Ligand

This article is about ligands in inorganic chemistry. For ligands in biochemistry, seeLigand (biochemistry).For other uses, seeLigand (disambiguation).

Cobalt complexHCo(CO)₄with five ligands

Incoordination chemistry,aligandis anionormoleculewith afunctional groupthat binds to a central metal atom to form acoordination complex.The bonding with the metal generally involves formal donation of one or more of the ligand'selectron pairs,often throughLewis bases.The nature of metal–ligand bonding can range fromcovalenttoionic.Furthermore, the metal–ligandbond ordercan range from one to three. Ligands are viewed as Lewis bases, although rare cases are known to involveLewis acidic"ligands".

Metals and metalloids are bound to ligands in almost all circumstances, although gaseous "naked" metal ions can be generated in a high vacuum. Ligands in a complex dictate thereactivityof the central atom, including ligand substitution rates, the reactivity of the ligands themselves, andredox.Ligand selection requires critical consideration in many practical areas, includingbioinorganicandmedicinal chemistry,homogeneous catalysis,andenvironmental chemistry.

Ligands are classified in many ways, including: charge, size (bulk), the identity of the coordinating atom(s), and the number of electrons donated to the metal (denticityorhapticity). The size of a ligand is indicated by itscone angle.

History

The composition ofcoordination complexeshave been known since the early 1800s, such asPrussian blueandcopper vitriol.The key breakthrough occurred whenAlfred Wernerreconciled formulas andisomers.He showed, among other things, that the formulas of many cobalt(III) and chromium(III) compounds can be understood if the metal has six ligands in anoctahedral geometry.The first to use the term "ligand" wereAlfred Wernerand Carl Somiesky, in relation to silicon chemistry. The theory allows one to understand the difference between coordinated and ionic chloride in the cobaltamminechlorides and to explain many of the previously inexplicable isomers. He resolved the first coordination complex calledhexolinto optical isomers, overthrowing the theory thatchiralitywas necessarily associated with carbon compounds.

Strong field and weak field ligands

Main article:Crystal field theory

In general, ligands are viewed as electron donors and the metals as electron acceptors, i.e., respectively,Lewis basesandLewis acids.This description has been semi-quantified in many ways, e.g.ECW model.Bonding is often described using the formalisms of molecular orbital theory.

Ligands and metal ions can be ordered in many ways; one ranking system focuses on ligand 'hardness' (see alsohard/soft acid/base theory). Metal ions preferentially bind certain ligands. In general, 'hard' metal ions prefer weak field ligands, whereas 'soft' metal ions prefer strong field ligands. According to the molecular orbital theory, the HOMO (Highest Occupied Molecular Orbital) of the ligand should have an energy that overlaps with the LUMO (Lowest Unoccupied Molecular Orbital) of the metal preferential. Metal ions bound to strong-field ligands follow theAufbau principle,whereas complexes bound to weak-field ligands followHund's rule.

Binding of the metal with the ligands results in a set of molecular orbitals, where the metal can be identified with a new HOMO and LUMO (the orbitals defining the properties and reactivity of the resulting complex) and a certain ordering of the 5 d-orbitals (which may be filled, or partially filled with electrons). In anoctahedralenvironment, the 5 otherwise degenerate d-orbitals split in sets of 3 and 2 orbitals (for a more in-depth explanation, seecrystal field theory):

• 3 orbitals of low energy: d_xy,d_xzand d_yzand
• 2 orbitals of high energy: d_z²and d_x²−y².

The energy difference between these 2 sets of d-orbitals is called the splitting parameter, Δ_o.The magnitude of Δ_ois determined by the field-strength of the ligand: strong field ligands, by definition, increase Δ_omore than weak field ligands. Ligands can now be sorted according to the magnitude of Δ_o(see the tablebelow). This ordering of ligands is almost invariable for all metal ions and is calledspectrochemical series.

