RESUMEN
N6-methyladenosine (m6A) methylation is a vital epigenetic mechanism associated with drug addiction. However, the relationship between m6A modification and oxycodone rewarding is less well explored. Based on an open field test, the present study evaluated oxycodone rewarding using chromatin immunoprecipitation PCR, immunofluorescence, and RNA sequencing. A marked increase in METTL14 protein and a decrease in PP1α protein due to oxycodone abundance in the striatal neurons were observed in a dose- and time-dependent manner. Oxycodone markedly increased LSD1 expression, and decreased H3K4me1 expression in the striatum. In the open field test, intra-striatal injection of METTL14 siRNA, HOTAIR siRNA, or LSD1 shRNA blocked oxycodone-induced increase in locomotor activity. The downregulation of PP1α was also inhibited after treatment with METTL14/HOTAIR siRNA and LSD1 shRNA. Enhanced binding of LSD1 with CoRest and of CoRest with the PP1α gene induced by oxycodone was also reversed by LSD1 shRNA. In addition, H3K4me1 demethylation was also blocked by the treatment. In summary, the investigation confirmed that METTL14-mediated upregulation of HOTAIR resulted in the repression of PP1α, which in turn facilitated the recruitment of LSD1, thus catalyzing H3K4me1 demethylation and promoting oxycodone addiction.
Asunto(s)
Metiltransferasas , Oxicodona , ARN Largo no Codificante , Animales , Masculino , Ratones , Cuerpo Estriado/metabolismo , Cuerpo Estriado/efectos de los fármacos , Desmetilación , Histona Demetilasas/metabolismo , Histona Demetilasas/genética , Histonas/metabolismo , Lisina/análogos & derivados , Metiltransferasas/metabolismo , Metiltransferasas/genética , Ratones Endogámicos C57BL , Oxicodona/farmacología , Proteína Fosfatasa 1/metabolismo , Proteína Fosfatasa 1/genética , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/genética , Regulación hacia ArribaRESUMEN
Luminescent materials with aggregation-induced emission (AIE) characteristics have been recognized as highly selective and sensitive probes for the detection of toxic metal ions in recent years. In this paper, a Au-Ag cluster-based coordination polymer [Au3Ag3(L)2(CN)6(H2O)2]n [1, L = 1,3-bis((diphenylphosphanyl)methyl)-4,5-dihydro-imidazolylidene] was prepared by in situ generation of the diphosphine N-heterocyclic carbene (PCNHCP)-type ligand L in the presence of the corresponding metal salts. Compound 1 exhibited 530 nm phosphorescence under 380 nm excitation with a QY of 6.30% and a lifetime (τ) of 7.14 µs in the solid state. 1 showed good AIE behavior in the mixture of MeOH/H2O while the best aggregation state (fwater = 90%, QY = 6.79%, τ = 6.70 µs) exhibited selective and sensitive emission quenching toward Cr(VI) ions. Ultralow detection limits of 9.7 ppb (w/w) for Cr2O72- and 17.9 ppb (w/w) for CrO42- were achieved.
RESUMEN
Reaction of a P/N/S hybrid ligand dpppyatc (N,N-bis((diphenylphosphaneyl)methyl)-N-(pyridin-2-yl)-amino-thiocarbamide) with Au(tht)Cl (tht=tetrahydrothiophene) and [Cu(MeCN)4]BF4 afforded cluster complex [Au2Cu(dpppyatc)2](BF4)2Cl (1). Upon excitation at 480â nm, 1 emitted orange phosphorescence at 646â nm, which was red-shifted to ~698â nm selectively in the presence of ammonia or amine vapor. This chromic photoluminescent response toward ammonia was sensitive and reversible. Complex1 could detect ammonia in aqueous solution down to concentrations of 2â ppm (w/w).
