Thermal study of some new quinolone ruthenium(III) complexes with potential cytostatic activity

A series of new complexes with mixed ligands of the type RuL _m (DMSO) _n Cl₃·xH₂O ((1) L: oxolinic acid (oxo), m = 1, n = 0, x = 4; (2) L: pipemidic acid (pip), m = 2, n = 1, x = 2; (3) L: enoxacin (enx), m = 2, n = 1, x = 0; (4) L: levofloxacin (levofx), m = 2, n = 2, x = 8; DMSO: dimethylsulfoxide) were synthesized and characterized by chemical analysis, IR and electronic data. Except oxolinic acid that behaves as bidentate, the other ligands (quinolone derivatives and DMSO) act as unidentate. Electronic spectra are in accordance with an octahedral stereochemistry. The thermal analysis (TG, DTA) in synthetic air flow elucidated the composition and also the number and nature of both water and DMSO molecules. The TG curves show 3–5 well-separated thermal steps. The first corresponds to the water and/or DMSO loss at lower temperatures followed either by quinolone thermal decomposition or pyrolisys at higher temperatures. The final product is ruthenium(IV) oxide.     

Analysis of plasma protein adsorption onto DC-Chol-DOPE cationic liposomes by HPLC-CHIP coupled to a Q-TOF mass spectrometer

Plasma protein adsorption is regarded as a key factor in the in vivo organ distribution of intravenously administered drug carriers, and strongly depends on vector surface characteristics. The present study aimed to characterize the “protein corona” absorbed onto DC-Chol-DOPE cationic liposomes. This system was chosen because it is one of the most efficient and widely used non-viral formulations in vitro and a potential candidate for in vivo transfection of genetic material. After incubation of human plasma with cationic liposomes, nanoparticle–protein complex was separated from plasma by centrifugation. An integrated approach based on protein separation by one-dimensional 12% polyacrylamide gel electrophoresis followed by the automated HPLC-Chip technology coupled to a high-resolution mass spectrometer was employed for protein corona characterization. Thirty gel lanes, approximately 2 mm, were cut, digested and analyzed by HPLC-MS/MS. Fifty-eight human plasma proteins adsorbed onto DC-Chol-DOPE cationic liposomes were identified. The knowledge of the interactions of proteins with liposomes can be exploited for future controlled design of colloidal drug carriers and possibly in the controlled creation of biocompatible surfaces of other devices that come into contact with proteins in body fluids.

Nitrogen- and oxygen-bridged bidentate phosphaalkene ligands

An overview is given on synthesis and structures of new bidentate phosphaalkene ligands [(RMe₂Si)₂CP]₂E (E = O, NR, N^?) and (RMe₂Si)₂CPN(R′)PR′′₂. Exceptional properties of these ligands, extending beyond predictable properties of phosphaalkenes are: (i) the NSi bond cleavage of [(iPrMe₂Si)₂CP]₂NSiMe₃ with Au^I and Rh^I chloro complexes under mild conditions leading to binuclear complexes of the 6π-delocalised imidobisphosphaalkene anion [(iPrMe₂Si)₂CP]₂N^?, and (ii) the chlorotropic formation of molecular 1:2 Pd^II and Pt^II metallochloroylid complexes with novel ylid-type ligands [(RMe₂Si)₂CP(Cl)N(R)PR₂]^?, and the transformation of a P-platina-P-chloroylid complex into a C-platina phosphaalkene by intramolecular chlorosilane elimination. Properties of the heavier congeners [(RMe₂Si)₂CP]₂E (E = S, Se, Te, PR, P^?, As^?) and (RMe₂Si)₂CPEPR′′₂ (E = S, Se, Te) are also described.     

Connections between discontinuous Galerkin and nonconforming finite element methods for the Stokes equations

We study a discontinuous Galerkin finite element method (DGFEM) for the Stokes equations with a weak stabilization of the viscous term. We prove that, as the stabilization parameter γ tends to infinity, the solution converges at speed γ^?1 to the solution of some stable and well‐known nonconforming finite element methods (NCFEM) for the Stokes equations. In addition, we show that an a posteriori error estimator for the DGFEM‐solution based on the reconstruction of a locally conservative H(div, Ω)‐tensor tends at the same speed to a classical a posteriori error estimator for the NCFEM‐solution. These results can be used to affirm the robustness of the DGFEM‐method and also underline the close relationship between the two approaches. © 2011 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2011     

