A novel photosensitizer based on hypocrellin B activated by cysteine over-expressed in cancer cells.

L-Cysteine (Cys)-activatable photosensitizer 3 was designed and synthesized based on hypocrellin B (1). Cys is a novel tumor-associated biomarker. 3 exhibited negligible photosensitizing ability without Cys. However, when 1 was released from 3 by reaction with Cys, the photosensitizing activity was restored. Furthermore, 3 showed selective and effective photo-cytotoxicity against only cancer cells such as HeLa and A549 cells that highly express Cys when irradiated with 660 nm light, which is inside the phototherapeutic window.

Diesters of monoimide of perylene-3,4,9,10-tetracarboxylic acid - Synthesis, characterization, and application for dyeing polyester fibre, polystyrene, and poly (methyl methacrylate) films.

Three dyes-diesters of monoimides of perylene-3,4,9,10-tetracarboxylic acid were synthesized in three-stage process: esterification, hydrolysis, and monoimidation as potential fluorescent light-stable colorants for high visibility safety wear. The structure of these compounds was confirmed by 1H nuclear magnetic resonance spectroscopy and mass spectrometry, and their spectroscopic and physicochemical properties were determined. Colorants were applied to dyeing polyester fibre and polystyrene and poly (methyl methacrylate) films. The light, wash, and rubbing fastness of the dyeings were determined, and chromaticity coordinates were measured and discussed.

Influence of core extension and side chain nature in targeting G-quadruplex structures with perylene monoimide derivatives.

A structure-activity relationship (SAR) study in terms of G-quadruplex binding ability and antiproliferative activity of six fluorescent perylenemonoimide (PMIs) derivatives is reported. A positive charge seems to be the key to target G4. This study also reveals the importance of the element substitution in the potential biological activity of PMIs, being the polyethylene glycol (PEG) chains in the peri position responsible for their antiproliferative activity. Among them, the cationic PMI6 with two PEG chains is the most promising compound since its fluorescence is enhanced in the presence of G-quadruplex structures. Moreover, PMI6 binds to the human telomeric G-quadruplex hTelo with high affinity and displays a high antiproliferative potential towards HeLa (cervical adenocarcinoma), A549 (lung adenocarcinoma) and A2780 (ovarian adenocarcinoma) cells. Its fate can be followed inside cells thanks to its fluorescent properties: the compound is found to accumulate in the mitochondria.

Construction of Function-Oriented Core-Shell Nanostructures in Hydrogen-Bonded Organic Frameworks for Near-Infrared-Responsive Bacterial Inhibition.

Exploration of effective ways to integrate various functional species into hydrogen-bonded organic frameworks (HOFs) is critically important for their applications but highly challenging. In this study, according to the "bottle-around-ship" strategy, core-shell heterostructure of upconversion nanoparticles (UCNPs) and HOFs was fabricated for the first time via a ligand-grafting stepwise method. The UCNPs "core" can effectively upconvert near-infrared (NIR) irradiation (980 nm) into visible light (540 nm and 653 nm), which further excites the perylenediimide-based HOF "shell" through resonance energy transfer. In this way, the nanocomposite inherits the high porosity, excellent photothermal and photodynamic efficiency, NIR photoresponse from two parent materials, achieving intriguing NIR-responsive bacterial inhibition toward Escherichia coli. This study may shed light on the design of functional HOF-based composite materials, not only enriching the HOF library but also broadening the horizon of their potential applications.

Near-IR oxime-based solvatochromic perylene diimide probe as a chemosensor for Pd species and Cu2+ ions in water and live cells.

A near-IR perylene diimide probe (OPR-PDI) containing an oxime-propargyl hybrid moiety at the bay position, was designed and synthesized for detection of Pd species and Cu2+ ions in 90% water, the solid state and MG-63 live cells. The aggregation tendency of OPR-PDI in different polarity solvents transmits solvatochromic and fluorochromic properties to differentiate certain organic solvents. Supramolecular aggregates of OPR-PDI in 90% water act as a dual chemosensor for palladium (Pd) species via de-propargylation or hydrolysis of the Schiff-base and Cu2+ ions via complexation with the O/N binding site with a low limit of detection (LOD) of the order of 7.9 × 10-8 M and 3.4 × 10-7 M respectively. TLC strips coated with OPR-PDI can be applied for sensing of Pd0 and Cu2+ ions in the solid state at levels as low as 34.6 ng cm-2 and 10.5 ng cm-2. OPR-PDI imprinted TLC strips could be used as paper sheets for writing coloured alphabets using Pd0 and Cu2+ ions as ink. Moreover, MTT assay showed that OPR-PDI has very low cytotoxicity (IC50 = 230 µM), good permeability, biocompatibility and can be applied for bio-imaging of Pd species and Cu2+ ions in MG-63 cells. DFT calculations, and cyclic voltammetric (CV) and NMR titration studies have also been discussed.

