**Free-Base and Metal Complexes of 5,10,15,20- Tetrakis(N-Methyl Pyridinium L)Porphyrin: Catalytic and Therapeutic Properties**

Juliana Casares Araujo Chaves, Carolina Gregorutti dos Santos, Érica Gislaine Aparecida de Miranda, Jeverson Teodoro Arantes Junior and Iseli Lourenço Nantes

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.68225

#### **Abstract**

Porphyrins are tetrapyrrole macrocycles that can coordinate transition metal ions such as iron, cobalt and magnesium and are able to perform a diversity of functions and applications. In biological systems, these molecules are associated with proteins involved in photosynthesis, cell respiration, cell death, antioxidant defence, among others. The stability and versatile applications of porphyrins inspired the synthesis of derivatives including 5,10,15,20-tetrakis(N-methyl pyridinium-4-yl)porphyrin (TMPyP) that is the object of the present chapter. In synthetic porphyrins such as TMPyP, the catalytic and photochemical properties can be achieved by the coordination with a diversity of central metal ions. In photodynamic therapy (PDT), TMPyP and other porphyrins act as photosensitizers. The photochemical properties of TMPyP and other porphyrins are also useful for the fabrication of solar cells. The catalytic properties require the presence of a central metal. The MnTMPyP have antioxidant activity that is influenced the capacity of membrane binding, substituents, and meso substituents. Manipulation of the interfacial confinement properties is one of the newest application areas of porphyrins. The association of porphyrins with different surfaces modulates the electronic and physicochemical properties of these molecules. All of these properties are the object of experimental and theoretical studies discussed in the present chapter.

**Keywords:** porphyrins, TMPyP, antioxidant activity, photodynamic therapy

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

### **1. Introduction**

Porphyrins constitute a group of aromatic organic molecules, composed of four pyrrole rings linked by methene (═CH─) bridges (5, 10, 15 and 20), that are the *meso*-carbon atoms/positions [1]. Free base porphyrins are able to complex with metal ions such as iron, zinc, copper and others at themacrocycle center to form metalloporphyrins. Therefore, the properties of a porphyrin can be modulated by the inserting or changing the central metal and appending different substituents at the *peripheral* (β-positions (2, 3, 7, 8, 12, 13,17 and 18)) and *meso* positions (**Figure 1**). Furthermore, the activity of a metalloporphyrin frequently involves redox cycling of the central metal. When peripheral and meso substituents are exclusively hydrogen atoms, and two of the four macrocycle nitrogen atoms are protonated, this molecule is known as a free-base porphine. When different organic groups are appended at the *peripheral* or *meso* positions, these compounds are known as porphyrins [2]. The manipulation of different substituents and central metal provides a wide diversity of biochemical functions for porphyrins.

In biological systems, the porphyrins are associated with proteins involved in important cellular processes such as photosynthesis, molecular oxygen transport, cell respiration, cell death, the combat of the oxidative stress, biological synthesis, fat acid oxidation and others [1, 3–5]. The iron protoporphyrin IX (known as heme group) is the biological metalloporphyrin present in almost all biological processes. Heme is the prosthetic group of myoglobin, hemoglobin and a diversity of enzymes such as peroxidases, cytochromes, NO• synthase and others. Besides iron ion, other metals are found in biological porphyrins, the magnesium ion in chlorophyll, and the cobalt ion in vitamin B 12 [6]. Biological and synthetic porphyrins and metalloporphyrins have been extensively investigated and applied in medicine, chemistry, sensing and other technological devices due to their catalytic, photochemical and photophysical properties [6, 7]. In biological systems, free-base porphyrins are largely used as photosensitizer (PS) in photodynamic therapy (PDT) [2, 5, 8, 9]. Otherwise, metalloporphyrins have been used for mimicking the function of hemeproteins such as cytochrome P-450 in oxidative catalysis and superoxide dismutase SOD against oxidative stress. Porphyrins are also used as building blocks and in transport chains of molecular devices [4, 9–11].

Porphyrins are versatile catalytic and therapeutic agents. The properties of porphyrins can be modulated by changing the central metal, substituents at the *peripheral* and *meso* positions and the microenvironment. Different microenvironments respond for the diversity of functions of heme group in the hemeproteins: oxygen transport, electron transport, hydroxylation, peroxide cleavage and others. The versatility of functions can also be achieved for synthetic porphyrins by manipulating their structures and microenvironments. One example of interchangeable functions of porphyrins is the substitution of the central metal in TMPyP (5,10,15,20-tetrakis(N-methyl pyridinium L)porphyrin). MnTMPyP exhibits antioxidant function, and it has been attributed to the superoxide dismutase (SOD)-like and

Free-Base and Metal Complexes of 5,10,15,20-Tetrakis(N-Methyl Pyridinium L)Porphyrin... http://dx.doi.org/10.5772/intechopen.68225 3

**Figure 1.** Free-base porphine with peripheral and meso positions.

**1. Introduction**

2 Phthalocyanines and Some Current Applications

porphyrins.

molecular devices [4, 9–11].

