**3. Ferrocenyl ureas and thiourea**

Among the various ferrocenyl derivative compounds are i.e. amides, amines, polyacids, polymers, ureas, thioureas, and sulfonamide derivatives [30]. A lot of work is happening on the applications of ferrocenyl urea and thiourea compounds due to their pronounced interactions, supramolecular chemistry, electrochemical characteristics, and DNA interactions. Following are some examples of ferrocenyl urea and thiourea derivative compounds checked for their various activities depicted in **Figure 3** [30].

#### **3.1 Ferrocenyl ureas**

*Photophysics, Photochemical and Substitution Reactions - Recent Advances*

**2. Ferrocene derivatives**

against various diseases, for example, bacterial and fungal contagions [10, 11], malaria [12], cancer [13], and human immunodeficiency virus (HIV) [14].

Extensive applications of ferrocene and its derivative compounds in material science, homogeneous catalysis [15], nonlinear optics [16], and molecular sensors are observed [17]. Furthermore, an unexpected biological activity is often witnessed upon incorporating a fragment of ferrocene into a molecule of an organic compound [18]. Many ferrocene derivative compounds exhibit stimulating cytotoxic, antimalarial, antitumor, antioxidant, antifungal, and DNA-cleaving activity [19–21]. The anticancer [22] perspective of ferrocenyl derivative compounds was first premeditated around the 1970s. Brynes and collaborators explored the counter tumor action of ferrocenyl compounds containing amide or amine moieties against leukemia P-388 of the lymphocytic system [23]. They administrated these derivative compounds to mice intraperitoneally using either water or surfactant with water as Tween-80: water. The anti-tumor action of these compounds was considerable enough to show that the incorporation of the ferrocenyl moiety into an appropriate bearer could provide a drug with elevated antitumorous activity (**Figure 1**) [23]. Extensive study is carried out about ferrocene and its derivative compounds as efficient chemotherapeutic agents [24]. Stability, electroactivity, and extraordinary spectroscopic actions of ferrocene-incorporated organometallics are reasoned for being auspicious contenders for various biological applicabilities [25–27]. With reversible redox characteristics and elevated cell penetrability owing to its extensive lipophilicity, ferrocenyl moiety is responsible for pronounced characteristics of ferrocenyl derivative

**52**

**Figure 2.**

**Figure 1.**

*Structure of ferrocene.*

*Ferrocenyl derivative verified against lymphocytic leukemia P-388.*

Urea (R1R2NC〓ONR3R4) is a striking building block in consequence of its widespread bioactivities and extensive bioavailability from natural products [31]. Among the urea derivative compounds, urea derivatives having aromaticity in them such as N-phenyl-N-(2-chloroethyl)urea and heterocyclic urea derivatives illustrate potential anticancer activities because of their efficient inhibitory effect against the receptor tyrosine kinases (RTKs) [32].

Urea is ascertained to be an appealing building obstruct for receptors of anion as it contributes two comparatively robust H-bonding positions [33]. The two N▬H groups in urea are able to make a bond with the only acceptor atom to form a ring structure comprising six-membered chelate or bind with two nearby oxygen atoms in an oxy-anion to give a ring structure consisting of eight-membered chelate as


**Figure 3.**

*Some representative ferrocenyl ureas and thioureas.*

**Figure 4.** *Ferrocenyl urea [34].*

**Figure 5.** *Molecular structure of 1-(3-bromobenzoyl)-3-(4-ferrocenylphenyl)urea.*

depicted in (**Figure 4**). These N-H groups are modified to supplement target anion and minimal intramolecular H-bonding to observe strong and selective binding characteristics [34] (**Figure 4**).

Over the past few years, assortment of urea-based hosts comprising one or more than one urea subunits is premeditated and tested for anion recognition and for being capable of sensing [35]. New perceptions into characteristics of interactions between urea and anionic moiety providing structural measures for considered designing of novel anion-selective receptors which contain two or additional urea binding groups have also been discovered in recent times [36]. On the other hand, there are few instances of ferrocenyl urea derivatives as redox active anionophores [37]. The molecular structure of a representative ferrocenyl urea derivative is presented in **Figure 5** [38].

