Towards Ruthenium(II)-Rhenium(I) Binuclear Complexes as Photosensitizers for Photodynamic Therapy.

## 1. Introduction Ruthenocene ((C The exceptional chemical and thermal stability of Rc contributes to various physicochemical applications [ In this article, we review recent advances in Rc chemistry, including its structural comparison with Fc, redox behavior, substituent effects, dimerization mechanisms, energy transfer, biocompatibility, flexible functionalization, and anti-proliferation properties. We also discuss Rc-based templates, anticancer bioconjugates, and photoactive systems for energy storage applications ( ## 2. Structural Comparison of Ruthenocene with Ferrocene Rc is structurally comparable to Fc, its metallocene counterpart, due to its stable 18-electron configuration that is not found commonly in other metallocenes [ Rc adopts an orthorhombic Pnma crystal lattice that remains stable up to about 4 GPa, beyond which irreversible pressure-induced structural perturbations and phonon anomalies are apparent; the molecule has a tendency to adopt an eclipsed conformation and has a moderate rotational energy barrier with respect to the staggered conformation [ The distinct electronic structures and redox behaviors of Rc and its derivatives are controlled by steric factors ( Structural features significantly influence the oxidation potentials in Rc-terminated oligoenes, which shift to lower values as conjugation increases, indicating stable two-electron redox processes [ ## 3. Electrochemical Behavior of Ruthenocene and Its Derivatives Electrochemically, Rc and its derivatives have been extensively studied as redox mediators [ ## 4. Ruthenocene and Its Derivatives as Electrochemical Sensors Rc-modified electrodes offer several advantages in terms of electrochemical sensing. It boosts electron mobility and can be used to promote electron transport between biological molecules and electrodes, resulting in stronger signals [ Rc derivatives can also be combined with biomolecules such as antibodies or DNA probes to build sensitive and selective biosensors [ Due to their tunable redox behavior and efficient electron-transfer characteristics, Rc-based systems have been widely explored in chemical and biosensing applications. Selective cation sensing, both optically and electrochemically, was enhanced by intramolecular electron-transfer interactions between homo- and heterometallic Fc-Rc triads [ Rc derivatives can be used to develop optical sensors. The addition of Rc to EuCl The mixed aza-substituted metallocenophanes, with a [2.2] and [3.3] Fc and Rc multifunctional molecular system, have potential in investigating the intramolecular transfer of charge and recognition in metal-based mechanisms. These combined metallocenes produced a localized excitation band in the near infrared that was indicative of intramolecular charge transfer via carbodiimide bridges connecting the Rc and Fc units [ To develop molecular sensors for the detection of specific ions, polyanionic biomolecules, and to facilitate redox catalysis and bioinorganic recognition processes, supramolecular host–guest macrocyclic receptor molecules were designed by attaching redox active ionophores (guests) to the host’s molecular cavities. Yin et al. [ The redox properties of ruthenium complexes containing ONO pincer frameworks and ruthenium-complex-bound norvalines are strongly influenced by Rc(pydc)(terpy) and Rc(pydc)(tBu-terpy) units [ Rc terminated dyads have been studied as redox active, optically responsive systems capable of intramolecular electron transfer and selective cation sensing, with practical optical detection potential and metal-ion recognition. The electrochemical, electrical, and cation sensing characteristics of Rc-terminated 2-aza-1,3-butadiene open and closed dyads were examined for intramolecular electron transfer and metal recognition mechanisms. Rc showed a quasireversible oxidation (ΔEp ≈ 0.11 V), which is useful redox behavior for sensing [ In general, Rc-based systems are more suitable than Fc for sensing applications in chloride-rich environments, as ferrocene becomes unstable in the presence of chloride ions due to its oxidation to the ferrocenium species. For example, ruthenium(II) acetylacetonate bis(2,2′-bipyridine-4-ylamino), [Rc(acac) [Rc(acac) These applications highlight the versatility and effectiveness of Rc-modified electrochemical sensors across various fields, particularly in biomedical diagnostics and metal-ion monitoring. All of these studies suggest that the role of Rc in enhancing sensing performance lies primarily in improving redox activity rather than merely increasing the electron-transfer kinetics. ## 5. Ruthenocene as Active Monomolecular Template and Stable Dimeric Complex Rc complexes have the potential to serve as active monomolecular templates for electrochemical surface studies. Weidner et al. [ Rc undergoes electrochemically irreversible oxidation and readily forms dimers on the electrode surface. Upon oxidation to ruthenocenium, it dimerizes to bis(η In another study [ ## 6. Tentative Applications of Ruthenocene in Energy Storage Current Rc-based energy storage research is largely confined to proof-of-concept studies involving Li–O The aromaticity of Rc also contributes to cyclic stability by delocalizing electrons across the ring system, making the molecule more stable overall [ In Li–O A Ru/Mo In Rc, ruthenium centers play an active role in tuning the electronic structure of electrocatalysts for biomass electrooxidation using ascorbic acid [ These studies demonstrate that Rc is a promising material for energy storage devices due to its special qualities, which include its high energy density, chemical stability and stable redox behavior. It has the potential to improve the efficiency and performance of batteries, making it a crucial area of study for next-generation energy storage research and development. Current Rc-based energy storage studies remain limited to isolated proof-of-concept systems. ## 7. Ruthenocene as Photoinitiators Rc also behaves as a photoinitiator to catalyze polymerization reactions. When Rc interacts with an electron-accepting solvent, it forms photoactive ground-state donor–acceptor complexes. These complexes undergo charge transfer-to-solvent transitions, resulting in absorption bands in the near ultraviolet region, which, under UV radiation, undergo oxidation to form a radical cation, while the solvent is reduced to a radical anion. This photoredox process initiates anionic polymerization of the monomer ( Substitution of the cyclopentadienyl rings affects the spectroscopic and photochemical behavior of Rc. The substitution of benzoyl groups on the rings shifts the absorption bands to longer wavelengths with significantly higher intensities compared to unsubstituted Rc [ The above investigations on Rc and its derivatives sought to determine the impact of employing various methodologies. All of these investigations aimed to explore the potential of Rc-based systems to improve the stability, reactivity, and general performance of Rc derivatives in electrochemical, photoinitiator, and energy storage systems by adding various ligands and functional groups. It offers new insights into the adaptability of Rc compounds and their potential for advancement in cutting-edge technology. ## 8. Biomedical Research Based on Ruthenocene and Its Derivatives Rc and its derivatives have received a lot of attention in biomedical research due to their unique chemical properties. Their uses include antiproliferative properties [ ## 9. Merits, Demerits, and Their Possible Solutions Rc complexes offer notable advantages for applications in electrochemical and biomedical fields due to their tunability, reversible redox behavior, and thermal stability. These properties support their use in energy storage, electrochemical sensing, and biological systems. Rc-controlled redox activity enables selective sensing and has been explored in targeted drug delivery, while its relatively high redox potential and favorable electron-transfer kinetics may enhance energy density and charge–discharge efficiency in electrochemical devices. However, several challenges remain. Further studies are needed to understand the long-term biological interactions, stability, and potential accumulation in tissues. Biological environments can influence Rc reactivity and stability, potentially affecting therapeutic performance. In electrochemical applications, surface by-products may lead to signal drift and reduced sensitivity, and interference from complex matrices can impact sensor selectivity. In addition, the relatively low intrinsic conductivity of Rc and material degradation under repeated redox cycling may limit performance in energy storage systems. These limitations can be addressed through material and design strategies including the incorporation of conductive polymers or carbon-based materials, surface modification to reduce fouling, and the development of biocompatible ligands or encapsulation systems to improve stability and biological compatibility. Rc derivatives have shown promising in vitro antiproliferative activity, but clinical translation remains limited due to insufficient in vivo data and an incomplete understanding of mechanisms. Future progress will depend on integrated structure–activity studies, in vivo evaluation, scalable synthesis, and rational device and therapeutic design. ## 10. Conclusions Ruthenocene has become a versatile organometallic scaffold with unique tunable redox properties, electronic flexibility, and a structural robustness when compared to its ferrocene analogue. This review highlights its applications in electrochemical sensing, energy storage systems, photochemical applications, and biomedical research. The redox responsive behavior of Rc is remarkably influenced by ligand environment, solvent systems, and supporting electrolytes, which allows for the formation of stable oxidation states and dimeric assemblies having functional adaptability. Rc-based systems show great potential in molecular sensing and redox labeling as well as in Li–O