Transition metal amino acid complexes are a large family of
coordination complex
A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...
es containing the conjugate bases of the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
s, the 2-aminocarboxylates. Amino acids are prevalent in nature, and all of them function as ligands toward the transition metals. Not included in this article are complexes of the amides (including peptide) and ester derivatives of amino acids. Also excluded are the polyamino acids including the
chelating agent
Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands are ...
s
EDTA
Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula H2N(CH2CO2H)2sub>2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes ev ...
and
NTA NTA may refer to:
* Nanoparticle Tracking Analysis, a method for visualizing and analyzing particles
* National Tax Agency, the official tax collecting agency of Japan
* National Tax Association, a non-profit organization in United States
* Nati ...
.
:
Binding modes

Most commonly, amino acids coordinate to metal ions as N,O bidentate ligands, utilizing the amino group and the carboxylate. They are "L-X" ligands. A five-membered chelate ring is formed. The chelate ring is only slightly ruffled at the sp
3-hybridized carbon and nitrogen centers.
For those amino acids containing coordinating substituents, the resulting complexes are more structurally diverse since these substituents can coordinate.
Histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the ...
,
aspartic acid
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α- amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pr ...
,
methionine, and
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, s ...
sometimes form tridentate N,N,O, N,O,O, S,N,O, and S,N,O complexes, respectively.
Using kinetically inert metal ions, complexes containing monodentate amino acids have been characterized. These complexes exist in either the N or the O linkage isomers. It can be assumed that such monodentate complexes exist transiently for many kinetically labile metal ions (e.g. Zn
2+).
Stoichiometry and structure
Homoleptic complexes (only amino acid ligands)
Mixing simple metal salts with solutions of amino acids near neutral or elevated pH often affords bis- or tris complexes. For metal ions that prefer octahedral coordination, these complexes often adopt the stoichiometry M(aa)
3 (aa = amino carboxylate, such as glycinate, H
2NCH
2CO
2−).
Complexes of the 3:1 stoichiometry have the formula is
2CC(R)HNH2)3">(O2CC(R)HNH2)3sup>z. Such complexes adopt
octahedral coordination geometry
In chemistry, octahedral molecular geometry, also called square bipyramidal, describes the shape of compounds with six atoms or groups of atoms or ligands symmetrically arranged around a central atom, defining the vertices of an octahedron. The o ...
. These complexes can exist in facial and meridional isomers, both of which are chiral. The stereochemical possibilities increase when the amino acid ligands are not
homochiral
Homochirality is a uniformity of chirality, or handedness. Objects are chiral when they cannot be superposed on their mirror images. For example, the left and right hands of a human are approximately mirror images of each other but are not their ow ...
.
Complexes with the 2:1 stoichiometry are illustrated by
copper(II) glycinate 2CC(R)HNH2)2">u(O2CC(R)HNH2)2 which exists both in anhydrous and pentacoordinate geometries. When the metal is square planar, these complexes can exist as cis and trans isomers. The stereochemical possibilities increase when the amino acid ligands are not
homochiral
Homochirality is a uniformity of chirality, or handedness. Objects are chiral when they cannot be superposed on their mirror images. For example, the left and right hands of a human are approximately mirror images of each other but are not their ow ...
. Homoleptic complexes are also known where the amino carboxylate is tridentate amino acids. One such complex is Ni(κ
3-histidinate)
2.
Peptides and proteins
In addition to the amino acids, peptides and proteins bind metal cofactors through their side chains. For the most part, the α-amino and carboxylate groups are unavailable for binding as they are otherwise engaged in the peptide bond. The situation is more complicated for the N-terminal and O-terminal residues where the α-amino and carboxylate groups are unavailable, respectively. Especially important in this regard are histidine (
imidazole
Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole, and has non ...
), cysteine (
thiolate
In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...
), methionine (
thioether
In organic chemistry, an organic sulfide (British English sulphide) or thioether is an organosulfur functional group with the connectivity as shown on right. Like many other sulfur-containing compounds, volatile sulfides have foul odors. A sul ...
).
Heteroleptic complexes (amino acids plus other ligands)

Mixed ligand complexes are common for amino acids. Well known examples include
2(glycinate)">o(en)2(glycinate)sup>2+, where en (
ethylenediamine
Ethylenediamine (abbreviated as en when a ligand) is the organic compound with the formula C2H4(NH2)2. This colorless liquid with an ammonia-like odor is a basic amine. It is a widely used building block in chemical synthesis, with approximately ...
) is a spectator ligand. In the area of organometallic complexes, one example of Cp*Ir(κ
3-methionine).
Synthesis and reactions

A well studied complex is
tris(glycinato)cobalt(III). Like several octahedral tris(amino carboxylate) complexes, it is isolated at a mixture of facial and meridional isomers. It is produced by the reaction of glycine with
sodium tris(carbonato)cobalt(III).
Commonly amino acid complexes are prepared by ligand displacement reactions of metal aquo complexes and the conjugate bases of amino acids:
:
4">tCl4sup>2- + 2H
2NCH(R)CO
2− →
2NCH(R)CO2)2">t(H2NCH(R)CO2)2 + 4 Cl
−
Relevant to
bioinorganic chemistry
Bioinorganic chemistry is a field that examines the role of metals in biology
Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent ...
, amino acid complexes can be generated by the hydrolysis of amino acid esters and amides (en =
ethylenediamine
Ethylenediamine (abbreviated as en when a ligand) is the organic compound with the formula C2H4(NH2)2. This colorless liquid with an ammonia-like odor is a basic amine. It is a widely used building block in chemical synthesis, with approximately ...
):
:
2CoOH(κ1N-H2NCH(R)CO2Et)">en)2CoOH(κ1N-H2NCH(R)CO2Et)sup>2+ →
2CoOH(κ2NO-H2NCH(R)CO2)">en)2CoOH(κ2NO-H2NCH(R)CO2)sup>2+ + EtOH
Because their 5-membered MNC
2O chelate ring is rather stable, amino acid complexes represent
protecting group
A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis.
In man ...
s for amino acids, allowing diverse reactions of the side chains.
Aminocarboxylate complexes
Organic compounds featuring two or more 2- and 3-aminocarboxylate groups are ligands of extensive use in nature, industry, and research. Famous examples include
EDTA
Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula H2N(CH2CO2H)2sub>2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes ev ...
and
NTA NTA may refer to:
* Nanoparticle Tracking Analysis, a method for visualizing and analyzing particles
* National Tax Agency, the official tax collecting agency of Japan
* National Tax Association, a non-profit organization in United States
* Nati ...
.
References
{{Coordination complexes
Coordination chemistry