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Binary mixtures of water with lower alcohols display non-linear phase behaviors upon mixing, which are attributed to potential cluster formation at the molecular level. Unravelling such elusive structures requires investigation of hydrogen-bonding sub-nanosecond dynamics. We employ high-resolution neutron time-of-flight spectroscopy with polarization analysis in combination with selective deuteration to study the concentration-dependent structural dynamics in the water rich part of the phase diagram of water-ethanol mixtures. This method enables simultaneous access to atomic correlations in space and time and allows us to separate spatially incoherent scattering probing self-diffusion of the ethanol fraction from the coherent scattering probing collective diffusion of the water network as a whole. Our observations indicate an enhanced rigidity of the hydrogen bond network at the mesoscopic length scale compared to the molecular scale as the ethanol fraction increases, which is consistent with the hypothesis of clusters.
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Hydrotropism is a convenient way to increase the solubility of drugs by up to several orders of magnitude, and even though it has been researched for decades with both experimental and simulation methods, its mechanism is still unknown. Here, we use caffeine/sodium benzoate (CAF-SB) as model system to explore the behaviour of caffeine solubility enhancement in water through NMR spectroscopy and neutron total scattering. 1H NMR shows strong interaction between caffeine and sodium benzoate in water. Neutron total scattering combined with empirical potential structure refinement, a systematic method to study the solution structure, reveals π-stacking between caffeine and the benzoate anion as well as Coulombic interactions with the sodium cation. The strongest hydrogen bond interaction in the system is between benzoate and water, which help dissolve CAF-SB complex and increase the solubility of CAF in water. Besides, the stronger interaction between CAF and water and the distortion of water structure are further mechanisms of the CAF solubility enhancement. It is likely that the variety of mechanisms for hydrotropism shown in this system can be found for other hydrotropes, and NMR spectroscopy and neutron total scattering can be used as complementary techniques to generate a holistic picture of hydrotropic solutions.
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Cafeína , Benzoato de Sodio , Cafeína/química , Espectroscopía de Resonancia Magnética , Benzoatos , Agua , NeutronesRESUMEN
Bis-heteroleptic cyclometalated iridium complexes of the form Ir(La)2(acac), where La is a substituted 2-phenylpyridine derivative and acac is an acetylacetonato ligand, are a useful class of luminescent organometallic complexes for a range of applications. Related tris-heteroleptic complexes of the form Ir(La)(Lb)(acac) offer the potential advantage of greater functionality through the use of two different cyclometalated ligands but are, in general, more difficult to obtain. We report the synthesis of divergent bis- and tris-heteroleptic triisopropylsilylethynyl-substituted intermediate complexes that can be diversified using a "chemistry-on-the-complex" approach. We demonstrate the methodology through one-pot deprotection and Sonogashira cross-coupling of the intermediate complexes with para-R-aryliodides (R = H, SMe, and CN). The photophysical and electrochemical behaviors of the resultant bis- and tris-heteroleptic complexes are compared, and it is shown that the tris-heteroleptic complexes exhibit subtly different emission and redox properties to the bis-heteroleptic complexes, such as further red-shifted emission maxima and lower extinction coefficients, which can be attributed to the reduced symmetry. It is demonstrated, supported by DFT and time-dependent DFT calculations, that the charge-transfer character of the emission can be altered via variation of the terminal substituent; the introduction of an electron-withdrawing cyano group in the terminal position leads to a significant red shift, while the introduction of an SMe group can substantially increase the emission quantum yield. Most notably, this convenient synthetic approach reduces the need to perform the often challenging isolation of tris-heteroleptic complexes to a single divergent intermediate, which will simplify access to families of complexes of the form Ir(La)(Lb)(acac).
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Phototherapy, the use of light to selectively ablate cancerous tissue, is a compelling prospect. Phototherapy is divided into two major domains: photodynamic and photothermal, whereby photosensitizer irradiation generates reactive oxygen species or heat, respectively, to disrupt the cancer microenvironment. Phthalocyanines (Pcs) are prominent phototherapeutics due to their desirable optical properties and structural versatility. Targeting of Pc photosensitizers historically relied on the enhanced permeation and retention effect, but the weak specificity engendered by this approach has hindered bench-to-clinic translation. To improve specificity, antibody and peptide active-targeting groups have been employed to some effect. An alternative targeting method exploits the binding of anticancer drugs to direct the photosensitizer close to essential cellular components, allowing for precise, synergistic phototherapy. This Perspective explores the use of Pc-drug conjugates as targeted anticancer phototherapeutic systems with examples of Pc-platin, Pc-kinase, and Pc-anthracycline conjugates discussed in detail.
