Amino acids ternary metal complexes

Table XIX contains stability constants for complexes of Ca2+ and of several other M2+ ions with a selection of phosphonate and nucleotide ligands (681,687-695). There is considerably more published information, especially on ATP (and, to a lesser extent, ADP and AMP) complexes at various pHs, ionic strengths, and temperatures (229,696,697), and on phosphonates (688) and bisphosphonates (688,698). The metal-ion binding properties of cytidine have been considered in detail in relation to stability constant determinations for its Ca2+ complex and complexes of seven other M2+ cations (232), and for ternary M21 -cytidine-amino acid and -oxalate complexes (699). Stability constant data for Ca2+ complexes of the nucleosides cytidine and uridine, the nucleoside bases adenine, cytosine, uracil, and thymine, and the 5 -monophosphates of adenosine, cytidine, thymidine, and uridine, have been listed along with values for analogous complexes of a wide range of other metal ions (700). Unfortunately comparisons are sometimes precluded by significant differences in experimental conditions.

Type IV includes chiral phases that usually interact with the enantiomeric analytes through the formation of metal complexes. There are usually used to separate amino acid enantiomers. These types of phases are also called ligand exchange phases. The transient diastereomeric complexes are ternary metal complexes between a transitional metal (usually Cu +), an amino acid enantiomeric analyte, and another compound immobilized on the CSP which is able to undergo complexation with the transitional metal (see also the ligand exchange section. Section 22.5). The two enantiomers are separated based on the difference in the stability constant of the two diastereomeric species. The mobile phases used to separate such enantiomeric analytes are usually aqueous solutions of copper (II) salts such as copper sulfate or copper acetate. To modulate the retention, several parameters—such as the pH of the mobile phase, the concentration of the copper ion, or the addition of an organic modifier such as acetonitrile or methanol in the mobile phase—can be varied. 

Schiff base formation between pyridoxal (140) and amino acids leads to complexes of type (141) which are in tautomeric equilibrium with (142). This tautomeric equilibrium leads to transamination, thus the same metal complexes can be obtained when either pyridoxal and alanine or pyridoxamine and pyruvic acid are allowed to react together in the presence of a metal ion. Hopgood" has studied the rates of transamination of 15 amino acids in the presence of zinc(II) and pyridoxal 5-phosphate (143). On mixing the reagents zinc(II)-aldimine complexes are rapidly formed (ca. 5 min) and these species subsequently transaminate in a slow second step. Ai" and Zn" systems have been particularly well studied.The role of the metal ion seems to involve both stabilization or trapping of the Schiff base, and in addition it also ensures the planarity of the conjugated ir-system. In the case of the aldimine tautomer, extensive H NMR studies have shown that formation of the ternary complex results in activation at the amino acid 2-carbon. At room temperature the reaction occurs without incorporation of into the aldehyde methine position indicating that the primary mechanism is carbanion formation rather than tautomerism. 

In more recent years attention has turned from studying the equilibria of binary metal-amino acid complexes to that of ternary complex formation in aqueous media, particularly to complexes of the type (aa)—M11—L, where L is some other ligand or a different amino acid to (aa), and M11 is a kinetically labile metal ion. Ternary complexes involving kinetically inert metal ions, e.g. Co,w and Pt", are more well known since they can be separated from mixtures and studied in isolation. Such is not the case with the labile systems. Because of the facile nature of their equilibria they must be studied in situ (claims regarding the separation of labile species by chromatographic procedures... 

An interesting correlation has been observed53 between the formation constant XCuL of the metal complex and its catalytic activity in a mixed ligand with an amino acid ester. Large values of XCUL (equation 13) lead to lower base hydrolysis rates in the ternary complex. The Lewis... 

Enantioselective metal chelation is a technique that has been applied to the separation of amino acid enantiomers. In the method, a transition metal-amino acid complex, such as copper(II)-aspartame, in which the full coordination of the complex has not been reached, is added to the buffer. The amino acid enantiomers are able to form ternary diastereomeric complexes with the metal-amino acid additive if there are differences in stability between the two complexes, enantioselective recognition can be achieved. 

Chiral ligand-exchange chromatography is based on the formation of diastereomeric ternary complexes that involve a transition metal ion (M), usually copper II a single enantiomer of a chiral molecule (L), usually an amino acid and the eitantiomers of the racemic solute R and S). The diastereomeric mixed chelate complexes formed in this system are represented by the formulas L-M-R and L-M-S. When these complexes have different stabilities, the less stable complex is eluted first, and the enantiomeric solutes are separated. 

The most important technique for enantiomeric separation in TLC is chiral ligand-exchange chromatography (LEC). LEC is based on the copper(II) complex formation of a chiral selector and the respective optical antipodes. Differences in the retention of the enantiomers are caused by dissimilar stabilities of their diastereomeric metal complexes. The requirement of sufficient stability of the ternary complex involves five-membered ring formation, and compounds such as a-amino and a-hydroxy-acids are the most suitable. 

There has been considerable interest in the chemistry of ternary complexes of copper(II) containing a bidentate aromatic nitrogen base such as 1,10-phen-anthroline (phen) or 2,2,-bipyridine (bpy) and a bidentate oxygen donor ligand or an amino acid,1 6 as some of these could possibly serve as models for enzyme-metal ion-substrate complexes. Two procedures are described below for the convenient, high-yield preparation of two such complexes. 

IV Formation of diastereomer ternary complexes involving a transition metal ion and a single enantiomer ligand (usually an amino acid)... 

Since histidine is perhaps the most frequently found and most important metal-binding site in biological systems, the CD spectra of ternary Cu(II) complexes containing L-histidine along with a second amino acid have been studied (Yamauchi et al, 1979). In neutral solution, they all show positive extrema at 630-620 nm. The Cu(II)-L-histidine complex itself has a large positive peak at around 680 nm. The CD spectral behavior of ternary Cu(II) complexes containing a variety of aliphatic amino acids has been discussed (Yamauchi et al, 1975 Sakurai et al, 1976a,b). 

Chiral ligand-exchange chromatography is based on the formation of diastereomeric ternary complexes that involve a transition metal ion, chiral ligand, and the amino acid enantiomers. Among transition metals, Cu(II) formed the most stable complexes... 

Kanekiyo, Y., Aizawa, S., Koshino, N., and Funahashi, S. (2000) Complexation equilibria of oxy-acid-2-amino-2-deoxy-D-gluconic acid-metal(II) ion ternary systems in aqueous solution as studied by poten-tiometry. Binding characteristics of borate and germanate. Inorg. Chim. Acta, 298, 154-164. 

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