Ruthenium-based Complexes Research Articles

DFT Computational Analysis of the Mechanism of Action of Ru(II) Polypyridyl Complexes as Photoactivated Chemotherapy Agents: From Photoinduced Ligand Solvolysis to DNA Binding.

Photoactivated chemotherapy (PACT) is a form of target-oriented cancer therapy that exploits light of the proper wavelength to selectively activate the drug. Among the prodrugs used for this purpose, ruthenium-based complexes are particularly interesting, as when irradiated by light, they can release ligands by forming aquo-complexes able to bind DNA in both single and double strand fashions, causing its distortion. Using as model system a Ru(II) polypyridyl complex that has been demonstrated to be a promising photochemotherapeutic agent, all of the key aspects of the photoinduced solvolysis process and subsequent DNA interaction have been scrutinized using density functional theory (DFT) and time-dependent-DFT (TDDFT). Photoexcitation, intersystem crossing, internal conversion, mechanism by which photoinduced ligand release, and subsequent aquation steps occur have been examined. Pathways leading to the formation of both cis and trans biaquated photoproducts have been described, and the formation of the cis form of the biaquated photoproduct being the most favorable one, its reaction with a guanine base has also been reported in order to account for DNA binding.

Functionalization of ionic liquids for heterogeneous catalysis in CO2 conversion: Cycloaddition of epoxides and hydrogenation

The mitigation of environmental impacts caused by greenhouse gas emissions has become increasingly urgent, and the use of CO2 as a primary carbon source is an alternative in chemical transformations, including the synthesis of organic carbonates, formic acid, or methanol. This work aims to synthesize ionic liquids from the imidazolium cation family to be used in the cycloaddition of CO2 with ILs anchored in SiO2-clay heterostructure, MCM-41 and KIT-6 mesoporous materials, as well as the hydrogenation of CO2 with ILs added to ruthenium complexes, i.e., two catalytic systems. The most satisfactory result for CO2 cycloaddition (TON PC = 226) was obtained using the IL (MeO)3Sipmim.Cl anchored in SiO2-clay heterostructure (0.16 mol%) as the catalyst and ZnBr2 (0.04 mol%) as the co-catalyst. The hydrogenation was conducted with the IL (edaO)3Sipmim.Cl and the ruthenium complex Ru-PNN were not successful, but with co-catalyst PEHA, formic acid/formamide was produced (TON Form = 552). The unique catalytic system that showed activity for forming methanol was the commercial Ru-MACHO, Ru-C29H30ClNOP2, (TON MeOH = 3.3). These results highlight the potential of ruthenium-based complexes and supported ionic liquids as active systems in CO2 conversion.

RUTHENIUM ORGANOMETALLIC COMPOUNDS IN CANCER TREATMENT

Organometallic complexes with ruthenium have shown promise as potential anticancer agents. These complexes represent a class of compounds that can exhibit unique mechanisms of action, and they may offer advantages or overcome some limitations associated with platinum-based drugs, such as cisplatin. Ruthenium-based complexes can have diverse mechanisms of action. They may interact with DNA, proteins, or other cellular components, leading to cytotoxic effects on cancer cells. The versatility of ruthenium coordination chemistry allows for the design of complexes with specific properties. Some cancers that become resistant to platinum-based drugs may still respond to ruthenium-based compounds. This reduced cross-resistance is attributed to differences in the mechanisms of action between platinum and ruthenium complexes. Researchers can design ruthenium complexes to target specific cellular pathways or processes associated with cancer. This targeted approach aims to enhance the selectivity of the treatment for cancer cells while minimizing the impact on normal cells. Ruthenium complexes often have unique structural features that contribute to their stability and reactivity. These features can be tailored to optimize the pharmacological properties of the compounds. Ruthenium-based complexes may be explored in combination with other anticancer agents to achieve synergistic effects and enhance overall treatment efficacy. Ongoing research continues to explore the potential of ruthenium-based organometallic complexes, and preclinical studies have demonstrated promising results. As with any emerging field, further investigations and clinical trials are needed to fully understand the therapeutic potential and safety profiles of these compounds for various types of cancers.