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Antineoplásicos , Nanopartículas , Neoplasias , Fotoquimioterapia , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Humanos , Indoles/química , Isoindoles , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Fototerapia/métodos , Microambiente TumoralRESUMEN
Ir-catalysed borylation of phthalonitrile produces both 4-(Bpin)phthalonitrile (1) and 3,5-bis(Bpin)phthalonitrile (2), which are potential divergent intermediates for the synthesis of functionalized phthalocyanines. To exemplify the utility of 2, we have prepared a series of 3,5-bis-arylphthalonitriles that in turn undergo sterically controlled regioselective cyclotetramization to give previously unknown C4h 1,3,8,10,15,17,22,24-octaarylphthalocyanines.
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Peptoids are biofunctional N-substituted glycine peptidomimics. Their self-assembly is of fundamental interest because they demonstrate alternatives to conventional peptide structures based on backbone chirality and beta-sheet hydrogen bonding. The search for self-assembling, water-soluble "minimal" sequences, be they peptide or peptidomimic, is a further challenge. Such sequences are highly desired for their compatibility with biomacromolecules and convenient synthesis for broader application. We report the self-assembly of a set of trimeric, water-soluble α-peptoids that exhibit a relatively low critical aggregation concentration (CAC â¼ 0.3 wt %). Cryo-EM and angle-resolved DLS show different sequence-dependent morphologies, namely uniform ca. 6 nm wide nanofibers, sheets, and clusters of globular assemblies. Absorbance and fluorescence spectroscopies indicate unique phenyl environments for π-interactions in the highly ordered nanofibers. Assembly of our peptoids takes place when the sequences are fully ionized, representing a departure from superficially similar amyloid-type hydrogen-bonded peptide nanostructures and expanding the horizons of assembly for sequence-specific bio- and biomimetic macromolecules.
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Employing neutron spectroscopy, we follow the tracer diffusion of two non-steroidal anti-inflammatory drug molecules, paracetamol (PCM) and ibuprofen sodium (IBU), in a supramolecular gel and the corresponding bulk solution. Both solutes show altered diffusion behaviour in the gel phase, deviating from each other and their bulk solution. Whilst picosecond diffusion of IBU is slightly quicker in the gel, this effect is significantly increased for PCM, which is up to 70% quicker in the gel than in solution. This effect is independent of changes in the solvent diffusion reported previously. An increased residence time of PCM in solution at lower temperatures points towards the onset of nucleation and crystallisation. This work reports one of the first experiments on the novel Backscattering and Time-of-Flight option (BATS) on the IN16B spectrometer at the Institut Laue-Langevin, France, which with its range and resolution in neutron energy and momentum transfer is ideally suited to observe this type of diffusion.
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Acetaminofén/química , Antiinflamatorios no Esteroideos/química , Difusión , Geles/química , Ibuprofeno/químicaRESUMEN
[This corrects the article DOI: 10.1021/acsmacrolett.9b01010.].
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Two different chromophores, namely a dipolar and an octupolar system, were prepared and their linear and nonlinear optical properties as well as their bioimaging capabilities were compared. Both contain triphenylamine as the donor and a triarylborane as the acceptor, the latter modified with cationic trimethylammonio groups to provide solubility in aqueous media. The octupolar system exhibits a much higher two-photon brightness, and also better cell viability and enhanced selectivity for lysosomes compared with the dipolar chromophore. Furthermore, both dyes were applied in two-photon excited fluorescence (TPEF) live-cell imaging.
