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Particular Compound (particular + compound)
Selected AbstractsFlow cytometry peripheral blood micronucleus test in vivo: Determination of potential thresholds for aneuploidy induced by spindle poisonsENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 4 2010Zoryana Cammerer Abstract Non-DNA binding genotoxins (e.g., aneugens), unlike DNA-binding genotoxins, are theoretically expected to show thresholded concentration-effect response curves. This is a major issue in genetic toxicology testing because the identification of thresholds in vivo can provide a safety margin for exposure to a particular compound. In the current study we measured micronucleus induction by flow cytometry to determine the dose-response curves for tubulin interacting agents, a specific class of aneugens. All experiments with aneugens, which include colchicine, vinblastine, vincristine, as well as the clastogen cyclophosphamide (CP) were performed in mice to avoid the splenic elimination of micronucleated reticulocytes, which has been described in rats. Flow cytometry analysis revealed a non-linear dose-dependent increase in micronuclei frequencies for all tested aneugens, and a linear dose response curve for the clastogen, CP. To determine whether micronucleus induction at higher doses was due to chromosome loss (aneuploidy) or chromosome breakage (clastogenicity), flow sorting of the micronucleated reticulocytes and fluorescent in situ hybridization (FISH) with a mouse pan centromeric probe were performed for vinblastine, vincristine, and colchicine. Statistical evaluation of the flow cytometry and FISH data was performed to determine the threshold levels for chromosome loss in vivo. The threshold concentrations for vinblastine, vincristine, and colchicine were found at 0.35, 0.017, and 0.49 mg kg,1, respectively. Environ. Mol. Mutagen., 2010. © 2009 Wiley-Liss, Inc. [source] Computational framework for predictive biodegradationBIOTECHNOLOGY & BIOENGINEERING, Issue 6 2009Stacey D. Finley Abstract As increasing amounts of anthropogenic chemicals are released into the environment, it is vital to human health and the preservation of ecosystems to evaluate the fate of these chemicals in the environment. It is useful to predict whether a particular compound is biodegradable and if alternate routes can be engineered for compounds already known to be biodegradable. In this work, we describe a computational framework (called BNICE) that can be used for the prediction of novel biodegradation pathways of xenobiotics. The framework was applied to 4-chlorobiphenyl, phenanthrene, ,-hexachlorocyclohexane, and 1,2,4-trichlorobenzene, compounds representing various classes of xenobiotics with known biodegradation routes. BNICE reproduced the proposed biodegradation routes found experimentally, and in addition, it expanded the biodegradation reaction networks through the generation of novel compounds and reactions. The novel reactions involved in the biodegradation of 1,2,4-trichlorobenzene were studied in depth, where pathway and thermodynamic analyses were performed. This work demonstrates that BNICE can be applied to generate novel pathways to degrade xenobiotic compounds that are thermodynamically feasible alternatives to known biodegradation routes and attractive targets for metabolic engineering. Biotechnol. Bioeng. 2009; 104: 1086,1097. © 2009 Wiley Periodicals, Inc. [source] Luminescent Excited-State Intramolecular Proton-Transfer (ESIPT) Dyes Based on 4-Alkyne-Functionalized [2,2,-Bipyridine]-3,3,-diol DyesCHEMISTRY - A EUROPEAN JOURNAL, Issue 14 2008Gilles Ulrich Dr. Abstract Functionalized 6,6,-dimethyl-3,3,-dihydroxy-2,2,-bipyridine dyes (BP(OH)2) exhibit relatively intense fluorescence from the relaxed excited state formed by excited-state intramolecular proton transfer (ESIPT). Bromo functionalization of (BP(OH)2) species followed by palladium(0)-catalyzed reactions allows the connection (via alkyne tethers) of functional groups, such as the singlet-emitter diazaboraindacene (bodipy) group or a chelating module (terpyridine; terpy). The X-ray structure of the terpy-based compound confirms the planarity of the 3,3,-dihydroxy-bipyridine unit. The new dyes exhibit relatively intense emission on the nanosecond timescale when in fluid solution, in the solid state at 298,K, and in rigid glasses at 77,K. In some cases, the excitation wavelength luminescence was observed and attributed to 1),inefficiency of the ESIPT process in particular compounds when not enough vibrational energy is introduced in the Franck,Condon state, which is populated by direct light excitation or 2),the presence of an additional excited state that deactivates to the ground state without undergoing the ESIPT process. For some selected species, the effect of the addition of zinc salts on the absorption and luminescence spectra was investigated. In particular, significant fluorescence changes were observed as a consequence of probable consecutive formation of a 1:1 and 1:2 molecular ratio of ligand/zinc adducts owing to coordination of ZnII ions by the bipyridyldiol moieties, except when an additional terpyridine subunit is present. In fact, this latter species preferentially coordinates to the ZnII ion in a 