Disease-drug interactions: utility of the conditional concept for experimental pharmacology and toxicology in the context of inflammation

Abstract

The discipline of physical chemistry has long recognized the nonideality of the phenomena it describes, the behaviour and interactions of ions and molecules. Thus even the simplest mathematical description of the properties of gaseous molecules (P=RT/V) has to be modified by the Van der Waal’s corrections, which allow for the intermolecular associations and other departures from ideal behaviour. This leads naturally to the concept of molecular “activity” for describing the effective quantity of a reagent and to allow for the various factors which cause the activity to be less than the concentration (except in the most dilute solutions). A third example of the chemist’s critical recognition of a departure from ideal behaviour is provided by the use of aconditional association/ dissociation constant, K’, to describe for example the binding of a metal ion (M⁺) by a metal ligand (L⁻). Since the experimental studies to measure M⁺: L⁻ interactions have of necessity to be conducted in non-ideal media, rarely at a standard temperature (0 °C), probably not at standard pressure, almost certainly with extraneous solutes (counterions to solubilize M⁺ and L⁻ respectively and other additives to control pH); it is only realistic to accept−the value of K’ derived from such experiments as not an absolute constant and only invariable if the experimental conditions are adequately defined (by pH, ionic strength, temperature, solvent composition, etc.). Nevertheless such conditional constants are of immense practical value. Together with other chemical constants obtained under defined conditions (particularly pH), such as equilibrium constants for enzyme reactions or redox potentials for electron transfer reactions, they are invaluable for both interpreting and for making predictions about the chemistry of biological systems.

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