Chelation

Type of physical science: Chemistry

Field of study: Chemical methods

Chelation denotes ring formation by a bi- or polydentate ligand bonded to a metal or a metal ion. Many biochemical processes, analytical determinations, and clinical procedures employ this structure in their chemistry.

Overview

Atoms joined to one another in molecules may form rings of atoms by combining with metals or metal ions, which serve as a center for the ring formation. This phenomenon of ring formation in the resulting complex compound is called chelation. The ring formed is called a chelate ring (pronounced "key-late," from the Greek kela, meaning "crab's claw").

Chelation is a special case of the theory of coordination chemistry. Coordination compounds contain a central atom or ion, usually surrounded by a cluster of ions or molecules. The molecules that form the cluster are called ligands (from the Latin ligare, which means "to bind" or "bond").

The beginning of coordination chemistry is dated from the discovery of cobaltamins in 1798. This complex compound was formed by combining a compound containing cobalt and ammonia molecules. The problem to be solved was, How could two molecules, complete in themselves, unite to form a third compound that was entirely different from either in terms of its chemical behavior? It was not until 1891 that a reasonable theory was developed. In that year, Alfred Werner published the first of his papers that were to form the basis of coordination theory.

It may be explained as follows: The cobalt compound, mentioned above, was held together by the attraction between the positively charged cobalt ion and the negatively charged chlorine atoms that formed the rest of the compound. This interaction Werner called the primary valence.

The ammonia molecules, which serve as ligands, have additional electrons, which bear negative charges, available to attract the positively charged colbalt ion. This type of attraction was called secondary valence. These attractions are called bonds. The term "valence" describes the combining power of atoms in bond formation.

Ligands, molecules or ions that bond to a metal or a metal ion, may be classified according to their manner of attachment to the central metal. The ammonia molecule (NH₃) in the example mentioned above uses a lone pair of electrons to form a bond with the cobalt ion (Co³⁺). The donation of the pair of electrons to the metal ion may be represented as follows: H₃N: → Co³⁺. Because the ammonia molecule attaches itself at one site, it is classed as a monodentate ligand. There are numerous examples of molecules attaching themselves at more than one site. A common example is that of ethylenediamine, en, which donates two lone pairs of electrons to form bonds and is thus a bidentate ligand. Bidentate ligands form chelate rings. Additional linkages used in the formation of chelates are classified as polydentate and include tri-, quadri-, penta-, and hexadentate ligands.

This type of chemistry can become quite complicated, since there are so many ways in which chelating agents can be arranged about a central metal or ion. These different arrangements are called isomers. For example, ethylenediamine molecules can be arranged about the cobalt metal ion (Co₃⁺) as shown in the figure.

The two chelated cobalt structures in the figure contain the same number and kinds of atoms, but they are not identical. They are nonsuperimposable images, just as a left hand is a nonsuperimposable mirror image of a right hand. Such forms are called isomers (from the Greek isomeres, "having equal parts"). This type of molecule is of great importance in living systems. An organism usually prefers one form over another. Other types of isomers also exist.

Some complex molecules tend to fall apart when placed in solution or subjected to heat or other destabilizing conditions. A chelated molecule, on the other hand, can withstand these changes to a greater extent. For example, when the nickel ion is surrounded by six ammonia molecules, it is less stable than the nickel ion surrounded by three bidentate en molecules by a factor of many millions.

The examples of chelated molecules thus far given describe inorganic, or nonliving, systems. Molecules that are a part of living organisms include many types of chelation.

Chlorophyll, the green coloring substance of leaves and plants associated with the production of carbohydrates through the use of the energy of sunlight, is a well-characterized metal chelate.

Two forms exist, the bluish-black chlorophyll a, and the yellowish-green chlorophyll b, which are used as dyes for cosmetics and oils. The ring system in chlorophyll contains four nitrogen atoms bonded to the center atom, magnesium, constituting a quadridentate ligand. This same type of chelation is observed in hemoglobin, the protein coloring matter of the red blood corpuscles. In the latter case, iron serves as the central atom to which the nitrogen atoms are bonded. The science of biochemistry describes chelation in terms of many other types of molecules, including the vitamins B12 molecule, and enzymes and bacterial systems that function in nitrogen fixation. Plant growth depends on this process.