For complexes with a tetrahedral surrounding, the d-orbitals again split into two sets, but this time in reverse order:

• 2 orbitals of low energy: d_z²and d_x²−y²and
• 3 orbitals of high energy: d_xy,d_xzand d_yz.

The energy difference between these 2 sets of d-orbitals is now called Δ_t.The magnitude of Δ_tis smaller than for Δ_o,because in a tetrahedral complex only 4 ligands influence the d-orbitals, whereas in an octahedral complex the d-orbitals are influenced by 6 ligands. When thecoordination numberis neither octahedral nor tetrahedral, the splitting becomes correspondingly more complex. For the purposes of ranking ligands, however, the properties of the octahedral complexes and the resulting Δ_ohas been of primary interest.

The arrangement of the d-orbitals on the central atom (as determined by the 'strength' of the ligand), has a strong effect on virtually all the properties of the resulting complexes. E.g., the energy differences in the d-orbitals has a strong effect in the optical absorption spectra of metal complexes. It turns out that valence electrons occupying orbitals with significant 3 d-orbital character absorb in the 400–800 nm region of thespectrum(UV–visible range). The absorption of light (what we perceive as thecolor) by these electrons (that is, excitation of electrons from one orbital to another orbital under influence of light) can be correlated to theground stateof the metal complex, which reflects the bonding properties of the ligands. The relative change in (relative) energy of the d-orbitals as a function of the field-strength of the ligands is described inTanabe–Sugano diagrams.

In cases where the ligand has low energy LUMO, such orbitals also participate in the bonding. The metal–ligand bond can be further stabilised by a formal donation ofelectron densityback to the ligand in a process known asback-bonding.In this case a filled, central-atom-based orbital donates density into the LUMO of the (coordinated) ligand. Carbon monoxide is the preeminent example a ligand that engages metals via back-donation. Complementarily, ligands with low-energy filled orbitals of pi-symmetry can serve as pi-donor.

Metal–EDTAcomplex, wherein the aminocarboxylate is a hexadentate (chelating) ligand

Cobalt(III) complex containing sixammonialigands, which are monodentate. The chloride is not a ligand.

Classification of ligands as L and X

Main article:Covalent bond classification method

Ligands are classified according to the number of electrons that they "donate" to the metal. L ligands areLewis bases.L ligands are represented byamines,phosphines,CO,N₂,andalkenes.Examples of L ligands extend to includedihydrogenand hydrocarbons that interact byagostic interactions.X ligands are halides andpseudohalides.X ligands typically are derived from anionic precursors such as chloride but includes ligands where salts of anion do not really exist such as hydride and alkyl.

Especially in the area oforganometallic chemistry,ligands are classified according to the "CBC Method" for Covalent Bond Classification, as popularized byM. L. H. Greenand "is based on the notion that there are three basic types [of ligands]... represented by the symbols L, X, and Z, which correspond respectively to 2-electron, 1-electron and 0-electron neutral ligands."

Polydentate and polyhapto ligand motifs and nomenclature

Denticity

Main articles:Denticityandchelate

Many ligands are capable of binding metal ions through multiple sites, usually because the ligands havelone pairson more than one atom. Such ligands are polydentate.Ligands that bind via more than one atom are often termedchelating.A ligand that binds through two sites is classified asbidentate,and three sites astridentate.The "bite angle"refers to the angle between the two bonds of a bidentate chelate. Chelating ligands are commonly formed by linking donor groups via organic linkers. A classic bidentate ligand isethylenediamine,which is derived by the linking of two ammonia groups with an ethylene (−CH₂CH₂−) linker. A classic example of a polydentate ligand is thehexadentatechelating agentEDTA,which is able to bond through six sites, completely surrounding some metals. The number of times a polydentate ligand binds to a metal centre is symbolized by "κⁿ",wherenindicates the number of sites by which a ligand attaches to a metal. EDTA⁴⁻,when it is hexidentate, binds as aκ⁶-ligand, the amines and the carboxylate oxygen atoms are not contiguous. In practice, the n value of a ligand is not indicated explicitly but rather assumed. The binding affinity of a chelating system depends on the chelating angle orbite angle.

