Metal complexes, inhibition

In contrast to the effects obtained with viruses mentioned earlier, rous sarcoma virus (RSV) is inactivated by direct contact with 2 [81]. Evidence for the drug action by a chelate compound was obtained by using concentrations of 3a and copper(II) sulfate, neither of which individually affected enzyme activity or transforming abilities [82]. In a later study these workers showed that several metal complexes inhibit the RNA dependent DNA polymerases and the transforming ability of RSV, the most active compound being a 1 1 copper(II)... 

In vitro, cydopentadienyl metal complexes were able to suppress the proliferation of normal or transformed tumor cells. Best activity was found for vanadocene dichloride in this respect. In vivo, numerous of the cydopentadienyl metal complexes inhibited the development of diverse experimental animal tumors (e.g., Ehrlich asdtes tumor, sarcoma 180, B16 melanoma, colon 38 cardnoma and Lewis lung cardnoma) and the growth of human cardnomas xenografted to nude mice. Espedally certain titanocene and ferricenium compoimds were cytostatically effective against human colorectal cardnomas. Moreover, titanocene complexes were shown to be antiviral agents and potent antiinflammatory compounds comparable to phenylbutazone. 

Other radical reactions not covered in this chapter are mentioned in the chapters that follow. These include additions to systems other than carbon-carbon double bonds [e.g. additions to aromatic systems (Section 3.4.2.2.1) and strained ring systems (Section 4.4.2)], transfer of heteroatoms [eg. chain transfer to disulfides (Section 6.2.2.2) and halocarbons (Section 6.2.2.4)] or groups of atoms [eg. in RAFT polymerization (Section 9.5.3)], and radical-radical reactions involving heteroatom-centered radicals or metal complexes [e g. in inhibition (Sections 3.5.2 and 5.3), NMP (Section 9.3.6) and ATRP (Section 9.4)]. 

Keppler BK, Friesen C, Moritz HG, Vongerichten H, Vogel E (1991) Tumor-Inhibiting Bis (/1-Diketonato) Metal Complexes. Budotitane, cis-Diethoxybis (l-phenylbutane-1,3-dionato) titanium (IV). 78 97-128... 

The interactions between metals and supports in conventional supported metal catalysts have been the focus of extensive research [12,30]. The subject is complex, and much attention has been focused on so-called strong metal-support interactions, which may involve reactions of the support with the metal particles, for example, leading to the formation of fragments of an oxide (e.g., Ti02) that creep onto the metal and partially cover it [31]. Such species on a metal may inhibit catalysis by covering sites, but they may also improve catalytic performance, perhaps playing a promoter-like role. 

Since variable-valence metals catalyze the decomposition of ROOH into radicals, autoxidation in the presence of these metals is inhibited by the respective complexing agents. 

Another situation is observed when salts or transition metal complexes are added to an alcohol (primary or secondary) or alkylamine subjected to oxidation in this case, a prolonged retardation of the initiated oxidation occurs, owing to repeated chain termination. This was discovered for the first time in the study of cyclohexanol oxidation in the presence of copper salt [49]. Copper and manganese ions also exert an inhibiting effect on the initiated oxidation of 1,2-cyclohexadiene [12], aliphatic amines [19], and 1,2-disubstituted ethenes [13]. This is accounted for, first, by the dual redox nature of the peroxyl radicals H02, >C(0H)02 and >C(NHR)02 , and, second, for the ability of ions and complexes of transition metals to accept and release an electron when they are in an higher- and lower-valence state. 

As mentioned above, in contrast to classic antioxidant vitamins E and C, flavonoids are able to inhibit free radical formation as free radical scavengers and the chelators of transition metals. As far as chelators are concerned their inhibitory activity is a consequence of the formation of transition metal complexes incapable of catalyzing the formation of hydroxyl radicals by the Fenton reaction. In addition, as shown below, some of these complexes, for example, iron- and copper-rutin complexes, may acquire additional antioxidant activity. 

Reversible inhibition caused by materials that can function as ligand. Many compounds will bind to a metal this might be the solvent or impurities in the substrate or the solvent. It can also be a functional group in the substrate or the product, such as a nitrile. Too many ligands bound to the metal complex may lead to inhibition of one of the steps in the catalytic cycle. Likely candidates are formation of the substrate-catalyst complex or the oxidative addition of hydrogen. Removal of the contaminant will usually restore the catalytic activity. 

For hydrogenation to take place, the substrate usually needs to bind to the metal complex, although exceptions are known to this rule [25]. Substrate inhibition can occur in a number of ways, for example if more than one molecule of substrate binds to the metal complex. At low concentration this may be a minor species, whereas at high substrate concentration this may be the only species. One example of this is the hydrogenation of allyl alcohol using Wilkinson s catalyst. Here, the rate dependence on the substrate concentration went through a maximum at 1.2 mmol IT1. The authors propose that this is caused by formation of a complex containing two molecules of allyl alcohol (Scheme 44.1) [26],... 

Many compounds or materials are capable of binding in a reversible fashion to a transition metal complex. If the binding is very strong, or if a large excess of the compound is present, then inhibition is likely to result. Although many examples of this phenomenon have been reported in the literature, only a few have been studied systematically. 

X. Wu, X. Li, F. King, J. Xiao, Angew. Chem. Int. Ed. 2005, 44, 3407. Surprisingly, no direct references to cyanide inhibition of hydrogenation catalysts could be found. For a general reaction showing the swift reaction of a transition metal complex with cyanide as a means to isolate the ligand, see for ex-... 

Several other metal complexes have promising photodynamic activity and are currently under development (248). Metalloporphyrins inhibit the enzyme heme oxygenase for example, chromium porphyrin and mesoporphyrin are potent inhibitors of heme oxygenase both in vitro and in vivo (249, 250) and are being used for the treatment of the neonatal jaundice. 

The 12-membered tetraamine cyclen and bicyclen have inferior anti-HIV activity and are more toxic compared to cyclams and bicyclams. However, Kimura et al. (372) have shown that complexation of the monomeric cyclen (84) to Ni(II), Cu(II), and Zn(II) reduces the toxicity and increases the anti-HIV activity. This is also true for the bicyclen (85), for which the combination of dimerization and metal complexation potentiates the inhibition against HIV-infected MOLT-4 cells (373). 

The synthesis of polyhalide salts, R4NX , used in electrophilic substitution reactions, are described in Chapter 2 and H-bonded complexed salts with the free acid, R4NHX2, which are used for example in acid-catalysed cleavage reactions and in electrophilic addition reactions with alkenes, are often produced in situ [33], although the fluorides are obtained by modification of method I.I.I.B. [19, 34], The in situ formation of such salts can inhibit normal nucleophilic reactions [35, 36]. Quaternary ammonium chlorometallates have been synthesized from quaternary ammonium chlorides and transition metal chlorides, such as IrClj and PtCl4, and are highly efficient catalysts for phase-transfer reactions and for metal complex promoted reactions [37]. 

Inhibition of a catalytic reaction by impurities present may take place and sometimes this may have a temporary character. If it is permanent one cannot be mistaken in the kinetic measurements. Impurities that are more reactive than the substrates to be studied may block the catalyst if they react according to a scheme like that of Figure 3.7. Only after all inhibitor has been converted the conversion of the desired substrate can start. Another type of deactivation that may occur is the formation of dormant states, which is very similar to inhibition. Either the regular substrate or an impurity may lead to the formation of a stable intermediate metal complex that does not react further. There are examples where such intermediates can be rescued from this dormant state for instance by the addition of another reagent such as dihydrogen (Chapter 10, dormant states in propene polymerisation). 

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