Intercalation (chemistry)

In chemistry, intercalation is the reversible inclusion of a molecule (or group) between two other molecules (or groups). Examples include DNA intercalation and graphite intercalation compounds.

DNA intercalation


There are several ways molecules (in this case, also known as ligands) can interact with DNA. Ligands may interact with DNA by covalently binding, electrostatically binding, or intercalating. Intercalation occurs when ligands of an appropriate size and chemical nature fit themselves in between base pairs of DNA. These ligands are mostly polycyclic, aromatic, and planar, and therefore often make good nucleic acid stains. Intensively studied DNA intercalators include berberine, ethidium bromide, proflavine, daunomycin, doxorubicin, and thalidomide. DNA intercalators are used in chemotherapeutic treatment to inhibit DNA replication in rapidly growing cancer cells. Examples include doxorubicin (adriamycin) and daunorubicin (both of which are used in treatment of Hodgkin's lymphoma), and dactinomycin (used in Wilm's tumour, Ewing's Sarcoma, rhabdomyosarcoma).

In order for an intercalator to fit between base pairs, the DNA must dynamically open a space between its base pairs by unwinding. The degree of unwinding varies depending on the intercalator; for example, ethidium cation (the ionic form of ethidium bromide found in aqueous solution) unwinds DNA by about 26°, whereas proflavine unwinds it by about 17°. This unwinding causes the base pairs to separate, or "rise", creating an opening of about 0.34 nm (3.4 Å). This unwinding induces local structural changes to the DNA strand, such as lengthening of the DNA strand or twisting of the base pairs. These structural modifications can lead to functional changes, often to the inhibition of transcription and replication and DNA repair processes, which makes intercalators potent mutagens. For this reason, DNA intercalators are often carcinogenic, such as the exo (but not the endo) 8,9 epoxide of aflatoxin B1, acridines such as proflavine or quinacrine, or ethidium bromide.

Intercalation as a mechanism of interaction between cationic, planar, polycyclic aromatic systems of the correct size (on the order of a base pair) was first proposed by Leonard Lerman in 1961. One proposed mechanism of intercalation is as follows: In aqueous isotonic solution, the cationic intercalator is attracted electrostatically to the surface of the polyanionic DNA. The ligand displaces a sodium and/or magnesium cation present in the "condensation cloud" of such cations that surrounds DNA (to partially balance the sum of the negative charges carried by each phosphate oxygen), thus forming a weak electrostatic association with the outer surface of DNA. From this position, the ligand diffuses along the surface of the DNA and may slide into the hydrophobic environment found between two base pairs that may transiently "open" to form an intercalation site, allowing the ethidium to move away from the hydrophilic (aqueous) environment surrounding the DNA and into the intercalation site. The base pairs transiently form such openings due to energy absorbed during collisions with solvent molecules.

Materials science
Many layered solids intercalate guest molecules. A famous example is the intercalation of potassium into graphite. Intercalation expands the "van der Waals gap" between sheets, which requires energy. Usually this energy is supplied by charge transfer between the guest and the host solid, i.e., redox. Two potassium graphite compounds are KC8 and KC24. Carbon fluorides (e.g., (CF)x and (C4F) are prepared by reaction of fluorine with graphitic carbon. The color is greyish, white, or yellow. The bond between the carbon and fluorine atoms is covalent, thus fluorine is not intercalated. Such materials have been considered as a cathodes in various lithium batteries. Treating graphite with strong acids in the presence of oxidizing agents, causes the graphite to oxidise. Graphite bisulfate, [C24]+[HSO4]-, is prepared by this approach using sulfuric acid and a little nitric acid or chromic acid. The analogous graphite perchlorate can be made similarly by reaction with perchloric acid.Aside from graphite, well-known intercalation hosts are the layered dichalcogenides such as tantalum disulfide and iron oxychloride.  In characteristic manner, intercalation is analyzed by X-ray diffraction, since the spacing between sheets increases, and by electrical conductivity, since charge transfer alters the number of charge carriers.

Aside from graphite, well-known intercalation hosts are the layered dichalcogenides such as tantalum disulfide and iron oxychloride. In characteristic manner, intercalation is analyzed by X-ray diffraction, since the spacing between sheets increases, and by electrical conductivity, since charge transfer alters the number of charge carriers.