Cytoxicity and Apoptotic Mechanism of Ruthenium(II) Amino Acid Complexes in Sarcoma-180 Tumor Cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Antiplasmodial activity of iron(II) and ruthenium(II) organometallic complexes against Plasmodium falciparum blood parasites

This work reports the in vitro activity against Plasmodium falciparum blood forms (W2 clone, chloroquine-resistant) of tamoxifen-based compounds and their ferrocenyl (ferrocifens) and ruthenocenyl (ruthenocifens) derivatives, as well as their cytotoxicity against HepG2 human hepatoma cells. Surprisingly with these series, results indicate that the biological activity of ruthenocifens is better than that of ferrocifens and other tamoxifen-like compounds. The synthesis of a new metal-based compound is also described. It was shown, for the first time, that ruthenocifens are good antiplasmodial prototypes. Further studies will be conducted aiming at a better understanding of their mechanism of action and at obtaining new compounds with better therapeutic profile.

Chemical and electrochemical investigations of cobalt cyanide and ruthenium ammine complexes

Part I.

The stoichiometry and kinetics of the reaction between Co(CN₅H^3- and HgX₂ (X = CN, OH) have been investigated. The products of the reaction are two new complexes, [(NC)₅Co-HgX]^3- and [(NC)₅Co-Hg-Co(CN)₅]^6-, whose spectra are reported. The kinetic measurements produced a value for the forward rate constant of the reaction Co(CN)₅H^3- + OH^- k₁/k_-1 Co(CN)₅^4- +H₂O, k1 = (9.7 ± 0.8) x 10^-2 M^-1 sec^-1 at 24°C, and an equilibrium constant for the reaction K = 10^-6 M^-1.

Part II.

Unusually large and sharp "adsorption waves" appear in cyclic voltammograms of Co(CN)₅^3- and several cobalt(III) pentacyano complexes at stationary mercury electrodes. The nature of the adsorbed species and the reasons for the absence of the adsorption waves in polarograms taken with a d.m.e. have been examined. The data are compatible with the adsorption, in all cases, of a coordinatively unsaturated cobalt(II) complex, Co(CN)₄^2-, by means of a cobalt-mercury bond. When the resulting adsorbed complex is reduced, a series of subsequent chemical and electrode reactions is initiated in which three faradays of charge are consumed for each mole of adsorbed complex. The adsorption of the anionic complex strongly retards the reduction of other negatively charged complexes.

Part III.

A number of formal redox potentials for Ru^III (NH₃)₅L + e = Ru^II (NH₃)₅L and Ru^III(NH₃)₄L₂ + e = Ru^II (NH₃)₄L₂ (where L is various ligands) has been measured by cyclic voltammetry, potentiometry, and polarography and are discussed in terms of the properties of the ligands, such as π-accepting capability. Reduction of coordinated pyrazine in the complexes, Ru(NH₃)₅ Pz²⁺, cis- and trans-Ru(NH₃)₄Pz₂²⁺, on a mercury electrode has been observed. The behavior of this reduction in various acidity of the solution as well as the reoxidation of the reduction products are discussed.

Quantitative electrochemiluminescence detection of proteins: Avidin-based sensor and tris(2,2 '-bipyridine) ruthenium(II) label

Quantitative electrochemilumineseence (ECL) detection of a model protein, bovine serum albumin (BSA) was achieved via biotin-avidin interaction using an avidin-based sensor and a well-developed ECL system of tris(2,2'-bipyridine) ruthenium(II) derivative as label and tri-n-propylamine (TPA) as coreactant. To detect the protein, avidin was linked to the glassy carbon electrode through passive adsorptions and covalent interaction with carboxylate-terminated carbon nanotubes that was used as binder to immobilize avidin onto the electrode. Then, biotinylated BSA tagged with tris(2,2'-bipyridine) ruthenium(II) label was attached to the prepared avidin surface.

Tris(2,2 '-bipyridyl) ruthenium(II) doped silica film modified indium tin oxide electrode and its electrochemiluminescent properties

An approach was reported to synthesize silica hybridized ruthenium bipyridyl complex through amidation reaction by covalent attachment of bis(bipyridyl)-4,4'-dicarboxy-2,2'-bipyridyl-ruthenium to (3-aminopropyl)-triethoxysilane. The hybrid complex then was gelatinized through acid catalytic hydrolysis method and a sol-gel modified indium, tin oxide electrode was prepared via spin coating technique. As prepared indium tin oxide electrode possesses good stability therein with excellent electrochemiluminescence behavior.