Hypericin photodynamic activity in DPPC liposomes - part II: stability and application in melanoma B16-F10 cancer cells.

Hypericin (Hyp) is considered a promising photosensitizer for Photodynamic Therapy (PDT), due to its high hydrophobicity, affinity for cell membranes, low toxicity and high photooxidation activity. In this study, Hyp photophysical properties and photodynamic activity against melanoma B16-F10 cells were optimized using DPPC liposomes (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) as a drug delivery system. This nanoparticle is used as a cell membrane biomimetic model and solubilizes hydrophobic drugs. Hyp oxygen singlet lifetime (τ) in DPPC was approximately two-fold larger than that in P-123 micelles (Pluronic™ surfactants), reflecting a more hydrophobic environment provided by the DPPC liposome. On the other hand, singlet oxygen quantum yield values (ΦΔ1O2) in DPPC and P-123 were similar; Hyp molecules were preserved as monomers. The Hyp/DPPC liposome aqueous dispersion was stable during fluorescence emission and the liposome diameter remained stable for at least five days at 30 °C. However, the liposomes collapsed after the lyophilization/rehydration process, which was resolved by adding the lyoprotectant Trehalose to the liposome dispersion before lyophilization. Cell viability of the Hyp/DPPC formulation was assessed against healthy HaCat cells and high-metastatic melanoma B16-F10 cells. Hyp incorporated into the DPPC carrier presented a higher selectivity index than the Hyp sample previously solubilized in ethanol under the illumination effect. Moreover, the IC50 was lower for Hyp in DPPC than for Hyp pre-solubilized in ethanol. These results indicate the potential of the formulation of Hyp/DPPC for future biomedical applications in PDT treatment.

Photophysical and structural aspects of perylene-doped 2-naphthol luminophors: Green emission by exciplex formation.

Several perylene (Pery)-doped 2-naphthol (2-NP) (Pery/2-NP) luminophors were prepared using conventional solid-state reaction techniques. Energy transfer in the excited state was examined using fluorescence spectroscopy and cyclic voltammetry. Fluorescence studies revealed exciplex formation by Pery in the form of structureless and broad spectra at higher concentrations with monomer quenching of 2-NP; a broad green emission was observed in the range 500-650 nm, peaking at 575 nm. Structural properties and thermal stability were analyzed using X-ray diffraction, scanning electron microscopy and TGA-differential scanning calorimetry. Highest occupied molecular orbital and lowest unoccupied molecular orbital energy levels were observed in the range 5.56-5.61 eV and 2.79-2.81 eV, respectively with a 2.77-2.82 eV band gap. The present study reveals these to be probable candidates for hole-transporting materials suitable in optoelectronics.

Self-Assembled Dual Helical Nanofibers of Amphiphilic Perylene Diimides with Oligopeptide Substitution.

We designed an asymmetric amphiphilic perylene diimide (PDI) with the oligopeptide substituting one of the imides. The self-assembly mechanism of this PDI in different solvents was investigated. Right-handed "dual" helical nanofibers/nanowires with a uniform lateral dimension of ∼8 nm are constructively self-assembled. The long-term ordered degree within the nanofibers stems from the delicate balance between π-π stacking of the PDI rings and ß-sheet-like hydrogen bond formed by the oligopeptide. The synergistic interplay between the hydrogen bond and π-π stacking rather than competition endows the nanofibers with the controllable longitudinal dimensions by different factors such as the concentration and solvents. The transition from the nanofibers to the small aggregates is also achieved by the addition of trifluoroacetic acid because of breakup of the hydrogen bonds, which is reversed by further addition of trimethylamine. The acid-base stimulation can be extended to different solvents as long as the existence of the unique hydrogen bonds.

