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Chapter 1
Introductory concepts: fundamentals of metal
complexes – an overview
1.1 Metal-ligand bond
In order to define the structure of a metal complex, one should know the coordination
number of the central metal in question, the conformation of the complex ion and
finally the nature of the bond between the metal and the ligand. On the other hand,
the nature of the bond itself is closely related to the coordination number and stereo-
chemistry and thus can be interpreted in terms of the reactivity of the metal complex.
The fundamental understanding of the metal-ligand bond is based on atomic
properties and electronic configuration, the nature of orbitals involved, properties
such as ionization potential and orientations of orbitals for overlapping, which eluci-
date their nature and bonding. Not going much into the details of these, at least a cur-
sory and simple discussion warrants an understanding of crystal field and ligand field
theories. To help one understand, the best sources have been used to put forward the
discussion.
1.2 Bond types
Based on the bond properties of metals, a category of bond type is essentially needed to
further our discussion. In an extreme ionic bond, the metal ion M
n+
is attached to a
certain number of ligands, either charged (e.g., Cl
-
) or uncharged (e.g., NH
3
). In the first
case, the metal is held through electrostatic attraction between oppositely charged ions.
On the other hand, when the ligand is neutral, Mn
n+
is held through attraction between
Mn
n+
and the dipole (static plus induced) on the neutral molecule (NH
3
). In the case of a
covalent bond (extreme rather than pure), the bond is essentially like the bond in H
2
.
Therefore, in complexes, the analogy is more apt with hetero nuclear bonds like C–H.
Due to the electronegativity difference the bond will have some polar character too.
However, a very simple understanding of the metal-ligand bond is presented in the
flow sheet diagram (Fig. 1.1).
Fig. 1.1: Bond types for metal-ligand interactions.
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1.2.1 σ bonds
Sigma bonds (σ bonds) are said to be the strongest covalent bonds formed by head-on
overlapping between atomic orbitals. For diatomic molecules, they are defined using
symmetry groups. Thus, using this approach, a σ bond is symmetrical with respect to
rotation about the bond axis. Examples are s + s, p
z
+p
z
,s+p
z
and d
z
2
+d
z
2
(here z is
defined as the axis of the bond). Startingfromtheextremecaseofanionicbond,
which is a highly polar σ type of bond, the M-L bond can be simplified. They are the
strongest type of covalent bond as they are formed by direct overlapping of orbitals.
The σ in Greek alphabets refers to sigma. If viewed down the bond axis, a σ MO has a
circular symmetry, sounding similar to “s” atomic orbitals. Typically, sigma bonds are
single bonds, whereas double bonds are a mix of σ and π bonds.
1.2.2 π bonds
There are three main types of π bonds in metal complexes. The most common sce-
nario is when a ligand such as CO or CN
–
donates its sigma nonbonding electrons to a
metal while accepting electron density from the metal via the overlapping of the
metal t
2g
orbital and a π
✶
orbital. Such a situation is called back bonding. In this case,
the ligand donates σ electron density to the metal, and the metal donates π electron
density to the ligand. A σ-donor π-acceptor is the precise action of the ligand. The situ-
ation can be visualized more effectively using the following examples (Fig. 1.2).
1.2.3 d–d π bonding
When an element such as phosphorus, having a σ symmetry ion pair and empty
metal 3d orbitals, binds to any metal having electrons in a t
2g
orbital, d–d π bonding
occurs. This is commonly found in examples of phosphine complexes, such as with
triphenyl phosphine, which is bonded to low-valent metals in transition or late transi-
tion metals. In this case, the back bonding is similar to that with CO, except that the
acceptor orbital is a phosphorus 3d orbital in place of π
✶
orbital. We can understand
that here the phosphine ligand acts as a σ-donor and π-acceptor, resulting in dπ–dπ
bonding (Fig. 1.3).
Fig. 1.2: σ-Donor π-acceptor back bonding.
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1.2.4 d–p π bond
This is the third type of metal-ligand π bonding that occurs when a π-donor ligand, e.g.,
an element having both a σ symmetry electron pair and a filled orthogonal p-orbital, is
bonding to a metal. This is illustrated in Fig. 1.4 for an O
2–
ligand. O
2–
acts as both a σ-
donor and a π-acceptor simultaneously. Examples of this kind are O
2–
,N
3–
,F
–
, etc.
A summary of different types of π bonds in metal complexes is presented in Fig. 1.5.
