Intrinsic activity measurements

Intrinsic Activity Measurements. Measurement of the intrinsic reaction rate is a standard test to characterize prereforming catalysts. The catalyst is exposed to steam... 

Notes aEffects measured in CHO p-5 cells transfected with the h-D2 receptor. Intrinsic activity measured relative to the full agonist quinpirole. In cases with less than 20% increase, blockade of quinpirole effects were measured to determine IC50. 

The term intrinsic activity (ia) was defined as a measure of the abiUty of the dmg—receptor complex to generate response. When ia = 1, a full agonist is defined when ia = 0, an antagonist is defined. Thus, values 0 < ia < 1 define partial agonists as follows, where R is the response to dmg and R is the maximum response achieved. 

Figure 10 shows that Tj is a unique function of the Thiele modulus. When the modulus ( ) is small (- SdSl), the effectiveness factor is unity, which means that there is no effect of mass transport on the rate of the catalytic reaction. When ( ) is greater than about 1, the effectiveness factor is less than unity and the reaction rate is influenced by mass transport in the pores. When the modulus is large (- 10), the effectiveness factor is inversely proportional to the modulus, and the reaction rate (eq. 19) is proportional to k ( ), which, from the definition of ( ), implies that the rate and the observed reaction rate constant are proportional to (1 /R)(f9This result shows that both the rate constant, ie, a measure of the intrinsic activity of the catalyst, and the effective diffusion coefficient, ie, a measure of the resistance to transport of the reactant offered by the pore stmcture, influence the rate. It is not appropriate to say that the reaction is diffusion controlled it depends on both the diffusion and the chemical kinetics. In contrast, as shown by equation 3, a reaction in solution can be diffusion controlled, depending on D but not on k. 

Before deriving the rate equations, we first need to think about the dimensions of the rates. As heterogeneous catalysis involves reactants and products in the three-dimensional space of gases or liquids, but with intermediates on a two-dimensional surface we cannot simply use concentrations as in the case of uncatalyzed reactions. Our choice throughout this book will be to express the macroscopic rate of a catalytic reaction in moles per unit of time. In addition, we will use the microscopic concept of turnover frequency, defined as the number of molecules converted per active site and per unit of time. The macroscopic rate can be seen as a characteristic activity per weight or per volume unit of catalyst in all its complexity with regard to shape, composition, etc., whereas the turnover frequency is a measure of the intrinsic activity of a catalytic site. 

Here, [R]T is the total concentration of receptors, and e (epsilon) is the intrinsic efficacy (not to be confused with intrinsic activity) e can be regarded as a measure of the contribution of individual receptors to the overall efficacy. 

All copolymers were prepared by solution polymerization, under adiabatic conditions, giving at least 99.9% conversions. The polymer gels were granulated and then dried at 90 °C to a residual water content of 10 to 12%. The active polymer content of each sample was calculated from the initial weight of the comonomers and the weight of the dried gel. Hydrolysis of the polymers was determined by conductometric titration to be less than 0.2% of the acrylamide charge. The molecular weight of the polymers was 8-10 million as determined by intrinsic viscosity measurements. 

Note the similarity to Langmuir-Hinshelwood kinetics.) The rate is expressed on the basis of the instantaneous number of solid carbon atoms, Nc. The rate r (measured at one gas composition) typically goes through a maximum as the carbon is converted. This is the result of a maximum in the intrinsic activity (related to the fraction of reactive carbon atoms, NCJNC) because of both a change in Nq> and a decrease in Nc. 

The activity in terms of 1st order rate constant khcalc was calculated in Table 2 from (8) and (9) with effective diffusivity Dejf=5.3-10 6 m2/s and intrinsic rate constant =33000 Nm3/h/m3 = 23 s"1 fitted to the measurements. This simple and useful method models the measured influence of particle size satisfactorily for a first optimization of particle size and shape. The 35% higher activity measured for the 9-mm Daisy compared to the 12-mm Daisy, however, exceeds the 25% expected from (8), and this illustrates the importance of measuring the activity of the actual shape. 

Ho vever this approach does not address inter-individual variability in CYP expression nor the apparent substrate specificity of RAFs. This may be overcome through the use of intersystem extrapolation factors (ISEFs) vhich compare the intrinsic activities of rCYP versus liver microsomes and provide CYP abundance scaling by mathematical means. This employs the RAF approach and adjusts for the actual amount of liver microsomes CYP present (measured by immunochemistry) rather than a theoretical amount (Equation 8.4). Such corrections can be made using nominal specific contents of individual CYP proteins in liver microsomes or more appropriately employ modeling and simulation software (e.g., SIMCYP www.simcyp.com) which takes into account population-based variability in CYP content. 

Aside from this concern, a prospective user should ascertain what precision level he / she needs and what structural features can be included while retaining that precision. In some research, the estimation of the relative hydrophobicity of a set of analogs is crucial, but the absolute values need not be precise. For instance, if one wants to know if hydrophobicity contributes to the activity of a certain toxiphore, regression analysis using a calculated log P can provide an answer even if the parent is mispredicted, as long as all of the analogs deviate by this same amount. Of course, the equation intercept, which is a measure of intrinsic activity, is then in error. 

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