**5. DNA interaction of ferrocenyl ureas and thioureas**

DNA is relatively the key target within cells for research work having small molecular entities important biologically, i.e., steroids, cancer-causing agents and other various modules of drugs [67]. The exploration of interactions of drug with DNA is far more imperative for consideration of characteristic molecular drug action mechanisms to its peculiar target and for fabrication of definite DNA-targeted drugs [68]. Usually, three binding approaches, intercalative mode of binding, groove binding, and electrostatic type of interactions, are involved in the noncovalent interactions

**59**

*Supramolecular Chemistry and DNA Interaction Studies of Ferrocenyl Ureas and Thioureas*

of small molecules with DNA [69]. The intercalative binding mode is resilient than the other two modes of binding due to the surface of intercalating molecule, which is

The introduction of a ferrocenyl group to molecules like urea and thiourea that bind with DNA is an auspicious strategy to take the ferrocene moiety in close proximity of DNA which most possibly boosts the probability of DNA damage and cell apoptosis. The above-discussed anticancer character of ferrocenyl derivatives is found to be reliant on mainly oxidation state of Fe in ferrocene moiety as approximate results clearly exhibited that the Fe(II) ferrocenyl derivative compound is

One of the Fe(II) compounds, ferrocifen, performs its action by altering the conformation of protein having receptor site as indicated by the results of the study carried out [74]. Binding of ferrocifen to estrogen receptor (ER) is considered to result in its dimerization, which is followed by attachment of the dimerized species to a particular targeted area of DNA. Reactive oxygen species (ROS), such as hydroxyl radicals (∙OH) produced as a result of electron transfer reactions, result in in-vivo formation of ferrocenium ion or formation of ferrocifen-ER complex. ROS produced can be responsible to damage DNA [75, 76] and may also control the anticancer activity by forming the radical metabolites that carry the biological impairment in cancerous regions [77].

To demonstrate the approach of interaction and the DNA binding constraints, different techniques are employed. Cyclic voltammetry is proved to be one of the most sophisticated and sensitive techniques to carryout DNA binding studies. Investigation of mode of interaction between DNA and derivative compounds is determined through shift in peak potential. Indication of intercalation of derivative compounds into double helix structured DNA comes from slightly positive shift of the peak potential. The ratio of binding of oxidized and reduced molecules is

= 0.05916 *log*(

respondingly. Positive shift is indicative for intercalation of derivative compounds with DNA. The formation of a supramolecular complex due to drug diffusion into DNA results in dropping of current in electrochemical analysis. Drop off in current is observed depending upon the number of transferred electrons, which is decreased upon formation of a supramolecular complex. Binding constant is

> [*DNA*] <sup>=</sup> *<sup>K</sup>*[(1 <sup>−</sup> *<sup>A</sup>*) \_\_\_\_\_\_\_ 1 − *i*/*io*

where is the binding constant, and *io* represent peak currents in the presence and absence of DNA, and is the proportionality constant. The plot of 1/[DNA]

Following are the examples of cyclic voltammetric results in **Figures 12** and **13** for the characteristic ferrocenyl thioureas discussed in Section 3.2 and their molecular

\_\_\_\_ *Kred*

are proper potentials of bound and free drug candidates, cor-

*Koxd*) (1)

− *K* (2)

sandwiched among aromatic and heterocyclic DNA base pairs [70–72].

found to have more activity than Fe(III)-containing compounds [73].

**5.2 DNA binding studies through cyclic voltammetry**

calculated using the following equation Eq. (1) [78, 79]:

calculated using the following equation Eq. (2) [80]:

\_\_\_\_\_\_ <sup>1</sup>

versus 1 <sup>−</sup> *<sup>i</sup>*/*io* produces binding constants.

structures in **Figures 9** and **10**.

− *Ef*°

*Eb*°

and *Ef*°

where *Eb*°

*DOI: http://dx.doi.org/10.5772/intechopen.84412*

**5.1 Activity of ferrocenyl moiety**

of small molecules with DNA [69]. The intercalative binding mode is resilient than the other two modes of binding due to the surface of intercalating molecule, which is sandwiched among aromatic and heterocyclic DNA base pairs [70–72].
