Topic
Aquation
About: Aquation is a research topic. Over the lifetime, 1443 publications have been published within this topic receiving 17507 citations.
Papers published on a yearly basis
Papers
More filters
TL;DR: The key role that hsA plays in defining the species found in vivo following intravenous treatment with NAMI-A is demonstrated, through prevention of oligomerization and maintenance of the oxidation state, to give protein-bound mono-nuclear Ru(III) species.
Abstract: The behaviour of the antimetastatic Ru(III) complex imidazolium [trans-RuCl4(1H-imidazole)(DMSO-S)] (NAMI-A) under physiological conditions and its interactions with human serum albumin (hsA) have been studied using electron paramagnetic resonance spectroscopy (EPR). In physiological buffer at pH 7.4, these experiments demonstrate that the DMSO ligand is replaced rapidly by water, and spectra from the subsequent formation of five other Ru(III) complexes show further aquation processes. Although EPR spectra from mono-nuclear Ru(III) complexes are visible after 24 h in buffer, a significant decrease in the overall signal intensity following the first aquation step is consistent with the formation of oxo-bridged Ru(III) oligomers. Incubation with hsA reveals very rapid binding to the proteinvia hydrophobic interactions. This is followed by coordination through ligand exchange with protein side chains, likely with histidine imidazoles and at least one other specific site. Similar behaviour is observed when the complex is incubated in human serum, indicating that hsA binding dominates speciation in vivo. The addition of ascorbic acid to NAMI-A in buffer leads to quantitative reduction, producing EPR-silent Ru(II) complexes. However, this process is prevented when the complex binds coordinatively to hsA. Together, these results demonstrate the key role that hsA plays in defining the species found in vivo following intravenous treatment with NAMI-A, through prevention of oligomerization and maintenance of the oxidation state, to give protein-bound mono-nuclear Ru(III) species.
72 citations
TL;DR: This class of organometallic osmium complexes has new and unusual features worthy of further exploration for the design of novel anticancer drugs.
Abstract: We report the synthesis and characterisation of 32 half sandwich phenylazopyridine OsII arene complexes [Os(η6-arene)(phenylazopyridine)X]+ in which X is chloride or iodide, the arene is p-cymene or biphenyl and the pyridine and phenyl rings contain a variety of substituents (F, Cl, Br, I, CF3, OH or NO2). Ten X-ray crystal structures have been determined. Cytotoxicity towards A2780 human ovarian cancer cells ranges from high potency at nanomolar concentrations to inactivity. In general the introduction of an electron-withdrawing group (e.g. F, Cl, Br or I) at specific positions on the pyridine ring significantly increases cytotoxic activity and aqueous solubility. Changing the arene from p-cymene to biphenyl and the monodentate ligand X from chloride to iodide also increases the activity significantly. Activation by hydrolysis and DNA binding appears not to be the major mechanism of action since both the highly active complex [Os(η6-bip)(2-F-azpy)I]PF6 (9) and the moderately active complex [Os(η6-bip)(3-Cl-azpy)I]PF6 (23) are very stable and inert towards aquation. Studies of octanol–water partition coefficients (log P) and subcellular distributions of osmium in A2780 human ovarian cancer cells suggested that cell uptake and targeting to cellular organelles play important roles in determining activity. Although complex 9 induced the production of reactive oxygen species (ROS) in A2780 cells, the ROS level did not appear to play a role in the mechanism of anticancer activity. This class of organometallic osmium complexes has new and unusual features worthy of further exploration for the design of novel anticancer drugs.
71 citations
TL;DR: Synthese des complexes M(NH 3 ) 5 (OSO 2 CF 3 ) n+, m(NH 2 CH 3 ) 3 ) (OssO2CF 3 ) 2+, cis-M(en) 2 OssO 2 Cl(OSO2 2 CF3 ) + avec M = metal trivalent as discussed by the authors.
Abstract: Synthese des complexes M(NH 3 ) 5 (OSO 2 CF 3 ) n+ , M(NH 2 CH 3 ) 5 (OSO 2 CF 3 ) 2+ , cis-M(en) 2 (OSO 2 CF 3 ) 2 + et trans-M(en) 2 Cl(OSO 2 CF 3 ) + avec M=metal trivalent. Constantes de vitesse d'aquation
70 citations
TL;DR: A post-column reaction detector sensitive to platinum(II) complexes is presented in which sodium bisulfite is used as the derivatizing agent with potassium dichromate as an activating agent and the reaction detector is used to monitor the kinetics of aquation of cisplatin and to quantitate CDDP degradation in plasma.
Abstract: The development and evaluation of a post-column reaction detector sensitive to platinum(II) complexes is presented in which sodium bisulfite is used as the derivatizing agent with potassium dichromate as an activating agent. The influences of mobile phase changes (i.e., pH, organic modifiers, electrolytes), oxygen, metal ions, and order of reagent addition on reaction kinetics and product yield are defined and used in optimization of detector response. Detection at lambda/sub max/ 290 nm results in an on-line post-column sensitivity of 40-60 ng/mL for selected cis-dichloroplatinum complexes and a sensitivity of 300-1200 ng/mL for four (substituted)-malonato-platinum complexes. The reaction detector is used to monitor the kinetics of aquation of cisplatin (CDDP) and to quantitate CDDP degradation in plasma. As the sensitivity for CDDP in plasma is comparable to that achieved from high pressure liquid chromatography (HPLC) effluent fractionation/off-line flameless atomic absorption (AAS) quantitation, significant utilitiy for this time-efficient post-column reactor in clinical analysis is suggested. 33 references, 8 figures, 2 tables.
70 citations
TL;DR: The organometallic compounds showed similar cytotoxicity profiles and were proved to be moderately active against various human cancer cell lines and higher conditional stabilities were found in the case of the Rh(III) compounds at pH7.4.
70 citations