Selective cytotoxic Ru(II) arene Cp* complex salts [R-PhRuCp*](+)X(-) for X = BF4(-), PF6(-), and BPh4(-)

A novel series of ionic Ru(II) arene Cp* sandwich complexes has been synthesized and characterized. Screening results for cytotoxicity against a range of human tumor cell lines and normal human cells indicate that the complexes show promising anticancer activity, which varies with changes in the arene ligand and the anionic counterion.     

Design,synthesis,characterization,cytotoxic and structure activity relationships of novel Ru(Ⅱ) complexes

Platinum containing compounds have shown antineoplastic potential, but their clinical applications have been limited by high toxicity. Ruthenium containing complexes have long been known to be well suited for biological applications, and have long been utilized as replacements to popular platinum based-drugs. Here, we report a novel series of ruthenium(II) arene compounds bearing thiosemicarbazone and isonicotinylhydrazone ligands with potent anticancer activity their structure activity relationships and apoptosis was studied. The cytotoxic activity of the new ruthenium(II) arene compounds has been evaluated in several cell lines (Molt 4/C8, L1210, CEM, HL60 and BEL7402). Among them, ten complexes were found to be excellent in vitro growth inhibitory activity against various cell lines with IC50 in the sub-micromolar range.     

Half‐Sandwich Ruthenium(II) Biotin Conjugates as Biological Vectors to Cancer Cells

Ruthenium(II)–arene complexes with biotin‐containing ligands were prepared so that a novel drug delivery system based on tumor‐specific vitamin‐receptor mediated endocytosis could be developed. The complexes were characterized by spectroscopic methods and their in vitro anticancer activity in cancer cell lines with various levels of major biotin receptor (COLO205, HCT116 and SW620 cells) was tested in comparison with the ligands. In all cases, coordination of ruthenium resulted in significantly enhanced cytotoxicity. The affinity of Ru^II–biotin complexes to avidin was investigated and was lower than that of unmodified biotin. Hill coefficients in the range 2.012–2.851 suggest strong positive cooperation between the complexes and avidin. To estimate the likelihood of binding to the biotin receptor/transporter, docking studies with avidin and streptavidin were conducted. These explain, to some extent, the in vitro anticancer activity results and support the conclusion that these novel half‐sandwich ruthenium(II)–biotin conjugates may act as biological vectors to cancer cells, although no clear relationship between the cellular Ru content, the cytotoxicity, and the presence of the biotin moiety was observed.     

Ruthenium Complexes as Promising Candidates against Lung Cancer

Lung cancer is one of the most common malignancies with the highest mortality rate and the second-highest incidence rate after breast cancer, posing a serious threat to human health. The accidental discovery of the antitumor properties of cisplatin in the early 1960s aroused a growing interest in metal-based compounds for cancer treatment. However, the clinical application of cisplatin is limited by serious side effects and drug resistance. Therefore, other transition metal complexes have been developed for the treatment of different malignant cancers. Among them, Ru(II/III)-based complexes have emerged as promising anticancer drug candidates due to their potential anticancer properties and selective cytotoxic activity. In this review, we summarized the latest developments of Ru(II/III) complexes against lung cancer, focusing mainly on the mechanisms of their biological activities, including induction of apoptosis, necroptosis, autophagy, cell cycle arrest, inhibition of cell proliferation, and invasion and metastasis of lung cancer cells.     