Functionalization of multi-walled carbon nanotubes with coumarin derivatives and their biological evaluation

We report the synthesis and the characterization of different multi-walled carbon nanotubes (MWCNTs) linked to natural molecules, 5,7-coumarins and/or oleic acid, obtained from purified pristine MWCNTs by a cascade of chemical functionalization. The activities of these modified MWCNTs were investigated in vitro on human umbilical vein endothelial cells (HUVECs) by evaluating their ability to influence cell viability and to induce cell apoptosis. Our data showed that pristine MWCNTs are markedly cytotoxic; conversely, the carboxylated carbon nanotubes, much more readily dispersed in aqueous solutions and CNT-Link, the key intermediate designed by us for the drug anchorage, are biocompatible at the tested concentrations (1 and 10 μg ml(-1)).     

Regiodivergent synthesis of trisubstituted furans through Tf(2)O-catalyzed Friedel-Crafts acylation: a tool for access to tetrahydrofuran lignan analogues

3- or 4-Aroylfurans have been prepared selectively and in high yields from a common precursor by simple tuning of reaction conditions in Friedel-Crafts acylation promoted by triflic anhydride. The formation of products can be explained on the basis of the ring-chain tautomerism occurring in compounds equipped with two neighbouring carboxylic functions. Since 4-aroylfuran derivatives show a typical lignan backbone, suitable hydrogenation conditions were found out to gain tetrahydrofuran lignans.     

Synthesis of polyester nanoparticles in miniemulsion obtained by radical ring-opening of BMDO and their potential as biodegradable drug carriers

5,6-Benzo-2-methylene-1,3-dioxepane (BMDO) is used to obtain degradable polymeric nanoparticles via a statistical free-radical copolymerization with MMA and styrene in direct miniemulsion. The nanoparticles are analyzed by means of IR, NMR, DLS, SEM, and TEM. They show excellent cellular uptake and drug delivery properties. The cellular uptake into HeLa cells of particles resulting from copolymerization of BMDO with styrene is drastically enhanced compared to pure polystyrene. As a model drug system, paclitaxel is incorporated in PBMDO particles and its release and the effect on HeLa cells is studied and compared to commercial drug formulations. It is found that a drug delivery system based on PBMDO shows an excellent pharmacological effect.     

Identification of the plant origin of the botanical biomarkers of Mediterranean type propolis

Propolis is a honeybee product which bees produce by collecting resins from various botanical sources. The chemical composition of propolis is directly dependant on the availability of resinous plant materials in different geographic regions. This study was undertaken to evaluate the resinous plant sources used by bees to produce Mediterranean type propolis. Although this propolis type has already been the subject of numerous studies, its major botanical source had not yet been identified. In this study, using GC-MS analysis, we identify the resin of the common cypress, Cupressus_sempervirens, as the major plant source of the characteristic diterpene fingerprint profile of Mediterranean propolis.     

Longitudinal brain imaging of five malignant glioma patients treated with bevacizumab using susceptibility-weighted magnetic resonance imaging at 7 T

Malignant glioma is a rare tumor type characterized by prominent vascular proliferation. Antiangiogenic therapy with the monoclonal antibody bevacizumab is considered as a promising therapeutic strategy, although the effect on tumor vascularization is unclear. High-field susceptibility-weighted imaging (SWI) visualizes the microvasculature and may contribute to the investigation of antiangiogenic therapy responses in gliomas. We prospectively studied five adult malignant glioma patients treated with bevacizumab-containing regimens. In each patient, we performed three 7-T SWI and T1-weighted imaging investigations (baseline and 2 and 4 weeks after the start of bevacizumab treatment). In addition, we imaged a postmortem brain of a patient with glioblastoma using 7-T SWI and performed detailed histopathological analysis. We observed almost total resolution of brain edema in three of five patients after initiation of bevacizumab therapy. In one case with rapid increase of the lesion size despite bevacizumab therapy, SWI showed progressive increase of irregular hypointense structures, most likely corresponding to increasing amounts of pathological microvasculature. In one case with progressive neurological decline, 7-T images showed multiple intratumoral microhemorrhages after the first bevacizumab application. Correlation of postmortem neuroimaging with histopathology confirmed that SWI-positive structures correspond to tumor vasculature. The experience from our case series indicates that longitudinal 7-T SWI seems to be an appropriate method for investigation of changes in brain tumor vascularization over time under antiangiogenic therapy.