Biochemistry In biochemistry the substrate is known as a receptor. A receptor is a
protein molecule, embedded in either the
plasma membrane or the
cytoplasm of a cell, to which one or more specific kinds of signalling molecules may bind. 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. If a receptor can be isolated a synthetic drug can be developed either to stimulate the receptor, an
agonist or to block it, an
antagonist. 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. "Selectivity" when referring to a drug is relative. 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
chelating ligand is used to selectively remove a metal from the body. When the metal exists as a divalent ion, such as with
lead, Pb2+ or
mercury, Hg2+ selectivity against
calcium, Ca2+ and
magnesium, Mg2+, is essential in order that the treatment does not remove essential metals. Selectivity is determined by various factors. 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. It also forms stronger complexes with oxygen-donor ligands than with nitrogen-donor ligands.
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.
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
distribution coefficients, which describe the equilibrium distribution of an
analyte between the stationary phase and the mobile phase. 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. The resolution of a chromatographic column,
RS is related to the selectivity factor by: :R_S=\frac{\sqrt N}{4}\left(\frac{\alpha-1}{\alpha}\right)\left(\frac{k_B}{1+k_B}\right) where α is selectivity factor,
N is the number of
theoretical plates
kA and
kB are the
retention factors of the two analytes. Retention factors are proportional to distribution coefficients. In practice substances with a selectivity factor very close to 1 can be separated. 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 ion-exchange chromatography the selectivity coefficient is defined in a slightly different way
Solvent extraction Solvent extraction is used to extract individual
lanthanoid elements from the mixtures found in nature in ores such as
monazite. 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. Complete separation is effected by using a
countercurrent exchange method. A number of cells are arranged as a
cascade. After equilibration, the aqueous component of each cell is transferred to the previous cell and the organic component is transferred to the next cell, which initially contains only water. 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. 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). 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, 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 ==