Denticity (represented byκ) is nomenclature that described to the number of noncontiguous atoms of a ligand bonded to a metal. This descriptor is often omitted because the denticity of a ligand is often obvious. The complextris(ethylenediamine)cobalt(III)could be described as [Co(κ²-en)₃]³⁺.

Complexes of polydentate ligands are calledchelatecomplexes. They tend to be more stable than complexes derived frommonodentateligands. This enhanced stability, called thechelate effect,is usually attributed to effects ofentropy,which favors the displacement of many ligands by one polydentate ligand.

Related to the chelate effect is themacrocyclic effect.A macrocyclic ligand is any large ligand that at least partially surrounds the central atom and bonds to it, leaving the central atom at the centre of a large ring. The more rigid and the higher its denticity, the more inert will be the macrocyclic complex.Hemeis an example, in which theironatom is at the centre of aporphyrinmacrocycle, bound to four nitrogen atoms of the tetrapyrrole macrocycle. The very stabledimethylglyoximate complex of nickelis a synthetic macrocycle derived fromdimethylglyoxime.

Hapticity

Main article:Hapticity

Hapticity(represented by Greek letterη) refers to the number ofcontiguousatoms that comprise a donor site and attach to a metal center. Theη-notationapplies when multiple atoms are coordinated. For example,η²is a ligand that coordinates through two contiguous atoms.Butadieneforms bothη²andη⁴complexes depending on the number of carbon atoms that are bonded to the metal.

Ligand motifs

Trans-spanning ligands

Main article:Trans-spanning ligand

Trans-spanning ligands are bidentate ligands that can span coordination positions on opposite sides of a coordination complex.

Ambidentate ligand

Main article:Linkage isomerism

In contrast to polydentate ligands, ambidentate ligands can attach to the central atom in either one of two (or more) places, but not both. An example isthiocyanate,SCN⁻,which can attach at either the sulfur atom or the nitrogen atom. Such compounds give rise tolinkage isomerism.

Polydentate and ambidentate are therefore two different types of polyfunctional ligands (ligands with more than onefunctional group) which can bond to a metal center through different ligand atoms to form various isomers. Polydentate ligands can bond through one atom AND another (or several others) at the same time, whereas ambidentate ligands bond through one atom OR another. Proteins are complex examples of polyfunctional ligands, usually polydentate.

Bridging ligand

Main article:Bridging ligand

A bridging ligand links two or more metal centers. Virtually all inorganic solids with simple formulas arecoordination polymers,consisting of metal ion centres linked by bridging ligands. This group of materials includes all anhydrous binary metal ion halides and pseudohalides. Bridging ligands also persist in solution. Polyatomic ligands such ascarbonateare ambidentate and thus are found to often bind to two or three metals simultaneously. Atoms that bridge metals are sometimes indicated with the prefix "μ".Most inorganic solids are polymers by virtue of the presence of multiple bridging ligands. Bridging ligands, capable of coordinating multiple metal ions, have been attracting considerable interest because of their potential use as building blocks for the fabrication of functional multimetallic assemblies.

Binucleating ligand

Main article:Binucleating ligand

Binucleating ligands bind two metal ions.Usually binucleating ligands feature bridging ligands, such as phenoxide, pyrazolate, or pyrazine, as well as other donor groups that bind to only one of the two metal ions.