Electrochemiluminescent detection based on solid-phase extraction at tris(2,2 '-bipyridyl)ruthenium(II)-modified ceramic carbon electrode

A sensitive electrochemiluminescent detection scheme by solid-phase extraction at Ru(bpy)(3)(2+)-modified ceramic carbon electrodes (CCEs) was developed. The as-prepared Ru(bpy)(3)(2+)-modified CCEs show much better long-term stability than other Nafion-based Ru(bpy)(3)(2+)-modified electrodes and enjoy the inherent advantages of CCEs. The log-log calibration plot for dioxopromethazine is linear from 1.0 x 10(-9) to 1.0 x 10(-4) mol L-1 using the new detection scheme. The detection limit is 6.6 x 10(-10) mol L-1 at a signal-to-noise ratio of 3. The new scheme improves the sensitivity by similar to 3 orders of magnitude, which is the most sensitive Ru(bpy)(3)(2+) ECL method. The scheme allows the detection of dioxopromethazine in a urine sample within 3 min. Since Ru(bpy)(3)(2+) ECL is a powerful technique for determination of numerous amine-containing substances, the new detection scheme holds great promise in measurement of free concentrations, investigation of protein-drug interactions and DNA-drug interactions, pharmaceutical analysis, and so on.

Synthesis, crystal structure, spectroscopy and electroluminescence of zinc(II) complexes containing bidentate 2-(2-pyridyl)quinoline derivative ligands

Three bidentate ligands, 4-phenyl-2-(2-pyridyl)-quinoline (ppq), 6-(carbazol-9-yl)-4-phenyl-2-(2-pyridyl)-quinoline (cpq) and 6-diphenylamino-4-phenyl-2-(2-pyridyl)-quinoline (dpq) and their zinc(II) complexes, have been designed and synthesized. The crystal structure of [Zn(ppq)(2)Cl]PF6 shows that the central zinc atom is coordinated with one chloride and four nitrogen atoms from two ligands. The introduction of an electron-donating substituent such as carbazole or an aromatic amine group at the 6-position of the quinoline moiety can generate colored tunable Zn complexes, and the photoluminescence (PL) wavelength was modulated from 418 nm for [Zn(ppq)(2)Cl]PF6 to 591 nm for [Zn(cpq)(2)Cl]PF6 and 638 nm for [Zn(dpq)(2)Cl]PF6 in CH2Cl2 solution. The electroluminescence spectrum of [Zn(dpq)(2)Cl]PF6 exhibits pure red light emission with the Commission Internationale de L'Eclairage (CIE) coordinates (0.63, 0.36) and a maximum at 648 nm.

Electrochemiluminescence sensor using tris(2,2 '-bipyridyl)ruthenium(II) immobilized in Eastman-AQ55D-silica composite thin-films

An electrochemiluminescence (ECL) sensor with good long-term stability and fast response time has been developed. The sensor was based on the immobilization of tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)(3)(2+)) into the Eastman-AQ55D-silica composite thin films on a glassy carbon electrode. The ECL and electrochemistry of Ru(bpy)(3)(2+) immobilized in the composite thin films have been investigated, and the modified electrode was used for the ECL detection of oxalate, tripropylamine (TPA) and chlorpromazine (CPZ) in a flow injection analysis system and showed high sensitivity. Because of the strong electrostatic interaction and low hydrophobicity of Eastman-AQ55D, the sensor showed no loss of response over 2 months of dry storage. In use, the electrode showed only a 5% decrease in response over 100 potential cycles. The detection limit was 1 mumol l(-1) for oxalate and 0.1 mumol l(-1) for both TPA and CPZ (S/N = 3), respectively. The linear range extended from 50 mumol l(-1) to 5 mmol l(-1) for oxalate, from 20 mumol l(-1) to 1 mmol l(-1) for TPA, and from 1 mumol l(-1) to 200 mumol l(-1) for CPZ.

Electrochemiluminescence of tris(2,2 '-bipyridyl)ruthenium (II) ion-exchanged in polyelectrolyte-silica composite thin-films

The organic-inorganic hybrid, PSS-silica composite material was developed for the immobilization of tris(2,2'-bipyridyl)ruthenium(II) (Ru(bpy)(3)(2+)) on glassy carbon electrode via ion-exchange (PSS stands for poly(sodium 4-styrene-sulfonate)). The electrochemiluminescence (ECL) and electrochemistry of Ru(bpy)(3)(2-) immobilized in the composite thin films have been investigated with tripropylamine (TPA) as the coreactant. The immobilized Ru(bpy)(3)(2-) underwent a surface process. The modified electrode was used for the ECL detection of TPA and showed high sensitivity. Detection limit was 0,1 mumol L-1 for TPA (S/N = 3) with a linear range from 0.5 mumol L-1 to 5 mmol L-1 (R = 0.998), Moreover, the resulting modified electrode was stable over six months and the good stability may be due to the strong interaction between Ru(bpy)(3)(2-) and the high ion-exchange able PSS-silica composite films on GCE. Compared with other materials. the PSS-silica composite films containing incorporated Ru(bpy)(3)(2-) showed improved sensitivity and long-term stability, Thus, such composite thin film can be a promising material for the construction of ECL sensor.

