Isosterism definition

Using equation (6.34) and the definition of the isosteric heat of adsorption Had=T2(d(jIl ad) /T)pj,6 j one can show easily that the isosteric heat of adsorption, AHadj, is given by ... 

The isosteric replacement of atoms or gronps in a molecule is widely nsed in the design of antimetabolites or drngs that alter metabolic processes. Isosteric gronps, according to Erlenmeyer s definition, are isoelectronic in their outermost electron shell. However, since their size and polarity may vary, the term isostere is somewhat misleading. Isosteres are classified according to their valence (i.e., the number of electrons in the onter shell) ... 

Substances that have similar molecular and electronic characteristics but are not necessarily structurally related often have similar physical or other properties. Langmuir called this phenomenon isosterism, and coined the term isostere [67]. According to Langmuir s definition, isosteres are substances or substituents that have the same charge, caused by the same number and arrangement of electrons and the same number of atoms. 

As molecular orbital theory evolved over the years, several variations of Langmuir s definition of isosterism were expressed by others these are discussed in more recent publications [68, 69]. Burger s definition [68] of isosterism encompasses the aspects of the previous definitions and states that isosteres are chemical substances, atoms, or substituents that possess near equal or similar molecular shape and volume, approximately the same distribution of electrons, and which exhibit similar physicochemical properties. A few examples of isosteric atoms and substituents are provided in Figure 4.6. Many more examples are available in the literature [69-72], including metal isosteres [73]. 

The isosteric heats of adsorption synthesized in this way by the use of Equation 28 are based directly on the model of a mobile adsorbed film that we have developed they can be compared with values of qHt obtained by the use of the thermodynamic definition, which has no reference to any model—viz.,... 

This definition received rapid acceptance and is now commonly nsed. Moreover, Friedman considers that isosteres that exhibit opposite properties (antagonists) have also to be considered as bioisosteres, since nsnaUy they interact with the same recognition site. This is the case for para-ami-nobenzoic acid and para-aminobenzene-snlfonamide and also for glntamic acid and its phosphoific analogs. ... 

The nse of the word isosterism has been largely taken beyond its original meaning when employed in medicinal chemistry and Thomber " proposes a loose and flexible definition of the term bioisostere ... 

Some non-classical isosteres are reported in Table 15.5 and from a brief glance it can be noticed that they do not obey the steric and electronic definition of classical isosteres. A second notable characteristic of non-classical bioisosteres is that they do not have the same number of atoms as the substituent or moiety for which they are used as a replacement. 

This expression gives the definition of the enthalpy known as isosteric enthalpy of adsorption. Equation (3.9) can be simplified to... 

This relationship shows that it is possible to calculate the isosteric enthalpy of adsorption from calorimetric experiments. In summary, it has been shown how the enthalpies of adsorption are obtained either calorimetrically or from the dependence of the isotherms on temperature. Although the definitions given above for the different enthalpies of adsorption are rigorous, it is necessary to show that they exhibit the same properties as the enthalpy of vaporization, i.e., the heat necessary to vaporize one mole of liquid at constant pressure and using a reversible and isothermal process. Moreover, only the isosteric enthalpy is related in a simple way to the heat required in a process that is reversible and isothermic. Suppose that 8 moles of adsorbate are transferred to the gas phase at constant temperature and pressure. According to the first law of thermodynamics ... 

The isosteric heat of adsorption at low coverage on porous glass is definitely higher (17 kcal-mole- ) for the untreated surface in comparison to the methylated or sintered one (10-12 kcal mole- ) (3S). These values are approximately the same as found for CgHg on silica gel (39). 

The heat of adsorption is a measure of the energy required for regeneration in gas- or vapor-phase applications, and low values are desirable. It also indicates the temperature rise that can be expected due to adsorption under adiabatic conditions. Again, there are several definitions isosteric, differential, integral, and equilibrium, to name a few. The most relevant (because it applies to flow systems instead of batch systems) is the isosteric heat of adsorption, which is analogous to the heat of vaporization and is a weak function of temperature. The definition is... 

Starting in 1932, Erlenmeyer published a series of detailed studies on the isosterism concept, and particularly about its first applications to biological problems. Erlenmeyer proposed his own definition of isosteres as elements, molecules or ions in which the peripheral layers of electrons may be considered identical. Erlenmeyer also proposed three expansions of the isosterism concept ... 

Keeping in view the munerous advantageous applications of isosterism in resolving biological problems effectively, Friedman proposed the following definition of bio-isosterism —the phenomenon by which componnds usually fit the broadest definition of isosteres and possess the same type of biological activity. 

In Table XII is shown the effect of isosteric replacement of the 3-methylene moiety by oxygen or sulfur. Only a limited number of examples were studied so that a definitive assessment as to the effect of these substitutions is not really possible. The one 3-oxa analog (entry 2) possessed about 1-3% the activity of the parent compound. Results with the 3-thia derivatives (entries 3, 17) were variable, but the lla-hydroxy-lS, 16-... 

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