Structure-kinetic relationships

Quantitative structure-kinetics relationships (QSKRs) can deconstructed using one-compartment, first-order kinetics constants and a molecular descriptor. 

Equations 3 to 5 employ first-order, one-compartment kinetics constants where k, is the uptake constant, k-2 is the elimination constant, both in units of day", and T.,/2 is the half-life of elimination in days. These kinetics constants, derived from time-toxicity data, were regressed, via the geometric mean functional regression method, against log KQyj, producing a quantitative structure-kinetics relationship (QSKR) which is analogous to a QSAR. 

The essence of this limited preliminary study is that the one-compartment, first-order kinetics constants derived from toxicity data and converted to their equivalent bioconcentration-based kinetics values appears to be similar to bioconcentration-based data collected directly from bioconcentration studies. The basis for this similarity is a comparison based on a variation of OSAR approach the quantitative structure-kinetics relationships or QSKR. The QSKR approach, in this case the geometric mean regression relating log Kqw and log T,/2- produces regression coefficients of approximately +1.0 for both corrected toxicity-based and original bioconcentration-based data. 

A substantial body of data, including reaction kinetics, isotope effects, and structure-reactivity relationships, has permitted a thorough understanding of the steps in aromatic nitration. As anticipated from the general mechanism for electrophilic substitution, there are three distinct steps ... 

Structure-reactivity relationships can be probed by measurements of rates and equiUbria, as was diseussed in Chapter 4. Direct comparison of reaction rates is used relatively less often in the study of radical reactions than for heterolytic reactions. Instead, competition methods have frequently been used. The basis of competition methods lies in the rate expression for a reaction, and the results can be just as valid a comparison of relative reactivity as directly measured rates, provided the two competing processes are of the same kinetic order. Suppose that it is desired to compare the reactivity of two related compounds, B—X and B—Y, in a hypothetical sequence ... 

After an introductory chapter, phenomenological kinetics is treated in Chapters 2, 3, and 4. The theory of chemical kinetics, in the form most applicable to solution studies, is described in Chapter 5 and is used in subsequent chapters. The treatments of mechanistic interpretations of the transition state theory, structure-reactivity relationships, and solvent effects are more extensive than is usual in an introductory textbook. The book could serve as the basis of a one-semester course, and I hope that it also may be found useful for self-instruction. 

Nishioka and Fujita78) have also determined the Kd values fora- and (S-cyclodextrin complexes with p- and/or m-substituted phenyl acetates through kinetic investigations on the alkaline hydrolysis of the complexes. The Kd values obtained were analyzed in the same manner as those for cyclodextrin-phenol complexes to give the Kd(X) values (Table 5). The quantitative structure-activity relationships were formulated as Eqs. 30 to 32 ... 

Secondly, new techniques have been developed which allow a more detailed characterization of both polymer microstructures and the kinetics and mechanism of polymerizations. This has allowed mechanism-structure-property relationships to be more rigorously established. 

The fundamental understanding of the diazonio group in arenediazonium salts, and of its reactivity, electronic structure, and influence on the reactivity of other substituents attached to the arenediazonium system depends mainly on the application of quantitative structure-reactivity relationships to kinetic and equilibrium measurements. These were made with a series of 3- and 4-substituted benzenediazonium salts on the basis of the Hammett equation (Scheme 7-1). We need to discuss the mechanism of addition of a nucleophile to the P-nitrogen atom of an arenediazonium ion, and to answer the question, raised several times in Chapters 5 and 6, why the ratio of (Z)- to ( -additions is so different — from almost 100 1 to 1 100 — depending on the type of nucleophile involved and on the reaction conditions. However, before we do that in Section 7.4, it is necessary to give a short general review of the Hammett equation and to discuss the substituent constants of the diazonio group. 

Apart from mode of action and kinetics of wild type enzymes structure function relationships of these industrially important enzymes is of high interest to provide the necessary knowledge for genetic engineering of desired properties. As a first approach the identification of catalytically important residues was addressed in conjunction with the elucidation of the three dimensional structure [15]. 

In this chapter, the voltammetric study of local anesthetics (procaine and related compounds) [14—16], antihistamines (doxylamine and related compounds) [17,22], and uncouplers (2,4-dinitrophenol and related compounds) [18] at nitrobenzene (NB]Uwater (W) and 1,2-dichloroethane (DCE)-water (W) interfaces is discussed. Potential step voltammetry (chronoamperometry) or normal pulse voltammetry (NPV) and potential sweep voltammetry or cyclic voltammetry (CV) have been employed. Theoretical equations of the half-wave potential vs. pH diagram are derived and applied to interpret the midpoint potential or half-wave potential vs. pH plots to evaluate physicochemical properties, including the partition coefficients and dissociation constants of the drugs. Voltammetric study of the kinetics of protonation of base (procaine) in aqueous solution is also discussed. Finally, application to structure-activity relationship and mode of action study will be discussed briefly. 

Gammeltoft, S., Insulin receptors binding kinetics and structure-function relationship of insulin, Physiol. Rev., 64, 1321-1378, 1984. 

The crystallization kinetics of commercial polyolefins is to a large extent determined by the chain microstructure [58-60]. The kinetics and the regime [60] of the crystallization process determine not only the crystalline content, but also the structure of the interfaces of the polymer crystals (see also Chapter 7). This has a direct bearing on the mechanical properties like the modulus, toughness, and other end use properties of the polymer in fabricated items such as impact resistance and tear resistance. Such structure-property relationships are particularly important for polymers with high commercial importance in terms of the shear tonnage of polymer produced globally, like polyethylene and polyethylene-based copolymers. It is seen that in the case of LLDPE, which is... 

Skovsgaard, T., Stein, W. D., Structure—activity relationships of P-glycoprotein interacting drugs kinetic characterization of their effects on ATPase activity, Biochim. Biophys. Acta... 

For stilbene bromination, a markedly non-linear structure-reactivity relationship is observed (Fig. 5). Detailed analysis of the kinetic effects of two substituents, X and Y, on each aromatic ring shows that the three pathways leading to the C+ and carbocations and to the bromonium ion can... 

Atkinson, R. (1987) A structure-activity relationship for the estimation of the rate constants for the gas phase reactions of OH radicals with organic compounds. Int. J. Chem. Kinetics 19, 790-828. 

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