Two theories currently used to describe the interaction between ions or molecules and ligands are the crystal field theory and the valence bond theory. According to the former, there is an attraction between the positively charged metal ion and the negative electric field of the ligand that results from the electrons present in the ligand. The electrons in the metal rearrange themselves to accommodate this interaction. As a result, the molecule assumes different shapes, for example, that of a tetrahedron or a cube. This theory contrasts with the valence bond theory, in which a lone pair of electrons is donated to the metal or metal ion to form a bond.

A third theory, the molecular orbital theory, explains the formation of metal chelates in terms of the space in which an electron may be found. The treatment requires considerable background in both atomic and molecular structure.

Metallocenes, such as ferrocene, an iron complex, and cobaltocene, a cobalt complex, are closely related to the concept of chelation. In their structure, the metal ion lies between two ring systems and thus forms a "sandwich." The electrons in the ring systems bond to the central metal ion; thus, the structure resembles a polydentate ligand. Metal cluster compounds, which consist of metal atoms bonded to one another by the sharing of electrons, may also be considered as closely related to metal chelate compounds. Organic ions, mainly those containing carbon, hydrogen, and oxygen, may also be involved in the formation of clusters. These compounds find extensive use as catalysts, that is, those compounds that cause a chemical reaction to take place in a shorter time.

Applications

Heavy metals serve as metabolic poisons. Included in this group are, principally, lead and mercury. Cadmium, cobalt, gallium, lithium, thallium, and zinc are listed in this category, although their occurrence is less common. Arsenic, though not a metal, has metallic characteristics, and uses these characteristics in its action as a homicidal poison. All the above elements, when ingested, can also act as teratogens, or substances that cause birth defects. The activity of these elements in the body and their subsequent removal from the system involve chelation.

Arsenic and heavy metals poison the body by reacting with any inhibiting enzyme systems containing sulfur. The metal attaches itself to the sulfur on adjacent molecules, thus forming a strongly bonded metal chelate. This results in the effective elimination of the molecules. Removal of certain of the chelated molecules associated with the production of healthy red blood cells causes anemia. Certain inorganic ions containing arsenic also react with the sulfur in enzyme systems to form complexes that interfere with the body's normal biochemical processes.

Lewisite, an arsenic-containing poisonous gas, was used in World War I. Studies of how arsenic acts as a poison led to the development of an antidote known as BAL, British Anti-Lewisite. Lewisite poisons people by its reaction with protein groups containing sulfur in the manner described above. British scientists prepared a drug that contains these same sulfur-containing groups of atoms, which compete with those in the natural enzyme systems. The BAL, which bonds to the arsenic or to a metal, is a chelating agent. BAL also serves in a hospital's poison center to treat heavy metal poisoning.

Mercury and its salts tend to accumulate in the body, which means that the body has no quick way of eliminating the poison. A chronic buildup ensues, which can lead to severe illness.

BAL is a standard therapeutic item for removal of mercury from the system.

Lead is a commonly encountered heavy metal poison. The body's mechanism is such that it is able to eliminate much of the lead that often occurs in foods, beverages, tap water (mainly from lead-sealed pipes), and air, which is contaminated from its occurrence in auto exhausts. It is also found in old paint. When the intake of lead, frequently in the form of lead salts, exceeds the excretory amounts, about 2 milligrams of lead per day, an effective chelating agent, ethylenediaminetetraacetic acid, EDTA, is administered. Since EDTA itself would remove too much of the blood serum's calcium, the calcium disodium salt of EDTA is used. In solution, EDTA forms more stable complexes with the lead ion than with the calcium ion; therefore, the lead is effectively removed. The soluble, chelated lead is excreted in the urine. The EDTA itself is not metabolized; it is excreted unchanged by renal glomerular filtration.

Cadmium, a possible cause of hypertension, or high blood pressure, enters the human body from sources such as the dust from the wear and tear on tires, or from zinc-coated steel vessels from which it leeches out. Chelating agents for cadmium have been used as anti-hypertension drugs.

Analytical chemical procedures rely heavily on chelation. In a manner similar to the reaction in which an acid neutralizes a base, a complexing agent is reacted with a metal ion. The complexing agent (chelate) acts as a base in donating electrons to the metal ion, which acts as an acid in accepting the electrons. For example, magnesium salts in tap water may be identified by adding known amounts of EDTA to a water sample. The solution itself is made basic. An indicator, Eriochrome black T, itself a chelating agent, is added to the solution. After all the free magnesium ion is complexed, the EDTA extracts the magnesium present in the indicator and a blue color is produced. In the reaction, one EDTA molecule is used for each magnesium ion present. Calcium salts in water may be determined in the same manner.

