Modeling the Active Site of Nitrile Hydratase: Synthetic Strategies to Ensure Simultaneous Coordination of Carboxamido-N and Thiolato-S to Fe(III) Centers

A general strategy for synthesizing Fe(III) complexes of ligands containing carboxamido-N and thiolato-S donors
has been described. Reaction of the doubly deprotonated ligand PyPepS2- (where PyPepSH2 = N-2-mercaptophenyl-2‘-pyridinecarboxamide) with Fe(III) salts in DMF had previously afforded the Fe(III) complex (Et4N)[Fe(PyPepS)2]
without any problem(s) associated with autoredox reactions of the thiolate functionality. In the present work, similar
reactions with the doubly deprotonated ligand PiPepS2- (where PiPepSH2 = 2-mercapto-N-pyridin-2-yl-methylbenzamide) with Fe(III) salts, however, fail to afford any Fe(III) complex because of autoredox reactions. The break
in the conjugation in the PiPepSH2 ligand frame is the key reason for this difference in behavior between these two
very similar ligands. This is demonstrated by the fact that the same reaction with AqPepS2- (where AqPepSH2 =
2-mercapto-N-quinolin-8-yl-benzamide), another ligand with extended conjugation, affords the Fe(III) complex (Et4N)[Fe(AqPepS)2] (1) without any synthetic complication. It is therefore evident that ligands in which the carboxamide
and thiolate functionalities are kept in conjugation could be used to isolate Fe(III) complexes with carboxamido-N
and thiolato-S coordination. This finding will be very helpful in future research work in the area of modeling the
active site of Fe-containing nitrile hydratase.