: The Current Re-evaluation: Considerations of Selectivity, Toxicity and

Efficacy
New functional groups discovered of explosion in synthetic potential of organometallic
chemistry by the wide range area. The new discovery of Rosenberg in the field of metal-based
drugs is directly attributable. The discovery of the antitumor effects of the inorganic type’s drug
like cisplatin-1, which have works against the testicular cancer. The compounds have been
synthesized by Peyrone in 1844 [28] but after 120 years later that Rosenberg (1969) upgraded
the properties [29-30]. Till date near about 30,000 article were published on the platinum
complexes of organometallic compounds, which is an excellent approach to the subject can be
found [31] and overviews of metal antitumor agents can be found in the literature of Keppler
[32], Sadler [33] . Inorganic complexes were approved for the clinical trial or used as antitumor
drugs, which are Cisplatin-1, Carboplatin-2, Nedaplatin-3 and Oxaliplatin-4 (colorectal cancer).
Several others types of clinical testing and the mechanism of action have been examined [34].

O H2
H3N Cl H N O H3N O N O
3 O O
Pt Pt Pt
Pt
H3N Cl H3N O
H3N O O N O O
O
H2
1 2 3 4
The most important thing is that all platinum based complexes were used to impetus for
anticancer complexes, including cellular resistance to platinum which is sometimes encountered
in the clinic tests, cisplatin have some toxic side effects. This can be severe for its limited
activity against some other types of cancers [35]. In an attempt to overcome these difficulties, in
particular those linked to general toxicity, the possibility of using inorganic complexes of other
metals has been explored. For example, a ruthenium (III) salt, 5 (NAMI-A), [ImH] + [trans-
RuCl4 (DMSO) Im]–, imidazolium trans-imidazole (dimethyl sulfoxide) tetrachlororuthenate,
shows interesting anti- metastatic activity as well as possessing low toxicity [36]. Faze me
clinical trials indicate that it is well tolerated in human subjects [37].
 HN

H +
N N
Cl Cl Cl
Ru Ti
Cl Cl NH Cl
S
O CH3
CH3
5 6
Figure 1.3: Chemical structure of NAMI-A 5 and titanocene dichloride -6
The coordination chemistry of organometallic complexes of the same type have also
been studied and it have been considerable elsewhere, particularly in the field of metallocene
series with metals ions such as Titanium, Iron, Molybdenum, Vanadium, rhenium, Cobalt,
Ruthocenium and so on [38]. Titanocene dichloride-6 is an example, the structural comparisons
between Titanocene dichloride-6 and cisplatin- 1 is immediately clear. This organometallic
complex Titanocene dichloride-6 has been in clinical trials and was believed to react with diribo
nucleic acid in a similar to the cisplatin complex. However this complex is difficult for
formulation because of it’s under goes hydrolysis reaction. The clinical response was not
encouraging and trials have been abandoned. It should also be noted that the Titanium (IV)
products resulting from the hydrolysis process show a strong proliferative effect in hormone-
dependent breast cancers [39].

The structure contains two Cp units in which all five carbon atom of a cyclopentadienyl
ligand interacting with the metal center. Ferrocene has an eclipsed configuration in the gas phase
and is nearly eclipsed in the solid state. The barrier to rotation between the two rings is only 4±1
kJ/mol and this allows the rings to have free rotation. All the C-C bonds are of the same length
and the iron is equidistant from all the Cp ring carbons. Neutron diffraction has also shown that
the hydrogen atoms on the Cp rings are tilted slightly towards the iron center in ferrocene,
presumably because this shift permits a better overlap of the Fe orbitals with the pi-orbitals of the
Cp rings. In the recent years, ferrocene is widely applicable for the preparation of functional
derivatives used in many areas like catalysis, material science, hydrometallurgy, biology and
medicine. Ferrocene is also the safest additive used so far as it does not cause any environmental
pollution or health related hazardous [40]. It is claimed that, if used as fuel catalyst for rocket
propellant, it can improve the combustion speed by one to four times more, lower the
temperature of exhaust pipes and avoid infrared chase. When used in fuel oils as diesel oil, heavy
oil and light oil, it can eliminate smoke, save energy and reduce air pollution.
Metallocenes, including ferrocene, are also known to have a wide range of biological
applications. Ferrocene has attracted particular attention due to its aromatic character, stability
and low toxicity. It can also be easily derivative and the central iron atom is also easily oxidized
from Fe (II) to Fe (III). The medicinal application of ferrocene is currently an active area of
research with many reports showing its activity in vivo and in vitro and its potential as an anti-
tumor, anti-malarial and anti-fungal agent [41]. Therefore, the astounding diversity of the
chemistry demonstrated by this compound is unique in organometallic chemistry.

