Photosensitizer Unit Research Articles

Thrombin-sensitive dual fluorescence imaging and therapeutic agent for detection and treatment of synovial inflammation in murine rheumatoid arthritis

We have developed a thrombin-sensitive polymeric photosensitizer prodrug (T-PS) to selectively image and eradicate inflammatory lesions in rheumatoid arthritis (RA). Thrombin is a serine protease up-regulated in synovial tissues of rheumatoid arthritis (RA) patients. T-PS consists of a polymeric backbone, to which multiple photosensitizer (PS) units are tethered via short thrombin-cleavable peptide linkers.Fluorescence emission and phototoxicity of the prodrug are efficiently quenched due to the interaction of neighboring photosensitizer units. The prodrug is passively delivered to the inflammation site via the enhanced permeability and retention (EPR) effect. Subsequent site-selective proteolytic cleavage of the peptide linkers restores its photoactivity by increasing the mutual distance between PS.Whole animal imaging in murine collagen-induced arthritis, an experimental model of RA revealed a dose-dependent fluorescence increase in arthritic paws after systemic prodrug injection. In addition, administration of T-PS resulted in much higher fluorescence selectivity for arthritic joints as compared to the free PS. Irradiation of the arthritic joints induced light dose dependent phototoxic effects such as apoptosis, vascular damage and local hemorrhage. Long-term observations showed complete regression of the latter. Irradiated non-arthritic tissues or non-irradiated arthritic tissues showed no histological effects after photodynamic therapy with T-PS.This illustrates that T-PS can localize inflammatory lesions with excellent selectivity and induce apoptosis and vascular shut down after irradiation.

Photocatalytic CO 2 reduction with high turnover frequency and selectivity of formic acid formation using Ru(II) multinuclear complexes

Previously undescribed supramolecules constructed with various ratios of two kinds of Ru(II) complexes-a photosensitizer and a catalyst-were synthesized. These complexes can photocatalyze the reduction of CO(2) to formic acid with high selectivity and durability using a wide range of wavelengths of visible light and NADH model compounds as electron donors in a mixed solution of dimethylformamide-triethanolamine. Using a higher ratio of the photosensitizer unit to the catalyst unit led to a higher yield of formic acid. In particular, of the reported photocatalysts, a trinuclear complex with two photosensitizer units and one catalyst unit photocatalyzed CO(2) reduction (Φ(HCOOH) = 0.061, TON(HCOOH) = 671) with the fastest reaction rate (TOF(HCOOH) = 11.6 min(-1)). On the other hand, photocatalyses of a mixed system containing two kinds of model mononuclear Ru(II) complexes, and supramolecules with a higher ratio of the catalyst unit were much less efficient, and black oligomers and polymers were produced from the Ru complexes during photocatalytic reactions, which reduced the yield of formic acid. The photocatalytic formation of formic acid using the supramolecules described herein proceeds via two sequential processes: the photochemical reduction of the photosensitizer unit by NADH model compounds and intramolecular electron transfer to the catalyst unit.

Highly Activatable and Environment-Insensitive Optical Highlighters for Selective Spatiotemporal Imaging of Target Proteins

Optical highlighters are photoactivatable fluorescent molecules that exhibit pronounced changes in their spectral properties in response to irradiation with light of a specific wavelength and intensity. Here, we present a novel design strategy for a new class of caged BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) fluorophores, based on the use of photoremovable protecting groups (PRPGs) with high reduction potentials that serve as both a photosensitive unit and a fluorescence quencher via photoinduced electron transfer (PeT). 2,6-Dinitrobenzyl (DNB)-caged BODIPY was efficiently photoactivated, with activation ratios exceeding 600-fold in aqueous solutions. We then combined this photoactivatable fluorophore with a SNAP (mutant of O(6)-alkylguanine DNA alkyltransferase) ligand to obtain a small-molecule-based optical highlighter for visualization of protein dynamics, using the well-established SNAP tag technology. As proof of concept, we demonstrate spatiotemporal imaging of the fusion protein of epidermal growth factor receptor (EGFR) with SNAP tag in living cells. We also demonstrate highlighting of cells of interest in live zebrafish embryos, using the fusion protein of histone 2A with SNAP tag.

Development of highly efficient supramolecular CO2reduction photocatalysts with high turnover frequency and durability

New Ru(II)-Re(I) supramolecular photocatalysts with a rhenium(I) biscarbonyl complex as a catalyst unit were synthesized. They photocatalyzed CO2 reduction to CO using a wide-range of visible light, and their photocatalytic abilities were strongly affected by the phosphorus ligands on the Re site. Especially, Ru-Re(FPh), with two P(p-FPh)3 ligands, exhibited tremendous photocatalytic properties, i.e. TN(CO) = 207 and phi(CO) = 0.15, and, in addition, this is one of the fastest-operating photocatalysts for CO2 reduction to CO, with TF(CO) = 281 h(-1). We also clarified a balance of transferred electrons in this photocatalytic reaction and found that the two electrons necessary for CO formation were provided by two sequential reductive quenching processes of the excited Ru photosensitizer unit by the reductant BNAH.