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Compuestos de Anilina/química , Cationes/química , Supervivencia Celular , Estructura Molecular , Fotones , Solubilidad , Espectrometría de FluorescenciaRESUMEN
We report the self-diffusion in ethanol-water mixtures as a function of the water-ethanol ratio measured at different temperatures using quasi-elastic neutron spectroscopy (QENS). For our protiated samples, QENS is mainly sensitive to the dominant ensemble-averaged incoherent scattering from the hydrogen atoms of the liquid mixtures. The energy range and resolution render our experiment sensitive to the picosecond time scale and nanometer length scale. These observation scales complement different scales accessible by nuclear magnetic resonance techniques. Subsequent to testing different models, we find that a simple jump-diffusion model averaging over both types of molecules, water and ethanol, best fits our data.
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Solvent diffusion in a prototypical supramolecular gel probed by quasi-elastic neutron scattering on the picosecond timescale is faster than that in the respective bulk solvent. This phenomenon is hypothesized to be due to disruption of the hydrogen bonding of the solvent by the large hydrophobic surface of the gel network.
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Three water-soluble tetracationic quadrupolar chromophores comprising two three-coordinate boron π-acceptor groups bridged by thiophene-containing moieties were synthesised for biological imaging applications. Compound 3 containing the bulkier 5-(3,5-Me2 C6 H2 )-2,2'-(C4 H2 S)2 -5'-(3,5-Me2 C6 H2 ) bridge is stable over a long period of time, exhibits a high fluorescence quantum yield and strong one- and two-photon absorption (TPA), and has a TPA cross section of 268â GM at 800â nm in water. Confocal laser scanning fluorescence microscopy studies in live cells indicated localisation of the chromophore at the mitochondria; moreover, cytotoxicity measurements proved biocompatibility. Thus, chromophore 3 has excellent potential for one- and two-photon-excited fluorescence imaging of mitochondrial function in cells.
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Boranos/síntesis química , Colorantes Fluorescentes/química , Mitocondrias/metabolismo , Fluorescencia , Células HEK293 , Células Hep G2 , Humanos , Microscopía Fluorescente , Imagen Molecular/métodos , Estructura Molecular , Imagen Óptica , Solubilidad , Relación Estructura-Actividad , Tiofenos/química , AguaRESUMEN
The (B-Cl)-chloroboroles 2-chloro-1,3-di(4-R-phenyl)-2,4,5,6-tetra-hydrocyclopenta[c]borole (R = H, Br) undergo a novel dimerisation process in CH2Cl2 solution. The resulting unsymmetric dimers are highly fluxional in solution via reversible enantiomerisation through an intermediate with mirror symmetry. DFT calculations suggest an unusual dimerisation mechanism and provide insight into the dynamics of the dimers.
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Reactions of [Rh(κ(2) -O,O-acac)(PMe3 )2 ] (acac=acetylacetonato) and α,ω-bis(arylbutadiynyl)alkanes afford two isomeric types of MC4 metallacycles with very different photophysical properties. As a result of a [2+2] reductive coupling at Rh, 2,5-bis(arylethynyl)rhodacyclopentadienes (A) are formed, which display intense fluorescence (Φ=0.07-0.54, τ=0.2-2.5â ns) despite the presence of the heavy metal atom. Rhodium biphenyl complexes (B), which show exceptionally long-lived (hundreds of µs) phosphorescence (Φ=0.01-0.33) at room temperature in solution, have been isolated as a second isomer originating from an unusual [4+2] cycloaddition reaction and a subsequent ß-H-shift. We attribute the different photophysical properties of isomers A and B to a higher excited state density and a less stabilized T1 state in the biphenyl complexes B, allowing for more efficient intersystem crossing S1 âTn and T1 âS0 . Control of the isomer distribution is achieved by modification of the bis- (diyne) linker length, providing a fundamentally new route to access photoactive metal biphenyl compounds.
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The importance of the directional dependence of magnetic susceptibility in magnetic resonance and of electric susceptibility in the optical spectroscopy of lanthanide coordination complexes is assessed. A body of more reliable shift, relaxation and optical emission data is emerging for well-defined isostructural series of complexes, allowing detailed comparative analyses to be undertaken. Such work is highlighting the limitations of the current NMR shift and relaxation theories, as well as emphasising the absence of a compelling theoretical framework to explain optical emission phenomena.
