**3. Photophysics of the bioactive molecules**

In the recent years, new experimental and theoretical developments have occurred in the field of photoactivatable metal complexes which play active role in the field of medicine and biotechnology. Some metal-DNA complexes possess favorable emission properties, while some complexes also provide site-directed therapy. These properties help in oncology, where metal-based precursors generate excited state drugs with different mechanisms.

In this section, the computational techniques (time-dependent density functional theory) and ultrafast-pulsed radiation techniques will be discussed.

The delivery of light depends on the efficiency of light source. It should be efficient to activate the complex. The irradiation should occur in the strong MLCT transitions. However, in medicinal world the UV radiations are harmful but red region is preferred as it deeply penetrates the tissues. Two and three photon absorption can be achieved as the desirable condition is to activate complexes that absorb at shorter wavelength using laser beam that penetrates tissues deeply.

The use of organometallics has become a topic of interest for design of tractable therapeutic agents and theranostics [104]. The most promising organometallic complexes (and motifs) used in cancer therapy is RAPTA-C: [Ru(η6-*p*-cymene)Cl<sup>2</sup> (pta)] (pta = 1,3,5-triaza-phosphatricyclo [3.3.1.1]-decane; **Chart 1**), along with its osmium analogue and their corresponding functionalized derivatives [105]. These complexes exhibit antimetastatic properties *in vivo*. The quite strongly bonded phosphine and arene ligands, the chloride ligands rapidly interchange with water molecules. Arene-ruthenium derivatives can react with N- and S-donors so that they can bind to both nucleotides and proteins [106].

Porphyrins and their metalloderivatives are used for photodynamic therapy [107] and optical imaging and as theranostic agents [108]. Gold (III), Palladium (II), Palladium (III) inside the porphyrin rings and their derivatives can act as anticancer agents [109]. It is based on the concept of "optical bi-theranostic" (two modalities for therapy and one for optical imaging). Further as the intramolecular interactions between the two moieties alter their activities so this should be considered for designing and testing. Ruthenium and Iridium possess favorable photophysical properties which allow functional imaging of cells and tissues (e.g., DNA interactions) and provide site-directed therapy. The electronic transitions can be metal-centered (MC), ligand-

**Chart 1.** Structure of [Ru(η<sup>6</sup> -*p*-cymene) Cl<sup>2</sup> (pta)] (left) and [(η<sup>5</sup> -Cp)Ti((η<sup>5</sup> -C5 H4 -(CH<sup>2</sup> )4 -PPh2 -[Ru(η<sup>6</sup> -*p*-cymene)Cl<sup>2</sup> (pta)] (right).

centered (LC) or involve both the metal and the ligands: metal-to-ligand charge transfer (MLCT) (for readily oxidized metal ions and ligands with low-lying acceptor orbitals), or ligand-to-metal charge transfer (LMCT) (for readily reduced metal ions with strong donor ligands) (**Figure 5**).

A lot of research is carried out in the delivery of small molecules, which can act as second messengers and transmit signals into cells, for example, NO, carbon monoxide (CO), and hydrogen sulfide (H<sup>2</sup> S). Photoactive Pt (IV) diazido complexes also offer potential dual mode activity; excited singlet and triplet states can release reactive or biologically active ligands and form Pt (II) species which can bind to DNA. The introduction of extended conjugation into the amine ligands of square–planar Pt (II) complexes has allowed two-photon activation of ligand exchange using red and near-infrared (NIR) light. The wavelength for two-photon activation of *cis*-[PtCl2 (MOPEP)<sup>2</sup> ], where MOPEP is the *π*-conjugated ligand 4-[2-(4 methoxyphenyl)ethynyl]pyridine, is shorter than twice the single-photon absorption wavelength [110].

Another important optical phenomenon is "upconversion luminescence," which is discussed here.

#### **3.1. Upconversion luminescence**

**3. Photophysics of the bioactive molecules**

12 Recent Progress in Organometallic Chemistry

ultrafast-pulsed radiation techniques will be discussed.

in cancer therapy is RAPTA-C: [Ru(η6-*p*-cymene)Cl<sup>2</sup>


(pta)] (left) and [(η<sup>5</sup>





(pta)]

bind to both nucleotides and proteins [106].

penetrates tissues deeply.

**Chart 1.** Structure of [Ru(η<sup>6</sup>

(right).

In the recent years, new experimental and theoretical developments have occurred in the field of photoactivatable metal complexes which play active role in the field of medicine and biotechnology. Some metal-DNA complexes possess favorable emission properties, while some complexes also provide site-directed therapy. These properties help in oncology, where

In this section, the computational techniques (time-dependent density functional theory) and

The delivery of light depends on the efficiency of light source. It should be efficient to activate the complex. The irradiation should occur in the strong MLCT transitions. However, in medicinal world the UV radiations are harmful but red region is preferred as it deeply penetrates the tissues. Two and three photon absorption can be achieved as the desirable condition is to activate complexes that absorb at shorter wavelength using laser beam that

The use of organometallics has become a topic of interest for design of tractable therapeutic agents and theranostics [104]. The most promising organometallic complexes (and motifs) used

