Biology of the Compounds

The alkyl and alkoxy substituents of phosphate or phosphonate esters also affect the phosphorylating abiUty of the compound through steric and inductive effects. A satisfactory correlation has been developed between the quantitative measure of these effects, Tafts s O, and anticholinesterase activity as well as toxicity (33). Thus long-chain and highly branched alkyl and alkoxy groups attached to phosphoms promote high stabiUty and low biological activity. 

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

The proportion of ionized and unionized forms of a chemical compound can be readily calculated according to the above equation. It can be easily seen that pK is also a pH value at which 50% of the compound exists in ionized form. The ionization of weak acids increases as the pH increases, whereas the ionization of weak bases increases when the pH decreases. As the proportion of an ionized chemical increases, the diffusion of the chemical through the biological membranes is greatly impaired, and this attenuates toxicokinetic processes. For example, the common drug acetosalicylic acid (aspirin), a weak acid, is readily absorbed from the stomach because most of its dose is in an unionized form at the acidic pH of the stomach. 

After absorption, a chemical compound enters the circulation, which transfers it to all parts of the body. After this phase, the most important factor affecting the distribution is the passage of the compound through biological membranes. From the point of view of the distribution of a chemical compound, the organism can be divided into three different compartments (1) the plasma compartment (2) the intercellular compartment and (3) the intracellular compartment. In all these compartments, a chemical compound can be bound to biological macromolecules. The proportion of bound and unbound (free) chemical compound depends on the characteristics of both the chemical... 

From a practical point of view, saturation of elimination has important consequences. If the metabolism becomes saturated, the duration of the action of the compound is prolonged. In such a case, correct timing for collection of biological monitoring samples also becomes difficult to assess. Furthermore, saturation of metabolism may also have qualitative effects. For example, it has been argued (but not yet proved) that arsenic compounds cause cancer at high doses at which methylation of inorganic arsenic becomes saturated. ... 

Unquestionably, most practical planar chromatographic (PC) analytical problems can be solved by the use of a single thin-layer chromatographic (TLC) plate and for most analytical applications it would be impractical to apply two-dimensional (2-D) TLC. One-dimensional chromatographic systems, however, often have an inadequate capability for the clean resolution of the compounds present in complex biological samples, and because this failure becomes increasingly pronounced as the number of compounds increases (1), multidimensional (MD) separation procedures become especially important for such samples. 

The present work involves the study of methyl glycosides and O-isopropylidene ketals of various isomeric deoxy sugars by mass spectrometry. Several of the compounds selected for the present study have free hydroxyl groups, and interpretation of their mass spectra shows the scope of the study of these and related deoxy sugar derivatives by mass spectrometry without prior substitution of all hydroxyl groups. Some of the candidates (compounds 4, 7, 8 and 10) are structurally related to biologically-derived deoxy sugars. 

FIGURE 11.13 A collection of 10 responses (ordinates) to a compound resulting from exposure of a biological preparation to 10 concentrations of the compound (abscissae, log scale). The dotted line indicates the mean total response of all of the concentrations. The sigmoidal curve indicates the best fit of a four-parameter logistic function to the data points. The data were fit to Emax = 5.2, n = 1, EC5o = 0.4 pM, and basal = 0.3. The value for F is 9.1, df=6, 10. This shows that the fit to the complex model is statistically preferred (the fit to the sigmoidal curve is indicated). 

Many new drugs are discovered by studying the properties of compounds found in plants or other materials that have been used as medicines for centuries (Fig. F. 1). Once chemists have extracted a biologically active compound from a natural product, they identify its molecular structure so that it can be manufactured. This section focuses on the first step in identifying the molecular structure, the determination of the empirical and molecular formulas of the compound. 

A particular search command can contain dozens of such terms. Obviously, if one is careful about choosing the proper search terms, one can focus in on just the relevant papers, and leave out those that will not be useful. However, there will often be far more papers than can conveniently be handled, and there are other ways to limit searches. One such way is by using a narrow field. For example, a synthetic chemist may wish to find references in which a given compound is synthesized, but find, when he or she searches for that compound, that most of the references concern biological or medicinal uses of the compound. By using the command... 

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