Synthesis of unsymmetric perylenediimide dye molecule and its photochemical properties on lipid membrane.

Optical manipulation of cellular function is one of the important targets in chemical biology and medicine. To achieve manipulation of cellular function using small molecules, photochemical reaction, such as photo-isomerization and photo-induced electron transfer, is one of the most promising reactions. Especially, photo-induced electron transfer process may be the crucial for their further development of photo-functional agents in living cells. However, such molecules, which enable the modification of cellular function, are limited and the further development is necessary. Herein, we synthesized a novel unsymmetric perylenediimide dye and investigated the cellular staining upon the addition in the cell culture medium. Furthermore, we observed the fluorescence quenching upon the addition of ascorbic acid as electron donor and report the preliminary results to manipulate Ca2+ concentration in living cell line upon 488-nm light photoirradiation.

Perylene-functionalized graphene sheets modified with chitosan for voltammetric discrimination of tryptophan enantiomers.

A composite was prepared from graphene functionalized with 3,4,9,10-perylene tetracarboxylic acid and chitosan (rGO-PTCA-chitosan) by a chemical method. It involves non-covalent functionalization of rGO with PTCA followed by amidation reaction with chitosan. Scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy and electrochemical methods were used to characterize the composites. By combining the chiral features of chitosan and the excellent electrochemical behaviors of rGO-PTCA, a graphene-based material with enantioselectivity was constructed for electrochemical chiral recognition of tryptophan (Trp) enantiomers. A glassy carbon electrode (GCE) modified with rGO-PTCA-chitosan had a higher recognition capability for L-Trp than for D-Trp. Best operated at a working voltage near 0.78 V (vs. SCE), the enantioselectivity coefficient is 3.0. The sensor has a linear response in the 1 mM to 10 mM Trp concentration range and a 1.2 µM detection limit (at S/N = 3) for L-Trp, and of 3.0 µM to D-Trp. The sensor was successfully used to detect Trp enantiomers in real samples, and a recognition mechanism is presented. Graphical abstract Schematic presentation of a composoie prepared by graphene functionalized with 3,4,9,10-perylene tetracarboxylic acid and chitosan (rGO-PTCA-chitosan) via a chemical method. It involves non-covalent functionalization of rGO with PTCA followed by amidation reaction with chitosan and voltammetric determination of tryptophan enantiomers.

Rigid amphipathic fusion inhibitors demonstrate antiviral activity against African swine fever virus.

Rigid amphipathic fusion inhibitors (RAFIs) are a family of nucleoside derivatives that inhibit the infectivity of several enveloped viruses by interacting with virion envelope lipids and inhibiting fusion between viral and cellular membranes. Here we tested the antiviral activity of two RAFIs, 5-(Perylen-3-ylethynyl)-arabino-uridine (aUY11) and 5-(Perylen-3-ylethynyl)uracil-1-acetic acid (cm1UY11) against African swine fever virus (ASFV), for which no effective vaccine is available. Both compounds displayed a potent, dose-dependent inhibitory effect on ASFV infection in Vero cells. The major antiviral effect was observed when aUY11 and cm1UY11 were added at early stages of infection and maintained during the complete viral cycle. Furthermore, virucidal assay revealed a significant extracellular anti-ASFV activity for both compounds. We also found decrease in the synthesis of early and late viral proteins in Vero cells treated with cm1UY11. Finally, the inhibitory effect of aUY11 and cm1UY11 on ASFV infection in porcine alveolar macrophages was confirmed. Overall, our study has identified novel anti-ASFV compounds with potential for future therapeutic developments.

Synthesis and Self-Assembly of Bay-Substituted Perylene Diimide Gemini-Type Surfactants as Off-On Fluorescent Probes for Lipid Bilayers.

Interest in bay-substituted perylene-3,4:9,10-tetracarboxylic diimides (PDIs) for solution-based applications is growing due to their improved solubility and altered optical and electronic properties compared to unsubstituted PDIs. Synthetic routes to 1,12-bay-substituted PDIs have been very demanding due to issues with steric hindrance and poor regioselectivity. Here we report a simple one-step regioselective and high yielding synthesis of a 1,12-dihydroxylated PDI derivative that can subsequently be alkylated in a straightforward fashion to produce nonplanar 1,12-dialkoxy PDIs. These PDIs show a large Stokes shift, which is specifically useful for bioimaging applications. A particular cationic PDI gemini-type surfactant has been developed that forms nonfluorescent self-assembled particles in water ("off state"), which exerts a high fluorescence upon incorporation into lipophilic bilayers ("on state"). Therefore, this probe is appealing as a highly sensitive fluorescent labelling marker with a low background signal for imaging artificial and cellular membranes.