[3.3.1.1]-decane; **Chart 1**), along with its osmium analogue and their corresponding functionalized derivatives [105]. These complexes exhibit antimetastatic properties *in vivo*. The quite strongly bonded phosphine and arene ligands, the chloride ligands rapidly interchange with water molecules. Arene-ruthenium derivatives can react with N- and S-donors so that they can

Porphyrins and their metalloderivatives are used for photodynamic therapy [107] and optical imaging and as theranostic agents [108]. Gold (III), Palladium (II), Palladium (III) inside the porphyrin rings and their derivatives can act as anticancer agents [109]. It is based on the concept of "optical bi-theranostic" (two modalities for therapy and one for optical imaging). Further as the intramolecular interactions between the two moieties alter their activities so this should be considered for designing and testing. Ruthenium and Iridium possess favorable photophysical properties which allow functional imaging of cells and tissues (e.g., DNA interactions) and provide site-directed therapy. The electronic transitions can be metal-centered (MC), ligand-

(pta)] (pta = 1,3,5-triaza-phosphatricyclo

metal-based precursors generate excited state drugs with different mechanisms.

It is a nonlinear optical phenomenon, which absorb two or more photons and emit one photon. Compared with traditional luminescent materials, upconversion nanostructures have many advantages, such as weak background interference, long lifetime, low excitation energy, and strong tissue penetration, which are used in bioimaging and sensing. Similarly producing shorter wavelength light from longer wavelength irradiation involves the use of upconverting nanoparticles. For example: YF3 doped with lanthanide ions (Yb3+and Tm3+). Lanthanide-doped upconversion nanoparticles are used to mediate nitric oxide (NO) release from Roussin's black salt anion [Fe4 S3 (NO)<sup>7</sup> ] − in NIR light from a simple diode laser operating at 980 nm [110]. Cr (III) sensitizers around a central Er (III) acceptor also favor efficient nonlinear energy transfer and upconversion luminescence [111].

**Figure 5.** Schematic representation of the orbital and excited state diagram for (d<sup>6</sup> ) metal complex. Spin is represented by arrows (↑↓) for electronic transitions. (a) Spin up is represented for electronic transition in singlet state whereas spin down is represented for electronic transition in triplet state. (b) Jablonski diagram.

#### **3.2. Imaging and binding of photo-triggered DNA**

The simple and powerful strategy for selective destruction of cancer cells is to target the metal complexes to the tumor cells by photoactivation. Peptides releases the aqua species, [(η6-*p*-cym)Ru(bpm)(H<sup>2</sup> O)]2+in the visible range which bind to DNA. The other example is the cyclometalated iridium (III) polypyridine indole complexes, which have the intense luminescence (*λ*em= 540–616 nm, *τ* = 0.13–5.15 μs) [112]. Another interesting feature of these complexes is that they can deliver CO in the body [113], for example, MnI carbonyl complex [Mn(pqa) (CO)3]<sup>+</sup> (pqa =(2-pyridylmethyl)(2-quinolylmethyl)amine) [114] and manganese complexes [115]. The release of CO from these complexes is visibly monitored by time-resolved IR spectroscopy [116]. This property is also used to deliver other biologically active species also. [Rh(bpy)2(chrysi)]3+ targets single-base mismatches in DNA by noncovalent binding in UV/ visible region. As there is deficiency of mismatch repair in cancer cells, this technique can be used to detect the cancer cells [117, 118]. The other luminescent N-heterocylic carbene (NHC) cyclometalated platinum(II) complexes, which are localized in cytoplasmic structures, do not interact with nucleotides [119].

#### **4. Conclusions**

Unfortunately, like the macro organometallic complexes, the nanoparticles also carry some serious adverse effects. Though the adverse effects of nanoparticles depend on individual factors such as genetics, existing disease conditions, exposure, nanoparticle chemistry, size, shape, agglomeration state, and electromagnetic properties, the key to understanding the toxicity of nanoparticles is their size. Thus, it is very essential to understand the basic nature, structure, and the photophysics behind these particles. Nanoparticles are smaller than mammalian cells and cellular organelles, which allows them to penetrate these biological structures and disrupt their normal function. Nanoparticles are effective in glycoma treatment. This brain cancer is particularly difficult to treat as neurosurgery is ineffective, while chemotherapy suffers from the inability of therapeutics to cross the blood. Although the lack of self-error-correcting mechanism result in defect sites in these nanostructures, the high efficiency and relative simplicity of the novel approach demonstrates the potential power of using irreversible covalent bonds to generate adverse range of shape-persistent and robust nanostructures that is likely to enrich the repertoire of self-assembled nanomaterials and multidrug delivery. Finally, toxicity of nanoparticles could also be potentially utilized to destroy the cancer cells. Bioorganometallic compounds offer hope in the fight against the deadly diseases such as Malaria, HIV/AIDS, and EVD that have continued to devastate humans. There are expected challenges in this area of collaborative research as organometallic compounds are ideally synthesized under inert atmosphere in the absence of oxygen and water. These challenges are not too difficult to surmount, we therefore implore researchers to orient more into this relatively new multidisciplinary research area in the search for novel and potent anticancer and other drug candidates with reduced side effects, which can be a great service to the mankind.