RESUMEN
The lysine-specific demethylase 1 (KDM1A) is reported to be a regulator in learning and memory. However, the effect of KDM1A in oxycodone rewarding memory has yet to be studied. In our study, rewarding memory was assessed by using conditioned place preference (CPP) in male mice. Next generation sequencing and chromatin immunoprecipitation-PCR were used to explore the molecular mechanisms. Oxycodone significantly decreased PP1α mRNA and protein levels in hippocampal neurons. Oxycodone significantly increased KDM1A and H3K4me1 levels, while significantly decreased H3K4me2 levels in a time- and dose-dependent manner. Behavioral data demonstrated that intraperitoneal injection of ORY-1001 (KDM1A inhibitor) or intra-hippocampal injection of KDM1A siRNA/shRNA blocked the acquisition and expression of oxycodone CPP and facilitated the extinction of oxycodone CPP. The decrease of PP1α was markedly blocked by the injection of ORY-1001 or KDM1A siRNA/shRNA. Oxycodone-induced enhanced binding of CoRest with KDM1A and binding of CoRest with the PP1α promoter was blocked by ORY-1001. The level of H3K4me2 demethylation was also decreased by the treatment. The results suggest that oxycodone-induced upregulation of KDM1A via demethylation of H3K4me2 promotes the binding of CoRest with the PP1α promoter, and the subsequent decrease in PP1α expression in hippocampal neurons may contribute to oxycodone reward.
Asunto(s)
Epigénesis Genética , Histona Demetilasas , Oxicodona , Animales , Masculino , Epigénesis Genética/efectos de los fármacos , Ratones , Oxicodona/farmacología , Histona Demetilasas/metabolismo , Histona Demetilasas/genética , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Recompensa , Condicionamiento Psicológico/efectos de los fármacos , Ratones Endogámicos C57BL , Histonas/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Memoria/efectos de los fármacosRESUMEN
The atom-transfer radical addition (ATRA) reaction simultaneously forges carbon-carbon and carbon-halogen bonds. However, frequently-used photosensitizers such as precious transition metal complexes, or organic dyes have limitations in terms of their potential toxicity and recyclability. Three ß-ketoenamine-linked covalent organic frameworks (COFs) from 1,3,5-triformylphloroglucinol and 1,4-phenylenediamines with variable transient photocurrent and photocatalytic activity have been prepared. A COF bearing electron-deficient Cl atoms displayed the highest photocatalytic activity toward the ATRA reaction of polyhalogenated alkanes to give halogenated olefins under visible light at room temperature. This heterogeneous photocatalyst exhibited good functional group tolerance and could be recycled without significant loss of activity.
RESUMEN
A Schiff-base porous polymer has been impregnated with ruthenium trichloride for acceptor-free dehydrogenation coupling (ADC) of secondary alcohols with γ-amino- and 2-aminobenzyl alcohols to give pyridines and quinolines. This heterogenous catalyst exhibited high catalytic efficiency over repeated cycles with wide functional group tolerance.
RESUMEN
The reaction of CF3COOAg, 3-bdppmapy (N,N-bis(diphenylphosphanylmethyl)-3-aminopyridine) and HTZ (1,2,4-triazole-3-thiol) in CH2Cl2/MeOH resulted in a dinuclear Ag/P/S complex [Ag2(TZ)2(3-bdppmapy)2]·xSol (1·xSol). Crystals of 1·xSol converted to 1·2MeOH in air at room temperature and further to 1 under vacuum upon heating. The solid-state, room-temperature photoluminescent emission of 1·xSol (510 nm) shifted to 494 nm (1·2MeOH) and 486 nm (1). Grinding solids of 1·2MeOH in air resulted in amorphous 1G characterized by solid-state emission at 468 nm, which converted to 1GR with 513 nm emission upon MeOH treatment. Grinding 1GR in air returned 1G, and this interconversion was reproducible over five cycles. The solid-state photoluminescence of 1G changed in response to vapors containing low-molecular weight alcohols but remained unchanged after exposure to other volatile organic compounds (VOCs) or to water vapor. Test papers impregnated with 1G could detect methanol in vapors from aqueous solutions at concentrations above 50%. Complex 1G is, therefore, an example of a stimuli-responsive molecular sensor for the detection of alcohols.