Ruthenium-based complexes as anti-tumor agents

Extensive research into platinum-based chemotherapeutics has been underway for decades with ruthenium-based complexes emerging as interesting and potent candidates. Even still, there is no evidence of a single mechanism of action across all synthesized and tested Ru-based complexes, prompting the continuance of research in this field. In addition, the mechanism of action varies according to cell line and/or animal model and is seemingly highly individualized and personalized. In accordance with this, the ruthenium complexes are able to activate specific molecular pathways and interact with certain targets within the cell, sometimes reported simultaneously. In this review, we attempt to give a new perspective on ruthenium complexes’ anti-cancer properties and organize selected results from the past 15 years of research connecting their structure with the reported mechanism of action. These results corroborate the previously reported great potential that ruthenium complexes have on cancer in vitro. In addition, the review provides insight into Ru drugs in their clinical trials and their efficacy against cancer including a historical context on metallodrugs, particularly platinum-based complexes, and their antitumor capability.

Radical-mediated oxidative desulfurization of dibenzothiophene in a chromophore-enhanced photocatalytic system

This study presents a refined photocatalytic oxidative desulfurization (PODS) approach, leveraging a chromophore-enhanced system specifically designed for the selective degradation of dibenzothiophene (DBT). Employing a ruthenium-based complex (RuL) as a model sensitizer that can be activated by visible light, the system catalytically decomposes peroxydisulfate (S2O82−) into highly reactive radical species, key agents in facilitating efficient sulfur oxidation. In this system, the oxidative degradation of DBT proceeds through a well-defined pathway, sequentially transforming DBT into its sulfoxide (DBT-O) and subsequently into its sulfone (DBT-O2) derivatives, achieving nearly complete conversion to DBT-O2. The electron transfer dynamics within this photocatalytic system are examined through a concentration-dependent decrease in photoluminescence. Moreover, the effects of various electron donors and acceptors on the system’s catalytic activity, as well as the influence of structural modifications of the ruthenium sensitizer are investigated. Comparative evaluations with an alternative 9,10-dicyanoanthracene (DCA)-sensitized system underscore the superior efficiency and selectivity of the sulfate and/or hydroxyl radicals generated in the RuL/S2O82− system. Unlike the superoxide radicals produced in the DCA-sensitized system, the radicals generated in the RuL/S2O82− system exhibit significantly enhanced kinetics for DBT oxidation. The RuL/S2O82− photocatalytic system operates effectively under milder conditions without requiring hydrogen, positioning it as a promising alternative for sulfur removal and potentially contributing to more environmentally sustainable and economically viable fuel processing technologies.

Coulomb interactions for mediator-enhanced sensitized triplet-triplet annihilation upconversion in solution.

Sensitized triplet-triplet annihilation upconversion offers an attractive possibility to replace a high-energy photon by two photons with lower energy through the combination of a light-harvesting triplet sensitizer and an annihilator for the formation of a fluorescent singlet state. Typically, high annihilator concentrations are required to achieve an efficient initial energy transfer and as a direct consequence the most highly energetic emission is often not detectable due to intrinsic reabsorption by the annihilator itself. Herein, we demonstrate that the addition of a charge-adapted mediator drastically improves the energy transfer efficiency at low annihilator concentrations via an energy transfer cascade. Inspired by molecular dyads and recent developments in nanocrystal-sensitized upconversion, our system exploits a concept to minimize intrinsic filter effects, while boosting the upconversion quantum yield in solution. A sensitizer-annihilator combination consisting of a ruthenium-based complex and 9,10-diphenylanthracene (DPA) is explored as model system and a sulfonated pyrene serves as mediator. The impact of opposite charges between sensitizer and mediator - to induce coulombic attraction and subsequently result in accelerated energy transfer rate constants - is analyzed in detail by different spectroscopic methods. Ion pairing and the resulting static energy transfer in both directions is a minor process, resulting in an improved overall performance. Finally, the more intense upconverted emission in the presence of the mediator is used to drive two catalytic photoreactions in a two-chamber setup, illustrating the advantages of our approach, in particular for photoreactions requiring oxygen that would interfere with the upconversion system.