1.3 Coordination number
The coordination number, also called ligancy, of the central atom in a complex is the
number of atoms, molecules or ions bonded to it. The ion, molecule or atom surround-
ing the central metal is called a ligand. The coordination number generally helps in
determining the possible geometry of complexes, and there exist many possible geom-
etries for each value of the coordination number for the central atom. To summarize
the stereochemistry or geometries of various comple xes based on the coordination
number of the central atom, Tab 1.1 provides a tabular representation for the sake of
brevity.
Fig. 1.3: dπ–dπ bonding picture.
Fig. 1.4: d–p π bond picture.
Fig. 1.5: Types of π bonds.
1.3 Coordination number 3
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1.4 Classification of metals
1.4.1 Class A and class B metals
As per affinity for ligands in an aqueous matrix, metals have been classified into two
classes: A and B. Class A metals are disting uished by their order of affinity toward
halogens in aqueous solution. The order demarcates F
–
>Cl
–
>Br
–
>I
–
and they are
better at coordinating with more electronegative ligands. The post-transition metals
and inert pair elements fall into class B metals. Furthermore, from d
1
to d
3
, a gradual
change of class from A → B is observed.
Tab. 1.1: Molecular geometries and coordination numbers.
S. no. Coordination Nonbonding
pairs present
Type of
hybridization
Examples Shape of molecules
. sp HgCl
Linear
sp
SnCl
V-shaped
sp
H
O V-shaped
sp
dz
[Cl
]
–
Linear
sp
dz
dx
– y
– Linear
. sp
Cl
Trigonal
sp
NH
Pyramidal
sp
dz
ClF
T-shaped
sp
dz
dx
– y
– T-shaped or pyramidal
. sp
CH
Tetrahedral
sp
dz
SF
Irregular tetrahedral
sp
dz
dx
–y
[Cl
]
–
Square
. sp
dz
PF
Trigonal bipyramidal
sp
dz
dx
–y
IF
Square pyramidal
. sp
dz
dx
–y
SF
Octahedral
sp
d
[Sb F
]
–
Distorted octahedral
. sp
d
lF
Pentagonal bipyramidal
. sp
d
[TaF
]
–
TiCl
Two diarsine
dodecahedral
Square antiprism
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1.5 Metal-metal bond in coordination compounds
In complexes, the stable metal-metal bonds and their occurrence as well as stability
depend on the nature of surrounding ligands and the electronic configuration of the
metal-atom including the oxidation state of the metal. A tabular summary of common
types of metal-metal bonds is presented in Tab 1.2.
1.6 Ligands
Ligand in Latin means to tie or bind. Ligand means any ion or molecule that binds to
a transition-metal ion to form a complex, in the simplest words. Further, the number
of ligands attached to a metal ion is called ligancy or coordination number. The li-
gands are either simple ions or molecules, e.g., Cl
–
,NH
3
or ethylene diamine (NH
2
–
CH
2
–NH
2
). Depending on the number of groups through which a ligand donates elec-
trons, the classification of ligands or their denticity is defined (Tab 1.3). In coordina-
tion compounds or complexes, the following classes are described. Even on the basis
of the nature of the bond between ligand and metal, ligands are broadly classified as
1) Anionic ligands Cl
–
,Br
–
,CN
–
2) Cationic ligands NO
+
3) Neutral ligands CO, H
2
O, NH
3
Tab. 1.2: Categories of metal-metal bonds.
S. no. Category I Category II Category III Category IV Category V
. Solid metals
(multicentric
bonds)
Bonds in metals
have a small
number of
electrons
d
d
d
d
Complexes with
one or more
covalent bonds
Metal donor type, e.g.,
weak Ni–Ni in bisdimethyl
glyoxime–Ni complex
Ionic in alloys
Tab. 1.3: Various classes of ligands.
Unidentate Bidentate Polydentate Chelating Ambidentate
Ligands with
only one atom
for
coordinating, e,
g., NH
,Cl
–
and
H
O
When a ligand can
bind to a metal
through two separate
donor atoms, e.g.,
ethylene diamine
When there
are many
donor
atoms, e.g.,
EDTA
Ligands having more than
two or three donor sites
can form a ring-like
structure, e.g.,
acetylacetones,
ethylenediamine and EDTA.
Have the ability to
bind to center
metal through two
different elements,
e.g., SCN
–
1.6 Ligands 5
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Apart from the three classes described earlier, a classification based on density or
sites available for donation is summarized in Tab 1.3.
1.7 Isomerism and chirality
Isomerism is an important factor in clinical pharmacology or pharmacotherapeutics.
