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101.
Hillard EA Pigeon P Vessières A Amatore C Jaouen G 《Dalton transactions (Cambridge, England : 2003)》2007,(43):5073-5081
The ferrocenyl compound 2-ferrocenyl-1,1-bis(4-hydroxyphenyl)-but-1-ene (), is very cytotoxic against breast cancer cells (IC(50) = 0.44 microM against MDA-MB-231). We now report the synthesis of a new series of para- and meta- substituted mono- and di- ferrocenyl phenols [2-ferrocenyl-1-(3-hydroxyphenyl)-1-phenyl-but-1-ene (), 2-ferrocenyl-1-(3-hydroxyphenyl)-1-(4-hydroxyphenyl)-but-1-ene (), 1,2-di-ferrocenyl-1-(4-hydroxyphenyl)-but-1-ene (), and 1,2-di-ferrocenyl-1-(3-hydroxyphenyl)-but-1-ene ()] and their electrochemical and biochemical properties, especially in comparison to the previously reported "standard" compounds [2-ferrocenyl-1-(4-hydroxyphenyl)-1-phenyl-but-1-ene () and ()]. We also report the synthesis and characterization of the diphenyl analogue, 2-ferrocenyl-1,1-diphenyl-but-1-ene (). This structure-activity relationship study was motivated by our hypothesis that the cytotoxicity of is related to its ability to form a quinone methide structure after two in situ 1-electron oxidations, a process which requires the presence of at least one p-phenol. The mono-ferrocenyl compounds (including those previously reported) are reasonably well recognized by the oestrogen receptors alpha (RBAs = 0.9-9.6%) and beta (RBAs = 0.28-16.3%), although the bulkier di-ferrocenyl compounds show very little affinity. In vitro, the cytotoxic effects of the phenolic complexes are related to the positioning of the hydroxyl group (para- superior to meta-), and to the number of ferrocenyl groups (one superior to two), with IC(50) values against the MDA-MB-231 cell line ranging from 0.44-3.5 microM. On the hormone-dependent breast cancer cell line MCF-7, the observed effect seems to be the result of two components, one cytotoxic (antiproliferative) and one estrogenic (proliferative). Electrochemical studies show that only the compounds with a p-phenol engage in proton-coupled intramolecular electron transfer. 相似文献
102.
Combined wavelet transform-artificial neural network use in tablet active content determination by near-infrared spectroscopy 总被引:2,自引:0,他引:2
The pharmaceutical industry faces increasing regulatory pressure to optimize quality control. Content uniformity is a basic release test for solid dosage forms. To accelerate test throughput and comply with the Food and Drug Administration's process analytical technology initiative, attention is increasingly turning to nondestructive spectroscopic techniques, notably near-infrared (NIR) spectroscopy (NIRS). However, validation of NIRS using requisite linearity and standard error of prediction (SEP) criteria remains a challenge. This study applied wavelet transformation of the NIR spectra of a commercial tablet to build a model using conventional partial least squares (PLS) regression and an artificial neural network (ANN). Wavelet coefficients in the PLS and ANN models reduced SEP by up to 60% compared to PLS models using mathematical spectra pretreatment. ANN modeling yielded high-linearity calibration and a correlation coefficient exceeding 0.996. 相似文献
103.
Glenn Carroy Charlotte Daxhelet Dr. Vincent Lemaur Dr. Julien De Winter Prof. Edwin De Pauw Prof. Jérôme Cornil Prof. Pascal Gerbaux 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(13):4528-4534
Host–guest complexes are formed by the creation of multiple noncovalent bonds between a large molecule (the host) and smaller molecule(s) or ion(s) (the guest(s)). Ion‐mobility separation coupled with mass spectrometry nowadays represents an ideal tool to assess whether the host–guest complexes, when transferred to the gas phase upon electrospray ionization, possess an exclusion or inclusion nature. Nevertheless, the influence of the solution conditions on the nature of the observed gas‐phase ions is often not considered. In the specific case of inclusion complexes, kinetic considerations must be taken into account beside thermodynamics; the guest ingression within the host cavity can be characterized by slow kinetics, which makes the complexation reaction kinetically driven on the timescale of the experiment. This is particularly the case for the cucurbituril family of macrocyclic host molecules. Herein, we selected para‐phenylenediamine and cucurbit[6]uril as a model system to demonstrate, by means of ion mobility and collision‐induced dissociation measurements, that the inclusion/exclusion topology ratio varies as a function of the equilibration time in solution prior to the electrospray process. 相似文献
104.
