Copper tryptophanate

Crystal stmctures of complexes of copper(II) with aromatic amine ligands and -amino acids " " and dipeptides" have been published. The stmctures of mixed ligand-copper complexes of L-tryptophan in combination with 1,10-phenanthroline and 2,2 -bipyridine and L-tyrosine in combination with 2,2 -bipyridine are shown in Figure 3.2. Note the subtle difference between the orientation of the indole ring in the two 1,10-phenanthroline complexes. The distance between the two... 

In contrast, investigation of the effect of ligands on the endo-exo selectivity of the Diels-Alder reaction of 3.8c with 3.9 demonstrated that this selectivity is not significantly influenced by the presence of ligands. The effects of ethylenediamine, 2,2 -bipyridine, 1,10-phenanthroline, glycine, L-tryptophan and L-abrine have been studied. The endo-exo ratio observed for the copper(II)-catalysed reaction in the presence of these ligands never deviated more than 2% from the endo-exo ratio of 93-7 obtained for catalysis by copper aquo ion. 

First, the pH-dependence of the enantioselectivity of the reaction between 3.8c and 3.9 catalysed by the copper(L-tryptophan) complex has been studied. Above pH 5 the enantioselectivity reaches a plateau value (Figure 3.3). The diminished enantioselectivities observed at lower pH most likely... 

Likewise, the influence of the ligand catalyst ratio has been investigated. Increase of this ratio up to 1.75 1 resulted in a slight improvement of the enantioselectivity of the copper(L-tryptophan)-catalysed Diels-Alder reaction. Interestingly, reducing the ligand catalyst ratio from 1 1 to 0.5 1 resulted in a drop of the enantiomeric excess from 25 to 18 % instead of the expected 12.5 %. Hence, as anticipated, ligand accelerated catalysis is operative. 

Figure 3.5. Gibbs energies of complexation of 3.8a-g to the copper(II)(Lr tryptophan) complex versus those for complexation to copper aquo ion.

Among the many chiral Lewis acid catalysts described so far, not many practical catalysts meet these criteria. For a,/ -unsaturated aldehydes, Corey s tryptophan-derived borane catalyst 4, and Yamamoto s CBA and BLA catalysts 3, 7, and 8 are excellent. Narasaka s chiral titanium catalyst 31 and Evans s chiral copper catalyst 24 are outstanding chiral Lewis acid catalysts of the reaction of 3-alkenoyl-l,2-oxazolidin-2-one as dienophile. These chiral Lewis acid catalysts have wide scope and generality compared with the others, as shown in their application to natural product syntheses. They are, however, still not perfect catalysts. We need to continue the endeavor to seek better catalysts which are more reactive, more selective, and have wider applicability. 

Another important function of albumin is its ability to bind various ligands. These include free fatty acids (FFA), calcium, certain steroid hormones, bilirubin, and some of the plasma tryptophan. In addition, albumin appears to play an important role in transport of copper in the human body (see below). A vatiety of drugs, including sulfonamides, penicilhn G, dicumarol, and aspirin, are bound to albumin this finding has important pharmacologic implications. 

Ishimura Y, R Makino, R Ueno, K Sakaguchi, FO Brady, P Feigelson, P Aisen, O Hayaishi (1980) Copper is not essential for the catalytic activity of L-tryptophan 2,3-dioxygenase. J Biol Chem 255 3835-3837. 

Oxygenation and hydroxylation of a wide variety of biological materials almost always involves the participation of a metal ion, usually iron and sometimes copper. In one unique case, tryptophane pyrrolase, the iron is present as heme (75). The only dioxygenase enzyme reaction in which a metal ion has not been implicated is one involved in the degradation of vitamin B6 (16). 

Otto et al. studied asymmetric Diels-Alder reactions in the presence of the copper salts of glycine, L-valine, L-leucine, L-phenylalanine, L-tyrosine, l-tryptophan, and /V-a-L-tryptophan (L-abrine). The copper salt of L-abrine gave the highest enantioselectivity. Table 5 3 compares the solvent effect in this reaction, and clearly water is the best solvent among the solvent systems studied. 