Chemically engineered papain as artificial formate dehydrogenase for NAD(P)H regeneration

Organometallic complexes of the general formula [(η(6)-arene)Ru(N?N)Cl](+) and [(η(5)-Cp*)Rh(N?N)Cl](+) where N?N is a 2,2'-dipyridylamine (DPA) derivative carrying a thiol-targeted maleimide group, 2,2'-bispyridyl (bpy), 1,10-phenanthroline (phen) or ethylenediamine (en) and arene is benzene, 2-chloro-N-[2-(phenyl)ethyl]acetamide or p-cymene were identified as catalysts for the stereoselective reduction of the enzyme cofactors NAD(P)(+) into NAD(P)H with formate as a hydride donor. A thorough comparison of their effectiveness towards NAD(+) (expressed as TOF) revealed that the Rh(III) complexes were much more potent catalysts than the Ru(II) complexes. Within the Ru(II) complex series, both the N?N and arene ligands forming the coordination sphere had a noticeable influence on the activity of the complexes. Covalent anchoring of the maleimide-functionalized Ru(II) and Rh(III) complexes to the cysteine endoproteinase papain yielded hybrid metalloproteins, some of them displaying formate dehydrogenase activity with potentially interesting kinetic parameters.     

Tuning the reactivity of osmium(II) and ruthenium(II) arene complexes under physiological conditions

The Os(II) arene ethylenediamine (en) complexes [(eta(6)-biphenyl)Os(en)Cl][Z], Z = BPh(4) (4) and BF(4) (5), are inactive toward A2780 ovarian cancer cells despite 4 being isostructural with an active Ru(II) analogue, 4R. Hydrolysis of 5 occurred 40 times more slowly than 4R. The aqua adduct 5A has a low pK(a) (6.3) compared to that of [(eta(6)-biphenyl)Ru(en)(OH(2))](2+) (7.7) and is therefore largely in the hydroxo form at physiological pH. The rate and extent of reaction of 5 with 9-ethylguanine were also less than those of 4R. We replaced the neutral en ligand by anionic acetylacetonate (acac). The complexes [(eta(6)-arene)Os(acac)Cl], arene = biphenyl (6), benzene (7), and p-cymene (8), adopt piano-stool structures similar to those of the Ru(II) analogues and form weak dimers through intermolecular (arene)C-H...O(acac) H-bonds. Remarkably, these Os(II) acac complexes undergo rapid hydrolysis to produce not only the aqua adduct, [(eta(6)-arene)Os(acac)(OH(2))](+), but also the hydroxo-bridged dimer, [(eta(6)-arene)Os(mu(2)-OH)(3)Os(eta(6)-arene)](+). The pK(a) values for the aqua adducts 6A, 7A, and 8A (7.1, 7.3, and 7.6, respectively) are lower than that for [(eta(6)-p-cymene)Ru(acac)(OH(2))](+) (9.4). Complex 8A rapidly forms adducts with 9-ethylguanine and adenosine, but not with cytidine or thymidine. Despite their reactivity toward nucleobases, complexes 6-8 were inactive toward A549 lung cancer cells. This is attributable to rapid hydrolysis and formation of unreactive hydroxo-bridged dimers which, surprisingly, were the only species present in aqueous solution at biologically relevant concentrations. Hence, the choice of chelating ligand in Os(II) (and Ru(II)) arene complexes can have a dramatic effect on hydrolysis behavior and nucleobase binding and provides a means of tuning the reactivity and the potential for discovery of anticancer complexes.     

Ruthenium(II)/(III) complexes of 4-hydroxy-pyridine-2,6-dicarboxylic acid with PPh3/AsPh3 as co-ligand: impact of oxidation state and co-ligands on anticancer activity in vitro

With the aim to develop more efficient, less toxic, target specific metal drugs and evaluate their anticancer properties in terms of oxidation state and co-ligand sphere, a sequence of Ru(II), Ru(III) complexes bearing 4-hydroxy-pyridine-2,6-dicarboxylic acid and PPh(3)/AsPh(3) were synthesized and structurally characterized. Biological studies such as DNA binding, antioxidant assays and cytotoxic activity were carried out and their anticancer activities were evaluated. Interactions of the complexes with calf thymus DNA revealed that the triphenylphosphine complexes could bind more strongly than the triphenylarsine complexes. The free radical scavenging ability, assessed by a series of in vitro antioxidant assays involving DPPH radical, hydroxyl radical, nitric oxide radical, superoxide anion radical, hydrogen peroxide and metal chelating assay, showed that the Ru(III) complexes possess excellent radical scavenging properties compared to those of Ru(II). Cytotoxicity studies using three cancer lines viz HeLa, HepG2, HEp-2 and a normal cell line NIH 3T3 showed that Ru(II) complexes exhibited substantial cytotoxic specificity towards cancer cells. Furthermore, the Ru(II) complexes were found to be superior to Ru(III) complexes in inhibiting the growth of cancer cells.     

