The conventional method for creating targeted contrast agents is to conjugate separate targeting and fluorophore domains. In this study we report a new strategy based on incorporation of targeting moieties into the non-resonant structure of pentamethine and heptamethine indocyanines. Using the known affinity of phosphonates for bone minerals as a model system, we have synthesized two families of bifunctional molecules that target bone without the need for a traditional bisphosphonate. With peak fluorescence emission at ≈ 700 nm or ≈ 800 nm, these molecules can be used for FLARE dual-channel imaging. Longitudinal FLARE studies in mice demonstrate that phosphonated near-infrared fluorophores remain stable in bone for over 5 weeks, and histological analysis demonstrates incorporation into bone matrix. Taken together, we describe a new strategy for creating ultracompact, targeted, near-infrared fluorophores for various bioimaging applications.

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Inducement of high charge carrier density in organic field-effect transistors (OFETs) is a subject of immense interest due to its fundamental and applied impact on device operation. Here, the high performance of imidazolium-based ionic liquid (IL)gated OFETs is reported. By exploiting the p-doping of poly(3hexylthiophene-2,5diyl) (P3HT) in the ambient environment and using the IL-gating, high charge carrier density (10 16 cm −2 ) has been induced in P3HT, which has resulted in high hole mobility (20.2 cm 2 V −1 s −1 ). This is a remarkable improvement in fieldeffect mobility in organic polymer semiconductors. Along with high mobility, low threshold voltage (∼0.6 V), low subthreshold swing (∼100 mV dec −1 ), and specifically the high transconductance (>1 mS) position this class of devices as a strong candidate for electrical sensor platforms. The compatibility of ILs with biomolecules and the direct access to IL/P3HT interface make these devices suitable for in situ biosensors. The IL components (cation and anion) were varied (one at a time) to investigate the effect on the electrical performance of the OFETs. An increase in the gate-electrode metal work function leads to a systematic decrease in the threshold voltage (by up to 0.6 V). The mobility exhibits a negative power dependence on specific capacitance, a signature of polaronic selflocalization in organic semiconductors. The shelf life of the IL-gated OFETs is found to be more than 40 days.

The synthesis, crystal structure and luminescence properties of three cyclometalated Ir(III) complexes of general formula [(ppy)(2)Ir(pam)]X, where X = Cl(-) (1), PF(6)(-) (2), ClO(4)(-)(3), and pam = 2-picolylamine, are described. While 2 and 3 crystallize in a unique form, two pseudo-polymorphs, a solvated (1a) and a non-solvated (1b) species, have been observed for compound 1. 1a crystallizes in the monoclinic centrosymmetric space group P2(1)/c. On the contrary, 1b, 2 and 3 crystallize in the non-centrosymmetric space group P2(1)2(1)2(1) (1b) and Pca2(1) (2 and 3), respectively. All the crystalline supramolecular materials have been fully photophysically characterized. While 1 shows a bright blue-green emission in both solution and solvated crystalline state 1a, crystals of 1b, 2 and 3 show a significantly red shifted emission with respect to solution. Unexpectedly, and differently from 1a, mechanical stimuli-responsive colour and luminescence changes have been observed for 1b, 2 and 3. Upon mechanical grinding the colour of the crystalline solids changes from orange to yellow while the emission energy is partially (2 and 3) or completely (1b) converted from orange to green. The grinding-triggered colour and luminescence changes have been attributed to a crystal-to-amorphous phase conversion for all crystalline solids.

Highly stable symmetric and asymmetric squaraine fluorophores have been synthesized featuring an internal salt bridge between a quaternary ammonium cation and the central oxycyclobutenolate ring of the chromophore. Some of our newly synthesized symmetric and asymmetric compounds display increased molar absorptivity, quantum yield in serum, and thermal/photochemical stability over previously reported squaraine-based dyes. Consequently, both classes show great promise in resurfacing the normal environment-labile squaraine dyes as novel imaging agents and scaffolds for fluorescence sensing. Furthermore, incorporating a covalent attachment point away from the conjugated system allows for biological tagging applications without disturbing the optimum optical characteristics of the newly designed fluorophore.

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The semiconductor/dielectric interface is arguably the most important region in field-effect transistors. This article investigates the performance-enhancing effects of passivation of the dielectric surface by a self-assembled layer (SAM) of silanes on organic field-effect transistors. Apart from conventional figures of merit for the devices, the energetic distribution of the density of the in-gap trap-states (trap-DOS) and the contact resistance are evaluated using numerical methods. The investigation reveals that the surface passivation of the dielectric SiO2 has a dual effect on device operation. Firstly, it establishes quantitatively that the surface passivation leads to a significant reduction in the density of both shallow and deep traps in the organic semiconductor PBTTT-C14. This effect outweighs the impact of the SAM dipoles on the device turn-on. Secondly, the contact resistance gets lowered by a factor of more than 10 due to the improved top-surface morphology of the PBTTT-C14 thin film. The lower contact resistance in devices is corroborated by lower contact potential difference between PBTTT-C14 and gold, measured using scanning kelvin probe microscopy.

Noscapine, an opium-derived ‘kinder-gentler’ microtubule-modulating drug is in Phase I/II clinical trials for cancer chemotherapy. However, its limited water solubility encumbers its development into an oral anticancer drug with clinical promise. Here we report the synthesis of 9 third-generation, water-soluble noscapine analogs with negatively charged sulfonato and positively charged quaternary ammonium groups using noscapine, 9-bromonoscapine and 9-aminonoscapine as scaffolds. The predictive free energy of solvation was found to be lower for sulfonates (6a–c;8a–c) compared to the quaternary ammonium-substituted counterparts, explaining their higher water solubility. In addition, sulfonates showed higher charge dispersability, which may effectively shield the hydrophobicity of isoquinoline nucleus as indicated by hydrophobicity mapping methods. These in silico data underscore efficient net charge balancing, which may explain higher water solubility and thus enhanced antiproliferative efficacy and improved bioavailability. We observed that 6b, 8b and 8c strongly inhibited tubulin polymerization and demonstrated significant antiproliferative activity against four cancer cell lines compared to noscapine. Molecular simulation and docking studies of tubulin-drug complexes revealed that the brominated compound with a four-carbon chain (4b, 6b, 8b) showed optimal binding with tubulin heterodimers. Interestingly, 6b, 8b and 8c treated PC-3 cells resulted in preponderance of mitotic cells with multipolar spindle morphology, suggesting that they stall the cell cycle. Furthermore, in vivo pharmacokinetic evaluation of 6b, 8b and 8c revealed at least 1–2 fold improvement in their bioavailability compared to noscapine. To our knowledge, this is the first report to demonstrate novel water-soluble noscapine analogs that may pave the way for future pre-clinical drug development.