chemistry Chemistry is the scientific study of the properties and behavior of matter. It is a physical science within the natural sciences that studies the chemical elements that make up matter and chemical compound, compounds made of atoms, molecules a ...

, binding selectivity is defined with respect to the binding of

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

s to a substrate forming a

complex Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

. Binding selectivity describes how a ligand may bind more preferentially to one

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

than another. A selectivity coefficient is the

equilibrium constant The equilibrium constant of a chemical reaction is the value of its reaction quotient at chemical equilibrium, a state approached by a dynamic chemical system after sufficient time has elapsed at which its composition has no measurable tendency ...

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 Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...

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 Stoichiometry () is the relationships between the masses of reactants and Product (chemistry), products before, during, and following chemical reactions. Stoichiometry is based on the law of conservation of mass; the total mass of reactants must ...

. Then, the two interactions may be characterized by

s and .The constant used here are ''association'' constants. ''Dissociation'' constants are used in some contexts. A dissociation constant is the reciprocal of an association constant.

\begin
  \ce;& \quad K_ = \frac \\
  \ce;& \quad K_ = \frac
\end

where represents the

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'', ...

of substance X (A, B, C, …). A selectivity coefficient is defined as the ratio of the two equilibrium constants.

K_ = \frac

This selectivity coefficient is in fact the equilibrium constant for the displacement reaction

\ce; \quad K_ = \frac = \frac = \frac

It is easy to show that the same definition applies to complexes of a different stoichiometry, A_''p''B_''q'' and A_''p''C_''q''. 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, and .

Applications

Biochemistry

In biochemistry the substrate is known as a receptor. A receptor is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

molecule, embedded in either the

plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

or the

cytoplasm The cytoplasm describes all the material within a eukaryotic or prokaryotic cell, enclosed by the cell membrane, including the organelles and excluding the nucleus in eukaryotic cells. The material inside the nucleus of a eukaryotic cell a ...

of a cell, to which one or more specific kinds of signalling molecules may bind. A

may be a

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

or another small molecule, such as a

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

, a

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

, 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 bond In chemistry, a hydrogen bond (H-bond) is a specific type of molecular interaction that exhibits partial covalent character and cannot be described as a purely electrostatic force. It occurs when a hydrogen (H) atom, Covalent bond, covalently b ...

ing or

Van der Waals force In molecular physics and chemistry, the van der Waals force (sometimes van der Waals' force) is a distance-dependent interaction between atoms or molecules. Unlike ionic or covalent bonds, these attractions do not result from a chemical elec ...

s. If a receptor can be isolated a synthetic drug can be developed either to stimulate the receptor, an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

or to block it, an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.stomach ulcer drug

cimetidine Cimetidine, sold under the brand name Tagamet among others, is a histamine H2 receptor antagonist that inhibits stomach acid production. It is mainly used in the treatment of heartburn and peptic ulcers. With the development of proton pump ...

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 Ranitidine, previously sold under the brand name Zantac among others, is a medication used to decrease stomach acid production. It was commonly used in treatment of peptic ulcer disease, gastroesophageal reflux disease, and Zollinger–Ellis ...

. "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 ligandThe 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. is used to selectively remove a metal from the body. When the metal exists as a divalent ion, such as with

lead Lead () is a chemical element; it has Chemical symbol, symbol Pb (from Latin ) and atomic number 82. It is a Heavy metal (elements), heavy metal that is density, denser than most common materials. Lead is Mohs scale, soft and Ductility, malleabl ...

, Pb²⁺ or mercury, Hg²⁺ selectivity against

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

, Ca²⁺ and

magnesium Magnesium is a chemical element; it has Symbol (chemistry), symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 ...

, 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 transfusion Blood transfusion is the process of transferring blood products into a person's Circulatory system, circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used ...

s, the target metal ion is in the +3

oxidation state In chemistry, the oxidation state, or oxidation number, is the hypothetical Electrical charge, charge of an atom if all of its Chemical bond, bonds to other atoms are fully Ionic bond, ionic. It describes the degree of oxidation (loss of electrons ...

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. Chelation occurs with the two oxygen atoms. Wilson's disease is caused by a defect in

copper Copper is a chemical element; it has symbol Cu (from Latin ) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkish-orang ...

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. 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,

EDTA Ethylenediaminetetraacetic acid (EDTA), also called EDTA acid, is an aminopolycarboxylic acid with the formula . This white, slightly water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-solubl ...

may be administered as a calcium salt to reduce the removal of calcium from bone together with the heavy metal. Factors determining selectivity for lead against zinc, cadmium and calcium have been reviewed,

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 coefficient In the physical sciences, a partition coefficient (''P'') or distribution coefficient (''D'') is the ratio of concentrations of a compound in a mixture of two immiscible solvents at equilibrium. This ratio is therefore a comparison of the solub ...

s, 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, ''R''_S is related to the selectivity factor by: :

R_S=\frac\left(\frac\right)\left(\frac\right)

where α is selectivity factor, ''N'' is the number of theoretical plates ''k''_A and ''k''_B 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 Kerosene, or paraffin, is a combustibility, combustible hydrocarbon liquid which is derived from petroleum. It is widely used as a fuel in Aviation fuel, aviation as well as households. Its name derives from the Greek (''kērós'') meaning " ...

. Complete separation is effected by using a

countercurrent exchange Countercurrent exchange is a mechanism between two flowing bodies flowing in opposite directions to each other, in which there is a transfer of some property, usually heat or some chemical. The flowing bodies can be liquids, gases, or even solid ...

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 The periodic table, also known as the periodic table of the elements, is an ordered arrangement of the chemical elements into rows (" periods") and columns (" groups"). It is an icon of chemistry and is widely used in physics and other s ...

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, K_B,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 Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...

ion-selective membrane electrode utilizes the naturally occurring macrocyclic

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

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 A sensor is often defined as a device that receives and responds to a signal or stimulus. The stimulus is the quantity, property, or condition that is sensed and converted into electrical signal. In the broadest definition, a sensor is a devi ...

, 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 Luminescence is a spontaneous emission of radiation from an electronically or vibrationally excited species not in thermal equilibrium with its environment. A luminescent object emits ''cold light'' in contrast to incandescence, where an obje ...

. 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.

Notes

References

{{Pharmacology Equilibrium chemistry Pharmacodynamics