RESUMEN
Earth-abundant copper(I) coordination complexes of an imine-phosphine and a diimine have been developed as visible-light photocatalysts. Reaction of [Cu(MeCN)4]BF4 with hetero-bidentate phosphinopyrazole (phpz) ligand R1R2C3HN2PPh3 (R1 = R2 = H (1a); R1 = H, R2 = Me (1b); R1 = H, R2 = Ph (1c); R1 = R2 = Me (1d)) and 2,9-dimethyl-1,10-phenanthroline (dmp) gave four heteroleptic bis-chelate Cu(I) complexes [Cu(dmp)(R1R2C3HN2PPh3)]BF4 (R1 = R2 = H (2a); R1 = H, R2 = Me (2b); R1 = H, R2 = Ph (2c); R1 = R2 = Me (2d)) with distorted tetrahedral geometries. Complexes 2a-2d exhibited broad absorption in the visible spectrum and could facilitate photochemical intermolecular atom-transfer radical addition reactions of CBr4, or CCl3Br, CHI3 to styrenes in yields up to 91% and with a broad substrate scope. The absorption, emission, redox potential and photocatalytic activity were dependent on the substituents on the phpz ligand. Mechanistic studies supported an atom-transfer radical addition (ATRA) mechanism.
RESUMEN
A heterobimetallic coordination polymer [Au4(dppmt)4(AgCl)2]n (1) incorporating an in situ generated P-S ligand (dppmtH) was synthesized from the solvothermal reaction of Au(tht)Cl, AgCl, and dpppyatc in CH3CN/CH2Cl2 (dppmtH = (diphenylphosphino)methanethiol, tht = tetrahydrothiophene, dpppyatc = N,N-bis((diphenylphosphaneyl)methyl)-N-(pyridin-2-yl)-amino-thiocarbamide). The structure of 1 contains a one-dimensional helical Au-Au chain in which the unique [Au4Ag2S2] cluster units are connected by [Au2(dppmt)2] dimers. Upon excitation at 343 nm, 1 exhibited cyan (495 nm) phosphorescent emission at quantum yield (QY) = 22.3% and τ = 0.78 µs (λex = 375 nm). Coordination polymer 1 exhibited a rapid, selective, reversible, and visible vapor-chromic response on exposure to methanol (MeOH) vapor with its emission shifting to a more intense green (530 nm, λex = 388 nm) with QY = 46.8% and τ = 1.24 µs (λex = 375 nm). A polymethylmethacrylate film containing 1 served as a reversible chemical sensor for the sensitive detection of MeOH in air.
RESUMEN
A new Ag/Cu bimetallic cluster [Ag10Cu6(bdppthi)2(C≡CPh)12(EtOH)2](ClO4)4 (1, bdppthi = N,N'-bis(diphenylphosphanylmethyl)-tetrahydroimidazole) exhibited strong phosphorescent (PL) emission at 644 nm upon excitation at 400 nm. Removal of the coordinated EtOH molecules in 1 resulted in derivative 1a, which exhibited significant red-shifted emission at 678 nm. The structure and PL of 1 was restored on exposure to EtOH vapor. Cluster 1a also exhibited a vapor-chromic PL response towards other common organic solvent vapors including acetone, MeOH and MeCN. A PMMA film of 1a was developed as a reusable visible sensor for MeCN.
RESUMEN
Covalent organic frameworks (COFs) have recently emerged as prospective photoactive materials with noble Pt as a cocatalyst for photocatalytic hydrogen evolution. In this work, a series of SH-group-functionalized covalent organic frameworks, TpPa-1-SH-X, is prepared by reaction of p-phenylenediamine (Pa) and 1,3,5-triformylphloroglucinol (Tp) with p-NH2 C6 H4 SH as a modulating agent. The reaction of TpPa-1-SH-X with NiII acetylacetonate Ni(acac)2 gave nickel thiolate-immobilized TpPa-1 (TpPa-1-SNi-X). The highest hydrogen evolution rate was 10.87â mmol h-1 g-1 , which was an enhancement of 16.47, 3.83, and 1.84 times than that of the parent TpPa-1, covalent-bond-free [(p-NH2 C6 H4 S)2 Ni]n /TpPa-1-SH-10, and 3â wt % Pt-deposited TpPa-1, respectively. This enhanced photocatalytic hydrogen evolution is ascribed to enhanced crystallinity, the use of NiII thiolate as a cocatalyst and covalent bonding between the cocatalyst and TpPa-1.
RESUMEN
The photopromoted, Ni-catalyzed acceptorless dehydrogenation esterification of phenols and aromatic aldehydes has been achieved in an oxidant- and external photosensitizer-free manner. This reliable and atom-economical transformation was tolerant to a wide range of functional groups and proceeded efficiently to give various aryl benzoates in moderate to high yields. Additionally, this photocatalytic system displayed high activity for the hydrogen-evolution cross coupling of aliphatic aldehydes and phenols employing dual nickel and aromatic aldehyde catalysis.