Before EDTA had been investigated, the only really important complexing agent was the cyanide ion, which reacts with several metal ions, for example, those of silver and gold. The limitation of the cyanide ion is that it is unidentate, and therefore attaches itself to the metal ion by several steps. The series of steps causes a number of species to be present, thus complicating the procedure. EDTA accomplishes its work in one step, since it has six sites for chelation.

Humic acids are brown, polymeric constituents of the soil formed by the decay of organic matter. They are not well-defined compounds but a mixture of polymers built of complex chelating structures and nitrogen. The acids bind metal ions needed by plants and transport them through the soil. They also function in chemical exchange reactions in which one metal ion substitutes for another in the soil. Chlorosion results from a lack of iron in the soil and causes the yellowing of leaves in acid-loving plants. Adding an iron salt will not remedy the deficiency, because in moist soil, iron is converted into iron oxide or iron hydroxide, both of which are so slightly soluble that roots cannot absorb them. Chelated iron fertilizers, which complex the iron and render it soluble, are commercially available. Health food stores sell chelated metal ion products to ensure their absorption in the human system.

Applications of chelate chemistry continue to multiply as numerous investigators use their scientific knowledge to achieve a better life for humankind.

Context

Coordination chemistry is of fairly recent origin. Arabian chemists and alchemists were not aware of its existence. In the early nineteenth century, Diesbach accidentally synthesized Prussian blue, a pigment sought after by the artists of his time. Iron was involved in the early study of several classes of complexes, including the phthalocyanines. Phthalocyanine is a chelating agent composed of carbon, nitrogen, and hydrogen arranged in a complex ring formation called a macrocycle. The phthalocyanines are an important class of commercial pigments. Later studies were made by a number of chemists. Werner's work is of particular importance to the study at hand. Meanwhile, Friedrich August Kekule's structure of the benzene ring was published. This was a major step in the field of organic chemistry. Svante August Arrhenius' theory of ion formation followed, and, subsequently, inorganic chemistry came into its own. Important contributions were made to the theory of the covalent (electron-sharing) bond.

Electron dot structures, or Lewis structures, which represent bonding electrons, were subsequently applied to the theory of chelation by N. V. Sidgwick. Linus Pauling's valence bond theory followed. Substantial advances were made in areas such as heat stability, mechanisms of reaction, and synthesis. Studies of ligand substitution reactions were elucidated. The concepts developed in the studies mentioned above gradually found their way into many areas of scientific study.

Chelation chemistry is and will continue to be of extreme importance in biochemical studies. Metalloproteins, that is, those that incorporate one or more metal atoms as part of their structure, are a constant source of new insights into living systems. Respiratory proteins such as hemoglobin and myoglobin are examples of this type of chelated compound. Chelated iron is found in the whole gamut of life-forms, from bacteria to humans. Chelated copper, zinc, and miscellaneous other elements are essential to humans as living organisms.

The study of chelate chemistry is directly related to the field of organic chemistry in terms of structure and stability. Bidentate ring formation involves the formation of three-, four-, five-, and six-membered rings. Their stability in terms of ring formation is analogous to that observed in organic chemistry. Five- and six-membered rings are more stable. The benzene ring (C₆H₆), with its formation of six carbon atoms bonded in ring, has remarkable stability, as has the ethylenediamine complex, with its five-membered ring systems.

As theory continued to develop in the area of chelate chemistry, its tool, instrumentation, became more and more advanced. X-ray studies of solid materials showed the positions of individual atoms or ions that were present in the structure of the chelate much in the same way that bone structure is revealed by X ray. The absorption of light in the ultraviolet, visible, and infrared regions of the spectrum revealed much information on the manner in which the atoms in the molecule were held together. Magnetism, exhibited by certain nuclei, also reveals much about the chelated molecule in the form of nuclear magnetic resonance studies.

Magnetic imaging is in great clinical demand today as a diagnostic tool in detecting tumors and other bodily disorders. The addition of computers to the types of studies mentioned above has resulted in their more efficient use and has given deeper insight into the problems at hand.

Computer software, with its molecular modeling programs, has aided in the design of new molecules.

With the constant improvement of computer-driven instrumentation and more sophisticated computer programming, vast horizons lie ahead. In any case, the theoretical considerations of one era will undoubtedly generate tomorrow's advances.

