Synthesis, Characterization, and Properties of Mononuclear and Dinuclear Ruthenium(II) Complexes Containing Phenanthroline and Chlorophenanthroline

The study of photophysical and photochemical properties of ruthenium complexes is of great interest for fundamental practical reasons. Ruthenium complexes have been investigated for use in artificial photosynthesis. This paper deals with the synthesis and spectroscopic investigation of custom-designed ruthenium complexes containing phenanthroline and chloro-phenanthroline ligands. These complexes maybe useful for biological electron-transfer studies. The heteroleptic ruthenium monomer complex Ru(phen)2(Cl-phen) (where phen = 1,10-phenanthroline and Cl-phen=5-chloro-1,10-phenanthroline) was prepared in a two-step procedure previously developed in our laboratory. This monomer complex was used to prepare the ruthenium homometallic dimer complex, (phen)2Ru(phen-phen)Ru(phen)2, by utilizing the Ni-catalyzed coupling reaction. Both complexes were purified by extensive column chromatography. The identity and the integrity of the monomer complex were confirmed by elemental analysis. The calculated and the experimental values for the elemental analysis were in good agreement for the monomer complex. UV/Vis absorption spectroscopy, emission spectroscopy, and cyclic voltammetry were used to investigate the properties of both the complexes

Programmable multimetallic linear nanoassemblies of ruthenium–DNA conjugates

A new ruthenium–DNA conjugates family was synthesized, made up of a ruthenium complex bound to one or two identical DNA strands of 14–58 nucleotides. The formation of controlled linear nanoassemblies containing one to seven ruthenium complexes is described

Functionalisation of bolaamphiphiles with mononuclear bis(2,2'-bipyridyl)ruthenium(II) complexes for application in self assembled monolayers

A novel ruthenium(II) polypyridyl complex connected competently to a bolaamphiphile, containing amide linkages to provide rigidity via hydrogen bonding in the monolayer, has been prepared. The ruthenium(II) complexes of this ligand and of the intermediates in the synthesis were prepared by modification of the coordinated ligands, demonstrating the synthetic versatility and robustness of this family of complexes. All ruthenium complexes were characterised by electrochemical and spectroscopic techniques and were found to have similar properties to the parent complex [Ru(bipy)[3]][2][+], and remain versatile photosensitisers, with well-defined properties, despite extensive substitution of the bipy ligand

Intermolecular Dehydrative Coupling Reaction of Arylketones with Cyclic Alkenes Catalyzed by a Well-Defined Cationic Ruthenium-Hydride Complex: A Novel Ketone Olefination Method via Vinyl C–H Bond Activation

The cationic ruthenium−hydride complex [(η6-C6H6)(PCy3)(CO)RuH]+BF4− was found to be a highly effective catalyst for the intermolecular olefination reaction of aryl ketones with cycloalkenes. The preliminary mechanistic analysis revealed that an electrophilic ruthenium−vinyl complex is the key species for mediating both vinyl C−H bond activation and the dehydrative olefination steps of the coupling reaction

A ruthenium anticancer compound interacts with histones and impacts differently on epigenetic and death pathways compared to cisplatin

Ruthenium complexes are considered as potential replacements for platinum compounds in oncotherapy. Their clinical development is handicapped by a lack of consensus on their mode of action. In this study, we identify three histones (H3.1, H2A, H2B) as possible targets for an anticancer redox organoruthenium compound (RDC11). Using purified histones, we confirmed an interaction between the ruthenium complex and histones that impacted on histone complex formation. A comparative study of the ruthenium complex versus cisplatin showed differential epigenetic modifications on histone H3 that correlated with differential expression of histone deacetylase (HDAC) genes. We then characterized the impact of these epigenetic modifications on signaling pathways employing a transcriptomic approach. Clustering analyses showed gene expression signatures specific for cisplatin (42%) and for the ruthenium complex (30%). Signaling pathway analyses pointed to specificities distinguishing the ruthenium complex from cisplatin. For instance, cisplatin triggered preferentially p53 and folate biosynthesis while the ruthenium complex induced endoplasmic reticulum stress and trans-sulfuration pathways. To further understand the role of HDACs in these regulations, we used suberanilohydroxamic acid (SAHA) and showed that it synergized with cisplatin cytotoxicity while antagonizing the ruthenium complex activity. This study provides critical information for the characterization of signaling pathways differentiating both compounds, in particular, by the identification of a non-DNA direct target for an organoruthenium complex

Kinetic, Spectroscopic, and X-Ray Crystallographic Evidence for the Cooperative Mechanism of the Hydration of Nitriles Catalyzed by a Tetranuclear Ruthenium-μ-oxo-μ-hydroxo Complex

