Mechanistic Insights from Model Studies

One of the principal objectives of model catalyst studies is to relate observed changes in the structure, con sition, and size of single crystallites or of small collections of crystallites to mechanisms of sintering and redispersion. It may be possible under favcaable circumstances to observe direcdy mechanistic processes such as crystallite migration and spreading. In this section, mechanistic evidence frtan model catalysts studies is Hcsented and discussed. 

Evidence for particle migration of Pt on oxide supports is provided by three relatively recent studies. And and coworkers used in situ TEM to examine the sintering in vacuum of Pt on model alumina, silica, and carbon. They observed that at temperatures of 873 to 1023 

1 Decrease of a large particle nearby smaller particles 

The dashed arrows indicate the possible direction of particle migration or Ostwald ripening, and the crosses indicate the original position of the particles that have disappeared. 

Particle extension. Particles have a torus shape and a film appears to fill in the cavity. 

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Mechanistic Insight from Kinetic Studies on the Interaction of Model Palladium(II) Complexes with Nucleic Acid Components Tobias Rau and Rudi van Eldik... 

This chapter represents an update to the previous two editions, published in 19771 and 19892, and covers the literature of the period 1989-1994 with some references to 1995 papers. It deals mainly with electrophilic additions across the C=C, C=Si and Si=Si bonds and includes both theoretical (ab initio calculations, orbital approach, molecular modelling etc.) and experimental aspects. Particular attention is paid to mechanistic studies, facial selectivity and neighbouring group participation. Synthetic utilization of electrophilic addition is discussed only if including substantial mechanistic insight purely synthetic work is not covered. Aside from the classical reactions, such as hydration, bromination etc., newly included material comprises aziridination (Section VI), attack at C=C bond by an electron-deficient carbon (Section VII) and those electrophilic reactions which utilize a transition or non-transition metal as the electrophile (Section VIII). 

Lung cell cultures can provide mechanistic insights but they do not represent the complexity in the delivery and disposition of drugs in the human respiratory tract. Perfused lung organ studies provide the next level in complexity. Various animal models have been used with the view to predict quantitatively absorption of peptides and proteins from the human lungs. However, due to the major differences in the anatomy and physiology of respiration in primates, the predictive power of these models is quite limited as evidenced by the data in Fig. 2. (Animal models are, of course, essential in the assessment of safety and they can provide valuable mechanistic information.)... 

Observations from model catalyst studies reported in the last 10 years are summarized in Table 3. They provide confirmation of many of the conclusions reached in earlier studies regarding the complex mechanistic nature of sintering and redispersion processes [1,2] as well as new direct insights into sintering and redispersion mechanisms. Some important fundamental observations and principles that follow from this work include the following ... 

It has recently been discovered that immune modulating biologic agents can induce DIAI in a small percentage of patients (Pichler 2006 Weber 2004). Currently, there are no animal models to study the mechanism of these diseases, and, as a result, mechanistic insight into the role of cytokines has been derived from animal models of idiopathic SLE. 

A preliminary and essential step in a QSAR study is to evaluate the database to identify any outliers and hidden patterns, trends, and major groupings. Outliers refer to certain members of the database exhibiting mechanistic behaviors so different that the outlier cannot belong to the bulk of the data. Selecting suitable molecular descriptors, whether they are theoretical or empirical or are derived from readily available experimental characteristics of the structures, is an important step in the development of sound QSAR models. Many descriptors reflect simple molecular properties and thus can provide insight into the physicochemical nature of the activity or property under consideration. 

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