RESUMEN
We have developed a catalyst-free visible-light-driven C(sp2)-H arylation of unprotected phenols with arylbromides to give 2-arylated phenols. This reaction proceeds through the excitation of an electron donor-acceptor complex between a phenolate and an arylbromide, electron transfer, and debrominative C(sp2)-C(sp2) coupling.
RESUMEN
Notwithstanding some progress in nickel-catalyzed etherification of alkanols and arylhalides, the ability of such a Ni-catalyzed transformation employing phenols to diaryl ethers is unsuccessful due to phenolates with much lower reduction potentials, which suppress the oxidation of nickel(II) intermediates into requisite Ni(III) species. We herein report visible-light-initiated, nickel-catalyzed O-arylation of phenols with arylhalides using t-BuNH(i-Pr) as the base and thioxanthen-9-one as the photosensitizer under visible light. This photocoupling exhibits a broad substrate scope.
RESUMEN
A photoluminescent bimetallic cluster [Ag10 Cu6 (bdppthi)2 (C≡CPh)12 (MeOH)2 (H2 O)](ClO4 )4 (1, bdppthi=N,N'-bis(diphenylphosphanylmethyl)-tetrahydroimidazole} was synthesized from the PNNP type ligand bdppthi generated in-situ. Upon excitation at 365â nm, 1 exhibited strong phosphorescent emission at 630â nm, which was selectively quenched by NH3 in air or water. The sensing of NH3 was rapid and recoverable, with detection limits of 53â ppm (v/v) in N2 and 21â µmol/L (0.36â ppm, w/w) for NH3 â H2 O in water. Cluster 1 could potentially serve as a bifunctional chemical sensor for the efficient detection of ammonia in waste-gas and waste-water.
RESUMEN
Trinuclear complex [Au2Ag(dppmaphen)2(CN)2]PF6 photoluminesces on exposure to low molecular weight alcohols. This emission is likely due to C-Hπ interactions between the analyte and -PPh2 group, that inhibits non-radiative relaxation of the photoexcited state. Photoluminescene was quenched by removing the analyte under a stream of N2 or replacing it with H2O. This on/off switching was clearly visible, relatively rapid and recyclable.
RESUMEN
A photocatalyst- and transition-metal-free visible-light-induced cyclization of ortho-halothiobenzanilides has been developed. Upon irradiation with visible light, substrates undergo dehalogenative cyclization to 2-aryl benzothiazoles with high efficiency and selectivity. This photocyclization exhibits a high tolerance to various functional groups, is applicable for the synthesis of 2-alkyl benzothiazoles, and is easy to set up for gram-scale reaction.
RESUMEN
An efficient method has been developed for photocatalytic P(O)-C(sp2) coupling of (hetero)aryl halides with H-phosphine oxides or H-phosphites under the irradiation of visible light or sunlight. The thioxanthen-9-one/nickel dual catalysis mediates this phosphonylation to give arylphosphine oxides and arylphosphonates in moderate to excellent yields. This transformation is widely tolerant to a range of functional groups and proceeds efficiently on a gram scale.
RESUMEN
Ru-Catalyzed acceptorless dehydrogenative coupling (ADC) and auto-transfer-hydrogenative (ATH) reactions are effective, versatile transformations for the constructions of N-heteroaromatic compounds from alcohols. Water and hydrogen are the by-products and the starting alcohols are less toxic, more readily available and more easily handled than their halogenated counterparts. A variety of homogeneous ruthenium catalysts, alcohols and partner-substrates such as amines, ammonia, amidines and nitriles, have been used to build N-heteroaromatic compounds in one-pot, multi-step syntheses. This review details recently reported Ru catalysts employed for these reactions, describing the scope of each methodology, proposed reaction mechanisms, regioselectivity of coupling and applications in synthesis.
RESUMEN
Acyl radicals have been generated from α-keto acids using inexpensive and commercially available 2-chloro-thioxanthen-9-one as the photoredox catalyst under visible light illumination. These reactive species added to olefins or coupled with aryl halides via a bipyridyl-stabilized Ni(II) catalyst, enabling easy access to a diverse range of ketones. This reliable, atom-economical, and eco-friendly protocol is compatible with a wide range of functional groups.