Ghislaine Barouti Ali Khalil Clement Orione Kathleen Jarnouen Dr. Sandrine Cammas‐Marion Dr. Pascal Loyer Prof. Sophie M. Guillaume 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(8):2819-2830
Amphiphilic polycarbonate–poly(hydroxyalkanoate) diblock copolymers, namely, poly(trimethylene carbonate) (PTMC)‐b‐poly(β‐malic acid) (PMLA), are reported for the first time. The synthetic strategy relies on commercially available catalysts and initiator. The controlled ring‐opening polymerization (ROP) of trimethylene carbonate (TMC) catalyzed by the organic guanidine base 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene (TBD), associated with iPrOH as an initiator, provided iPrO?PTMC?OH, which served as a macroinitiator in the controlled ROP of benzyl β‐malolactonate (MLABe) catalyzed by the neodymium triflate salt (Nd(OTf)3). The resulting hydrophobic iPrO?PTMC‐b‐PMLABe?OH copolymers were then hydrogenolyzed into the parent iPrO?PTMC‐b‐PMLA?OH copolymers. A range of well‐defined copolymers, featuring different sizes of segments (Mn,NMR up to 9300 g mol?1; ÐM=1.28–1.40), were thus isolated in gram quantities, as evidenced by NMR spectroscopy, size exclusion chromatography, thermogravimetric analysis, differential scanning calorimetry, and contact angle analyses. Subsequently, PTMC‐b‐PMLA copolymers with different hydrophilic weight fractions (11–75 %) self‐assembled in phosphate‐buffered saline upon nanoprecipitation into well‐defined nano‐objects with Dh=61–176 nm, a polydispersity index <0.25, and a negative surface charge, as characterized by dynamic light scattering and zeta‐potential analyses. In addition, these nanoparticles demonstrated no significant effect on cell viability at low concentrations, and a very low cytotoxicity at high concentrations only for PTMC‐b‐PMLA copolymers exhibiting hydrophilic fractions over 47 %, thus illustrating the potential of these copolymers as promising nanoparticles. 相似文献
105.
Bioorthogonal Probes for the Study of MDM2‐p53 Inhibitors in Cells and Development of High‐Content Screening Assays for Drug Discovery 下载免费PDF全文
Pier Luca D'Alessandro Nicole Buschmann Markus Kaufmann Dr. Pascal Furet Frederic Baysang Reto Brunner Dr. Andreas Marzinzik Dr. Thomas Vorherr Dr. Therese‐Marie Stachyra Dr. Johannes Ottl Dr. Dimitrios E. Lizos Dr. Amanda Cobos‐Correa 《Angewandte Chemie (International ed. in English)》2016,55(52):16026-16030
To study the behavior of MDM2‐p53 inhibitors in a disease‐relevant cellular model, we have developed and validated a set of bioorthogonal probes that can be fluorescently labeled in cells and used in high‐content screening assays. By using automated image analysis with single‐cell resolution, we could visualize the intracellular target binding of compounds by co‐localization and quantify target upregulation upon MDM2‐p53 inhibition in an osteosarcoma model. Additionally, we developed a high‐throughput assay to quantify target occupancy of non‐tagged MDM2‐p53 inhibitors by competition and to identify novel chemical matter. This approach could be expanded to other targets for lead discovery applications. 相似文献
106.
Dr. Simon Pascal Léo Bucher Dr. Nicolas Desbois Dr. Christophe Bucher Dr. Chantal Andraud Prof. Dr. Claude P. Gros 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(14):4971-4979
The synthesis of dyad and triad aza‐BODIPY‐porphyrin systems in two steps starting from an aryl‐substituted aza‐BODIPY chromophore is described. The properties of the resulting aza‐BODIPY‐porphyrin conjugates have been extensively investigated by means of electrochemistry, spectroelectrochemistry, and absorption/emission spectroscopy. Fluorescence measurements have revealed a dramatic loss of luminescence intensity, mainly due to competitive energy transfer and photoinduced electron transfer involving charge separation followed by recombination. 相似文献
107.
108.