Competition between glutathione and guanine for a ruthenium(II) arene anticancer complex: detection of a sulfenato intermediate

The organometallic anticancer complex [(eta6-bip)Ru(en)Cl]+ (1; bip = biphenyl, en = ethylenediamine) selectively binds to guanine (N7) bases of DNA (Novakova, O.; Chen, H.; Vrana, O.; Rodger, A.; Sadler, P. J.; Brabec, V. Biochemistry 2003, 42, 11544-11554). In this work, competition between the tripeptide glutathione (gamma-L-Glu-L-Cys-Gly; GSH) and guanine (as guanosine 3',5'-cyclic monophosphate, cGMP) for complex 1 was investigated using HPLC, LC-MS and 1H,15N NMR spectroscopy. In unbuffered solution (pH ca. 3), the reaction of 1 with GSH gave rise to three intermediates: an S-bound thiolato adduct [(eta6-bip)Ru(en)(GS-S)] (4) and two carboxylate-bound glutathione products [(eta6-bip)Ru(en)(GSH-O)]+ (5, 6) during the early stages (<6 h), followed by en displacement and formation of a tri-GS-bridged dinuclear Ru(II) complex [((eta6-bip)Ru)2(GS-mu-S)3]2- (7). Under physiologically relevant conditions (micromolar Ru concentrations, pH 7, 22 mM NaCl, 310 K), the thiolato complex 4 was unexpectedly readily oxidized by dioxygen to the sulfenato complex [(eta6-bip)Ru(en)(GS(O)-S)] (8) instead of forming the dinuclear complex 7. Under these conditions, competitive reaction of complex 1 with GSH and cGMP gave rise to the cGMP adduct [(eta6-bip)Ru(en)(cGMP-N7)]+ (10) as the major product, accounting for ca. 62% of total Ru after 72 h, even in the presence of a 250-fold molar excess of GSH. The oxidation of coordinated glutathione in the thiolato complex 4 to the sulfenate in 8 appears to provide a facile route for displacement of S-bound glutathione by G N7. Redox reactions of cysteinyl adducts of these Ru(II) arene anticancer complexes could therefore play a significant role in their biological activity.     

基于萘普生-芳基金属配合物的抗癌及抗炎性能

以萘普生(NPX)为前体, 分别与芳基钌(Ru)、 锇(Os)及铱(Ir)二聚体反应制备了3个单核配合物[Ru(η ⁶-p-cymene)(NPX-bpy)Cl]Cl(1), [Os(η ⁶-p-cymene)(NPX-bpy)Cl]Cl(2)和[Ir(η ⁵-Cp ^*)·(NPX-bpy)Cl]Cl(3). 利用元素分析、 电喷雾质谱和核磁共振波谱对3个配合物的组成和结构进行了表征, 并研究了其细胞毒性. 结果表明, 3个配合物对几种肿瘤细胞株均无毒性(IC₅₀>100 μmol/L), 仅配合物1对NB-4细胞有中等程度的毒性(IC₅₀=45.2 μmol/L), 且毒性大于配合物2和3, 这可能与配合物1在细胞核内具有更高的富集量有关. 此外, 3个配合物均可有效抑制COX-2的表达, 保留了萘普生的抗炎性质, 实现了金属配合物抗癌及抗炎的多功能化应用.     