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We report a general and selective method to synthesize 2,7-disubstituted pyrene derivatives containing two different substituents by sequential Ir-catalyzed borylation and substitution chemistry. To demonstrate the utility of our approach, we synthesized 2-cyano-7-(N,N-diethylamino)pyrene (3), a pyrene analogue of the widely studied chromophore 4-(N,N-dimethylamino)benzonitrile (DMABN). Compound 3 and the monosubstituted compounds 2-(N,N-diethylamino)pyrene (1) and 2-cyanopyrene (2) have been structurally characterized. Their electronic and optical properties have been studied by a combination of absorption and emission spectroscopies, lifetime and quantum yield measurements, and modeling by DFT and TD-DFT. The photophysical properties of 3 are compared to those of DMABN and 2-cyano-7-(N,N-dimethylamino)-4,5,9,10-tetrahydropyrene, and we show that 2,7-disubstituted pyrene is a moderately effective π-bridge for the construction of donor-acceptor compounds. It is also shown that donor or acceptor groups are only effective at the 2,7-positions of pyrene if they are suitably strong, leading to a switch in the energetic ordering of the HOMO-1 and HOMO or the LUMO and LUMO+1 of pyrene, respectively.
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Reduction of 2-(BMes2)pyrene (B1) and 2,7-bis(BMes2)pyrene (B2) gives rise to anions with extensive delocalization over the pyrenylene bridge and between the boron centers at the 2- and 2,7-positions, the typically unconjugated sites in the pyrene framework. One-electron reduction of B2 gives a radical anion with a centrosymmetric semiquinoidal structure, while two-electron reduction produces a quinoidal singlet dianion with biradicaloid character and a relatively large S0-T1 gap. These results have been confirmed by cyclic voltammetry, X-ray crystallography, DFT/CASSCF calculations, NMR, EPR, and UV-vis-NIR spectroscopy.
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Two tetrahydocarbazolone derivatives were found to show multiple unsolvated crystal forms. A persistent dimer motif was detected in solution by FTIR spectroscopy that is maintained in the kinetic crystal forms. Rationally introduced steric bulk induces the formation of a more stable catemeric form.
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Carbazoles/química , Cristalografía por Rayos X , Enlace de Hidrógeno , Cinética , Modelos Moleculares , Estructura Molecular , Soluciones , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
C-modified 7-deazaadenosines containing a diphenylacetylene moiety have been synthesised using cross-coupling approaches. The C-modified nucleosides exhibit remarkable fluorescence properties, including high quantum yields. Solvatochromic studies show a near linear correlation between the Stokes shift and solvent polarity which is indicative of intramolecular charge transfer. DFT calculations have allowed us to correlate the experimentally observed photophysical properties with the calculated HOMO-LUMO energy gaps within a series of real and model compounds.
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Diseño de Fármacos , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Tubercidina/química , Tubercidina/síntesis química , Técnicas de Química Sintética , Transporte de Electrón , Modelos Moleculares , Conformación Molecular , Teoría CuánticaRESUMEN
The push-pull character of a series of donor-bithienyl-acceptor compounds has been tuned by adopting triphenylamine or 1,1,7,7-tetramethyljulolidine as a donor and B(2,6-Me2 -4-RC6 H2)2 (R=Me, C6 F5 or 3,5-(CF3)2 C6 H3) or B[2,4,6-(CF3 )3 C6 H2]2 as an acceptor. Ir-catalyzed C-H borylation was utilized in the derivatization of the boryl acceptors and the tetramethyljulolidine donor. The donor and acceptor strengths were evaluated by electrochemical and photophysical measurements. In solution, the compound with the strongest acceptor, B[2,4,6-(CF3)3 C6 H2]2 ((FMes)2 B), has strongly quenched emission, while all other compounds show efficient green to red (ΦF =0.80-1.00) or near-IR (NIR; ΦF =0.27-0.48) emission, depending on solvent. Notably, this study presents the first examples of efficient NIR emission from three-coordinate boron compounds. Efficient solid-state red emission was observed for some derivatives, and interesting aggregation-induced emission of the (FMes)2 B-containing compound was studied. Moreover, each compound showed a strong and clearly visible response to fluoride addition, with either a large emission-color change or turn-on fluorescence.