Cationic BODIPY Photosensitizers for Mitochondrion-Targeted Fluorescence Cell-Imaging and Photodynamic Therapy.

The straightforward synthesis of three cationic boron-dipyrromethene (BODIPY) derivatives and their mitochondria-targeting and photodynamic therapeutic (PDT) capabilities are reported. Two cancer cell lines (HeLa and MCF-7) were used to investigate the PDT activity of the dyes. Compared to their non-halogenated counterparts, halogenated BODIPY dyes exhibit lower fluorescence quantum yields and enable the efficient production of singlet oxygen species. Following LED light irradiation at 520 nm, the synthesized dyes displayed good PDT capabilities against the treated cancer cell lines, with low cytotoxicity in the dark. In addition, functionalization of the BODIPY backbone with a cationic ammonium moiety enhanced the hydrophilicity of the synthesized dyes and, consequently, their uptake by the cells. The results presented here collectively demonstrate the potential of cationic BODIPY-based dyes as therapeutic drugs for anticancer photodynamic therapy.

Water-soluble polyglycerol-dendronized poly(norbornene)s with functional side-chains.

High molecular weight polyglycerol-dendronized poly(norbornene)s (PGD-PNBs) were prepared via ring-opening metathesis polymerization of norbornene monomers containing amine functional groups on the side-chains followed by dendron growth from the olefins of PNB backbones using iterative dihydroxylation and allylation. The fourth-generation PGD-PNB with a degree of polymerization of ca. 500 is thus functionalized with 16 peripheral hydroxyl groups as well as a single amine on each repeat unit of the PNB backbone. Furthermore, the amine functionality could be used to install hydrophobic fluorophores such as coumarin and pyrene, thereby obtaining the final PGD-PNB structures which are highly water-soluble and fluorescent.

Raman spectrum identification based on the correlation score using the weighted segmental hit quality index.

In this paper, we consider a novel method for identification of Raman spectra recorded on different instruments with different wavelengths. Since the conventional hit quality index (HQI) is vulnerable to intensity variation, it needs intensity calibration or standardization for each spectrometer, which causes additional time consuming work. To simplify this process and enhance the identification performance, we propose a new scoring method which is defined as the weighted sum of the HQIs from segmented spectra by windowing. To show the effectiveness of the proposed method, the experiments were carried out with 10 kinds of chemicals with their spectra recorded on 3 different instruments with different laser wavelengths. According to the identification results with 14 033 chemicals, the proposed method identified all test chemicals without error, which indicates that the proposed method could be used as a promising alternative to the existing methods.

Water-Soluble Polyglycerol Dendrimers with Two Orthogonally Reactive Core Functional Groups for One-Pot Functionalization.

The synthesis of a water-soluble polyglycerol dendrimer with two orthogonal functional groups at the core is reported. The two groups, an azide and amine group, are highly reactive towards alkyne and activated ester moieties, respectively. The orthogonality of the two chemical reactions is demonstrated by the ability to conjugate quantitatively either group, independent of the other and in either order. The orthogonal functionalization of the azide- and amine-cored dendrimer can be accomplished in a stepwise or a one-pot synthetic protocol. All resulting bifunctional dendrimers are fully soluble in water as the water-soluble dendritic scaffold decorated with 48 hydroxyl groups on the surface successfully solubilizes both the hydrophobic fluorophore and targeting group.

Patchy particle self-assembly via metal coordination.

Colloids with high-symmetry patches are functionalized with metal-coordination-based recognition units and assembled into larger chain architectures, demonstrating for the first time the use of metal coordination as a specific force in colloidal self-assembly. The cross-linked poly(styrene)-based patchy particles are fabricated by encapsulation of colloidal clusters following a two-stage swelling and polymerization methodology. The particle patches, containing carboxylic acid groups, are site-specifically functionalized either with a triblock copolymer (TBC), bearing primary alcohols, alkyl chains, and palladated pincer receptors, synthesized by ring-opening metathesis polymerization, or with a small molecule bearing a pyridine headgroup. Functionalizing with a TBC provides design flexibility for independently setting the range of the interaction and the recognition motif.

A dendritic single-molecule fluorescent probe that is monovalent, photostable and minimally blinking.

Single-molecule fluorescence techniques have emerged as a powerful approach to understanding complex biological systems. However, a challenge researchers still face is the limited photostability of nearly all organic fluorophores, including the cyanine and Alexa dyes. We report a new, monovalent probe that emits in the far-red region of the visible spectrum with properties desirable for single-molecule optical imaging. This probe is based on a ring-fused boron-dipyrromethene (BODIPY) core that is conjugated to a polyglycerol dendrimer (PGD). The dendrimer makes the hydrophobic fluorophore water-soluble. This probe exhibits excellent brightness, with an emission maximum of 705 nm. We have observed strikingly long and stable emission from individual PGD-BODIPY probes, even in the absence of anti-fading agents such as Trolox, a combined oxidizing-reducing agent often used in single-molecule studies for improving the photostability of common imaging probes. These interesting properties greatly simplify use of the fluorophore.