Electrochemiluminescence of tris(2,2 '-bipyridine)ruthenium(II) immobilized in poly(p-styrenesulfonate)-silica-Triton X-100 composite thin-films

The electrochemiluminescence (ECL) of tris(2,2'-bipyridine)ruthenium(ii) [Ru(bpy)(3)(2+)] immobilized in poly(p-styrenesulfonate) (PSS)-silica-Triton X-100 composite films was investigated. The cooperative action of PSS, sol-gel and Triton X-100 attached Ru(bpy)(3)(2+) to the electrode strongly, and the presence of Triton X-100 prevented drying fractures of the sol-gel films during gelation and even on repeated wet-dry cycles. The modified electrode was used for the ECL detection of oxalate, tripropylamine (TPA) and NADH in a flow injection analysis (FIA) system with a newly designed flow cell. The detection scheme exhibited good stability, short response time and high sensitivity. Detection limits were 0.1, 0.1 and 0.5 mu mol L-1 for oxalate, TPA and NADH, respectively, and the linear concentration range extended from 0.001 to 1 mmol L-1 for the three analytes. Applications of the flow cell in ECL and electrochemical detection, as well as the immobilization of reagents based on the cooperative action, are suggested.

Four novel screw-like tris(1,10-phenanthroline) ruthenium(II) bishexafluorophosphate derivatives

Four novel screw-like Ru(II) complexes, tris(5-lauramide-1,10-phenanthroline)Ru(II) bishexafluorophosphate, tris(5-myristamide-1,10-phenanthroline)Ru(II) bishexafluorophosphate, tris(5-palmitamide-1,10-phenanthroline)Ru(II) bishexafluorophosphate and tris (5-stearamide-1,10-phenanthroline)Ru(II) bishexafluorophosphate have been efficiently synthesized. They are confirmed by the techniques of IR, H-1 NMR, H-1-H-1 COSY and ES-MS. Also, their electrochemistry, fluorescence and electrochemiluminescence are reported.

Chemical influences on the luminescence of ruthenium diimine complexes and its response to oxygen

Different luminescent, hydrophillic ruthenium diimine cationic complexes are rendered soluble in the hydrophobic medium of a plasticised polymer through ion-pair coupling with a hydrophobic anion, such as tetraphenyl berate. Based on this approach, a number of different oxygen sensitive films, i.e., luminescent, thin plastic films which respond to oxygen-the latter quenches the luminescence were prepared, using the polymer, cellulose acetate, plasticised with tributylphosphate. Of the resultant thin oxygen sensitive films tested, the one containing the luminescent ion-pair ruthenium (II) tris(4,7-diphenyl-1,IO-phenanthroline) ditetraphenyl berate, [Ru(dpp)(3)(2+)(Ph4B-)(2)], was found to be the most sensitive, and its response characteristics were subsequently studied as a function of plasticiser content, temperature and stability in use, and with age. The major response characteristics, i.e., film sensitivity towards oxygen and response and recovery times, depend very strongly upon the overall level of plasticiser present in film; the film is more sensitive and faster in response and recovery the greater the level of plasticiser employed. Thus, the response of the film towards oxygen can be tuned by varying the level of plasticiser in the film. Film sensitivity towards oxygen is largely independent on temperature, whereas its response and recovery times decrease with increasing temperature (E-a = -10.3+/-0.4 kJ mol(-1)). The sensitivity of a typical luminescent film is very stable when used continuously over a 24-h period, decreases by ca. 20% with age when stored at ambient temperature over a period of 29 days, but very little over the same period of time when stored in the freezer section of a fridge. (C) 1997 Elsevier Science S.A.

Mono(Eta(5)-cyclopentadienyl)metal(II) complexes with thienyl acetylide chromophores: synthesis, electrochemical studies, and first hyperpolarizabilities

A series of mono(eta(5)-cyclopentadienyl)metal-(II) complexes with nitro-substituted thienyl acetylide ligands of general formula [M(eta(5)-C5H5)(L)(C C{C4H2S}(n)NO2)] (M = Fe, L = kappa(2)-DPPE, n = 1,2; M = Ru, L = kappa(2)-DPPE, 2 PPh3, n = 1, 2; M = Ni, L = PPh3, n = 1, 2) has been synthesized and fully characterized by NMR, FT-IR, and UV-Vis spectroscopy. The electrochemical behavior of the complexes was explored by cyclic voltammetry. Quadratic hyperpolarizabilities (beta) of the complexes have been determined by hyper-Rayleigh scattering (HRS) measurements at 1500 nm. The effect of donor abilities of different organometallic fragments on the quadratic hyperpolarizabilities was studied and correlated with spectroscopic and electrochemical data. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were employed to get a better understanding of the second-order nonlinear optical properties in these complexes. In this series, the complexity of the push pull systems is revealed; even so, several trends in the second-order hyperpolarizability can still be recognized. In particular, the overall data seem to indicate that the existence of other electronic transitions in addition to the main MLCT clearly controls the effectiveness of the organometallic donor ability on the second-order NLO properties of these push pull systems.