Metal–ligand multiple bond

Main article:Metal–ligand multiple bond

Some ligands can bond to a metal center through the same atom but with a different number oflone pairs.Thebond orderof the metal ligand bond can be in part distinguished through the metal ligandbond angle(M−X−R). This bond angle is often referred to as being linear or bent with further discussion concerning the degree to which the angle is bent. For example, an imido ligand in the ionic form has three lone pairs. One lone pair is used as a sigma X donor, the other two lone pairs are available as L-type pi donors. If both lone pairs are used in pi bonds then the M−N−R geometry is linear. However, if one or both these lone pairs is nonbonding then the M−N−R bond is bent and the extent of the bend speaks to how much pi bonding there may be.η¹-Nitric oxide can coordinate to a metal center in linear or bent manner.

Spectator ligand

Main article:Spectator ligand

A spectator ligand is a tightly coordinating polydentate ligand that does not participate in chemical reactions but removes active sites on a metal. Spectator ligands influence the reactivity of the metal center to which they are bound.

Bulky ligands

Main article:Ligand cone angle

Bulky ligands are used to control the steric properties of a metal center. They are used for many reasons, both practical and academic. On the practical side, they influence the selectivity of metal catalysts, e.g., inhydroformylation.Of academic interest, bulky ligands stabilize unusual coordination sites, e.g., reactive coligands or low coordination numbers. Often bulky ligands are employed to simulate the steric protection afforded by proteins to metal-containing active sites. Of course excessive steric bulk can prevent the coordination of certain ligands.

TheN-heterocyclic carbeneligand calledIMesis a bulky ligand by virtue of the pair of mesityl groups.

Chiral ligands

Main article:Chiral ligand

Chiral ligands are useful for inducing asymmetry within the coordination sphere. Often the ligand is employed as an optically pure group. In some cases, such as secondary amines, the asymmetry arises upon coordination. Chiral ligands are used inhomogeneous catalysis,such asasymmetric hydrogenation.

Hemilabile ligands

Main article:Hemilability

Hemilabile ligands contain at least two electronically different coordinating groups and form complexes where one of these is easily displaced from the metal center while the other remains firmly bound, a behaviour which has been found to increase the reactivity of catalysts when compared to the use of more traditional ligands.

Non-innocent ligand

Main article:Non-innocent ligand

Non-innocent ligands bond with metals in such a manner that the distribution of electron density between the metal center and ligand is unclear. Describing the bonding of non-innocent ligands often involves writing multipleresonance formsthat have partial contributions to the overall state.

Common ligands

See also:Complex (chemistry) § Naming complexes

Virtually every molecule and every ion can serve as a ligand for (or "coordinate to" ) metals. Monodentate ligands include virtually all anions and all simple Lewis bases. Thus, thehalidesandpseudohalidesare important anionic ligands whereasammonia,carbon monoxide,andwaterare particularly common charge-neutral ligands. Simple organic species are also very common, be they anionic (RO⁻andRCO⁻
₂) or neutral (R₂O,R₂S,R_3−xNH_x,andR₃P). The steric properties of some ligands are evaluated in terms of theircone angles.

Beyond the classical Lewis bases and anions, all unsaturated molecules are also ligands, utilizing their pi electrons in forming the coordinate bond. Also, metals can bind to the σ bonds in for examplesilanes,hydrocarbons,anddihydrogen(see also:Agostic interaction).

In complexes ofnon-innocent ligands,the ligand is bonded to metals via conventional bonds, but the ligand is also redox-active.

Examples of common ligands (by field strength)

In the following table the ligands are sorted by field strength(weak field ligands first):

