Biomimetic Applications of Metal Systems Supported by Scorpionates

Abstract

It is well established that a number of metal ions are essential to life (Frausto da Silva & Williams, 2001; Bertini et al., 2006). A major determinant of their functional relevance in living systems is that a substantial fraction of enzymes requires metal for its catalytic activity. A wide variety of metal-dependent enzymes is found in nature which acts in fundamental biological processes, including photosynthesis, respiration and nitrose fixation (Bertini et al., 2001). Over the years, a wealth of knowledge on enzymes has been accumulated, including data on three-dimensional structures, kinetic and biochemical properties, and reaction mechanisms (Andreini et al., 2008). As metalloprotein chemistry is governed by the environment close to the metal center(s), a fertile field of investigation is concerned with the preparation of low molecular weight complexes that mimic the structural or functional features of protein active sites. The synthetic analogue or model approach provides insights into bioinorganic systems through the synthesis and study of closely related ‘model’ compounds. It garners structural, electronic, spectroscopic, and chemical information crucial to a complete understanding of enzyme behavior. Scorpionates have been extensively used in biomimetic chemistry as “spectator ligands” but are not directly involved in the metal-based reactivity. A common approach for obtaining synthetic analogs of the type [{XYZ}M-L] (M = metal; L = OH, H2O, Cys, etc.) involves the application of tridentate ligands which incorporate the requisite X, Y, and Z donor groups to mimic the protein residues that bind metals at the active site. In particular, tripodal ligands in which the X, Y, and Z groups are attached to a common tetrahedral (or trigonal pyramidal) center have proven to be of particular benefit for several reasons: a) tripodal ligands enforce the “facial” binding that is required to create a tetrahedral metal center, b) tripodal ligands typically possess only a single relevant binding conformation, c) as a consequence of the directional nature of tripodal ligands, it is possible to incorporate substituents that directly influence the steric environment about the metal center, and d) the substituents on these ligands can be readily modified to provide a mean to influence both the size of the coordination pocket and the electronic properties of the metal center. One of the most versatile tripodal ligand typology that can be utilized for biomimetic purposes is represented by the scorpionates. The azole rings of these ligands can in fact be considered as good models of the histidine residues of proteins, and their spatial disposition provides the steric arrangements found in many active sites. In addition, from a synthetic point of view,