**Abstract**

Photodynamic therapy (PDT) is a less-invasive treatment of cancer and precancerous lesions. Porphyrin derivatives have been used and studied as the photosensitizers for PDT. In general, the biomacromolecules oxidation by singlet oxygen, which is produced through energy transfer from the photoexcited photosensitizers to oxygen molecules, is an important mechanism of PDT. However, the traditional PDT effect may be restricted, because tumors are in a hypoxic condition and in certain cases, PDT enhances hypoxia via vascular damage. To solve this problem, the electron transfer-mediated oxidation of biomolecules has been proposed as the PDT mechanism. Specifically, porphyrin phosphorus(V) complexes demonstrate relatively strong photooxidative activity in protein damage through electron transfer. Furthermore, other photosensitizers, *e.g.*, cationic free-base porphyrins, can oxidize biomolecules through electron transfer. The electron transfer-supported PDT may play the important roles in hypoxia cancer therapy. Furthermore, the electron transfer-supported mechanism may contribute to antimicrobial PDT. In this chapter, recent topics about the biomolecules photooxidation by electron transfer-supported mechanism are reviewed.

**Keywords:** Photoinduced electron transfer, porphyrin phosphorus(V) complex, protein oxidation, cationic porphyrin, phenothiazine dyes

### **1. Introduction**

Photodynamic therapy (PDT) is a less-invasive treatment of cancer and other nonmalignant conditions [1–3]. This treatment is a medicinal application of photochemistry. Antimicrobial treatment, called as antimicrobial photodynamic therapy (aPDT) or photodynamic antimicrobial chemotherapy (PACT), is also important application [4–7]. In the case of cancer treatment, less-toxic PDT reagents, photosensitizers, cause oxidative damage to biomolecules, including protein, nucleic acids, and/or other compounds, under visible-light irradiation. This photosensitized reaction results in necrosis or apoptosis of cancer cells [1–3]. As the PDT photosensitizers, porphyrins have been extensively studied and used [8–11]. For example, porfimer sodium [12, 13] and talaporfin sodium [13], an oligomer and a monomer of a free-base anionic porphyrin, respectively, are well-known photosensitizers in clinical use. In general, the porphyrin photosensitizer (*e.g.*, almost 60 mg/body for talaporfin sodium) is given for the target tissue, followed by irradiation of the visible light (e.g., 664 nm, 150 mW cm−2, and 10 J cm−2). To reduce the risk of adverse side effects, the development of efficient photosensitizers that work with harmless weak light is important. Furthermore, consideration of PDT mechanism is also important to develop effective photosensitizer. Most of porphyrins have relatively large quantum

yield (ΦΔ) for singlet oxygen (1 O2), a reactive oxygen species (ROS), generation [14]. 1 O2 can be easily generated by relatively small energy photon of long wavelength visible light and/or near infrared radiation (wavelength ≳ 770 nm) through energy transfer from photoexcited photosensitizer to oxygen molecule [15–17]. Radiation in the long wavelength region called "optical window", 600 ~ 1300 nm, can penetrate human tissue deeply [18]. Therefore, 1 O2 is the important reactive species of porphyrin-based PDT. However, the phototoxic effect of 1 O2 on PDT is restricted because of the hypoxic condition of tumors [19–22]. Furthermore, in certain cases, PDT itself enhances hypoxia [23] via vascular damage [24]. This "hypoxia problem" of tumor is very important to improve the PDT effect.

Oxidation is defined as the oxygenation, hydrogen extraction, and electron extraction. Electron extraction from biomolecules to photoexcited photosensitizer is also the mechanism of oxidative biomolecule damage. This electron transfer oxidation may be an important mechanism to resolve the "hypoxia problem" and to develop the effective PDT photosensitizers. Phosphorus(V) porphyrins [25, 26] and cationic free-base porphyrins [27] have relatively strong oxidative activity through electron transfer [28]. Furthermore, electron transfer process can be control by surroundings condition, for example pH of medium [29, 30].

In this chapter, recent studies about the electron transfer-supported photosensitizer for PDT are reviewed. The examples of activity control of photosensitizer for the cancer-selective PDT are also introduced. In the last section, the role of electron transfer mechanism in aPDT is discussed.