Fishing for G-Quadruplexes in Solution with a Perylene Diimide Derivative Labeled with Biotins.

A new fluorescent, non-cytotoxic perylene diimide derivative with two biotins at the peri position, PDI2B, has been synthesized. This molecule is able to interact selectively with G-quadruplexes with scarce or no affinity towards single- or double-stranded DNA. These features have made it possible to design a simple, effective, safe, cheap, and selective method for fishing G-quadruplex structures in solution by use of PDI2B and streptavidin coated magnetic beads. The new cyclic method reported leads to the recovery of more than 80 % of G-quadruplex structures from solution, even in the presence of an excess of single-stranded or duplex DNA as competitors. Moreover, PDI2B is a G4 ligand that can display higher thermal stabilization and greater affinity for 2- over 3-tetrad quadruplexes, which constitutes a novel type of behavior.

Fluorine-Containing Dibenzoanthracene and Benzoperylene-Type Polycyclic Aromatic Hydrocarbons: Synthesis, Structure, and Basic Chemical Properties.

Intramolecular photocyclization of stilbene derivatives (Mallory reaction) is one of the efficient methods for building polycyclic aromatic hydrocarbon (PAH) frameworks, and is also expected to be applicable to synthesis of fluorine-containing PAHs (F-PAHs). In this study, dibenzoanthracene-type (4a) and benzoperylene-type (4b) F-PAHs were synthesized using the Mallory reaction of the 1,4-distyrylbenzene-type π-conjugated molecule (3a), which was prepared by addition-defluorination of available octafluorocyclopentene (OFCP) and aryllithium in three steps. The structure of 4a originating from π⁻π interaction was characterized by X-ray crystallographic analysis. The absorption maxima of UV-Vis spectra and emission maxima of photoluminescence spectra of the PAHs were positioned at a longer wavelength compared to those of the corresponding unsubstituted PAHs, presumably due to the electron-withdrawing nature of perfluorocyclopentene (PFCP) units. The effect of PFCP units in F-PAHs was also studied by time-dependent density functional theory (TD-DFT) calculation.

Multichromophoric Perylenediimide-Silicon Phthalocyanine-C60 System as an Artificial Photosynthetic Analogue.

Sequential photoinduced energy transfer followed by electron transfer and the formation of charge-separated states, which are primary events of natural photosynthesis, have been demonstrated in a newly synthesized multichromophoric covalently linked triad, PDI-SiPc-C60 . The triad comprises a perylenediimide (PDI), which primarily fulfils antenna and electron-acceptor functionalities, silicon phthalocyanine (SiPc) as an electron donor, and fulleropyrrolidine (C60 ) as a second electron acceptor. The multi-step convergent synthetic procedure developed here produced good yields of the triad and control dyads, PDI-SiPc and SiPc-C60 . The structures and geometries of the newly synthesized donor-acceptor systems have been established from spectral, computational, and electrochemical studies with reference to appropriate control compounds. Ultrafast energy transfer from 1 PDI* to SiPc in the case of PDI-SiPc and PDI-SiPc-C60 was witnessed. An energy-level diagram established from spectral and electrochemical data suggested the formation of two types of charge-separated states, that is, PDI-SiPc.+ -C60.- and PDI.- -SiPc.+ -C60 from the 1 SiPc* in the triad, with generation of the latter being energetically more favorable. However, photochemical studies involving femtosecond transient spectroscopy revealed the formation of PDI-SiPc.+ -C60.- as a major charge-separated product. This observation may be rationalized in terms of the closer spatial proximity to SiPc of C60 compared to PDI in the triad. The charge-separated state persisted for a few nanoseconds prior to populating the 3 SiPc* state during charge recombination.

Self-assembly, optical, thermal and electrochemical properties of bis-N-benzyl perylene diimide dye.