Consola S Blanzat M Perez E Garrigues JC Bordat P Rico-Lattes I 《Chemistry (Weinheim an der Bergstrasse, Germany)》2007,13(11):3039-3047
A new kind of catanionic assembly was developed that associates a sugar-based surfactant with a non-steroidal anti-inflammatory drug (NSAID). Three different assemblies using indomethacin, ibuprofen and ketoprofen as NSAIDs were easily obtained in water by an acid-base reaction. These assemblies formed new amphiphilic entities because of electrostatic and hydrophobic effects in water and led to the spontaneous formation of vesicles. These catanionic vesicles were then tested as potential NSAID delivery systems for dermatological application. The anti-inflammatory activity was evaluated in vivo, and this study clearly showed an improved therapeutic effect for NSAIDs that were formulated as catanionic vesicles. These vesicles ensured a slower diffusion of the NSAID through the skin. This release probably increased the time of retention of the NSAID in the targeted strata of the skin. Thus, the present study suggests that this catanionic bioactive formulation could be a promising dermal delivery system for NSAIDs in the course of skin inflammation treatment. 相似文献
109.
Hafizovic J Bjørgen M Olsbye U Dietzel PD Bordiga S Prestipino C Lamberti C Lillerud KP 《Journal of the American Chemical Society》2007,129(12):3612-3620
MOF-5 is the archetype metal-organic framework and has been subjected to numerous studies the past few years. The focal point of this report is the pitfalls related to the MOF-5 phase identification based on powder XRD data. A broad set of conditions and procedures have been reported for MOF-5 synthesis. These variations have led to materials with substantially different adsorption properties (specific surface areas in the range 700 to 3400 m(2)/g). The relatively low weight loss observed for some as synthesized samples upon solvent removal is also indicative of a low pore volume. Regrettably, these materials have all been described as MOF-5 without any further comments. Furthermore, the reported powder XRD patterns hint at structural differences: The variations in surface area are accompanied by peak splitting phenomena and rather pronounced changes in the relative peak intensities in the powder XRD patterns. In this work, we use single-crystal XRD to investigate structural differences between low and high surface area MOF-5. The low surface area MOF-5 sample had two different classes of crystals. For the dominant phase, Zn(OH)2 species partly occupied the cavities. The presence of Zn species makes the hosting cavity and possibly also adjacent cavities inaccessible and thus efficiently reduces the pore volume of the material. Furthermore, the minor phase consisted of doubly interpenetrated MOF-5 networks, which lowers the adsorption capacity. The presence of Zn species and lattice interpenetration changes the symmetry from cubic to trigonal and explains the peak splitting observed in the powder XRD patterns. Pore-filling effects from the Zn species (and partly the solvent molecules) are also responsible for the pronounced variations in powder XRD peak intensities. This latter conclusion is particularly useful for predicting the adsorption properties of a MOF-5-type material from powder XRD. 相似文献
110.
Thiosulfinates are an emerging class of oxidized sulfur species that are frequently supposed to be involved in biochemical processes. Reaction of 12- and 10-membered ring pseudopeptidic thiosulfinates 1a (4,4,7,7-tetramethyl-1,3,4,7,8,10-hexahydro-5,6,1,10-benzodithiadiazacyclododecine-2,9-dione 5-oxide) and 1b (3,3,6,6-tetramethyl-1,8-dihydro-4,5,1,8-benzodithiadiazecine-2,7(3H,6H)-dione 4-oxide) with a Ni(II) salt leads after ring cleavage under alkaline conditions to the isolation of diamidato/thiolato/sulfinato complexes. These two thiolato/sulfinato complexes of nickel, which can also be prepared by dioxygen oxidation of the parent diamidato/dithiolato complexes, were characterized by X-ray crystallography. They show a square-planar geometry with a S-bonded sulfinato ligand. A similar reaction between 1b and a Zn(II) salt leads to a thiolato/sulfinato complex with an O-bonded sulfinate via the intermediate formation of a mixed thiolato/sulfinic ester. On the basis of 1H NMR, IR, and mass analyses, the sulfinic ester in the intermediate is proposed to be O-bonded to the zinc center. Then, an in-depth study of the cleavage of these thiosulfinates with the oxyanions RO- and HO- was performed. This led, after trapping of the open species with CH3I, to the identification of three polyfunctionalized products containing a methyl thioether, with either an isothiazolidin-3-one S-oxide, a methyl sulfone, or a methyl sulfinic ester. All of these products arise from a selective nucleophilic attack at the sulfinyl sulfur, promoted either directly by RO- or HO- or by an internal peptidic nitrogen of the thiosulfinate after deprotonation with RO- or HO-. 相似文献