Binding selectivity
In chemistry, binding selectivity is defined with respect to the binding of ligands to a substrate forming a complex. Binding selectivity describes how a ligand may bind more preferentially to one receptor than another. A selectivity coefficient is the equilibrium constant for the reaction of displacement by one ligand of another ligand in a complex with the substrate. Binding selectivity is of major importance in biochemistry[1] and in chemical separation processes.
Selectivity coefficient
The concept of selectivity is used to quantify the extent to which one chemical substance, A, binds each of two other chemical substances, B and C. The simplest case is where the complexes formed have 1:1 stoichiometry. Then, the two interactions may be characterized by equilibrium constants KAB and KAC.[note 1]
A selectivity coefficient is defined as the ratio of the two equilibrium constants.
It is easy to show that the same definition applies to complexes of a different stoichiometry, ApBq and ApCq. The greater the selectivity coefficient, the more the ligand C will displace the ligand B from the complex formed with the substrate A. 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.
Applications
Biochemistry
In biochemistry the substrate is known as a receptor. A receptor is a
If a receptor can be isolated a synthetic drug can be developed either to stimulate the receptor, an
It is important to note that "selectivity" when referring to a drug is relative and not absolute. For example, in a higher dose, a specific drug molecule may also bind to other receptors than those said to be "selective".
Chelation therapy
Chelation therapy is a form of medical treatment in which a
Selectivity is determined by various factors. In the case of
Wilson's disease is caused by a defect in copper metabolism which results in accumulation of copper metal in various organs of the body. The target ion in this case is divalent, Cu2+. This ion is classified as borderline in the scheme of Ahrland, Chatt and Davies.[6] This means that it forms roughly equally strong complexes with ligands whose donor atoms are N, O or F as with ligands whose donor atoms are P, S or Cl. Penicillamine, which contains nitrogen and sulphur donor atoms, is used as this type of ligand binds more strongly to copper ions than to calcium and magnesium ions.
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. For example,
Chromatography
In column chromatography a mixture of substances is dissolved in a mobile phase and passed over a stationary phase in a column. A selectivity factor is defined as the ratio of
where α is selectivity factor, N is the number of
In ion-exchange chromatography the selectivity coefficient is defined in a slightly different way[9]
Solvent extraction
Solvent extraction
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.
Chemical sensors
A potentiometric selectivity coefficient defines the ability of an ion-selective electrode to distinguish one particular ion from others. The selectivity coefficient, KB,C is evaluated by means of the emf response of the ion-selective electrode in mixed solutions of the primary ion, B, and interfering ion, C (fixed interference method) or less desirably, in separate solutions of B and C (separate solution method).[12] For example, a potassium ion-selective membrane electrode utilizes the naturally occurring macrocyclic antibiotic valinomycin. In this case the cavity in the macrocyclic ring is just the right size to encapsulate the potassium ion, but too large to bind the sodium ion, the most likely interference, strongly.
Chemical sensors,[13][14] are being developed for specific target molecules and ions in which the target (guest) form a complex with a sensor (host). 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. An indicator is associated with the sensor which undergoes a change when the target forms a complex with the sensor . The indicator change is usually a colour change (gray to yellow in the illustration) seen in absorbance or, with greater sensitivity, luminescence. The indicator may be attached to the sensor via a spacer, in the ISR arrangement, or it may be displaced from the sensor, IDA arrangement.
See also
- Binding
- Affinity
- Functional selectivity
Notes
- ^ The constant used here are association constants. Dissociation constants are used in some contexts. A dissociation constant is the reciprocal of an association constant.
- ^ The term "ligand" here refers to binding to a metal. In the definition of selectivity coefficient this "ligand" is in fact the substrate and ligand in that definition is the metal ion.
References
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