Finding the best location: Improving the anti-amyloid ability of ruthenium(III) complexes with pyridine ligands

Alzheimer's disease (AD) is a devastating neurological disorder where one of the primary pathological hallmarks are aggregate deposits of the peptide amyloid-beta (Aβ). Although the Food and Drug Administration (FDA) has recently approved therapeutics that specifically target Aβ, resulting in the removal of these deposits, the associated costs of such treatments create a need for effective, yet cheaper, alternatives. Metal-based compounds are propitious therapeutic candidates as they exploit the metal-binding properties of Aβ, forming stable interactions with the peptide, thereby limiting its aggregation and toxicity. Previously, ruthenium-based complexes have shown a strong ability to modulate the aggregation and cytotoxicity of Aβ, where the incorporation of a primary amine on the coordinated heterocyclic ligand gave the greatest activity. To determine the importance of the location of the primary amine on the pyridine ligand, thereby establishing structure-activity relationships (SAR), four complexes (RuP1–4) were prepared and evaluated for their ability to coordinate and subsequently modulate the aggregation and cytotoxicity of Aβ. Coordination to Aβ was determined using three complementary spectroscopic methods: UV–Vis, 1H NMR, and circular dichroism (CD). Similarly, the impact of the complexes on Aβ aggregation was evaluated using three sequential methods of turbidity, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Overall, the location of the primary amine on the pyridine ligand did affect the resultant anti-Aβ performance, with the 2-aminopyridine complex (RuP2) being the most active. This SAR will provide another guiding principle in the design of future metal-based anti-Aβ complexes.

Ru-Based Organometallic Agents Bearing Phenyl Hydroxide: Synthesis and Antibacterial Mechanism Study against Staphylococcus aureus.

The development of antimicrobial agents with novel model of actions is a promising strategy to combat multiple resistant bacteria. Here, three ruthenium-based complexes, which acted as potential antimicrobial agents, were synthesized and characterized. Importantly, three complexes all showed strong bactericidal potency against Staphylococcus aureus. In particular, the most active one has a MIC of 6.25 μg/mL. Mechanistic studies indicated that ruthenium complex killed S. aureus by releasing ROS and damaging the integrity of bacterial cell membrane. In addition, the most active complex not only could inhibit the biofilm formation and hemolytic toxin secretion of S. aureus, but also serve as a potential antimicrobial adjuvant as well, which showed synergistic effects with eight traditional antibiotics. Finally, both G. mellonella larva infection model and mouse skin infection model all demonstrated that ruthenium complex also showed significant efficacy against S. aureus in vivo. In summary, our study suggested that ruthenium-based complexes bearing a phenyl hydroxide are promising antimicrobial agents for combating S. aureus.

Ruthenium complexes for breast cancer therapy

Abstract Breast cancer cells have long been inhibited by polypyridine Ru(II) complexes, which are excellent antitumor agents. Due to their multi-targeting properties, this class of ruthenium complexes has received increasing attention as anticancer drug candidates approach to various cellular targets. The aim of this review is to give information about the ligands that were carefully chosen for ruthenium complexes. There has been a great deal of interest in using ruthenium-based complexes to treat breast cancer. Several species have shown potential as treatment candidates. However, further research is needed to determine how these agents affect the metastatic potential of breast cancer cells. The mechanism of action of Ru-based anticancer candidates NAMI-A and KP1019 during phase I clinical trials has been discussed. This article explains hormone-positive breast cancer and triple-negative breast-cancer treatment by using Ru complexes. Although platinum (Pt-based) anticancer medication is widely used in cancer treatment, a minor improvement has been seen and that is Platinum replaced with Ruthenium for its anticancer properties. We have also highlighted the best effective ruthenium-based complexes in treating T.N.B.C. (triple-negative breast cancer) here in this collection.

A cellular NO sensor based on aggregation-induced electrochemiluminescence and photoelectron transfer of a novel ruthenium(II) complex

Here, we present a dual amplification strategy of electrochemiluminescence (ECL) based on aggregation-induced and photoelectron transfer (PET) inhibition using a designed ruthenium-based complex for the highly sensitive detection of nitric oxide (NO). A novel ruthenium(II) complex ([Ru(phen)2(DA-phen)]2+, DA-phen: 5,6-diamino-1,10-phenanthroline) was synthesized that uses the O-diaminophenyl group for specific recognition of NO and the ruthenium metal center with 1,10-phenanthroline as the luminophore. In the first step, the 1,10-phenanthroline groups function as the aggregation part. Increasing the volume fraction of a poor solution (H2O: fw, v%) in the DMSO mixture system from 0% to 80% yielded an increase in the fluorescence (FL) and electrochemiluminescence (ECL) intensities by 3- and 42-fold when compared with the FL and ECL intensities in pure DMSO, respectively. The second step involves a PET process. Reacting the complex with NO in physiological pH aqueous media under aerobic conditions to afford its triazole derivative, [Ru(phen)2(TA-phen)]2+ (TA-phen: 5,6-triazole-1,10-phenanthroline), inhibited the electron transfer process, yielding a remarkable further increase in the FL and ECL efficiencies of the Ru(II) complex. The ECL intensities was 86-fold higher in the presence of NO. This dual amplification strategy enabled the sensitive detection of NO from 1.8 × 10–10 to 1.8 × 10–5 M with a detection limit of 60 pM (S/N = 3) and offered excellent specificity with no detectable interference by RNS and metal ions. Furthermore, selective NO detection in cells was achieved using this complex. Thus, this assay should be suitable for applications in environmental toxicology research and early clinical diagnosis.

