Copper complexes biological applications

The use of chiral bis(oxazoline) copper catalysts has also been often reported as an efficient and economic way to perform asymmetric hetero-Diels-Alder reactions of carbonyl compounds and imines with conjugated dienes [81], with the main focus on the application of this methodology towards the preparation of biologically valuable synthons [82]. Only some representative examples are listed below. For example, the copper complex 54 (Scheme 26) has been successfully involved in the catalytic hetero Diels-Alder reaction of a substituted cyclohexadiene with ethyl glyoxylate [83], a key step in the total synthesis of (i )-dihydroactinidiolide (Scheme 30). 

There has been great interest in Cu(II) as a result of its role in biology, and the versatility in its available radioactive isotopes. The chemistry of bis(thiosemicarbazonato) metal complexes has received much interest over the last decade with particular interest in the copper complexes that are known blood perfusion tracers and also display hypoxic selectivity. Biomedical applications revolve around its redox chemistry (12,83-88,98-104). 

Several copper enzymes will be discussed in detail in subsequent sections of this chapter. Information about major classes of copper enzymes, most of which will not be discussed, is collected in Table 5.1 as adapted from Chapter 14 of reference 49. Table 1 of reference 4 describes additional copper proteins such as the blue copper electron transfer proteins stellacyanin, amicyanin, auracyanin, rusticyanin, and so on. Nitrite reductase contains both normal and blue copper enzymes and facilitates the important biological reaction NO) — NO. Solomon s Chemical Reviews article4 contains extensive information on ligand field theory in relation to ground-state electronic properties of copper complexes and the application of... 

In an early review, Hyde [272] discussed ENDOR in proteins, including flavo-proteins, copper proteins, hemeproteins, two-iron ferrodoxin and bacteriochloro-phyll. Kevan and Kispert s book [19] is an introductory text on ENDOR (electron nuclear double resonance) and ELDOR (electron electron double resonance) techniques. Poole [11] includes a chapter on double resonance techniques in his text. Schweiger [21] has covered ENDOR of transition metal complexes, including a section on biological applications. Recent reviews of ENDOR spectroscopy of chlorophylls [273], heme and heme proteins [274] and iron sulfur proteins [275] demonstrate how additional detail can be obtained from ENDOR data. 

Experimental antitumor agents such as streptonigrin, bisthiosemicarbazones, and perhaps monothiosemicarbazones must form iron or copper complexes to become biologically active as catalysts of oxidant damage to cells. In sum, metal-based catalysis of redox reactions in cells describes a major topic in cancer therapeutics. Nevertheless, it has remained underdeveloped as a theme for study and application. The sections below provide a coordinated review and perspective on the subject of redox-active, metal-dependent drugs in cancer chemotherapy. 

Hi. Biological Applications. Copper(II) bis(dithiocarbamate) complexes have a number of potential biological applications. For example, while dithio-carbamate salts (R = Me, Ft) are potent inhibitors of a clonogenic response in human C34 bone marrow cells, addition of copper sulfate greatly potentiates the hematotoxicity, suggesting a more general role for copper in dithiocarba-mate-induced hematotoxicity (1779). 

Willis (W12) has recently summarized the principles and applications of this method. A short note appeared recently regarding the use of atomic absorption spectrometry for serum and urine copper analysis (B15). The sensitivity of this method for copper is rather less than for such other biologically important trace metals as magnesium, zinc, and sodium. The sensitivity can be improved by extracting the copper as dithiocarbamate or pyrollidinedithiocarbamate complex (A7) into methyl isobutyl ketone. While this method is less sensitive than some others, it is nevertheless very specific and the apparatus is only moderately expensive. 

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