1:1 molecular ratio and further inhibits ZnII interaction. In the hybrid Bodipy/BP(OH)2 species, complete energy transfer from the BP(OH)2 to the bodipy fluorophore occurs, leading to exclusive emission from the lowest-lying bodipy subunit. Des composés colorés à base de 6,6,-dimethyl-3,3,-dihydroxy-2,2,-bipyridine (BP(OH)2) ont été synthétisés et présentent une fluorescence relativement intense issue de la relaxation d,un état excité provenant d,un transfert de proton dans l,état excité (ESIPT). La bromation de dérivés (BP(OH)2) suivie d,un couplage croisé catalysé par du Pd0sous-ligandé permet de connecter (par l,intermédiaire de pont alcyne) des groupes fonctionnels comme un groupe émetteur singulet de type boradiazaindacène (Bodipy) ou un module chélatant universel (une terpyridine). Une structure par diffraction aux rayons X a été obtenu avec le dérivé terpyridine, celle ci confirme la planéité de l,unité 3,3,-dihydroxy-bipyridine. Les nouveaux fluorophores possèdent une émission relativement intense avec une durée de vie de l,ordre de la nanoseconde, en solution et à l,état solide à 298,K ainsi que dans un verre à 77,K. Dans certain cas, la luminescence dépend de la longueur d,onde d,excitation, ce phénomène est attribué à (i) l,inefficacité du processus ESIPT, quand trop peu d,énergie vibrationnelle est introduite dans l,état Franck-Condon peuplé directement par la lumière d,excitation (ii) la présence d,un état excité supplémentaire qui désactive l,état fondamental sans passer par un processus ESIPT. Pour certains composés, l,effet de l,addition de sels de Zinc sur les spectres d,absorption et d,émission a été étudié : en particulier, des changements significatifs de fluorescence ont été observés, probablement due à la formation consécutive de complexes ligand/zinc de st,chiométrie 1:1 et 1:2, provenant de la coordination des cations ZnIIpar l,unité bipyridyl-diol, sauf quand une fonction terpyridine est présente. En fait, dans cette dernière espèce le zinc est préférentiellement coordiné par la terpyridine dans un ratio 1:1, et toute coordination supplémentaire de Zinc semble inhibée. Dans le composé hybride Bodipy/BP(OH)2,un transfert d,énergie quantitatif est observé du BP(OH)2vers le fluorophore Bodipy, entraînant une émission exclusive de la sous-unité Bodipy. Composti basati sulla subunità 6,6,-dimetil-3,3,-dididrossi-2,2,-bipiridina (BP(OH)2), variamente funzionalizzati, presentano fluorescenza relativamente intensa da stati eccitati formati attraverso trasferimento protonico nello stato eccitato (ESIPT). Bromo-funzionalizzazione dei composti di tipo BP(OH)2, seguita da reazioni catalizzate da Pd(0), permettono di connettere (con legame alchinico) gruppi funzionali quali il diazaboroindacene (Bodipy) o un modulo chelante (terpiridina) al frammento BP(OH)2. La struttura ai raggi X del composto contenente la terpiridina conferma la planarità dell,unità 3,3,-diidrossi-bipiridina. Le nuove specie presentano intensa emissione nella scala dei nanosecondi, in soluzione fluida ed allo stato solido a 298,K ed in matrice rigida a 77,K. In alcuni casi, la luminescenza dipende dalla lunghezza d,onda di eccitazione: questo fenomeno è attribuito a (i) inefficienza del processo ESIPT, quando non sufficiente energia vibrazionale è introdotta nello stato Franck-Condon a seguito di eccitazione luminosa o (ii) alla presenza di uno stato eccitato addizionale che si disattiva allo stato fondamentale senza passare dallo stato eccitato prodotto attraverso il meccanismo ESIPT. Per composti selezionati è stato anche studiato l,effetto della presenza di sali di zinco sulle proprietà di assorbimento elettronico e di luminescenza: significativi cambiamenti della fluorescenza sono stati osservati, come conseguenza della consecutiva formazione di addotti 1:1 e 1:2 (rapporto molare BP(OH)2/zinco), dovuta alla coordinazione di cationi di ZnIIda parte del bipiridil-diolo, che si verifica in tutti i casi studiati tranne in presenza di una subunità terpiridinica. In quest,ultimo caso, infatti, si forma soltanto l,addotto 1:1, e ulteriore coordinazione di cationi di ZnIIappare inibita. Nella specie ibrida Bodipy/BP(OH)2si verifica un completo trasferimento di energia elettronica dal BP(OH)2 al Bodipy, che porta ad emissione esclusivamente dalla subunità Bodipy, a piû bassa energia. [source] Ru-catalyzed Asymmetric Hydrogenation of Aryl Ketones Using Tetrazole Derived NH2 -hybrid LigandCHINESE JOURNAL OF CHEMISTRY, Issue 12 2009Fusheng Bie Abstract Readily available chiral hybrid NH2/tetrazole ligand [(S)-TEA, 1] in combination with Ru-BINAP or Ru-DIOP complexes catalyzes the asymmetric hydrogenation of a number of simple ketones with moderate enantioselectivity (up to 72% ee). The tetrazole functionality results in reversal of the typically observed chiral-induction for related systems and allows for hydrogenation to be uncharacteristically conducted in (non-protic) THF solvent. The observed catalyst performance is sensitive to the reaction conditions employed and the particular compounds involved. The origins of such features are considered to derive from the added functionality provided by the tetrazole moiety in 1, which due to its modular nature provides a good basis for further development. [source] | |||||||||||||