Metal enolates biochemicals

Stable metal complexes can be favorably formed when a bidentate metal-binding site is available, such as a- and -diketone moieties which are the tautomeric forms of a- and /3-ketoenols. Some /S-diketonate complexes of paramagnetic lanthanides such as Pr(III), Eu(III) and Yb(III) have been extensively utilized as paramagnetic shift reagents for structural assignment of molecules with complicated stereochemistry prior to 2D techniques in NMR spectroscopy. Their syntheses and application are discussed in separate chapters in this volume. The examples below provide some dynamic and structural basis for better understanding of metal enolates in biomolecules and biochemical processes. 

B. Enol-containing Biochemicals and Pharmaceuticals and Their Metal... 

The carbonyl functionality is one of the most abundant functional groups in biomolecules and pharmaceuticals, including many a- and /3-carbonyl derivatives of ketones and aldehydes and their enol tautomers, which upon deprotonation can form entropy-favored 5-membered (37) and 6-membered (38) chelates with metal ions. In this section, the role of metal ions in the action of some enol-containing biochemicals and pharmaceuticals and the structures of their metal complexes are discussed. 

TCs are well documented to bind various metal ions, including alkaline earth metals, Al(ni) and transition metals VO(II), Cr(III), Mn(II), Fe(II/III), Co(II), Ni(II), Cu(II) and Zn(II) . TC can form 2 1 TC-metal complexes with transition metal ions in non-aqueous solution, in which the metal is bound at the 2-amido and 3-enolate chelating sites . TCs are present in plasma mainly in the Ca(II)-bound form or Mg(n)-bound form to a lesser extent, when they are not bound to proteins such as serum albumin. Thus, the bioavailability of TCs should be dependent upon the physical and biochemical properties of their metal complexes instead of their metal-free form. 

Stereochemically stable sec-alcohols can be racemized via an oxidation-reduction sequence catalyzed by (transition) metal complexes based on Al, Ru, Rh, and Ir [218, 219]. More labile allylic alcohols could be racemized using a vanadium-catalyst [220]. However, both racemization techniques have their potential pitfalls, since transition metal complexes may cause enzyme deactivation, whose biochemical mechanism is only poorly understood. Furthermore, some transition metal complexes are incompatible with the commonly used enol esters serving as acyl donors. 

One of the standard methods for preparing enantiomerically pure compounds is the enantioselective hydrogenation of olefins, a,/3-unsaturated amino acids (esters, amides), a,/3-unsaturated carboxylic acid esters, enol esters, enamides, /3- and y-keto esters etc. catalyzed by chiral cationic rhodium, ruthenium and iridium complexes ". In isotope chemistry, it has only been exploited for the synthesis of e.p. natural and nonnatural H-, C-, C-, and F-labeled a-amino acids and small peptides from TV-protected a-(acylamino)acrylates or cinnamates and unsaturated peptides, respectively (Figure 11.9). This methodology has seen only hmited use, perhaps because of perceived radiation safety issues with the use of hydrogenation procedures on radioactive substrates. Also, versatile alternatives are available, including enantioselective metal hydride/tritide reductions, chiral auxiliary-controlled and biochemical procedures (see this chapter. Sections 11.2.2 and 11.3 and Chapter 12). 

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