The tetranuclear ruthenium-oxo-hydroxo-hydride complex {[(PCy3)(CO)RuH]4(μ4-O)(μ3-OH)(μ2-OH)} (1) was found to be a highly cooperative catalyst for the nitrile hydration reaction. The cooperative mechanism of the hydration of benzonitrile was established by Hill inhibition kinetics. The treatment of a nitrile substrate with complex 1 led to the catalytically relevant nitrile-coordinated tetraruthenium complex 3. The X-ray structure of the nitrile-coordinated complex 3 showed a considerably “relaxed” tetrameric core structure compared to that of 1. The hydration of para-substituted benzonitriles p-X-C6H4CN with an electron-withdrawing group (X = Cl, Br, CO2H, CF3) exhibited cooperative kinetics, as indicated by the sigmoidal saturation kinetics, while the hydration of nitriles with an electron-donating group (X = OH, OMe, t-Bu, CH3) obeyed Michaelis–Menten saturation kinetics. The formation of a ruthenium hydride species was observed during the hydration of methacrylonitrile, and its monomeric nature was established by using DOSY NMR techniques

The synthesis and characterization of new higher nuclearity arene-ruthenium-sulfur clusters : a thesis presented in partial fulfillment of the requirements for the degree of Master of Science in Chemistry at Massey University, New Zealand

This thesis describes a project investigating the synthesis and characterization of new higher nuclearity arene-ruthenium-sulfur clusters and arene-ruthenium-nitrogen complexes. The thesis is divided into four chapters, with the introduction in Chapter One. The synthesis and characterization of new higher nuclearity arene-ruthenium-sulfur clusters are described in Chapter Two. These include two novel clusters, [Ru₅S₄(cymene)₄](PF₆)₂, [Ru₄(S₂)(SO)(cymene)₄](PF₆)₂ and one known cluster, [Ru₃S₂(cymene)₃](PF₆)₂. The X-ray crystallographic structures of these three arene-ruthenium-sulfur clusters are discussed in detail including how the number of valence electrons influences the structure, how the solid state structure and single crystal structure effect each other and how the structures determine the chemical shifts and other characters of the clusters. The unusual signals of these three clusters on ¹H NMR spectra are discussed carefully. The mechanisms of formation of arene-ruthenium-sulfur clusters are described in detail. Some electrochemistry and calculations (quantum chemistry) are also involved. The synthesis and characterization of arene-ruthenium-nitrogen complexes are described in Chapter Three. These include two new mono-nuclear complexes, [RuCl₂(NH₃)(cymene)], [Ru(NH₃)₃(cymene)](PF₆)₂, one novel amide dimer [RuCl(NH₂)(cymene)]₂ and one known complex, [RuCl(NH₃)₂(cymene)]PF₆. The mechanisms of reactions in which they are formed are also discussed. In Chapter Four, the experimental data is presented. The X ray crystallography of [Ru₅S₄(cymene)₄](PF₆)₂, [Ru₄(S₂)(SO)(cymene)₄](PF₆)₂, [RuCl₂(NH₃)(cymene)] and [RuCl(NH₂)(cymene)]₂ is described in detail

Controlling platinum, ruthenium, and osmium reactivity for anticancer drug design

The main task of the medicinal chemist is to design molecules that interact specifically with derailed or degenerating processes in a diseased organism, translating the available knowledge of pathobiochemical and physiological data into chemically useful information and structures. Current knowledge of the biological and chemical processes underlying diseases is vast and rapidly expanding. In particular the unraveling of the genome in combination with, for instance, the rapid development of structural biology has led to an explosion in available information and identification of new targets for chemotherapy. The task of translating this wealth of data into active and selective new drugs is an enormous, but realistic, challenge. It requires knowledge from many different fields, including molecular biology, chemistry, pharmacology, physiology, and medicine and as such requires a truly interdisciplinary approach. Ultimately, the goal is to design molecules that satisfy all the requirements for a candidate drug to function therapeutically. Therapeutic activity can then be achieved by an understanding of and control over structure and reactivity of the candidate drug through molecular manipulation

New trends for metal complexes with anticancer activity

Medicinal inorganic chemistry can exploit the unique properties of metal ions for the design of new drugs. This has, for instance, led to the clinical application of chemotherapeutic agents for cancer treatment, such as cisplatin. The use of cisplatin is, however, severely limited by its toxic side-effects. This has spurred chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. Recent trends in the field are discussed in this review. These include the more selective delivery and/or activation of cisplatin-related prodrugs and the discovery of new non-covalent interactions with the classical target, DNA. The use of the metal as scaffold rather than reactive centre and the departure from the cisplatin paradigm of activity towards a more targeted, cancer cell-specific approach, a major trend, are discussed as well. All this, together with the observation that some of the new drugs are organometallic complexes, illustrates that exciting times lie ahead for those interested in ‘metals in medicine