Mitochondrial-targeted cyclometalated Ir(III)-5,7-dibromo/dichloro-2-methyl-8-hydroxyquinoline complexes and their anticancer efficacy evaluation in Hep-G2 cells.

## Introduction Coordination complexes of transition metals have become indispensable in various fields of science and technology. This class of compounds has, indeed, experienced an explosive growth over the past decades finding applications in advanced material science, industrial catalytic processes either homogeneous and heterogeneous, diagnostic imaging, energy storage and so on. In addition to classical, inorganic, and coordination compounds, organometallic complexes have also found application: the first example was Arsphenamine, also known as compound 606. Discovered by serendipity in 1909 by Ehrlich and co-workers, it was used as an effective antimicrobial drug against syphilis. The World Health Organization (WHO) has classified AMR bacteria as a global health emergency, with profound implications in medical, veterinary, food, and economic fields. Despite the increasing demand for new antimicrobials, investment committed to their discovery and development remains insufficient. New compounds, with innovative chemical structures and novel mechanisms of action, are critically needed to combat MDR pathogens evolving resistance to existing antibiotic classes. Such innovation is essential for restoring the efficacy of antimicrobial therapies and ensuring the long-term sustainability of infection control strategies. Among the various families of coordination compounds, pyridine-derived complexes are particularly promising. Pyridines are considered as privileged structures in medicinal chemistry: ubiquitous in nature (DNA, alkaloids, vitamins, coenzymes, etc.) they have been often used in the design of drug candidates such as antitumor, antibacterial, antifungal, antiviral, analgesic, anti-inflammatory and antidiabetic. Transition metal complexes of N In addition, several complexes, including N Some of the authors have found that cationic complexes exhibit superior activity compared to neutral analogs. ## Mechanistic Connections Between Antimicrobial and Anticancer Activity A compelling feature of transition metal complexes and, in particular, of triazole derivatives is their frequent exhibition of dual antimicrobial and anticancer activity, a phenomenon that reflects overlapping molecular targets and mechanisms of action in bacterial and cancer cells. This dual bioactivity is not coincidental but arises from fundamental similarities in the cellular vulnerabilities exploited by these complexes. These mechanistic connections provide a rational basis for the parallel development of metal-based therapeutics for infectious diseases and oncology. DNA represents a critical target for both antimicrobial and anticancer metal complexes. As an example, Copper­(II) triazolopyrimidine complexes synthesized by Ruta and colleagues exhibited DNA intercalating capacity and nuclease-like activity, contributing to both their antiproliferative effects and antimicrobial activity. Other major mechanisms leading to antimicrobial and anticancer activity comprise membrane targeting, redox activity and generation of reactive oxygen species (ROS) that damage multiple cellular targets. In the present manuscript, we report, as outcomes of a multidisciplinary project, the synthesis and biological activity of noble metal complexes containing a 1,4-substituted-1,2,3-triazole-pyridine ligand. More in detail, we describe the results obtained with the 2-(1-benzyl-1 As reported above, studies have revealed that transition metal complexes with nitrogen ligands possess the capacity to exhibit both antimicrobial and anticancer activity. ## Conclusions Over the past few decades, the escalating antimicrobial resistance (AMR) crisis has driven an intensive search for alternative therapeutic compounds, with noble metal complexes emerging as a premier class of candidates. In this study, we synthesized and characterized a series of platinum­(II), palladium­(II), and gold­(III) complexes chelated with the ligand 2-(1-benzyl-1 In conclusion, these findings underscore the potential of such N ## Experimental Section Unless otherwise stated, all reagents were purchased from commercial sources and used without further purification. The Cyclic voltammetry experiments were carried out in a three-electrode, single compartment cell with an AUTOLAB PGSTAT12 instrument using the specific software NOVA 2.1. The working electrode was a Pt disk (diameter 2 mm); a graphite bar was the counter electrode, and Ag/AgCl with a suitable salt bridge was the reference electrode. Before each experiment, the working electrode was polished with 1 and 0.3 μm alumina powder, then rinsed with distilled water in an ultrasonic bath, and finally rinsed with acetone. The concentration of the complex was 1.5 × 10