Since isomers differ in their action as drugs. The pharmacodynamics and pharmaco-
kinetics (PK) are the most important areas of drug design and development. The
knowledge of isomerism is extremely helpful in introducing safer and more effective
drugs, and this in drug design is a key factor. Many of the current drugs switch from
racemic mixtures to one of their isomers, which is more effective. Cetirizine, for ex-
ample, is one such case. Levocetirizine is safer and more effective. However, since the
present book deals with the therapeutic applications of metal complexes, it warrants
a cursory, conceptual and brief explanation of isomerism, chirality as well as related
factors. For simplicity and clear understanding, the matter is being incorporated with-
out losing the primary focus of the book.
Historically, as soon as the development of coordination compounds and their ap-
plications emerged, understanding isomerism significantly helped in later develop-
ments. The very existence of coordination compounds with the same formula yet
different structures became crucial. Such compounds with the same formula but differ-
ent structures are called isomers. Since the structural formulas govern the properties of
these compounds (isomers), it was important to know which isomer we are dealing
with. It is significant to know that isomers are compounds having the same molecular
formula but different stru ctures and do not necessarily have the same physical or
chemical properties. Although it is relevant to mention different types of isomers like
stereoisomers, enantiomers and geometrical isomers, two basic types of interest from
our point of view are structural isomers and stereoisomers. The two classes thus are
a) Structural isomers
b) Stereoisomers
1.8 Structural isomers
Isomers that have the same molecular formula yet differ in structure are called struc-
tural isomers. They differ in which atoms are bonded to one another and differ in bond
types. Thus, this type of isomer can be classified further into the following types:
(i) Ionization isomers
When ligands that are bound to a metal center exchange places with an anion or neutral
molecule outside of the coordination sphere, this kind of isomerism is exhibited. This
gives rise to different chemical properties. Figure 1.6 depicts this kind of isomerism.
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(ii) Hydrate isomers/solvent isomers
When isomerism results from the replacemen t of a coordinated group by a solvent
molecule, this is called solvate isomerism. When the solvent is water, it is called hy-
drate isomerism. CrCl
3
.6H
2
O is the best example, which may contain 4, 5 or 6 water
molecules in its coordination sphere. This example shows how properties differ as the
number of water molecules differs in the sphere:
Example of water elaborates the isomerism, yet many solvents are found in host crys-
tals and change the properties, and isomers are called hydrate isomers. Although
water imparts different properties due to its reactivity, other solvents may or may not
impact to that extent.
(iii) Coordinate isomers
Compounds containing complex anionic/cationic parts that can interchange some li-
gands are coordinate isomers. This means that there are two compounds bound to-
gether, one having a negative charge and the other with a positive charge. Thus, in
this class, the anion and cation complexes of a coordination compound exchange one
or more ligands. The following example provides an apt description of this type.
Fig. 1.6: Ionization isomers.
[CrCl
(H
O)
]Cl.H
O Bright green-colored
[CrCl(H
O)
]Cl
.H
O Gray green-colored
[Cr(H
O)
]Cl
Violet-colored
Fig. 1.7: Example of hydrate isomers.
[Co(NH
3
)
6
][Cr(CN)
6
] [Cr(NH
3
)
6
][Co(CN)
6
]
NH
3
3+
NH
3
NH
3
NH
3
Co
H
3
N
H
3
N
3
-
Cr
NC
NC
CN
CN
CN
CN
NH
3
3+
NH
3
NH
3
NH
3
Cr
H
3
N
H
3
N
3
-
Co
NC
NC
CN
CN
CN
CN
Fig. 1.8: Example of coordination isomers.
1.8 Structural isomers 7
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(iv) Linkage isomers
Ambidentate ligands are those that can coordinate in more than one way. Examples
of such ligands, particularly monodentate ones, are SCN
–
/NCS
–
NO
2
–
/ONO. When such
ligands form a complex, linkage isomer ism occur s. NO
2
–
and ONO
–
are examples
where the ligand can donate through a nitrogen atom (NO
2
–
) or through an oxygen
atom (ONO
–
). The same is the case when SCN
–
or NCS
–
binds through sulfur and nitro-
gen atoms. To classify, the following figure is useful: SCN
–
or NCS
–
.
1.9 Geometric isomers
Metal complexes differing only in the placement of ligands adjacent to each other
(cis) or across from one another (trans) show geometric isomerism. This is significant
in the case of square planar as well as octahedral complexes.
