in [Ph(pz(tBu))Bt(tBu)]Zn(SPh) of 2.37 Angstrom compares well with the EXAFS-derived distance of 2.31 Angstrom found in the homocysteine-bound form of Met E.