Highly selective binding of organometallic ruthenium ethylenediamine complexes to nucleic acids: novel recognition mechanisms

We have investigated the recognition of nucleic acid derivatives by organometallic ruthenium(II) arene anticancer complexes of the type [(eta(6)-arene)Ru(II)(en)X] where en = ethylenediamine, arene = biphenyl (Bip), tetrahydroanthracene (THA), dihydroanthracene (DHA), p-cymene (Cym) or benzene (Ben), X = Cl(-) or H(2)O using (1)H, (31)P and (15)N ((15)N-en) NMR spectroscopy. For mononucleosides, [(eta(6)-Bip)Ru(en)](2+) binds only to N7 of guanosine, to N7 and N1 of inosine, and to N3 of thymidine. Binding to N3 of cytidine was weak, and almost no binding to adenosine was observed. The reactivity of the various binding sites of nucleobases toward Ru at neutral pH decreased in the order G(N7) > I(N7) > I(N1), T(N3) > C(N3) > A(N7), A(N1). Therefore, pseudo-octahedral diamino Ru(II) arene complexes are much more highly discriminatory between G and A bases than square-planar Pt(II) complexes. Such site-selectivity appears to be controlled by the en NH(2) groups, which H-bond with exocyclic oxygens but are nonbonding and repulsive toward exocyclic amino groups of the nucleobases. For reactions with mononucleotides, the same pattern of site selectivity was observed, but, in addition, significant amounts of the 5'-phosphate-bound species (40-60%) were present at equilibrium for 5'-TMP, 5'-CMP and 5'-AMP. In contrast, no binding to the phosphodiester groups of 3', 5'-cyclic-GMP (cGMP) or cAMP was detected. Reactions with nucleotides proceeded via aquation of [(eta(6)-arene)Ru(en)Cl](+), followed by rapid binding to the 5'-phosphate, and then rearrangement to give N7, N1, or N3-bound products. Small amounts of the dinuclear species, e.g., Ru-O(PO(3))GMPN7-Ru, Ru-O(PO(3))IMPN1-Ru, Ru-O(PO(3))TMPN3-Ru, Ru-N7IMPN1-Ru, and Ru-N7InoN1-Ru were also detected. In competitive binding experiments for [(eta(6)-Bip)Ru(en)Cl](+) with 5'-GMP versus 5'-AMP or 5'-CMP or 5'-TMP, the only final adduct was [(eta(6)-Bip)Ru(en)(N7-GMP)]. Ru-H(2)O species were more reactive than Ru-OH species. The presence of Cl(-) or phosphate in neutral solution significantly decreased the rates of Ru-N7 binding through competitive coordination to Ru. In kinetic studies (pH 7.0, 298 K, 100 mM NaClO(4)), the rates of reaction of cGMP with [(eta(6)-arene)Ru(II)(en)X](n+) (X = Cl(-) or H(2)O) decreased in the order: THA > Bip > DHA > Cym > Ben, suggesting that N7-binding is promoted by favorable arene-purine hydrophobic interactions in the associative transition state. These findings have revealed that the diamine NH(2) groups, the hydrophobic arene, and the chloride leaving group have important roles in the novel mechanism of recognition of nucleic acids by Ru arene complexes, and will aid the design of more effective anticancer complexes, as well as new site-specific DNA reagents.     

Organometallic ruthenium(II) diamine anticancer complexes: arene-nucleobase stacking and stereospecific hydrogen-bonding in guanine adducts

