Synthesis, cytotoxicity, and COMPARE analysis of ferrocene and [3]ferrocenophane tetrasubstituted olefin derivatives against human cancer cells

Herein we report the antiproliferative effects of a series of 28 compounds against the MDA-MB-231 breast cancer cell line, including the synthesis of seven new [3]ferrocenophanyl and four new ferrocenyl compounds. For each p-R-phenyl substitution pattern investigated, the [3]ferrocenophanyl derivatives were more cytotoxic than the corresponding ferrocenyl derivative, with the highest activity found for compounds with protic substituents. Theoretical calculations of the HOMO-LUMO gap for the molecules in the Fe3(+) oxidation state suggest a higher reactivity for the [3]ferrocenophanyl derivatives. A lead compound from each series, a [3]ferrocenophanyl and a ferrocenyl compound, possessing two phenol groups, were screened against the NCI/DTP 60-cell-line panel. The mean activity over all cell lines was better than cisplatin for both compounds, and both compounds showed subpanel selectivity for leukemia, CNS cancer, and renal cancer. Low systemic toxicity and lack of interaction with DNA (when in the reduced form), suggest that the compounds may act as prodrugs.     

The presence of a ferrocenyl unit on an estrogenic molecule is not always sufficient to generate in vitro cytotoxicity

We recently reported the dual (antihormonal and cytotoxic) functionality of ferrocifens, which are organometallic complexes derived from hydroxytamoxifen, the standard molecule in the treatment of hormone-dependent breast cancers. To test the hypothesis that the presence of a ferrocenyl substituent on molecules with an affinity for the estrogen receptor is sufficient to give them cytotoxic properties in vitro, we prepared complexes derived from estradiol with a ferrocenyl substituent at positions 7alpha and 17alpha. The complexes thus obtained retain a satisfactory level of affinity for the estrogen receptor (RBA values higher than 12 %). At low concentrations (0.1-1 microM) the complexes show an estrogenic effect in vitro equivalent to that of estradiol on hormone-dependent (MCF-7) breast cancer cells, and no cytotoxic effect on hormone-independent (MDA-MB-231) breast cancer cells. At high concentrations (up to 50 microM) the 17alpha-ethynylferrocenyl estradiol and 7alpha-ferrocenylmethylthio estradiol become cytotoxic (IC(50)=13.2 microM and 18.8 microM, respectively) while the 17alpha-ferrocenylestradiol remains non toxic. The low toxicity of these compounds support our hypothesis that electronic communication between the ferrocenyl and phenol moieties in the hydroxyferrocifens series is a key parameter in the generation of cytotoxic effects at submicromolar concentrations.     

Blanchiment et qualité des légumes et des fruits surgelés. Revue. I. Introduction et aspects enzymatiques

The first section of a three-part bibliographic study, this article successively examines the role, advantages and drawbacks of blanching, the enzymatic systems of foodstuffs, the localisation of peroxidase and catalase enzymes, methods of controlling blanching, the validity of tests, the regeneration of peroxidasic activity, the relation between temperature and the duration of blanching. Reasons are given as to why it is not possible to establish schedules for blanching, similar to what exists for sterilisation. It is shown that significant residual peroxidasic activity may not have undesirable consequences on maintaining the quality of a good number of quick frozen vegetables stored at − 18°C.

Résumé

Premier volet d'une étude bibliographique qui en comporte trois, l'article examine successivement: le rôle, les avantages et les inconvénients du blanchiment; les sytèmes enzymatiques des denrées, localisation des peroxydases et des catalases, méthodes de contrôle du blanchiment, validité des tests, régénération de l'activité peroxydasique, relation température et durée de blanchiment. Il est expliqué pourquoi il n'est pas possible d'établir des barêmes de blanchiment comme il existe des barêmes de stérilisation. Une activité peroxydasique résiduelle significative peut être sans conséquences défavorables sur le maintien de la qualité de bon nombre de légumes surgelés conservés à − 18°C.     

Acoustoelastic effect in concrete material under uni-axial compressive loading

This study deals with the general matter of non-destructive evaluation of pre-stressed structures in civil engineering. Usually such structures are composed of concrete and are steel reinforced. Proposed idea is the evaluation of mechanical stress state of a concrete body (instead of steel cables) via ultrasonic non-destructive evaluation (NDE), by using the link between ultrasonic velocities and mechanical stresses provided by the acoustoelasticity theory. Velocities of the ultrasonic waves (longitudinal and transversal with different polarizations) are observed during propagation through a concrete body submitted to uni-axial loading (compressive testing). Obvious variations in velocity are found depending on the mechanical stress state (e.g. Δc=92 m/s at σ=16 MPa for longitudinal waves). Thus acoustoelastic behavior of concrete is demonstrated. Further analyses provide acoustoelastic coefficients of concrete about ten times higher than the common ones of steel. The feasibility of stress evaluation using ultrasounds in concrete structures is proved under laboratory conditions.     