Aggregation-Induced Electrochemiluminescence and Nitric Oxide Recognition by Halogen Bonding with a Ruthenium(II) Complex.

In this study, a new strategy for NO detection based on the aggregation-induced electrochemical luminescence (AIECL) of a ruthenium-based complex and the halogen bonding effect was developed. First, [Ru(phen)2 (phen-Br2 )]2+ (phen : 1,10-phenanthroline, phen-Br2 : 3,8-dibromo-1,10-phenanthroline) was synthesized and exhibited aggregation-induced emission (AIE) and AIECL properties in a poor solvent (H2 O). [Ru(phen)2 (phen-Br2 )]2+ exhibited greatly enhanced AIECL properties compared to its AIE intensity. When the volume fraction of water (fw , v %) in the H2 O-acetonitrile (MeCN) system was increased from 30 to 90 %, the photoluminescence and electrochemiluminescence (ECL) intensities were three- and 800-fold that of the pure MeCN system, respectively. Dynamic light scattering and scanning electron microscopy results indicated that [Ru(phen)2 (phen-Br2 )]2+ aggregated into nanoparticles. AIECL is sensitive to NO because of its halogen bonding effect. The C-Br⋅⋅⋅N bond between [Ru(phen)2 (phen-Br2 )]2+ and NO increased the distance of complex molecules, resulting in ECL quenching. A detection limit of 2 nM was obtained with 5 orders of magnitude linear range. The combination of the AIECL system and the halogen bond effect expands the theoretical research and applications in biomolecular detection, molecular sensors, and stages of medical diagnosis.

DSSCs based on unsymmetrical A3B type Zn(II) and TiO(IV) naphthalenephthalocyanine/porphyrin cocktail dyes: A potential alternative for ruthenium based sensitizers

To increase the efficiency of dye-sensitized solar cells (DSSCs), there is still a need for alternative dyes that can absorb a broad spectrum of sunlight and maintain high conversion efficiencies. In order to meet these requirements, a cocktail dye made up of novel phthalocyanines together with a porphyrin have been designed. The novel unsymmetrical phthalocyanines are two ferrocenylphenoxy-naphthalenephthalocyanine (FPNPc) with Zn (ZnFPNPc) or TiO (TiOFPNPc) at the inner core and 4-ferrocenylphenoxy and 4-carboxybenzo substituents at peripheral positions. In order to increase their UV–Vis absorption capacity, cocktails have been prepared with the synthesized new dyes (ZnFPNPc or TiOFPNPc) and YD2 porphyrin dye. The full characterization of novel synthesized dyes has been performed by UV–Vis absorption, FTIR, H1-NMR, MALDI-TOF, electrochemical, TD-DFT techniques. In this work we have prepared DSSCs based on YD2 and phthalocyanine dye molecule with different cocktail ratio (YD2 + ZnFPNPc or YD2 + TiOFPNPc ratios: 1:1, 1:2, 2:1, 1:3, 3:1, 1:4 and 4:1). The best solar cell performance has been performed in the cases of YD2 + ZnFPNPc (3:1) (9.96%) and YD2 + TiOFPNPc (3:1) (10.72%) cocktail dyes. Due to the high efficiency values obtained, these new cocktail dyes are expected to be a good alternative to the ruthenium-based complex dyes used in DSSCs and pave the way for potential alternative dyes.

Fine-tuning the cytotoxicity of ruthenium(II) arene compounds to enhance selectivity against breast cancers.