Ligand	formula (bonding atom(s) in bold)	Charge	Most common denticity	Remark(s)
Iodide(iodo)	I−	monoanionic	monodentate
Bromide(bromido)	Br−	monoanionic	monodentate
Sulfide(thio or less commonly "bridging thiolate" )	S2−	dianionic	monodentate (M=S), or bidentate bridging (M−S−M')
Thiocyanate(S-thiocyanato)	S−CN−	monoanionic	monodentate	ambidentate (see also isothiocyanate, below)
Chloride(chlorido)	Cl−	monoanionic	monodentate	also found bridging
Nitrate(nitrato)	O−NO− 2	monoanionic	monodentate
Azide(azido)	N−N− 2	monoanionic	monodentate	Very Toxic
Fluoride(fluoro)	F−	monoanionic	monodentate
Hydroxide(hydroxido)	O−H−	monoanionic	monodentate	often found as a bridging ligand
Oxalate(oxalato)	[O−CO−CO−O]2−	dianionic	bidentate
Water(aqua)	O−H2	neutral	monodentate
Nitrite(nitrito)	O−N−O−	monoanionic	monodentate	ambidentate (see also nitro)
Isothiocyanate(isothiocyanato)	N=C=S−	monoanionic	monodentate	ambidentate (see also thiocyanate, above)
Acetonitrile(acetonitrilo)	CH3CN	neutral	monodentate
Pyridine(py)	C5H5N	neutral	monodentate
Ammonia(ammine or less commonly "ammino" )	NH3	neutral	monodentate
Ethylenediamine(en)	NH2−CH2−CH2−NH2	neutral	bidentate
2,2'-Bipyridine(bipy)	NC5H4−C5H4N	neutral	bidentate	easily reduced to its (radical) anion or even to its dianion
1,10-Phenanthroline(phen)	C12H8N2	neutral	bidentate
Nitrite(nitro)	N−O− 2	monoanionic	monodentate	ambidentate (see also nitrito)
Triphenylphosphine	P−(C6H5)3	neutral	monodentate
Cyanide(cyano)	C≡N− N≡C−	monoanionic	monodentate	can bridge between metals (both metals bound to C, or one to C and one to N)
Carbon monoxide(carbonyl)	–CO, others	neutral	monodentate	can bridge between metals (both metals bound to C)

The entries in the table are sorted by field strength, binding through the stated atom (i.e. as a terminal ligand). The 'strength' of the ligand changes when the ligand binds in an alternative binding mode (e.g., when it bridges between metals) or when the conformation of the ligand gets distorted (e.g., a linear ligand that is forced through steric interactions to bind in a nonlinear fashion).

Other generally encountered ligands ( Alpha betical)

In this table other common ligands are listed in Alpha betical order.