Principal terms

COORDINATION COMPOUND: a compound formed by the union of a metal ion with a ligand or complexing agent; the ligands surround the metal ion

ELECTRON: a negatively charged subatomic particle present in all atoms; the number and arrangement of these particles determine the chemical and physical properties of individual atoms

ENZYME: a biological catalyst; life depends on a complex network of chemical reactions brought about by specific enzymes, and any modification of the enzyme pattern may have far-reaching consequences for the living organism

INORGANIC CHEMISTRY: the chemistry of all the elements and their compounds except compounds of carbon and hydrogen and their derivatives, which are studied in organic chemistry

ION: a positively charged atom formed by the loss of electrons, or a negatively charged atom formed by the gain of electrons; complex ions also exist, which involve the gain or loss of electrons

LIGAND: the molecules or ions bonded to the central atom or ion in a coordination compound

LONE ELECTRON PAIRS: pairs of electrons that are free to form a bond with metal ions; a colon is used to symbolize a lone electron pair in this article

MECHANISM: the detailed steps that occur in a chemical reaction

MOLECULE: the smallest part of a substance capable of independent existence; composed of either a single atom or a number of atoms

NUCLEUS: a central region, very small by comparison with the total size of an atom, in which almost all the mass and the positive charge of the atom are concentrated

POLYMER: a very large molecule formed by linking together many smaller molecules

Bibliography

Bailar, John C., Jr., et al. CHEMISTRY. New York: Harcourt Brace Jovanovich, 1984. This text is written for freshman college students and describes itself as "user friendly." The chapter on coordination chemistry includes chelation, metallocenes, metal clusters, and practical applications in nature. A glossary of all significant terms is included.

Basolo, Fred, and Ronald C. Johnson. COORDINATION CHEMISTRY. New York: W. A. Benjamin, 1964. This volume was introduced as part of the general chemistry monograph series, designed to be read by freshman college students. The treatment of the coordinate bond in terms of the valence bond, crystal field, and molecular orbital theories is diagrammatically represented and clearly explained. The stereochemistry of chelates, including optical isomerism, is simplistic in its approach.

Graddon, D. P. AN INTRODUCTION TO COORDINATION CHEMISTRY. International Series of Monographs on Inorganic Chemistry. Oxford, England: Pergamon Press, 1961. This monograph presents an excellent historical introduction to the subject of chelation, followed by the theories of coordination chemistry including the ligand-field theory and stereochemistry. In contrast to some later publications in the field, the material is presented in a simple, basic manner. Numerous illustrations are given. Practical applications, such as solvent extraction, are explained.

Kauffman, George B., and H. Harry Szmant. THE CENTRAL SCIENCE: ESSAYS ON THE USES OF CHEMISTRY. Fort Wayne, Tex.: Christian University Press, 1984. This short volume provides excellent background material for the reader who has little knowledge of the subject. It touches upon areas such as chemistry and nutrition, chemistry and medicine, and chemistry and forensic science. Macromolecules such as proteins and enzymes are simply described.

Mallonk, Thomas E., and Haiwon Lee. "Designer Solids and Surfaces." JOURNAL OF CHEMICAL EDUCATION 67 (October, 1990): 37-53. The article describes supramolecular structures such as those that occur in zeolites and bind diooxygen, thus imitating the action of hemoglobin. Other articles described in the symposium, such as "Molecular Recognition in Aqueous Solution," "Supramolecular Complexation," and "Catalysis," give worthwhile theoretical considerations.

Murmann, R. Kent. INORGANIC COMPLEX COMPOUNDS. New York: Reinhold, 1964. This brief volume presents the topic to beginning chemistry students and students in neighboring fields. Some of the basic concepts involved in the formation of metal complexes are described. Thermodynamic stabilities, modes of bonding, cobalt (III) ion stereochemistry, and theoretical applications are included.

Welcher, Frank J. THE ANALYTICAL USES OF ETHYLENEDIAMINE TETRAACETIC ACID. Princeton, N.J.: D. Van Nostrand, 1957. The volume describes procedures for the use of EDTA as the major chelating agent in metallurgical as well as chemical processes. Its function in inhibiting unwanted catalytic effects is outlined.

Left-handed config. of chelated cobalt ion and its mirror image

Quantum Mechanics of Molecules

Solvation and Precipitation

X-Ray and Electron Diffraction

X-Ray Determination of Molecular Structure