#### **3.2 Ferrocenyl thioureas**

Replacement of an oxygen atom in urea moiety by a sulfur atom results in thiourea formation, the characteristics of which are significantly diverged than those of urea due to the variation in electronegative character among sulfur and oxygen atoms [39]. Thiourea-based compounds and complexes have also been explored for several biological activities because of the thio-carbonyl group, which influences biochemical activity by lipophilic or hydrophilic character and electronic properties of derivative compounds [40].

**55**

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

The lipophilicity/hydrophilic characters and the electronic properties of thiourea

derivative compounds are greatly inclined due to the presence of thio-carbonyl moiety which in turn affects the labile nature of leaving substituents, hence regulating the biochemical activity. Various ferrocenyl thiourea derivative compounds have been discovered, which are significantly important for various features of antitumorous agents due to their inhibitory rejoinder against receptor tyrosine kinases (RTKs), protein tyrosine kinases (PTKs), and NADH oxidases [41, 42]. Various thiourea derivatives exhibited bioactivities against different infectious diseases, leukemias, and solid tumors, for example, aroylthioureas, diarylsulphonylureas, N-nitrosoureas, and benzoylureas [43]. The molecular structure of a representative ferrocenyl urea

*Molecular structure of 1-(2-florobenzoyl)-3-(2-chloro,4-ferrocenylphenyl)thiourea.*

**4. Supramolecular chemistry of ferrocenyl ureas and thioureas**

Supramolecular chemistry [44] focuses on the design and synthesis of "Supramolecular Entities" [45], i.e., compound elements held together by noncovalent connections including hydrogen bonding, bonds with halogens, forces of coordination, or π-π connections (**Figure 7**) [46]. Research in supramolecular chemistry and crystal engineering is principally centered around host-guest arrangements, binding of anion and cation, coordination polymers, developments of self-assembly networks, biological simulators, gels, fibers, liquid polymers, crystals, and other

Supramolecular chemistry objects to the considerations of interactions between molecules and packing patterns in molecular crystals and, consequently, usage of information spawned for potential novel material designing gathered with targeted structures and proficient characteristics [48–50]. From this objective, one can consider assembling molecular crystals having a multitude of noncovalent interactions among which a prominent position is occupied by H-bonds owing to their noticeable directionalities and reasonably high strength [51]. Hydrogen bonds are characteristically much weaker in comparison to covalent bonds though and hence have minimum predictability, which

often destabilizes the crystal designing process utilizing these interactions [52].

While considering the molecular synthesis, synthetic schemes are confidently planned by researchers for molecules comprising very complex framework. In synthesizing crystalline organic solids, the term engineering can be invoked infrequently in its true sense. Taking from supramolecular structure to design a crystal

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

derivative compound is depicted in **Figure 6** [40].

**4.1 Supramolecular chemistry**

**Figure 6.**

various types of materials [47].

*Supramolecular Chemistry and DNA Interaction Studies of Ferrocenyl Ureas and Thioureas DOI: http://dx.doi.org/10.5772/intechopen.84412*

**Figure 6.** *Molecular structure of 1-(2-florobenzoyl)-3-(2-chloro,4-ferrocenylphenyl)thiourea.*

The lipophilicity/hydrophilic characters and the electronic properties of thiourea derivative compounds are greatly inclined due to the presence of thio-carbonyl moiety which in turn affects the labile nature of leaving substituents, hence regulating the biochemical activity. Various ferrocenyl thiourea derivative compounds have been discovered, which are significantly important for various features of antitumorous agents due to their inhibitory rejoinder against receptor tyrosine kinases (RTKs), protein tyrosine kinases (PTKs), and NADH oxidases [41, 42]. Various thiourea derivatives exhibited bioactivities against different infectious diseases, leukemias, and solid tumors, for example, aroylthioureas, diarylsulphonylureas, N-nitrosoureas, and benzoylureas [43]. The molecular structure of a representative ferrocenyl urea derivative compound is depicted in **Figure 6** [40].
