Antibiotic resistance is one of the most urgent and savior health problems in the whole world; along with health care, it badly affects agricultural and veterinary industries [1,2]. Antibiotic-resistant bacteria cause infections that are difficult to treat and require high doses of antibiotics or substituted methods. According to a recent report by WHO (April 2021), the current development pipeline of antibiotics and clinically ratified antibiotics are inadequate to fight against drug-resistant bacteria [3]. Furthermore, according to the Centers for Disease Control U.S., every year, approximately 2.8 million people are infected by drug resistance pathogens, causing around 35,000 deaths, and it has been estimated that this death ratio could increase to 10 million/year by 2050 [4,5]. The death rate caused by microbes in 2019 is shown in Fig. 1. Thus, with insight into these scenarios, there is considerable interest in the synthesis and development of new antibacterial material, strategies, and treatment methods to maximize the inhibition percentage of bacteria effectively.

Photodynamic therapy (PDT) is a promising noninvasive antibacterial technique with high efficacy and non-toxic properties. This technique involves the interaction of light with photosensitizer (PS) and the production of reactive species, which destroy microorganisms. Thus, selecting photosensitizers is decisive for photo-induced antibacterial effect; it should selectively target bacteria and be nontoxic to healthy mammalian cells. To obtain such type of PS, the positively charged surface PS has a robust selective targeting ability toward bacteria due to the anionic nature of the bacterial outer membrane [7].

In this regard, transition metals benefit luminescence and therapeutics with highly diverse structures, variable-oxidation states, and high synthetic availability, allowing modulation (pharmacokinetics) without affecting the therapeutic process [8]. Thus, complexes of transition metals have long fluorescent lifetimes, long Stoke shifts, and high stability, and all these properties enable them to surpass auto-fluorescence, avoid self-quenching, and show stability toward irradiations for an extended period [9].

Due to the above-mentioned characteristics, many transition metal complexes are used as photosensitizers with tunable photo-physicochemical properties. Although transition metal complexes have been widely used as PDT agents toward cancer cells [10,11], their use against bacteria is limited. In current research, Ruthenium/Iridium complexes have been proven to be two of the most effective antibacterial PDT candidates because of their exciting photo-physical properties such as an excellent light absorption capability, high chemical stability, high quantum yield of singlet oxygen, and long luminescence lifetime [12,13]. Ruthenium and Iridium belong to the platinum family and exhibit numerous shared physical and chemical properties. These elements exhibit a silvery-white appearance, high density, hardness, and exceptional corrosion resistance. They possess partially filled d-shells, have similar chemical behaviors, high melting and boiling points, and form stable complexes with various ligands. These complexes share common characteristics, including a wide range of coordination numbers, oxidation states, and tunable redox characteristics. Numerous studies have shown that Ruthenium and Iridium-based complexes exhibit highly effective biological properties in medicinal chemistry. In 2019, Collins et al. synthesized multi-nuclear Ru(II) complexes containing the bridging ligand bis[4(4′-methyl-2,2′-bipyridyl)]-1,7-heptane and used against six strains of Gram-positive (S. aureus, S. aureus (MRSA)) and Gram-negative bacteria (E.coli stains MG1655, APEC, and UPEC and P. aeruginosa), which showed promising antibacterial efficiency [14]. However, the majority of the studies regarding transition metal complexes as photosensitizers toward bacteria demonstrated that Gram-positive (G+) bacteria have been more susceptible to PDT as compared to Gram-negative (G−) bacteria [15,16]. In 2020, Frei and co-workers studied Re(I) tricarbonyl complexes with three different tridentate ligands. They evaluated their antibacterial activity against Gram (G+) positive and Gram negative (G−) bacteria with irradiation of UV lamp at 365 nm for one hour (ca. 3 Jcm−2) before standard overnight incubation, which revealed promising bactericidal effect against Gram-positive bacteria [17].

Many comprehensive reviews have recently covered transition metal-based photosensitizers for PDT; however, the reviews were based on broad-area applications of PSs, such as against cancers, bio-imaging, etc. The present review will mainly focus on the antibacterial photodynamic therapeutic effect of Ruthenium and Iridium complexes-based PSs. This study has a detailed discussion about transition metals (Ru and Ir) PSs, the photodynamic process, their mechanism of action, and ROS generation. In this study, we shed light on the Ru and Ir complexes' synthesis process and design. As reported in the literature, various structures of Ru and Ir complexes and their efficacy toward both Gram-positive and Gram-negative bacteria provide valuable insights and ideas for future development and design of PSs with enhanced antibacterial properties. These findings have significant potential for advancing our understanding of the mechanism of PSs and their applications in treating bacterial infections. In conclusion, we present potential avenues for future research and development strategies to enhance the photodynamic efficacy of Ruthenium and Iridium complexes against bacterial infections.