Organometallic ruthenium(II) arene anticancer complexes of the type [(eta(6)-arene)Ru(II)(en)Cl][PF(6)] (en = ethylenediamine) specifically target guanine bases of DNA oligomers and form monofunctional adducts (Morris, R., et al. J. Med. Chem. 2001). We have determined the structures of monofunctional adducts of the "piano-stool" complexes [(eta(6)-Bip)Ru(II)(en)Cl][PF(6)] (1, Bip = biphenyl), [(eta(6)-THA)Ru(II)(en)Cl][PF(6)] (2, THA = 5,8,9,10-tetrahydroanthracene), and [(eta(6)-DHA)Ru(II)(en)Cl][PF(6)] (3, DHA = 9,10-dihydroanthracene) with guanine derivatives, in the solid state by X-ray crystallography, and in solution using 2D [(1)H,(1)H] NOESY and [(1)H,(15)N] HSQC NMR methods. Strong pi-pi arene-nucleobase stacking is present in the crystal structures of [(eta(6)-C(14)H(14))Ru(en)(9EtG-N7)][PF(6)](2).(MeOH) (6) and [(eta(6)-C(14)H(12))Ru(en)(9EtG-N7)][PF(6)](2).2(MeOH) (7) (9EtG = 9-ethylguanine). The anthracene outer ring (C) stacks over the purine base at distances of 3.45 A for 6 and 3.31 A for 7, with dihedral angles of 3.3 degrees and 3.1 degrees, respectively. In the crystal structure of [(eta(6)-biphenyl)Ru(en)(9EtG-N7)][PF(6)](2).(MeOH) (4), there is intermolecular stacking between the pendant phenyl ring and the purine six-membered ring at a distance of 4.0 A (dihedral angle 4.5 degrees). This stacking stabilizes a cyclic tetramer structure in the unit cell. The guanosine (Guo) adduct [(eta(6)-biphenyl)Ru(en)(Guo-N7)][PF(6)](2).3.75(H(2)O) (5) exhibits intramolecular stacking of the pendant phenyl ring with the purine five-membered ring (3.8 A, 23.8 degrees) and intermolecular stacking of the purine six-membered ring with an adjacent pendant phenyl ring (4.2 A, 23.0 degrees). These occur alternately giving a columnar-type structure. A syn orientation of arene and purine is present in the crystal structures 5, 6, and 7, while the orientation is anti for 4. However, in solution, a syn orientation predominates for all the biphenyl adducts 4, 5, and the guanosine 5'-monophosphate (5'-GMP) adduct 8 [(eta(6)-biphenyl)Ru(II)(en)(5'-GMP-N7)], as revealed by NMR NOE studies. The predominance of the syn orientation both in the solid state and in solution can be attributed to hydrophobic interactions between the arene and purine rings. There are significant reorientations and conformational changes of the arene ligands in [(eta(6)-arene)Ru(II)(en)(G-N7)] complexes in the solid state, with respect to those of the parent chloro-complexes [(eta(6)-arene)Ru(II)(en)Cl](+). The arene ligands have flexibility through rotation around the arene-Ru pi-bonds, propeller twisting for Bip, and hinge-bending for THA and DHA. Thus propeller twisting of Bip decreases by ca. 10 degrees so as to maximize intra- or intermolecular stacking with the purine ring, and stacking of THA and DHA with the purine is optimized when their tricyclic ring systems are bent by ca. 30 degrees, which involves increased bending of THA and a flattening of DHA. This flexibility makes simultaneous arene-base stacking and N7-covalent binding compatible. Strong stereospecific intramolecular H-bonding between an en NH proton oriented away from the arene (en NH(d)) and the C6 carbonyl of G (G O6) is present in the crystal structures of 4, 5, 6, and 7 (average N...O distance 2.8 A, N-H...O angle 163 degrees ). NMR studies of the 5'-GMP adduct 8 provided evidence that en NH(d) protons are involved in strong H-bonding with the 5'-phosphate and O6 of 5'-GMP. The strong H-bonding from G O6 to en NH(d) protons partly accounts for the high preference for binding of [(eta(6)-arene)Ru(II)en](2+) to G versus A (adenine). These studies suggest that simultaneous covalent coordination, intercalation, and stereospecific H-bonding can be incorporated into Ru(II) arene complexes to optimize their DNA recognition behavior, and as potential drug design features.     

Design,synthesis and in vitro bioactivity of mixed ligand Ru(II) complexes bearing the fluoroquinolone antibacterial agents

Transition Metal Chemistry - Mixed ligand Ru(II) phenanthroline complexes of the type [Ru(1,10-phen)2Flq]ClO4 (RPFlq-1-3) and “piano-stool”-type Ru(II) arene complexes...     