Ligand	Formula (bonding atom(s) in bold)	Charge	Most common denticity	Remark(s)
Acetylacetonate(acac)	CH3−CO−CH2−CO−CH3	monoanionic	bidentate	In general bidentate, bound through both oxygens, but sometimes bound through the central carbon only, see also analogous ketimine analogues
Alkenes	R2C=CR2	neutral		compounds with a C−C double bond
Aminopolycarboxylic acids(APCAs)
BAPTA(1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)
Benzene	C6H6	neutral		and other arenes
1,2-Bis(diphenylphosphino)ethane(dppe)	(C6H5)2P−C2H4−P(C6H5)2	neutral	bidentate
1,1-Bis(diphenylphosphino)methane(dppm)	(C6H5)2P−CH2−P(C6H5)2	neutral		Can bond to two metal atoms at once, forming dimers
Corroles			tetradentate
Crown ethers		neutral		primarily for alkali and alkaline earth metal cations
2,2,2-cryptand			hexadentate	primarily for alkali and alkaline earth metal cations
Cryptates		neutral
Cyclopentadienyl(Cp)	C 5H− 5	monoanionic		Although monoanionic, by the nature of its occupied molecular orbitals, it is capable of acting as a tridentate ligand.
Diethylenetriamine(dien)	C4H13N3	neutral	tridentate	related to TACN, but not constrained to facial complexation
Dimethylglyoximate(dmgH−)		monoanionic
1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)
Diethylenetriaminepentaacetic acid (DTPA) (pentetic acid)
Ethylenediaminetetraacetic acid(EDTA) (edta4−)	(−OOC−CH2)2N−C2H4−N(CH2-COO−)2	tetraanionic	hexadentate
Ethylenediaminetriacetate	−OOC−CH2NH−C2H4−N(CH2-COO−)2	trianionic	pentadentate
Ethyleneglycolbis(oxyethylenenitrilo)tetraacetate(egta4−)	(−OOC−CH2)2N−C2H4−O−C2H4−O−C2H4−N(CH2−COO−)2	tetraanionic	octodentate
Fura-2
Glycinate(glycinato)	NH2CH2COO−	monoanionic	bidentate	other α-amino acid anions are comparable (but chiral)
Heme		dianionic	tetradentate	macrocyclic ligand
Iminodiacetic acid(IDA)			tridentate	Used extensively to makeradiotracersforscintigraphyby comple xing the metastable radionuclidetechnetium-99m.For example, incholescintigraphy,HIDA, BrIDA, PIPIDA, and DISIDA are used
Nicotianamine				Ubiquitous in higherplants
Nitrosyl	NO+	cationic		bent (1e−) and linear (3e−) bonding mode
Nitrilotriacetic acid(NTA)
Oxo	O2−	dianion	monodentate	sometimes bridging
Pyrazine	N2C4H4	neutral	ditopic	sometimes bridging
Scorpionate ligand			tridentate
Sulfite	O−SO2− 2 S−O2− 3	monoanionic	monodentate	ambidentate
2,2';6',2″-Terpyridine(terpy)	NC5H4−C5H3N−C5H4N	neutral	tridentate	meridional bonding only
Triazacyclononane(tacn)	(C2H4)3(NR)3	neutral	tridentate	macrocyclic ligand see also theN,N′,N″-trimethylated analogue
Tricyclohexylphosphine	P(C6H11)3orPCy3	neutral	monodentate
Triethylenetetramine(trien)	C6H18N4	neutral	tetradentate
Trimethylphosphine	P(CH3)3	neutral	monodentate
Tris(o-tolyl)phosphine	P(o-tolyl)3	neutral	monodentate
Tris(2-aminoethyl)amine(tren)	(NH2CH2CH2)3N	neutral	tetradentate
Tris(2-diphenylphosphineethyl)amine (np3)		neutral	tetradentate
Tropylium	C 7H+ 7	cationic
Carbon dioxide	–CO2,others	neutral		seemetal carbon dioxide complex
Phosphorus trifluoride(trifluorophosphorus)	–PF3	neutral

Ligand exchange

Aligand exchange(also calledligand substitution) is achemical reactionin which a ligand in a compound is replaced by another. Two general mechanisms are recognized:associative substitutionor bydissociative substitution.

A generalized example of ligand association

Associative substitutionclosely resembles theS_N2mechanism in organic chemistry. A typically smaller ligand can attach to an unsaturated complex followed by loss of another ligand. Typically, the rate of the substitution is first order in entering ligand L and the unsaturated complex.

A generalized example of ligand dissociation

Dissociative substitutionis common for octahedral complexes. This pathway closely resembles theS_N1mechanism in organic chemistry. The identity of the entering ligand does not affect the rate.

Ligand–protein binding database

BioLiPis a comprehensive ligand–protein interaction database, with the 3D structure of the ligand–protein interactions taken from theProtein Data Bank.MANORAAis a webserver for analyzing conserved and differential molecular interaction of the ligand in complex with protein structure homologs from the Protein Data Bank. It provides the linkage to protein targets such as its location in the biochemical pathways, SNPs and protein/RNA baseline expression in target organ.

See also

• Bridging carbonyl
• Crystal field theory
• DNA binding ligand
• Inorganic chemistry
• Josiphos ligands
• Ligand dependent pathway
• Ligand field theory
• Ligand isomerism
• Spectrochemical series

External links

• See the modeling of ligand–receptor–ligand binding in Vu-Quoc, L.,Configuration integral (statistical mechanics),2008. This wiki site is down; seethis article in the Internet Archive from 2012 April 28.