Fluorogenic Rhodamine Probes with Pyrrole Substitution Enables STED and Lifetime Imaging of Lysosomes in Live Cells.

Fluorogenic dyes with high brightness, large turn-on ratios, excellent photostability, favorable specificity, low cytotoxicity, and high membrane permeability are essential for high-resolution fluorescence imaging in live cells. In this study, we endowed these desirable properties to a rhodamine derivative by simply replacing the N, N-diethyl group with a pyrrole substituent. The resulting dye, Rh-NH, exhibited doubled Stokes shifts (54 nm) and a red-shift of more than 50 nm in fluorescence spectra compared to Rhodamine B. Rh-NH preferentially exists in a non-emissive but highly permeable spirolactone form. Upon binding to lysosomes, the collective effects of low pH, low polarity, and high viscosity endow Rh-NH with significant fluorescence turn-on, making it a suitable candidate for wash-free, high-contrast lysosome tracking. Consequently, Rh-NH enabled us to successfully explore stimulated emission depletion (STED) super-resolution imaging of lysosome dynamics, as well as fluorescence lifetime imaging of lysosomes in live cells.

Ground-state intramolecular proton transfer inhibits the selective methylation on quinoline and pyridine derivatives.

Methylation is one of the crucial steps for drug discovery, organic synthesis, and catalysis. Despite being a versatile and well-known chemical reaction, its chemoselectivity has not been well addressed. In this paper, we reported a thorough experimental and computational investigation of the selective N-methylation of N-heterocyclic compounds, mainly quinolines and pyridines. These reactions were conducted in a base-free manner under ambient conditions using iodomethane as the methylating reagent, exhibited good chemoselectivity, and were tolerant of other amine, carboxyl, or hydroxyl functional groups without needing protection. To this end, 13 compounds were synthesized as a proof-of-concept and 7 crystal structures were obtained. However, the chemoselectivity failed in the presence of a thiol group. Detailed quantum chemical calculations provided insights into the N-methylation mechanism and its selectivity and demonstrated that the isomerization induced by ground-state intramolecular proton transfer (GSIPT) in the presence of a thiol group inhibits the N-methylation.

A Descriptor for Accurate Predictions of Host Molecules Enabling Ultralong Room-Temperature Phosphorescence in Guest Emitters.

Although doping can induce room-temperature phosphorescence (RTP) in heavy-atom free organic systems, it is often challenging to match the host and guest components to achieve efficient intersystem crossing for activating RTP. In this work, we developed a simple descriptor ΔE to predict host molecules for matching the guest RTP emitters, based on the intersystem crossing via higher excited states (ISCHES) mechanism. This descriptor successfully predicted five commercially available host components to pair with naphthalimide (NA) and naphtho[2,3-c]furan-1,3-dione (2,3-NA) emitters with a high accuracy of 83 %. The yielded pairs exhibited bright yellow and green RTP with the quantum efficiency up to 0.4 and lifetime up to 1.67 s, respectively. Using these RTP pairs, we successfully achieved multi-layer message encryption. The ΔE descriptor could provide an efficient way for developing doping-induced RTP materials.

Lithium-Templated Formation of Polyhedral Oligomeric Silsesquioxanes (POSS).

A coordination complex, lithium hepta(i-butyl)silsesquioxane trisilanolate (1; Li-T7), a stable intermediate in silsesquioxane (SQ) syntheses, was successfully isolated in 65% yield and found to be highly soluble in nonpolar solvents such as hexane. The structure of Li-T7 was confirmed by NMR, IR spectroscopy, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, electrospray ionization mass spectrometry, and computational simulation, providing detailed elucidation of the intermolecular self-association of the SQ cage with a box-shaped Li6O6 polyhedron through strong coordination bonds. After acid treatment, Li-T7 undergoes lithium-proton cationic exchange, yielding hepta(i-butyl)silsesquioxane trisilanol (2; H-T7) quantitatively. The high yield of H-T7 seems to be influenced by Li-O bonding in the Li-T7 complex that affects the selective formation of hepta(i-butyl)silsesquioxane trisilanolate and the bulky i-butyl groups which may prevent decomposition or SQ cage-rearrangement even at reflux under alkaline conditions. Single-crystal X-ray crystallography confirms the presence of the dumbbell-shaped SQ partial cages through strong intermolecular hydrogen bonds. Interestingly, lowering the polarity of the reaction solution by adding dichloromethane results in formation of the cubic octa(i-butyl)silsesquioxane (3; T8) cage in a good yield (47%), which is isolated by crystallization from the reaction solution.

