Binding selectivity
Binding selectivity is of major importance in biochemistry[1] and in chemical separation processes.
This selectivity coefficient is in fact the equilibrium constant for the displacement reaction
It is easy to show that the same definition applies to complexes of a different stoichiometry, ApBq and ApCq.
An alternative interpretation is that the greater the selectivity coefficient, the lower the concentration of C that is needed to displace B from AB.
Selectivity coefficients are determined experimentally by measuring the two equilibrium constants, KAB and KAC.
A ligand may be a peptide or another small molecule, such as a neurotransmitter, a hormone, a pharmaceutical drug, or a toxin.
The specificity of a receptor is determined by its spatial geometry and the way it binds to the ligand through non-covalent interactions, such as hydrogen bonding or Van der Waals forces.
The stomach ulcer drug cimetidine was developed as an H2 antagonist by chemically engineering the molecule for maximum specificity to an isolated tissue containing the receptor.
The further use of quantitative structure-activity relationships (QSAR) led to the development of other agents such as ranitidine.
For example, in a higher dose, a specific drug molecule may also bind to other receptors than those said to be "selective".
In the case of iron overload, which may occur in individuals with β-thalessemia who have received blood transfusions, the target metal ion is in the +3 oxidation state and so forms stronger complexes than the divalent ions.
deferoxamine, a naturally occurring siderophore produced by the actinobacter Streptomyces pilosus and was used initially as a chelation therapy agent.
Synthetic siderophores such as deferiprone and deferasirox have been developed, using the known structure of deferoxamine as a starting point.
Treatment of poisoning by heavy metals such as lead and mercury is more problematical, because the ligands used do not have high specificity relative to calcium.
Factors determining selectivity for lead against zinc, cadmium and calcium have been reviewed,[7] In column chromatography a mixture of substances is dissolved in a mobile phase and passed over a stationary phase in a column.
The selectivity factor is equal to the selectivity coefficient with the added assumption that the activity of the stationary phase, the substrate in this case, is equal to 1, the standard assumption for a pure phase.
This is particularly true in gas-liquid chromatography where column lengths up to 60 m are possible, providing a very large number of theoretical plates.
In one process, the metal ions in aqueous solution are made to form complexes with tributylphosphate (TBP), which are extracted into an organic solvent such as kerosene.
In this way the metal ion with the most stable complex passes down the cascade in the organic phase and the metal with the least stable complex passes up the cascade in the aqueous phase.
[11] If solubility in the organic phase is not an issue, a selectivity coefficient is equal to the ratio of the stability constants of the TBP complexes of two metal ions.
For lanthanoid elements which are adjacent in the periodic table this ratio is not much greater than 1, so many cells are needed in the cascade.
A potentiometric selectivity coefficient defines the ability of an ion-selective electrode to distinguish one particular ion from others.
[12] For example, a potassium ion-selective membrane electrode utilizes the naturally occurring macrocyclic antibiotic valinomycin.
The sensor is designed to be an excellent match in terms of the size and shape of the target in order to provide for the maximum binding selectivity.