Polyglycerol-Dendronized Perylenediimides as Stable, Water-Soluble Fluorophores.

The synthesis and photophysical properties of water-soluble, fluorescent polyglycerol-dendronized perylenediimides 1-4 are reported. The polyglycerol dendrons, which are known to be highly biocompatible, are found to confer high water-solubility on the perylenediimide in aqueous media while retaining its excellent fluorescent properties. Furthermore, intramolecular cross-linking of the polyglycerol dendrons using the ring-closing metathesis reaction not only enhances the photostability but also reduces the size of perylenediimide-cored dendrimers. The permeability of the various dendritic shells is probed using heavy metal ion quenchers and compared to non-dendritic but water-soluble perylenediimide 5.

Monovalent, clickable, uncharged, water-soluble perylenediimide-cored dendrimers for target-specific fluorescent biolabeling.

Herein we report the synthesis of water-soluble polyglycerol-dendronized perylenediimides with a single reactive group that undergoes high-yielding click reactions. Single-molecule studies and target-specific biolabeling are reported, including the highly specific labeling of proteins on the surface of living bacterial and mammalian cells.

Main-chain supramolecular block copolymers.

Block copolymers are key building blocks for a variety of applications ranging from electronic devices to drug delivery. The material properties of block copolymers can be tuned and potentially improved by introducing noncovalent interactions in place of covalent linkages between polymeric blocks resulting in the formation of supramolecular block copolymers. Such materials combine the microphase separation behavior inherent to block copolymers with the responsiveness of supramolecular materials thereby affording dynamic and reversible materials. This tutorial review covers recent advances in main-chain supramolecular block copolymers and describes the design principles, synthetic approaches, advantages, and potential applications.

Supramolecular ABC triblock copolymers via one-pot, orthogonal self-assembly.

A heterotelechelic poly(norbornene imide) containing two terminal and orthogonal hydrogen-bonding receptors, N,N'-bis[6-(alkanoylamino)pyridin-2-yl] isophthalamide (often referred to as the Hamilton receptor or Wedge) and 2,7-diamido-1,8-naphthyridine (DAN), at the opposite ends of the polymer was synthesized via ring-opening metathesis polymerization (ROMP) through the employment of a Hamilton receptor-functionalized ruthenium initiator and a DAN-based chain-terminator. In parallel, two monotelechelic polymers containing either cyanuric acid (CA)- or ureidoguanosine (UG)-end groups that are complementary to the hydrogen-bonding receptors along the poly(norbornene imide) were synthesized either also via ROMP by terminating the polymerization of norbornene octyl ester with a CA-based chain-terminator or by the reaction of poly(ethylene oxide) with UG. Complete incorporations of the hydrogen-bonding receptors at the chain-ends of all polymers were confirmed by (1)H NMR spectroscopy. The telechelic polymers can be self-assembled into ABC triblock copolymers following either a stepwise or a one-pot, orthogonal self-assembly protocol. The self-assembly process was monitored by (1)H NMR spectroscopy, revealing full orthogonality of the two recognition pairs, Hamilton receptor-CA and DAN-UG. The resulting supramolecular ABC triblock copolymers were further characterized by a series of methods including 2-D NOESY, isothermal titration calorimetry, and viscometry, proving that the two orthogonal hydrogen-bonding interactions are strong enough to hold the three polymer chains together. We suggest that a self-assembly methodology solely based on the fully orthogonal hydrogen-bonding recognition motifs will allow for an easy and rapid synthesis of architecturally controlled supramolecular polymeric assemblies with a high degree of complexity.

Supramolecular alternating block copolymers via metal coordination.

A bimetallic ruthenium olefin metathesis initiator was synthesized and used to polymerize functionalized norbornenes, affording polymers that are living at both polymer chain-ends. Using this bis-ruthenium initiator strategy and combining it with functional chain-terminators, highly-efficient syntheses of either SCS-Pd(II) pincer- or pyridine-functionalized symmetrical telechelic polymers were developed. The terminal functional group incorporation was confirmed by 1H NMR spectroscopy analyses. The telechelic polymers were self-assembled into block copolymers by means of metal coordination between corresponding terminal recognition units. The self-assembly process was monitored by 1H NMR spectroscopy revealing nearly quantitative functionalization. The resulting supramolecular block copolymers were further characterized by viscometry and dynamic light scattering.

Supramolecular ABC triblock copolymers.

Just add it! Ruthenium initiators functionalized with hydrogen-bonding sites were utilized in ring-opening metathesis polymerization to prepare heterotelechelic polymers with hydrogen-bonding and metal-coordination units in a single step. Supramolecular ABC triblock copolymers were then self-assembled in one pot by simply adding complementary telechelic polymers to a solution of the heterotelechelic polymer (see picture).

Bis-1,4-(p-diarylaminostryl)-2,5-dicyanobenzene derivatives with large two-photon absorption cross-sections.

Synthesis and physical properties of novel multibranched two-photon materials are reported. The compound with three units of 4-(p-diphenylaminostyryl)-2,5-dicyanostyryl moieties attached to the central triphenylamine core exhibits a very large two-photon absorption cross-section.