Aryl-Modified Pentamethyl Cyanine Dyes at the C2' Position: A Tunable Platform for Activatable Photosensitizers.

Pentamethyl cyanine dyes are promising fluorophores for fluorescence sensing and imaging. However, advanced biomedical applications require enhanced control of their excited-state properties. Herein, a synthetic approach for attaching aryl substituents at the C2' position of the thio-pentamethine cyanine (TCy5) dye structure is reported for the first time. C2'-aryl substitution enables the regulation of both the twisted intramolecular charge transfer (TICT) and photoinduced electron transfer (PET) mechanisms to be regulated in the excited state. Modulation of these mechanisms allows the design of a nitroreductase-activatable TCy5 fluorophore for hypoxic tumor photodynamic therapy and fluorescence imaging. These C2'-aryl TCy5 dyes provide a tunable platform for engineering cyanine dyes tailored to sophisticated biological applications, such as photodynamic therapy.

Ultrafast synthesis of silicone elastomers using silsesquioxane cages as crosslinkers.

Cross-linked siloxane/silsesquioxane-based elastomers were easily prepared in 15 min via the anionic ring-opening polymerization of cyclotetrasiloxane (D4) and a polyhedral oligomeric silsesquioxane, using K2CO3 as a catalytic base in dimethylformamide at 70 °C. The resulting silicone elastomers have high mechanical strength, good thermal stability, and good superhydrophobic properties.

Stepwise on-demand functionalization of multihydrosilanes enabled by a hydrogen-atom-transfer photocatalyst based on eosin Y.

Organosilanes are of vital importance for modern human society, having found widespread applications in functional materials, organic synthesis, drug discovery and life sciences. However, their preparation remains far from trivial, and on-demand synthesis of heteroleptic substituted silicon reagents is a formidable challenge. The generation of silyl radicals from hydrosilanes via direct hydrogen-atom-transfer (HAT) photocatalysis represents the most atom-, step-, redox- and catalyst-economic pathway for the activation of hydrosilanes. Here, in view of the green characteristics of neutral eosin Y (such as its abundance, low cost, metal-free nature, absorption of visible light and excellent selectivity), we show that using it as a direct HAT photocatalyst enables the stepwise custom functionalization of multihydrosilanes, giving access to fully substituted silicon compounds. By exploiting this strategy, we realize preferable hydrogen abstraction of Si-H bonds in the presence of active C-H bonds, diverse functionalization of hydrosilanes (for example, alkylation, vinylation, allylation, arylation, deuteration, oxidation and halogenation), and remarkably selective monofunctionalization of di- and trihydrosilanes.

Anion identification using silsesquioxane cages.

Anthracene-conjugated octameric silsesquioxane (AnSQ) cages, prepared via Heck coupling between octavinylsilsesquioxane (OVS) and 9-bromoanthracene, thermodynamically display intramolecular excimer emissions. More importantly, these hosts are sensitive to each anionic guest, thereby resulting in change of anthracene excimer formation, displaying the solvent-dependent fluorescence and allowing us to distinguish up to four ions such as F-, OH-, CN- and PO4 3- by fluorescence spectroscopy. Depending on the solvent polarity, for example, both F- and CN- quenched the fluorescence emission intensity in THF, but only F- could enhance the fluorescence in all other solvents. The presence of PO4 3- results in fluorescence enhancements in high polarity solvents such as DMSO, DMF, and acetone, while OH- induces enhancements only in low polarity solvents (e.g. DCM and toluene). A picture of the anion recognizing ability of AnSQ was obtained through principal component analysis (PCA) with NMR and FTIR confirming the presence of host-guest interactions. Computational modeling studies demonstrate the conformation of host-guest complexation and also the change of excimer formation. Detection of F-, CN- and OH- by AnSQ hosts in THF is noticeable with the naked eye, as indicated by strong color changes arising from charge transfer complex formation upon anion addition.

Silsesquioxane cages as fluoride sensors.

Pyrene functionalized silsesquioxane cages (PySQ) not only provide significant fluorescence from pyrene-pyrene excimers with a very large Stokes shift (Δλ = 143 nm, 69 930 cm-1) in DMSO but also exhibit fluoride capture results coincidentally with a π-π* fluorescence enhancement. On the other hand, PySQ-F- in THF significantly exhibits π-π* fluorescence quenching and a color change can be observed with the naked eye from light yellow to deep orange by forming a charge-transfer (CT) complex among the pyrenyl rings. Moreover, PySQ selectively captures F- with a response time of <2 min and with a very low detection limit (1.61 ppb), while 19F NMR is used to confirm encapsulation of F- with Δδ = 19 ppm.