Flexible methylene containing N,N'-bis-(benzyl)-3,4,9,10-perylenebis(dicarboximide) (1) was synthesized. Self-assembled microstructures (hollow tubes, average length and width: 7.7 and 0.8 µm) of 1 were also prepared (T-1). Comparative studies of the optical, thermal and electrochemical properties of 1 and T-1 have been extensively carried out. The T-1 hallow tubes have shown extremely broad absorption in the near-infrared (300-800 nm) region (NIR) even in solution and intensified conductivity in the solid-state compared to 1. Under daylight and a UV lamp (365 nm), the emission colors of 1 are uniform pink and fluorescent yellow, respectively. Under the same conditions the colors of T-1 change to deep brown and glowing red, respectively. Two different isopotential points obtained through CV scans for 1 indicate the presence of two interconvertible chromophores within the system. The results clearly indicate that the anodic and cathodic processes are extremely intensified in the self-assembled T-1 structure.

Perylenediimide-based glycoclusters as high affinity ligands of bacterial lectins: synthesis, binding studies and anti-adhesive properties.

The synthesis of eight perylenediimide-based glycoclusters was readily performed from hexa- and tetra-propargylated cores through azide-alkyne "click" conjugation. Variations in the carbohydrate epitope (Glc, Gal, Man, Fuc) and the linker arm provided molecular diversity. Interactions with LecA and LecB, two proteins involved in the adhesion of Pseudomonas aeruginosa to host tissues, were evaluated by microcalorimetry (ITC). In both cases high affinities were obtained with Kd values in the nanomolar range. Further evaluation of their anti-adhesive properties using cultured epithelial cells demonstrated their potent anti-adhesive activities against Pseudomonas aeruginosa with only 30-40% residual adhesion observed. The fluorescence properties of the PDI core were then investigated by confocal microscopy on cell-bacteria cultures. However, the red fluorescence signal of the PDI-based glycocluster was too weak to provide significant data. The present study provides another type of anti-adhesive glycocluster against bacterial infection with a large aromatic PDI core.

Electronic Interactions of n-Doped Perylene Diimide Groups Appended to Polynorbornene Chains: Implications for Electron Transport in Organic Electronics.

A polymer consisting of a polynorbornene backbone with perylene diimide (PDI) pendant groups on each monomeric unit is synthesized via ring opening metathesis polymerization. The PDI pendant groups along the polymer backbone, studied by UV-vis absorption, fluorescence emission, and electron paramagnetic resonance spectroscopy in addition to electrochemical methods, show evidence of molecular aggregation and corresponding electronic coupling with neighboring groups, which forms pathways for efficient electron transport from one group to another in a specific reduced form. When n-doped, the title polymer shows redox conductivity of 5.4 × 10-3 S cm-1 , comparable with crystalline PDI materials, and is therefore a promising material for use in organic electronics.

Supramolecular Radical Anions Triggered by Bacteria In†Situ for Selective Photothermal Therapy.

A supramolecular complex that can be selectively reduced to radical anions in situ by facultative anaerobic bacteria is reported. To this end, a water-soluble bifunctional monomer bearing perylene diimide was synthesized, and its supramolecular complex with cucurbit[7]uril was fabricated on the basis of host-guest complexation, which could be reduced to forming radical anions in the presence of E. coli. It was found that this supramolecular complex could display different ability of generating radical anions by facultative anaerobic and aerobic bacteria in terms of their various reductive abilities. The selective antibacterial activity of the supramolecular complex could be realized by the photothermal performance of the radical anions under near-infrared irradiation. It is anticipated that this method may lead to a novel bacteria-responsive photothermal therapy to regulate balance of bacterial flora.

DNA-Templated Synthesis of Perylenediimide Stacks Utilizing Abasic Sites as Binding Pockets and Reactive Sites.

DNA is considered to be a promising biomolecule as a template and scaffold for arranging and organizing functional molecules on the nanoscale. The construction and evaluation of DNAs containing multiple functional molecules that are useful for optoelectronic devices and sensors has been studied. In this paper we report the efficient incorporation of perylenediimide (PDI) units into DNA by using abasic sites both as binding sites and as reactive sites and the construction of PDI stacks within the DNA structure, accomplished through the preorganization of the PDI units in the hydrophobic pocket within the DNA. Our approach could become a valuable method for construction of DNA/chromophore hybrid structures potentially useful for the design of DNA-based devices and biosensors.