Copper(II) complexes of amino acids have been explored as chiral Lewis acid catalysts in the Diels-Alder reaction of 3-phenyl-l-(2-pyridyl)-2-propen-l-one with cyclopentadiene. The best results were obtained using /V-methyl-/.-tryptophan, but more interestingly, the highest ee values for the major endo adduct were achieved in aqueous solution273. 

Plastocyanin from parsley, a copper protein of the chloroplast involved in electron transport during photosynthesis, has been reported to have a fluorescence emission maximum at 315 nm on excitation at 275 nm at pH 7 6 (2°8) gjncc the protein does not contain tryptophan, but does have three tyrosines, and since the maximum wavelength shifts back to 304 nm on lowering the pH to below 2, the fluorescence was attributed to the emission of the phenolate anion in a low-polarity environment. From this, one would have to assume that all three tyrosines are ionized. A closer examination of the reported emission spectrum, however, indicates that two emission bands seem to be present. If a difference emission spectrum is estimated (spectrum at neutral pH minus that at pH 2 in Figure 5 of Ref. 207), a tyrosinate-like emission should be obtained. 

Some tryptophans do not exhibit phosphorescence because of quenching by specific sites from within the protein. The absence of phosphorescence could be due to quenching of either the singlet state or the triplet state. For example, in horse heart cytochrome c the tryptophan is adjacent to the heme, and its fluorescence is quenched by Forster transfer to the heme. Since the singlet state is populating the triplet state, the lack of observable phosphorescence is likely to be due to an unpopulated triplet state. Another example where the redox center of the protein interacts with the tryptophan excited states is found in azurin. The copper(II) quenches both the singlet and triplet states.(28)... 

Among protein aromatic groups, histidyl residues are the most metal reactive, followed by tryptophan, tyrosine, and phenylalanine.1 Copper is the most reactive metal, followed in order by nickel, cobalt, and zinc. These interactions are typically strongest in the pH range of 7.5 to 8.5, coincident with the titration of histidine. Because histidine is essentially uncharged at alkaline pH, complex-ation makes affected proteins more electropositive. Because of the alkaline optima for these interactions, their effects are most often observed on anion exchangers, where complexed forms tend to be retained more weakly than native protein. The effect may be substantial or it may be small, but even small differences may erode resolution enough to limit the usefulness of an assay. 

Cytochrome c oxidase contains one heme a and one heme a, besides two copper atoms Cu EPR detectable when oxidized and CUj EPR undetectable With L-tryptophan 2,3-dioxygenase (EC 1.13.11.11), another heme protein, it has been... 

The reaction that leads to BCA color formation as a result of the reduction of Cu2+ is also strongly influenced by the presence of any of four amino acid residues (tyrosine, tryptophan, cysteine, or cystine) in the amino acid sequence of the protein. Unlike the Coomassie dye-binding (Bradford) methods, which require a minimum mass of protein to be present for the dye to bi nd, the presence of only a single amino acid residue in the sample may result in the formation of a colored BC A-Cu+ chelate. This is true for any of the four amino acids cited above. Studies done with di- and tripeptides indicate that the total amount of color produced is greater than can be accounted for by the simple addition of the color produced with each BCA-reactive amino acid, so the peptide backbone must contribute to the reduction of copper as well. 

Starting at the far left, we see a water molecule, two common amino acids, alanine and tryptophan, a segment of a DNA double helix, a segment of a protein single helix, and the folded polypeptide chain of the enzyme copper, zinc superoxide dismutase or SOD. 

NBD-amino acids (serine, threonine, valanie, phenylalanine, and histidine) were separated by using a 20 mM ammonium acetate buffer (pH 9.0) containing 10 mM copper acetate, 20 mM L-prolinamide, and 1 mM SDS. The elution order was the L-enantiomer followed by the D-form except in NBD-histidine. Weng et al. [32] described chiral separation of tryptophan on a poly(methyl methacrylate) microfluidic chip coated with bovine serum albumin (32 mm... 

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