In the case of a square planar complex, all varieties are equivalent. Thus, it is un-
important which corner is occupied by a ligand B in an MAB
3
type of complex. This
means that only a single geometric isomer is possible, giving rise to all four identical
chemical structures. These four structures can be superimposed by rotating the com-
plex in space. Figure 1.10 depicts the situation more precisely.
In the case of an MA
2
B
2
-type square planar complex, the situation changes, and there
are two possible isomers. The A ligands can be across from each other, giving a trans
structure, or they can be on the same side, forming a cis structure. Thus, in the case of
MA
2
B
2,
there are four cis isomers and two trans isomers as shown in Fig. 1.11. The cis
and trans isomers are chemically different since by simply flipping or rotating the
molecule,, we cannot convert a cis structure to a trans structure.
NH
3
NH
3
NH
3
NH
3
Co Co
N
NO
2+ 2+
O
O
O
NH
3
NH
3
H
3
NH
3
N
H
3
NH
3
N
Fig. 1.9: Example of linkage isomer ligands.
M
B
A
M
A
AA
=
M
A
M
A
=
A
B
BB
A
=
A
AA
A
Fig. 1.10: Square planar complex MA
3
B type showing a chemically identical isomer.
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The chemically different cis and trans structures have different therapeutic values in
the anticancer drug cisplatin. While cisplatin is effective against cancer of reproduc-
tive organs, the trans isomer is inactive:
cis − Pt NH
3
ðÞ
2
− active
trans − Pt NH
3
ðÞ
2
− inactive
Another type of complex where geometric isomerism plays a significant rol e is the
octahedral type. These complexes also show cis and trans structures. When the struc-
Fig. 1.11: Cis-trans isomers of MA
2
B
2
type.
(a)
(b)
(c)
Fig. 1.12: (a) MA
5
B-type complex (only by rotating the molecule in space the other image can be
superimposed). (b) MA
4
B
2
octahedral cis and trans isomers. (c) MA
3
B
3
octahedral fac and mer isomers.
1.9 Geometric isomers 9
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ture of an octahedral complex is drawn, it is depicted as if four of the inplane ligands
are different from the two “along the axis” ligands. We also designate these as equato-
rial and axial ligands for the sake of convenience. We can draw three different types,
viz., MA
5
B, MA
4
B
2
and MA
3
B
3
structures. A pict orial representation in Fig. 1.12 will
clarify the concept for an octahedral complex of the MA
5
B type more aptly.
In MA
4
B
2
, two isomers – cis and trans – are possible, as shown in Fig. 1.12b.
In the case of an MA
3
B
3
type of complex, when ligand A is replaced by one B, the
situation changes. When the three ligands of the other type occupy opposite triangu-
lar faces of the octahedron, they are called fac (facial) isomers. When th e opposite
situation is imagined, with the three ligands of each kind occupying opposite triangu-
lar faces or on the meridian of the complex, it is termed as mer isomer. Figure 1.12c
depicts this.
1.10 Conclusion
Isomerism and stereochemistry play a critical role in drug action, and thus metal com-
plexes and their stereochemistry are equally significant. The drug and the shape of
the molecule as a drug determine how a particular molecule interacts with different
biological molecules such as enzymes and receptors present in the body. However,
the above sections apprise a reader of the basics, and much detail is beyond the
scope. Further reading can be done from standard text books the topic.
1.11 Chirality
Any molecule that is non-superimposable on its mirror image is called a chiral mole-
cule, and this property is called chirality. Such molecules are extremely important in
chemistry and, in particular, medicinal chemistry. A rough estimate is that more than
half of the drugs in use are chiral compounds. Furthermore, nearly 90% of chiral drugs
are marketed as racemates, having an equimolar mixture of two enantiomers [1]. They
may have the same chemical structures; yet most isomers of chiral drugs show signifi-
cant differences in their ph armaceutical as well as metabolic properties . From this
point of view, a cursory understanding of chiral chemistry is more than desirable for
any discussion on the medicinal application of metal complexes as drugs.
The founder of chiral chemistry was Louis Pasteur, who separated for the first
time in 1848 two isomers of sodium ammonium tartrate [2, 3]. Chiral chemistry plays
an important role in the entire life sciences including plants, animals and even phar-
maceutical and allied industries. However, the important role of chiral chemistry can
be envisaged and realized by the fact that the 2001 Nobel Prize in Chemistry was
awarded to three scientists, William S. Knowles, Prof. P. K. Barry Sharpless and Prof.
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