Redox Reactions of Coordination Compounds in the Biomedical Environment

Introduction

Redox balance is fundamental and significant for maintaining physiological activities in organisms. Bioactive small molecules including reactive oxygen species (ROS), reactive nitrogen species (RNS) and reactive sulfur species (RSS) are very important signal molecules involved in redox balance in the human body (Gao et al., 2019). They are vital in human physiology, participating in physiological processes such as cell signal transduction (Zuo et al., 2022), cell protection (Cao et al., 2018), vasodilation (Xu et al., 2022), and immunity and metabolism (Yang et al., 2020) within a normal level. However, abnormal redox species levels can cause disorders in the human body and induce various diseases (Wang et al., 2021). For instance, ROS and RNS are associated with some pathological processes such as Alzheimer's disease (AD) (Bhatt et al., 2021), diabetes (Rendra et al., 2019), cardiovascular diseases (Xu et al., 2019), ageing and cancer (Kim et al., 2019), while RSS play an important role in maintaining redox balance and as antioxidants and a free radical scavenger (Sawa et al., 2022). Therefore, it is meaningful to keep an eye on maintaining the level of redox species in a reasonable range in vivo.

Metal complexes are very broad and important molecular systems. The regulation of redox balance using the structural advantages of metal complexes is of great significance to the diagnosis and treatment of clinical diseases and has aroused extensive attention and interest from researchers. Cis-platin is the most classic example of metal complex antitumor application. However, it is well known that cis-platin will not selectively inhibit tumors. Therefore, its cytotoxicity will cause damage to normal body tissues resulting in detrimental side effects which are often worried about by users (Perse, 2021; Chovanec et al., 2017). To reduce the toxicity of cis-platin, scientists have modified cis-platin with different functional groups in the axial direction, such as a targeted group (Fang et al., 2019) or photoreactive group (Ponte et al., 2019; Gao et al., 2021) to obtain Pt(IV) prodrugs with lower cytotoxicity. Under certain conditions, such as in a highly reducing tumor microenvironment, non-toxic Pt(IV) prodrugs can be reduced to toxic Pt(II) drugs, which further kill tumor cells (Figure 1) (Babu et al., 2020; Karmakar et al., 2019). Compared with cis-platin, ruthenium(II) complexes display more variability in their structural design, ligand exchange ability, good thermodynamic stability, abundant photochemical, photophysical and redox properties, as well as low toxicity and can be easily absorbed and quickly metabolized by the body with a different anti-tumor mechanism than cis-platin. In recent years, ruthenium complexes have attracted wide attention in the field of metal-organic chemistry, making them the most promising antitumor drugs after platinum-based drugs. At the same time, ruthenium (II) complexes are also believed to be able to involve in some redox reactions regulated by intracellular biomolecules such as GSH and NADPH (Liu et al., 2022), which can effectively improve anticancer activity and safety.

Figure 1.

Representative examples of platinum prodrugs and drug releasing mechanisms

In this chapter, we will give a brief introduction to the main redox species in living organisms and the way of detecting the products generated from the redox reaction. We also report the state-of-the-art on the applications of using ruthenium complexes in regulating the redox process to achieve the ultimate antitumor goals.