Conformation of DNA modified by monofunctional Ru(II) arene complexes: recognition by DNA binding proteins and repair. Relationship to cytotoxicity

We analyzed DNA duplexes modified at central guanine residues by monofunctional Ru(II) arene complexes [(eta(6)-arene)Ru(II)(en)(Cl)](+) (arene = tetrahydroanthracene or p-cymene, Ru-THA or Ru-CYM, respectively). These two complexes were chosen as representatives of two different classes of Ru(II) arene compounds for which initial studies revealed different binding modes: one that may involve DNA intercalation (tricyclic-ring Ru-THA) and the other (mono-ring Ru-CYM) that may not. Ru-THA is approximately 20 times more toxic to cancer cells than Ru-CYM. The adducts of Ru-THA and Ru-CYM have contrasting effects on the conformation, thermodynamic stability, and polymerization of DNA in vitro. In addition, the adducts of Ru-CYM are removed from DNA more efficiently than those of Ru-THA. Interestingly, the mammalian nucleotide excision repair system has low efficiency for excision of ruthenium adducts compared to cisplatin intrastrand crosslinks.     

Ferrocenoyl pyridine arene ruthenium complexes with anticancer properties: synthesis, structure, electrochemistry, and cytotoxicity

Organometallic ruthenium(II) complexes of general formula [Ru(eta(6)-arene)Cl(2)(NC(5)H(4)OOC-C(5)H(4)FeC(5)H(5))], where arene = C(6)H(6) (1), C(6)H(5)Me (2), p-iPrC(6)H(4)Me (3), and C(6)Me(6) (4), and of general formula [Ru(eta(6)-arene)Cl(2)](2)(NC(5)H(4)OOC-C(5)H(4)FeC(5)H(4)-COOC(5)H(4)N), where arene = p-iPrC(6)H(4)Me (5) and C(6)Me(6) (6), have been synthesized and characterized, the molecular structures of these complexes being confirmed by single-crystal X-ray structure analysis of complex 4 as a representative example. The redox properties and in vitro anticancer activities of complexes 1-6 have been studied. All the compounds are moderately cytotoxic toward the A2780 and A2780cisR (cisplatin-resistant) human ovarian carcinoma cell lines. The diruthenium arene complexes 5 and 6 are about twice as active as their mononuclear analogues 3 and 4. Cyclic voltammetry revealed a good correlation of the RuII/RuIII redox potentials of 1-4 and the number of alkyl substituents in the arene ligand.     

Photocontrolled DNA binding of a receptor-targeted organometallic ruthenium(II) complex

A photoactivated ruthenium(II) arene complex has been conjugated to two receptor-binding peptides, a dicarba analogue of octreotide and the Arg-Gly-Asp (RGD) tripeptide. These peptides can act as "tumor-targeting devices" since their receptors are overexpressed on the membranes of tumor cells. Both ruthenium-peptide conjugates are stable in aqueous solution in the dark, but upon irradiation with visible light, the pyridyl-derivatized peptides were selectively photodissociated from the ruthenium complex, as inferred by UV-vis and NMR spectroscopy. Importantly, the reactive aqua species generated from the conjugates, [(η(6)-p-cym)Ru(bpm)(H(2)O)](2+), reacted with the model DNA nucleobase 9-ethylguanine as well as with guanines of two DNA sequences, (5')dCATGGCT and (5')dAGCCATG. Interestingly, when irradiation was performed in the presence of the oligonucleotides, a new ruthenium adduct involving both guanines was formed as a consequence of the photodriven loss of p-cymene from the two monofunctional adducts. The release of the arene ligand and the formation of a ruthenated product with a multidentate binding mode might have important implications for the biological activity of such photoactivated ruthenium(II) arene complexes. Finally, photoreactions with the peptide-oligonucleotide hybrid, Phac-His-Gly-Met-linker-p(5')dCATGGCT, also led to arene release and to guanine adducts, including a GG chelate. The lack of interaction with the peptide fragment confirms the preference of such organometallic ruthenium(II) complexes for guanine over other potential biological ligands, such as histidine or methionine amino acids.     

