Nano-confined squaraine dye assemblies: new photoacoustic and near-infrared fluorescence dual-modular imaging probes in vivo.

For the purpose of near-infrared (NIR) fluorescence and photoacoustic (PA) tomography dual-modular imaging, self-assembly of squaraine (SQ) dyes is constructed in the hydrophobic phospholipid bilayers of liposomes (SQ⊂L) with variable mixing ratios of SQ and phospholipids from 1:500 to 1:10 (w/w). When doping minimal amounts of SQ, molecularly dispersed SQ in bilayers shows remarkable fluorescence. Interesting, the PA signal is enhanced with increase of SQ in the nanoconfined bilayer region, which is attributed to the formation of SQ-based H-aggregates and enhanced thermal conversion efficiency (η). SQ⊂L shows satisfactory chemical and thermal stabilities and photobleaching resistance. SQ⊂L is well-distributed in the cytoplasm of MCF-7 cells and its fluorescence signal remains for 7 days without dramatic quenching owing to the good stability of SQ⊂L. Furthermore, SQ⊂L is subjected to in vivo NIR fluorescence imaging to evaluate the whole-body biodistribution in organ level. Particularly, PA imaging with deeper tissue penetration capability is utilized to investigate the heterogeneous distribution SQ⊂L inside solid tumor. The majority of SQ⊂L are enriched in the area where the blood vessels are generated, implying that the liposomal nanocarriers exhibit lower tumor tissue penetration capability after the vascular leakage. This result is validated by histological examination of tumor tissue in parallel.

Synthesis and molecular properties of acceptor-substituted squaraine dyes.

A broad series of more than 20 acceptor-substituted squaraines was synthesized that feature different acceptor functionalities at the central squaraine four-membered ring. The influence of these acceptor units on the reactivity of semisquaraine precursors and stability of the respective squaraines were explored. Thereby the dicyanovinyl group was found to be the most versatile acceptor group that enabled various modifications at the donor moiety of the squaraine scaffold, leading to an extended series of dicyanovinyl-functionalized squaraines. The variation of donor units afforded a set of NIR fluorophores that cover a wavelength region from the visible at about 650 nm far into the NIR up to 920 nm with fluorescence quantum yields between 0.93 and 0.11 and outstanding optical brightness. This excellent optical property is related to a rigid molecular scaffold that is fixed in an all-cis configuration by the additional dicyanovinyl acceptor unit. The change of the molecular symmetry from C(2h) to C(2v) upon functionalization of the squaraine core with dicyanovinyl acceptor group has been confirmed in solution by electro-optical absorption (EOA) spectroscopy, revealing permanent ground-state dipole moments µ(g) in the range between 4.3 and 6.4 D. These dipole moments direct an antiparallel packing of the molecules in the solid state according to single-crystal X-ray analyses achieved for four dicyanovinyl-functionalized squaraines. The structural properties, the EOA results, as well as the band shapes of the optical spectra indicate that these polymethine dyes are cyanine-type chromophores. It is worth noting that the orientation of the dipole moment vectors is orthogonal to the orientation of the transition dipole moment vectors, which is an uncommon but characteristic feature of this rather novel class of polymethine dyes. With regard to applications of these dyes in organic solar cells, their redox properties were also studied by cyclic voltammetry.

Aggregation-dependent photovoltaic properties of squaraine/PC61BM bulk heterojunctions.

In this study, we investigated bulk-heterojunction solar cells composed of PC(61)BM and squaraine dyes with different donor subunits. Both, H- and J-aggregates, have been observed for the squaraine dyes in the mixture, even for the same dye depending on the annealing conditions of the blends. Supramolecular organization of the squaraine dyes noticeably affects solar cell performance. The J-aggregate exhibits a red-shift of the absorption maximum that results in a significant increase in the short-circuit current and decrease in the open-circuit voltage compared to the as-cast device. The H-aggregate shows a blue-shift in the absorption maximum and concomitantly only a moderate increase in the short-circuit current as well as an increase in the open-circuit voltage. The course of domain growth during annealing was monitored by local photocurrent mapping.

Copper-Free Alternatives to Access Ketone Building Blocks from Grignard Reagents.

Grignard reactions are an efficient way to form carbon-carbon bonds with widespread applications in large-scale processes. Classically, the electrophiles of choice to form ketones from Grignard reagents are acid chlorides. The reactions are typically catalyzed by additives such as CuCl to increase selectivity and yields. This work was focused on the use of acetic anhydride as an alternative to acetic chloride in the synthesis of 4-fluoro-2-(trifluoromethyl)acetophenone (3), a useful intermediate for the synthesis of active agricultural ingredients. The use of acetic anhydride as an electrophile not only equals but also surpasses acetic chloride in yield and selectivity, while also being more tolerable toward higher reaction temperatures. Furthermore, the reaction was performed in the absence of any additive, making it a highly attractive process for large-scale production. Computational mechanistic studies suggest that this advantageous behavior can be ascribed to the superior complexation of carboxylic acid anhydrides in the transition state.

Supramolecular adducts of squaraine and protein for noninvasive tumor imaging and photothermal therapy in vivo.

Extensive efforts have been devoted to the development of near-infrared (NIR) dye-based imaging probes and/or photothermal agents for cancer theranostics in vivo. However, the intrinsic chemical instability and self-aggregation properties of NIR dyes in physiological condition limit their widely applications in the pre-clinic study in living animals. Squaraine dyes are among the most promising NIR fluorophores with high absorption coefficiencies, bright fluorescence and photostability. By introducing dicyanovinyl groups into conventional squaraine (SQ) skeleton. These acceptor-substituted SQ dyes not only show superior NIR fluorescence properties (longer wavelength, higher quantum yield) but also exhibit more chemical robustness. In this work, we demonstrated highly stable and biocompatible supramolecular adducts of SQ and the natural carrier protein, i.e., bovine serum albumin (BSA) (SQ⊂BSA) for tumor targeted imaging and photothermal therapy in vivo. SQ was selectively bound to BSA hydrophobic domain via hydrophobic and hydrogen bonding interactions with up to 80-fold enhanced fluorescence intensity. By covalently conjugating target ligands to BSA, the SQ⊂BSA was capable of targeting tumor sites and allowed for monitoring the time-dependent biodistribution of SQ⊂BSA, which consequently determined the protocol of photothermal therapy in vivo. We envision that this supramolecular strategy for selectively binding functional imaging agents and/or drugs into human serum albumin might potentially utilize in the preclinical and even clinic studies in the future.