Ruthenium-based complexes have been suggested as promising anticancer drugs exhibiting reduced general toxicity compared to platinum-based drugs. In particular, Ru(η6-arene)(PTA)Cl2 (PTA = 1,3,5-triaza-7-phosphaadamantane), or RAPTA, complexes have demonstrated efficacy against breast cancer by suppressing metastasis, tumorigenicity, and inhibiting the replication of the human tumor suppressor gene BRCA1. However, RAPTA compounds have limited cytotoxicity, and therefore comparatively high doses are required. This study explores the activity of a series of RAPTA-like ruthenium(II) arene compounds against MCF-7 and MDA-MB-231 breast cancer cell lines and [Ru(η6-toluene)(PPh3)2Cl]+ was identified as a promising candidate. Notably, [Ru(η6-toluene)(PPh3)2Cl]Cl was found to be remarkably stable and highly cytotoxic, and selective to breast cancer cells. The minor groove of DNA was identified as a relevant target.

Stimuli-responsive platinum and ruthenium complexes for lung cancer therapy.

Lung cancer is the most common cause of cancer-related deaths worldwide. More efficient treatments are desperately needed. For decades, the success of platinum-based anticancer drugs has promoted the exploration of metal-based agents. Four ruthenium-based complexes have also entered clinical trials as candidates of anticancer metallodrugs. However, systemic toxicity, severe side effects and drug-resistance impeded their applications and efficacy. Stimuli-responsiveness of Pt- and Ru-based complexes provide a great chance to weaken the side effects and strengthen the clinical efficacy in drug design. This review provides an overview on the stimuli-responsive Pt- and Ru-based metallic anticancer drugs for lung cancer. They are categorized as endo-stimuli-responsive, exo-stimuli-responsive, and dual-stimuli-responsive prodrugs based on the nature of stimuli. We describe various representative examples of structure, response mechanism, and potential medical applications in lung cancer. In the end, we discuss the future opportunities and challenges in this field.

How Computations Can Assist the Rational Design of Drugs for Photodynamic Therapy: Photosensitizing Activity Assessment of a Ru(II)-BODIPY Assembly.

Ruthenium-based complexes represent a new frontier in light-mediated therapeutic strategies against cancer. Here, a density functional-theory-based computational investigation, of the photophysical properties of a conjugate BODIPY-Ru(II) complex, is presented. Such a complex was reported to be a good photosensitizer for photodynamic therapy (PDT), successfully integrating the qualities of a NIR-absorbing distyryl-BODIPY dye and a PDT-active [Ru(bpy)3]2+ moiety. Therefore, the behaviour of the conjugate BODIPY-Ru(II) complex was compared with those of the metal-free BODIPY chromophore and the Ru(II) complex. Absorptions spectra, excitation energies of both singlet and triplet states as well as spin–orbit-matrix elements (SOCs) were used to rationalise the experimentally observed different activities of the three potential chromophores. The outcomes evidence a limited participation of the Ru moiety in the ISC processes that justifies the small SOCs obtained for the conjugate. A plausible explanation was provided combining the computational results with the experimental evidences.

Transition metals of arene derivatives with functionalized ionic liquid: DFT investigation, biological applications and electrochemical behavior of complexes

Mononuclear transition metal complexes based on ionic liquid have been prepared and characterized in detail. The biological properties of the three complexes were evaluated using radical scavenging activity, reducing power, antibacterial effect, DNA binding and cleavage activity. Among the complexes, [3-[(2R)-2-({[dichloro(η6-benzene)ruthenium]diphenylphosphanyl}oxy)-2-phenylethyl]-1-methyl-1H-imidazol-3-ium chloride] (4), demonstrated the highest radical scavenging (64.7 %) and reducing power activity (0.467) at 200 μg/ml concentration. The highest zone of inhibition was obtained from [3-[(2R)-2-({[dichloro(η6-p-cymene)ruthenium]diphenyl phosphanyl}oxy)-2-phenylethyl]-1-methyl-1H-imidazol-3-ium chloride] (3), against Bacillus cereus as 14 mm. Furthermore, all complexes were determined to have DNA binding and cleavage activities. Furthermore, theoretical DFT computations have also been carried out for the cationic complexes, to obtain minimum energy configuration of molecules. The effects of the chemical structures of three cationic complexes were also examined in relation to the variable property of electron-donating ligands for ruthenium-based complexes and iridium complex and their potential energy levels in ground and excited states HOMO and LUMO were determined.