106Ru radiolabelling of the antitumour complex [(eta6-fluorene)Ru(en)Cl]PF6

The organometallic half-sandwich Ru(II) arene anticancer complex [(eta(6)-fluorene)Ru(en)Cl]PF(6) () has been synthesized in high yield and purity on a micromole scale with incorporation of the beta-emitting radioisotope (106)Ru (half-life = 1.01 y) using a refined procedure involving conversion of RuCl(3) into [(eta(6)-fluorene)RuCl(2)](2), and then [(eta(6)-fluorene)Ru(CH(3)CN)(2)Cl]PF(6) as intermediates. Distribution studies 0.25 h post i.v. injection of (106)Ru- at a dose of 25 mg kg(-1) show that (106)Ru is well distributed throughout the tissues of a rat. This appears to be the first report of the radiolabelling of a potential ruthenium antitumour agent for distribution/biological studies.     

The Development of Ru(II)-Based Photoactivated Chemotherapy Agents

Photoactivated chemotherapy (PACT) is a novel cancer treatment method that has drawn increasing attention due to its high selectivity and low side effects by spatio-temporal control of irradiation. Compared with photodynamic therapy (PDT), oxygen-independent PACT is more suitable for treating hypoxic tumors. By finely tuning ligand structures and coordination configurations, many Ru(II) complexes can undergo photoinduced ligand dissociation, and the resulting Ru(II) aqua species and/or free ligands may have anticancer activity, showing their potential as PACT agents. In this mini-review, we summarized the progress in Ru(II)-based PACT agents, as well as challenges that researchers in this field still face.     

X-ray diffraction and NMR studies on a series of Binap-based Ru(II) hydroxyphosphine pi-arene complexes

A series of new Ru(II) arene phosphine complexes derived from Binap have been prepared. Specifically, reaction of Ru(OAc)(2)(Binap) with 3,5-(CF(3))(2)C(6)H(3))(4)B (BArF).H(OEt(2))(2), is shown to afford new mono- and dinuclear Ru(II) hydroxyphosphine pi-arene complexes via a series of P-C bond cleavage reactions. The dinuclear Ru(II) pi-arene complexes contain bridging P(O)(OH)(2) ligands. Crystal structures of five new complexes are reported and suggest an eta(4)-arene rather than an eta(6)-arene coordination mode. However, in solution, their (13)C NMR data are more consistent with a strongly distorted eta(6)-coordination mode. PGSE (1)H and (19)F diffusion measurements on the dinuclear complexes suggest hydrogen bonding of the triflate anion and ion-pairing of the BArF(-) anion.     

Review: recent advances and future development of metal complexes as anticancer agents

Since the initial discovery of applications of platinum complexes in the clinical treatment of many kinds of cancers, the efficiency of platinum complexes in inhibiting the proliferation of various types of tumors surprised researchers working on the development of anticancer drugs. Meanwhile, despite the potent clinical treatment patients get from platinum complexes, there are also disadvantages including limited solubility in aqueous media and side effects like ototoxicity, myelosuppression, nephrotoxicity, and poor selectivity toward healthy cells. For this reason, efforts have been made to search for novel solutions. Non-platinum complexes (like Fe, Pd, Ru, Cu, Bi, Zn, etc.) were found with potential anticancer activities. We here review the properties of five metal complexes as anticancer agents and make comparisons among them in biological features and cytotoxic activity. Seeking the interrelation between microstructure and mechanism of anticancer, we hope this review provides distinct insights into future study of anticancer agents.     

Maleimide-functionalised organoruthenium anticancer agents and their binding to thiol-containing biomolecules

Ru(II)(arene) anticancer compounds with maleimide functionality were prepared to allow selective interaction with thiol-containing biomolecules and thereby enforcing the selective delivery of the compounds to the tumour.