Varieties of metal complexes have been used as drugs and are well known to increase their
activity [42-43]. Moreover; several drugs have been administered as metal complexes and shows
higher activity towards specific targets. Ferrocene schiff bases are a special class of azomethine
compound [44] which is found to contain ionic and neutral moieties. The β nitrogen present in
these compounds coordinated to the metal atom has an interesting stereochemistry whereas
nitrogen remains uncoordinated. On the other hand the remaining oxygen atom can form a
covalent bond with the metal atom. Some metal complexes of thiosemicarbazone/semi carbazone
have also been reported to show potential antitumor [45], antibacterial [46], antiviral [47], anti-
fungal [48] and anti- malarial activities [49]. The use of organometallic compounds like
ferrocenyl compounds as bioactive molecule have been growing rapidly and several useful
applications, hence ferrocene is more stable, nontoxic and has interesting redox properties.
Many ferrocene based compounds have anti-tumor, anti-malarial, anti-fungal, and cytotoxic and
diribo nucleic acid cleaving activities. Some of these ferrocenyl compounds have been used as
ligands which can form many types of metal complexes.

The interest in the research of metal complexes of ferrocene based ligands is based on
expectation that the cyclopentadienyl metal moiety in ferrocene may cause electronic effects on
the coordination behavior of the donor centers of these ligands that may influence the in vitro
antibacterial, antifungal properties of such organometallic based compounds. In the present
work, a synthetic strategy has been developed to prepare various Schiff base compounds
containing organometallic species like ferrocene.

Ferrocene based compounds with porphyrins were already associated with various
important manners with different real objectives. These compounds have its own donor-acceptor
level and they have electrochemical activities have especially used for its own advantages to
investigate the photo induced electron transfer processes, to imitate mimic photosynthesis active
sites [50-51]. It’s an exact number of times; their synthetically importance for the development
of molecular based electronic devices were prepared for multiple oxidation-reduction active
centers [52-53] or molecular electrogenic sensors [54]. Their ability to turned outside to accept
or donate the several electrons at distinct potentials are particularly interesting in multi-electron
oxidation –reduction redox catalytic reactions[55] and the multi-bit information storage at the
molecular level can be used [56-57]. The nature of porphyrins based organometallic compounds
linkage between these oxidation-reduction active centers also have been shown to in vigorous
influence for their ‘communication’ and numerous studies will understanding these interactions.

Due to its rare structural properties and electronic properties, combined with large
chemical reactivity, the oxidation-reduction sympathetic unit of ferrocene has been without
doubt. It is largely associated with metallocene and there are few examples of porphyrins
associated with non iron containing metallocenes or organometallic compound fragments [58-
59]. The large number of applications of ferrocene & porphyrins or porphyrins based
organometallic compounds can be found in the literature. We have chosen to review these
structural functions of their association mode, which have been accomplished directly through
various sites linked to the meso or β-pyrrolic positions of porphyrins based compounds. Since
the discovery of ferrocene cyclopentadienyl have been among the most important ligands in
organo-transition metal chemistry because they form a wide range of stable complexes whose
steric and electronic properties can easily be tailored by varying the ring substituent’s [60]. A
vast number of mono, cyclopentadienyl transition metal complexes have been reported in recent
years. Cp based transition metal compounds were being designed to serve the various purposes
like molecular sensor, molecular ferromagnetic, electrochemical agents, molecular switches,
liquid crystal and drugs [61]. The η5- cyclopentadienyl and related early transition metal
derivatives have been marked as an important source to serve the purposes of structural,
synthetic and catalytic organometallic chemistry. They are useful compounds which have
found applications as reagents in organic chemistry [62], as soluble Ziegler-Natta catalysts
and as cancer static compounds [63-64]. The Cp based transition metal compounds connect
the link between organometallic chemistry to biology, medicine and molecular biotechnology
[65]. Recent research has been focused to explore the chemistry of Organometallic Schiff
bases of ferrocene or Ruthenocene compound based complexes can act as an important in
antibacterial activity to the ferrocenium ion or rurhenocenium [66-68]. Ferrocene use as a
model for non- linear optical films &sensors [69-71]. The structure of ferrocene is as much
vital as its characteristics.

Ferrocene organometallic compound was first prepared in 1951 by two different

research scientist groups. It has two types of isomers one is orange coloured compound ,
stable, insoluble
0
in water and melting point of 173 C [72-73]. The observations which have prevent
the
possibility that the bonding in the ferrocene molecule with Carbon-Iron sigma bonding or
ionic bonding. The correct structure of ferrocene was developed, again by two research
groups. It has only one C-H stretching frequency, carbon atoms were electronically equivalent
developed & observed from Infrared spectrum by Wilkinson, and all carbon atoms have equal
in bonding with iron atom [74].

Ferrocene have sandwich structure which observed from X-ray diffraction studies by
Fischer & Pfab [75] confirmed & proposed, in which two cyclopentadienyl rings attached
with central iron atom were located. Ferrocene compounds carries aromaticity was confirmed
by Woodward, who performed electrophilic aromatic substitution reactions, such as the
Friedel- Crafts acylation with Aluminum trichloride on the ferrocene compound. Ferrocene
have found
6
that its reactivity is 3 x 10 times faster than aromatic benzene [76]. Ferrocene have two types
of
structure one is eclipsed (D 5h) and another is staggered (D 5d) conformation due to its two
cyclopentadienyl (Cp) rings. The energy of rotation about the Fe-Cp axis is very small and the
ground state structures of ferrocene may show either of these conformations.