Multi-center Sites

Details of the method developed by Kissin to determine the number of different active sites and the polymerization kinetics of each type of site were published in the Handbook of Transition Metal Polymerization Catalysts [68]. Some important conclusions from this publication are summarized below. 

GPC curves obtained from ethylene homopolymers at two ethylene concentrations. 

A summary of the 1-hexene content of the polyethylene produced by each type of active site is shown in Table 2.13. 

The multicenter site analysis revealed that some of the active centers behave differently in the presence of an a-olefin such as 1-hexene. For example  

The reaction order n for each center with respect to in ethylene homopolymerization reactions was significantly greater than first order. 

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There are other trial design concepts for you to be aware of. A clinical trial can be carried out at a single site or it can be a multi-center trial. In a single-site trial all of the patients are seen at the same clinical site, and in a multi-center trial several clinical sites are used. Multi-center trials are needed sometimes to eliminate site-specific bias or because there are more patients required than a single site can enroll. 

We first consider proteins containing a single type of a copper site starting with mononuclear ones. Subsequently, binuclear sites and multi-centered copper proteins will be discussed. 

Fig. 16.17. Mechanism of the carbocupration of acetylene (R = H) or terminal alkynes (R H) with a saturated Gilman cuprate. The unsaturated Gilman cuprate I is obtained via the cuprolithiation product E and the resulting carbolithiation product F in several steps—and stereoselectively. Iodolysis of I leads to the formation of the iodoalkenes J with complete retention of configuration. Note The last step but one in this figure does not only afford I, but again the initial Gilman cuprate A B, too. The latter reenters the reaction chain "at the top" so that in the end the entire saturated (and more reactive) initial cuprate is incorporated into the unsaturated (and less reactive) cuprate (I). - Caution The organometallic compounds depicted here contain two-electron, multi-center bonds. Other than in "normal" cases, i.e., those with two-electron, two-center bonds, the lines cannot be automatically equated with the number of electron pairs. This is why only three electron shift arrows can be used to illustrate the reaction process. The fourth red arrow—in boldface— is not an electron shift arrow, but only indicates the site where the lithium atom binds next.

Figure 4-5. Points of electrochemical control in enzyme voltammetry. The voltammetry reports on the electrochemical control centre , the redox site (solid) up to which electron exchange with the electrode is fast. For single-centre redox enzymes (A), the electrochemical control centre is the active site. For multi-centered redox enzymes the electrochemical control centre may be a relay centre (B), or the active site redox group if catalysis is not impeded by the rate of intramolecular electron exchange (C). Further scenarios are also possible, as described in the text.

Another Raf kinase inhibitor, sunitinib (Sutent), was approved in 2006 based on a multi-center, international randomized trial enrolling 750 patients with treatment-naive metastatic renal cell carcinoma (Motzer et al. 2007). In that study, patients were randomized to receive either Sutent or interferon-a (IFN-a). Common metastatic sites included lung, lymph nodes, bone, and liver. There were 96 events (25.6%) of progression/death on Sutent compared with 154 events (41.1%) on IFN-a. Median progression-free survival was 47.3 weeks for Sutent-treated patients and 22.0 weeks for patients treated with IFN. Objective response rate on the Sutent arm was 27.5 vs 5.3% on IFN-a arm. 

It can be seen from Eqs. (7.100)-(7.103) that the law of multi-center TPD is not described through simulation TPD law in each site independently, especially when the energy difference between the two sites is not significant. If the energies of two sites are very different in other words, then the TPD peak is separated from each other. At this time, when desorption occurs on one site with the temperature increasing, another site with high energy does not desorb. As a result, desorption process of two sites may be treated by the method of TPD on uniform surface, respectively. 

To illustrate this point, let us discuss the following hypothetical mechanism with two reaction routes and when adsorption of multi-centered species occurs requiring a cluster of several metal surface sites ... 

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