An ionophore is a lipid-soluble molecule that transports ions across a cell membrane. Ionophores are important because the interior of the lipid bilayer of the membrane is hydrophobic, so ions cannot pass through easily because they are charged.
An ionophore is also a lipophilic complexing agents capable of reversibly binding ions. They are also called ion carriers. The latter name reflects the fact that these compounds also catalyze ion transport across hydrophobic membranes such as liquid polymeric membranes as in the carrier-based ion selective electrodes or lipid bilayer as in the living cell and synthetic vesicles (liposomes).
Some ionophores are synthesized by microorganisms to import ions into their cells, but majority of synthetic ion carriers have been prepared in the laboratory with an aim to selectively and reversibly bind a particular charged specie. Selective ionophores ans so as carrier-based electrodes selective for a various biologically or enviromentally important cations, anions, organic and inorganic, have been known for about 30 years and have found many applications in research and routine analysis.
The two broad classifications of ionophores synthesized by microorganisms are:
- Carrier ionophores that bind to a particular ion and shield its charge from the surrounding environment. This makes it easier for the ion to pass through the hydrophobic interior of the lipid membrane. An example of a carrier ionophore is valinomycin, a molecule that transports a single potassium cation. Carrier ionophores may be proteins or other molecules.
- Channel formers that introduce a hydrophilic pore into the membrane, allowing ions to pass through without coming into contact with the membrane's hydrophobic interior. An example of a channel former is gramicidin A. Channel forming ionophores are usually large proteins.
Mechanism of action
Transmembrane ion concentration gradients (membrane potential) is required for the proper functioning and survival of microorganisms. Ionophores disrupt the membrane potential by conducting ions through a lipid membrane in the absence of a protein pore, and thus could exhibit cytotoxic properties. They are produced naturally by a variety of microbes and act as a defense against competing microbes. Many antibiotics, particularly the macrolide antibiotics, are ionophores that exhibit high affinities for Na+ or K+. The structure of the sodium and potassium complexes of antibiotics have been repeatedly verified by X-ray crystallography.
In laboratory research, ionophores are used to increase the permeability of biological membranes to certain ions. Additionally, some ionophores are used as antibiotics and/or as growth-enhancing feed additives for certain feed animals, such as cattle (see monensin).
Most prominent synthetic ionophores are based on crown ethers, cryptands, and calixarenes. These synthetic species are often macrocyclic. Some synthetic agents are not macrocyclic, e.g., carbonyl cyanide-p-trifluoromethoxyphenylhydrazone. Even simple organic compounds, such as phenols, exhibit ionophoric properties.
List of representative biological ionophores
With the ion(s) they act upon:
- Beauvericin (Ca2+, Ba2+)
- Calcimycine or A23187 (Mn2+, Ca2+, Mg2+)
- Carbonyl cyanide m-chlorophenyl hydrazone (CCCP) (H+)
- Enniatin (ammonium)
- Gramicidin A (H+, Na+, K+)
- Ionomycin (Ca2+)
- Lasalocid (K+, Na+, Ca2+, Mg2+)
- Monensin (Na+, H+)
- Nigericin (K+, H+, Pb2+)
- Nonactin (ammonium ionophore I)
- Nystatin (K+)
- Salinomycin (K+)
- Valinomycin (potassium ionophore I)
- Siderophore - Fe3+ binding compounds, found in microbes and grasses
- Chem Rev. 1997 Dec 18;97(8):3083-3132. Carrier-Based Ion-Selective Electrodes and Bulk Optodes. 1. General Characteristics. Bakker E1, Bühlmann P, Pretsch E.
- Chem Rev. 1998 Jun 18;98(4):1593-1688. Carrier-Based Ion-Selective Electrodes and Bulk Optodes. 2. Ionophores for Potentiometric and Optical Sensors. Bühlmann P1, Pretsch E, Bakker E.
- IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book") (1997). Online corrected version: (2006–) "Ionophore".
- "Ionophores - MeSH Result".
- Greenwood, Norman N.; Earnshaw, Alan (1997). Chemistry of the Elements (2nd ed.). Butterworth-Heinemann. ISBN 0080379419.
- Steinrauf, L. K.; Hamilton, J. A.; Sabesan, M. N. (1982). "Crystal structure of valinomycin-sodium picrate. Anion effects on valinomycin-cation complexes". Journal of the American Chemical Society 104 (15): 4085. doi:10.1021/ja00379a008.
- The US Department of Agriculture sent a letter to Tyson Foods to remove labels for chickens that said "raised without antibiotics" because of the use of ionophores in their feed. Kabel, Marcus; Christine Simmons (2007-11-20). "USDA Revokes OK for Tyson Chicken Labels". Retrieved 2007-11-20.[dead link]
- Antonenko, YN; Yaguzhinsky, LS (18 February 1988). "The ion selectivity of nonelectrogenic ionophores measured on a bilayer lipid membrane: nigericin, monensin, A23187 and lasalocid A.". Biochimica et biophysica acta 938 (2): 125–30. PMID 19927398.
- Fluka ionophores for ion-selective electrodes
- Medical Information database Reference.MD
- Structures and Properties of Naturally Occurring Polyether Antibiotics, J. Rutkowski, B. Brzezinski; open access review article
- Polyether ionophores—promising bioactive molecules for cancer therapy, A. Huczyński; open access review article