Rhodamine B oxidation promoted by P450-bioinspired Jacobsen catalysts/cellulose systems.

In this work, we investigated the preparation of P450-bioinspired Mn(iii)-Schiff base complexes supported on DEAE-cellulose ((R,R)-Jacobsen/Cell(NEt2) and (S,S)-Jacobsen/Cell(NEt2), respectively) to oxidize substrates of biological interest. Catalysts were characterized by several physical techniques. UV-Vis spectroscopy with diffuse reflectance (DR/UV-Vis) analysis featured peculiar electronic transitions for both complexes. Fourier transform infrared (FTIR) spectra evidenced the characteristic band of imine groups (HC[double bond, length as m-dash]N) for bioinspired/Cell(NEt2) materials. Immobilization ratios in cellulose fibres were confirmed by atomic absorption spectroscopic (GF-AAS) analyses. Catalytic essays were conducted during rhodamine B (RhB) oxidation. Supported materials attained oxidative yields close to those of homogeneous systems, and cellulose may be stabilizing the active intermediate catalytic species. Reactions may be driven through two different intermediates: MnV(O) and MnIII(O-OH)salen. Homogeneous reactions suggest an asymmetric catalysis. Heterogeneous system reaction yields are similar, and salen complexes anchored on cellulose conformation would interfere on complex intermediate species configuration. The four possible RhB-oxidation products obtained by the reaction with the homogeneous (S,S)-Jacobsen catalyst and meta-chloroperoxybenzoic acid (m-CPBA) system were suggested by 1H NMR analysis, and a catalytic mechanism was proposed.

Cytotoxicity, cellular uptake, and subcellular localization of a nitrogen oxide and aminopropyl-ß-lactose derivative ruthenium complex used as nitric oxide delivery agent.

This work investigates how the luminescent ruthenium-nitrite complexes cis-[Ru(py-bodipy)(dcbpy)2(NO2)](PF6) (I) and cis-[Ru(py-bodipy)(dcbpy-aminopropyl-ß-lactose)2(NO2)](PF6) (II) behave toward the melanoma cancer cell line B16F10. The chemical structure and purity of the synthesized complexes were analyzed by UV-Visible and FTIR spectroscopy, MALDI, HPLC, and 1H NMR. Spectrofluorescence helped to determine the fluorescence quantum yields and lifetimes of each of these complexes. In vitro MTT cell viability assay on B16F10 cancer cells revealed that the complexes possibly have a tumoricidal role. The metal-nitrite complexes evidenced the dichotomous NO nature: at high concentration, NO exerted a tumoricidal effect, whereas cancer cells grew at low NO concentration. Flow cytometry or fluorescence microscopy aided cellular uptake calculation. Cell staining followed by fluorescence microscopy associated with organelle markers such as DAPI and Rhodamine 123 detected preferential intracellular localization of the ruthenium-nitrite py-bodipy and aminopropyl lactose derivative ruthenium complex in mitochondria. Thus, the cytotoxicity of compounds (I) and (II) against B16F10 cancer cell line show concentration-dependent results. The present studies suggest that nitric oxide ruthenium derivative compounds could be new potential chemotherapeutic agents against cytotoxic cells.

Metabolism evaluation of the anticancer candidate AC04 by biomimetic oxidative model and rat liver microsomes.

Jacobsen reagents, in the presence of monooxygen donors, appear as an alternative to produce metabolites from biological active compounds. This reaction may mimic the oxidation and oxygenation reactions of cytochrome P450 (CYP450) enzymes upon various drugs and biologically active compounds. Acridines represent a well-known group of polyaromatic compounds capable of acting as DNA intercalating agents. Viewing to search for new anticancer agents, one promising new acridine, the 5-acridin-9-ylmethylene-3-(4-methyl-benzyl)-thiazolidine-2,4-dione (AC04) (2), has been studied by our group and the in vitro metabolism was investigated in this work, aiming to advance in the pre-clinical pharmacokinetic investigation. A systematic investigation of the gas-phase reaction, supported by computational chemistry, of the AC04 (2) was studied to help the structure elucidation of possible in vivo metabolites. To confirm the methodology, the oxidized product was obtained in large scale for NMR analysis and the data confirmed the structure. In addition, AC04 (2) was submitted to an in vitro metabolism assay employing rat liver microsomes and also, a pilot study was conducted in rats after AC04 intravenous (i.v.) dosing of 1.5 mg/kg. A single oxidized product was obtained from microsomal metabolism and detected in rat plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis corresponding to the same product formed by Jacobsen-catalyzed reaction. These results indicate that Jacobsen oxidation reactions, combined with in vitro metabolism assays employing isolated microsomes, might replace some in vivo metabolism studies, thus reducing the use of animals in new chemical entities pre-clinical investigation.