Two-dimensional ECD FT-ICR mass spectrometry of peptides and glycopeptides

2D FT-ICR MS allows the correlation between precursor and fragment ions by modulating ion cyclotron radii for fragmentation modes with radius-dependent efficiency in the ICR cell without the need for prior ion isolation. This technique has been successfully applied to ion-molecule reactions, Collision-induced dissociation and infrared multiphoton dissociation. In this study, we used electron capture dissociation for 2D FT-ICR MS for the first time, and we recorded two-dimensional mass spectra of peptides and a mixture of glycopeptides that showed fragments that are characteristic of ECD for each of the precursor ions in the sample. We compare the sequence coverage obtained with 2D ECD FT-ICR MS with the sequence coverage obtained with ECD MS/MS and compare the sensitivities of both techniques. We demonstrate how 2D ECD FT-ICR MS can be implemented to identify peptides and glycopeptides for proteomics analysis.     

Effect of skin fracture on failure of a bilayer polymer structure

A thin skin of low tensile failure strain, if bonded to the tensile surface of an un-notched impact bend specimen of much tougher material, can change the global failure mode from ductile to brittle. A novel model of this well-known effect is developed and applied to results from impact tests on a tough core of polyamide-polyethylene blend, with a single skin of brittle EVOH. At a fixed crosshead speed, notched specimens of the blend become brittle at a relatively low temperature T _bt. Un-notched bilayer specimens continue to show skin fracture up to a considerably higher temperature T _fs; above this temperature they do not fail at all but below T _bt they too fail in a brittle manner. Within the temperature range from T _fs down to T _bt there is a transition from crack arrest, either at the skin/core interface or further into the core where a crack would not normally propagate, to brittle fracture. This brittle fracture temperature is predicted by modelling the process as a three-phase impact event. In the first phase, the striker bends the bilayer quasi-statically. The second phase begins with instantaneous fracture of the skin at its failure strain. The skin ends retract at finite speed, and a craze grows in the adjacent core material to accommodate the local strain singularity. The last phase is a striker-driven impact event similar to that in a notched bend specimen of the core material, except that the crack-tip craze already bears the adiabatic temperature distribution generated while it was driven open by skin retraction. The criterion for craze decohesion, and hence for a crack jump, is the same adiabatic decohesion criterion which accounts for the speed-dependence of impact fracture in notched monolayer specimens. Applied computationally, this model predicts whether a bilayer structure fails in a brittle way or whether cracks initiated in the skin are arrested, either temporarily or permanently, at the skin/core interface.     

Blanchiment et qualité des légumes et des fruits surgelés. Revue. 3. Aspects nutritionnels et hygiéniques,conclusionsBlanching and quality of frozen vegetables and fruit. Review. 3. Nutritional and hygienic aspects,conclusions

The third and final section of a bibliographic study (see Int. J. Refrig.7 (1984) 384–388 and 8 (1985) 48–53), this article deals with the effects of blanching on vitamins and soluble nutrients as well as the sanitary state of quick frozen fruit and vegetables. Blanching and hydrocooling cause important losses in the soluble nutrients of products, consequently they cause extensive water pollution. The advantages produced by steam blanching are totally lost during hydrocooling. The hygienic quality of frozen vegetables is closely related to the bacterial counts of water and the cleanliness of equipment situated upstream of the blancher. The replacement of blanching by a less aggressive chemical treatment, as regards frozen vegetable quality, may be a solution for the future, but it will be some time before it can be applied to industry.     

Pyridazino-1,3a,6a-Triazapentalenes as Versatile Fluorescent Probes: Impact of Their Post-Functionalization and Application for Cellular Imaging

Pyridazino-1,3a,6a-triazapentalenes (PyTAP) are compact fused 6/5/5 tricyclic scaffolds which exhibit promising fluorescent properties. Chemically stable, they can be post-functionalized using standard Pd-catalyzed cross-coupling chemistry. Several original PyTAP bearing additional unsaturated substituents in positions 2 and 8 were synthetized and their spectroscopic properties analyzed. They have been successfully tested as fluorescent probes for cellular imaging.