Recent advances and application of ruthenium complexes in tumor malignancy

Ruthenium-based complexes have a wide range of targets and mechanisms for anticancer activities. For the treatment of malignant malignancy, ruthenium-based drugs have special features. We establish the use of ruthenium-based complexes in the treatment of cancers throughout this review paper. The most common cause of cancer death is metastases, which alternate with primary tumors. Chemotherapy is generally ineffective against all solid human tumors and metastases. The ruthenium based complexes include metal-based complexes like NAMI-A and KP1019, as well as organometallic complexes like RM175, RAPTA-T, and RDC11. The ruthenium metal based complexes were discussed in this review study, together with the remaining clinical anticancer medicines, to explore tumor malignancy.

Ruthenium(II) complexes targeting membrane as biofilm disruptors and resistance breakers in Staphylococcus aureus bacteria

The development of ruthenium-based complexes or antimicrobial peptides are identified as a promising strategy for combating drug-resistant bacteria. In this work, four biphenyl-based antibacterial ruthenium complexes by targeting membrane integrity, which act as antimicrobial peptides mimics, were designed and synthesized. In vitro antimicrobial screening demonstrated that four complexes could absolutely inhibit the growth of Staphylococcus aureus (S. aureus) with MIC values ranging from 15.6 to 100 μg/mL. The most active complex Ru(Ⅱ)-1 (MIC = 15.6 μg/mL) could kill S. aureus through targeting the membrane integrity without detectably resistance frequencies. Further investigation including bacteria biofilm formation, hemolysin activity and checkerboard assay were performed as well. The results revealed that Ru(Ⅱ)-1 could inhibit the biofilm formation and α-hemolysis secretion in S. aureus at subinhibitory concentration. More interestingly, the combination use of Ru(Ⅱ)-1 and five traditional antibiotics showing synergistic effect. Finally, based on the mouse model of S. aureus skin infection, Ru(Ⅱ)-1 showed important antibacterial efficacy against S. aureus in vivo, and almost non-toxic against mouse tissue. Our study indicates that introducing membrane targeting ligands onto ruthenium complexes may be an underappreciated strategy for developing antibacterial agents.

A biocompatible ruthenium-based composite fluorescent probe using bovine serum albumin as a scaffold for ethylene gas detection and its fluorescence imaging in plant tissues

The detection of phytohormone ethylene is significant for extending the shelf-life of postharvest and controlling plant maturity. In this work, we report a biocompatible fluorescent probe for trace detection of the phytohormone ethylene based on the mechanism of the olefin metathesis reaction. The probe was prepared by simply incubating the ruthenium-based complex (FPRu) with bovine serum albumin (BSA). Then the structure of the probe was characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR) and circular dichroism circular dichroism (CD). The probe possesses a satisfactory detection of limit (LOD) for ethylene (1.17 ppm) and a decent linear range (4–250 ppm). Moreover, the probe-based test paper could also detect ethylene vapor with the naked eye, completing the visualization effect. Ethylene concentration monitoring at plant maturity could be done in solution and vapor. In particular, due to the protection of the hydrophobic pocket of BSA, the ruthenium-based fluorescent probe was also effectively applied to the fluorescence imaging in plant tissues. This work provides a new strategy to achieve highly selective detection and fluorescence imaging of ethylene in plant tissues without complicated operations and expensive instruments, which is of great significance for plant biology, agriculture and the food industry.

A Dual-Pronged Approach: A Ruthenium(III) Complex That Modulates Amyloid-β Aggregation and Disrupts Its Formed Aggregates.

Alzheimer's disease (AD) is a devastating neurological disorder for which soluble oligomers of the peptide amyloid-β (Aβ) are now recognized as the neurotoxic species. Metal-based therapeutics are uniquely suited to target Aβ, with ruthenium-based (Ru) complexes emerging as propitious candidates. Recently, azole-based Ru(III) complexes were observed to modulate the aggregation of Aβ in solution, where the inclusion of a primary amine proximal to the ligand coordination site improved the activity of the complexes. To advance these structure-activity relationships, a series of oxazole-based Ru complexes were prepared and evaluated for their ability to modulate Aβ aggregation. From these studies, a lead candidate, Oc, emerged that had superior activity relative to its azole predecessors in modulating the aggregation of soluble Aβ and diminishing its cytotoxicity. Further evaluation of Oc demonstrated its ability to disrupt formed Aβ aggregates, resulting in smaller amorphous species. Because altering both sides of the aggregation equilibrium for Aβ has not been previously suggested for metal-based complexes for AD, this work represents an exciting new avenue for improved therapeutic success.