Porphyrins constitute a group of aromatic organic molecules, composed of four pyrrole rings linked by methene (═CH─) bridges (5, 10, 15 and 20), that are the *meso*-carbon atoms/positions [1]. Free base porphyrins are able to complex with metal ions such as iron, zinc, copper and others at themacrocycle center to form metalloporphyrins. Therefore, the properties of a porphyrin can be modulated by the inserting or changing the central metal and appending different substituents at the *peripheral* (β-positions (2, 3, 7, 8, 12, 13,17 and 18)) and *meso* positions (**Figure 1**). Furthermore, the activity of a metalloporphyrin frequently involves redox cycling of the central metal. When peripheral and meso substituents are exclusively hydrogen atoms, and two of the four macrocycle nitrogen atoms are protonated, this molecule is known as a free-base porphine. When different organic groups are appended at the *peripheral* or *meso* positions, these compounds are known as porphyrins [2]. The manipulation of different substituents and central metal provides a wide diversity of biochemical functions for

In biological systems, the porphyrins are associated with proteins involved in important cellular processes such as photosynthesis, molecular oxygen transport, cell respiration, cell death, the combat of the oxidative stress, biological synthesis, fat acid oxidation and others [1, 3–5]. The iron protoporphyrin IX (known as heme group) is the biological metalloporphyrin present in almost all biological processes. Heme is the prosthetic group of myoglobin, hemoglobin and a diversity of enzymes such as peroxidases, cytochromes, NO• synthase and others. Besides iron ion, other metals are found in biological porphyrins, the magnesium ion in chlorophyll, and the cobalt ion in vitamin B 12 [6]. Biological and synthetic porphyrins and metalloporphyrins have been extensively investigated and applied in medicine, chemistry, sensing and other technological devices due to their catalytic, photochemical and photophysical properties [6, 7]. In biological systems, free-base porphyrins are largely used as photosensitizer (PS) in photodynamic therapy (PDT) [2, 5, 8, 9]. Otherwise, metalloporphyrins have been used for mimicking the function of hemeproteins such as cytochrome P-450 in oxidative catalysis and superoxide dismutase SOD against oxidative stress. Porphyrins are also used as building blocks and in transport chains of

Porphyrins are versatile catalytic and therapeutic agents. The properties of porphyrins can be modulated by changing the central metal, substituents at the *peripheral* and *meso* positions and the microenvironment. Different microenvironments respond for the diversity of functions of heme group in the hemeproteins: oxygen transport, electron transport, hydroxylation, peroxide cleavage and others. The versatility of functions can also be achieved for synthetic porphyrins by manipulating their structures and microenvironments. One example of interchangeable functions of porphyrins is the substitution of the central metal in TMPyP (5,10,15,20-tetrakis(N-methyl pyridinium L)porphyrin). MnTMPyP exhibits antioxidant function, and it has been attributed to the superoxide dismutase (SOD)-like and glutathione peroxidase (GPx)-mimetic capacities [12, 13], while FeTMPyP exhibits pro-oxidant activity that responds to the toxicological effects of these compounds [14]. The prooxidant activity of FeTMPyP has been attributed to the generation of free radicals due to the homolytic cleavage of peroxides. The introduction and modification of substituents in a metalloporphyrin changes the redox potential and the solubility. In this regard, TMPyP and TPPS4 are examples of synthetic porphyrins made water soluble by the *meso* substitution of pyridine and sulfonate groups, respectively. Depending on the *meso* substituent, there is the possibility of a refined modulation of the porphyrin activity by isomerization. Previous studies comparing SOD activity of *ortho, meta* and *para* isomers of MnTMPyP (**Figure 2**) showed that the former exhibits the most effective SOD-like activity due to an appropriate combination of redox potential and electrostatic facilitation [15–18]. *Para* MnTMPyP exhibits a lower redox potential value that disfavors SOD activity [19]. However, the association of *para* MnTMPyP to negatively charged membranes (phosphatidylcholine (PC)/phosphatidylserine (PS)) modulates its redox potential toward a more efficient SOD activity [20]. Thus, the study of Araujo-Chaves et al. [13] is an example of the modulation of a porphyrin activity by the microenvironment. The different activities of TMPyP and other porphyrins are described herein.

**Figure 2.** *Ortho, meta* and *para* isomers of MnTMPyP.
