Biological systems general considerations

So far, as in Equation (3.33), the hydrolyses of ATP and other high-energy phosphates have been portrayed as simple processes. The situation in a real biological system is far more complex, owing to the operation of several ionic equilibria. First, ATP, ADP, and the other species in Table 3.3 can exist in several different ionization states that must be accounted for in any quantitative analysis. Second, phosphate compounds bind a variety of divalent and monovalent cations with substantial affinity, and the various metal complexes must also be considered in such analyses. Consideration of these special cases makes the quantitative analysis far more realistic. The importance of these multiple equilibria in group transfer reactions is illustrated for the hydrolysis of ATP, but the principles and methods presented are general and can be applied to any similar hydrolysis reaction. 

In general, the performance of any polymeric drug delivery system is highly dependent on both the therapeutic result desired and the milieu in which the system must operate. Both of these considerations are set by the interaction between the delivery system and the biological system in which it must operate. Most drug delivery systems, then, are intended to achieve one of the following three goals ... 

Nevertheless, fluoride does lead to a reduction in the solubility of hydroxyapatite in aqueous solution, even in the absence of trace levels of fluoride in solution, and hence can be seen to have an effect in the solid state as well [57], Apatites are complex and diverse materials which have the general formula Caio(P04)eX2 (X = F, Cl, OH) and they represent a crystallographic system, in which there can be considerable replacement of species. Thus, with little or no change in the dimensions of the crystal lattice, there can be exchanges of OH for F, Ca + for Sr +, and PO4 for CO and all of these are known to occur in biological systems. Natural hydroxyapatite, for example, is often partially carbonate substituted [58]. 

A considerable body of evidence has appeared which indicates that the receptor site in an enzyme may be located in a very flexible pocket, and that protein molecules in general can show a startlingly large degree of conformational flexibility. This does not affect the nature of steric effects in biological systems. Excluding steric effects in the transport step of bioactivity (2.1) we may divide the steric effect into two components ... 

Type of Service. The type of service—quality assurance, methods development, or routine testing—for each instrument or laboratory is a general consideration, as is the question of whether several types of service will be required of the system. A quality assurance laboratory associated with a chemicals production facility has far simpler needs in terms of analytical capability than a methods development laboratory or one that normally analyzes biological samples for pharmacologically active compounds at sub-ppm or even ppb concentrations. On the other hand, the data storage and reduction needs of a quality assurance laboratory are usually much more pressing than those of a methods development laboratory. 

The iron porphyrins and related compounds constitute an extremely important class of coordination complex due to their chemical behaviour and involvement in a number of vital biological systems. Over recent years a vast amount of work on them has been published. Chapter 21.1 deals with the general coordination chemistry of metal porphyrins, hydroporphyrins, azaporphyrins, phthalocyanines, corroles, and corrins. Low oxidation state iron porphyrin complexes are discussed in Section 44.1.4.5 and those containing nitric oxide in Section 44.1.4.7, while a later section in this chapter (44.2.9.2) is mainly concerned with iron(III) and higher oxidation state porphyrin complexes. Inevitably however, a considerable amount of information on iron(II) complexes is contained in that section as well as in Chapter 21.1. Therefore in order to prevent excessive duplication, the present section is restricted to highlighting some of the more important aspects of the coordination chemistry of the iron(II) porphyrins while the related unusually stable phthalocyanine complexes are discussed in the previous section. 

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