Artificial photosynthetic reaction centers coupled to light-harvesting antennas

We analyze a theoretical model for energy and electron transfer in an artificial photosynthetic system. The photosystem consists of a molecular triad (i.e., with a donor, a photosensitive unit, and an acceptor) coupled to four accessory light-harvesting-antenna pigments. The resonant energy transfer from the antennas to the artificial reaction center (the molecular triad) is described here by the Förster mechanism. We consider two different kinds of arrangements of the accessory light-harvesting pigments around the reaction center. The first arrangement allows direct excitation transfer to the reaction center from all the surrounding pigments. The second configuration transmits energy via a cascade mechanism along a chain of light-harvesting chromophores, where only one chromophore is connected to the reaction center. We show that the artificial photosynthetic system using the cascade energy transfer absorbs photons in a broader wavelength range and converts their energy into electricity with a higher efficiency than the system based on direct couplings between all the antenna chromophores and the reaction center.

Switchable Ternary Nanoporous Supramolecular Network on Photo-Regulation

Controlled regulation of the switchable behavior of the supramolecular network is central to the potential application in the molecular scale nanodevices. In this work, it is reported that the reversible accommodation of the guest molecules in the nanoporous supramolecular network can be regulated by the UV/visible light. The nanoporous complex template of TCDB/4NN-Macrocycle(trans,trans,trans,trans) with photosensitive units is well-defined. After the UV irradiation, the template can be switched on to encapsulate coronene molecules due to the formation of a new photoisomer(trans,cis,trans,cis) and switched off to expel coronene from the inner cavities under the visible light. The photoregulated switchable multicomponent supramolecular guest-host network provides a novel strategy for fabricating the functional nanodevices at the molecular scale.

Synthesis and characterization of optically active poly(amide-imide)s containing photosensitive chalcone units in the main chain

A series of new optically active poly(amide-imide)s were synthesized by direct polycondensation reaction of 4,4′-diaminochalcone with several N-trimellitylimido-L-amino acids using a tosyl chloride (TsCl), pyridine (Py) and dimethylformamide (DMF) system as condensing agent. The resulting thermally stable poly(amide-imide)s were obtained in good to high yields and inherent viscosities ranging between 0.35 dL/g and 0.58 dL/g and were characterized with FTIR, 1H-NMR, CHN, Ultraviolet, TGA and DTG techniques.

Water electrolysis and photoelectrolysis on electrodes engineered using biological and bio-inspired molecular systems

Photoelectrocatalytic cells for water splitting should combine one or two photosensitive units with a water oxidation catalyst at the anode and a hydrogen evolution catalyst at the cathode. In this perspective article, we first show how a chemist can take the naturally occurring multi-electron catalysts for these two electro- and photochemical reactions, photosystem II and hydrogenases, as a source of inspiration for the design of original, efficient and robust molecular catalysts. The focus of this article is given to the immobilisation of these natural or bio-inspired catalysts onto conducting surfaces and the design of electrode and photoelectrode materials for hydrogen evolution/uptake and water oxidation.

Thrombin-sensitive photodynamic agents: A novel strategy for selective synovectomy in rheumatoid arthritis

Protease-sensitive macromolecular prodrugs have attracted interest for bio-responsive drug delivery to sites with up-regulated proteolytic activities such as inflammatory or cancerous lesions. Here we report the development of a novel polymeric photosensitizer prodrug (T-PS) to target thrombin, a protease up-regulated in synovial tissues of rheumatoid arthritis (RA) patients, for minimally invasive photodynamic synovectomy. In T-PS, multiple photosensitizer units are tethered to a polymeric backbone via short, thrombin-cleavable peptide linkers. Photoactivity of the prodrug is efficiently impaired due to energy transfer between neighbouring photosensitizer units. T-PS activation by exogenous and endogenous thrombin induced an increase in fluorescence emission by a factor of 16 after in vitro digestion and a selective fluorescence enhancement in arthritic lesions in vivo, in a collagen-induced arthritis mouse model. In vitro studies on primary human synoviocytes showed a phototoxic effect only after enzymatic digestion of the prodrug and light irradiation, thus demonstrating the functionality of T-PS induced PDT. The developed photosensitizer prodrugs combine the passive targeting capacity of macromolecular drug delivery systems with site-selective photosensitizer release and activation. They illuminate lesions with pathologically enhanced proteolytic activity and induce cell death, subsequent to irradiation.

Submolecular Observation of Photosensitive Macrocycles and Their Isomerization Effects on Host−Guest Network

The macrocyclic compounds consisting of photosensitive units as parts of the frame have been extensively studied to mimic photoregulated functions in nature. In this paper, controlled assembly of well-ordered arrays of photosensitive macrocyclic rectangles is demonstrated by using a host-guest molecular template. 4NN-Macrocycle molecules are observed to photoisomerize from trans-trans-trans-trans (t,t,t,t) to a range of isomers including trans-trans-trans-cis (t,t,t,c) and trans-cis-trans-cis (t,c,t,c) isomers after irradiation of UV light. The photoisomers are also observed to affect the guest-host network characteristic appreciably. In the STM observations we can distinguish three (t,t,t,t) conformational isomers, three (t,t,t,c) conformational isomers, and one (t,c,t,c) isomer, which self-assemble into different adlayers with TCDB on a HOPG surface. This study provides a facile approach to study the photoisomerization processes of the azobenzene groups and the conformational photoisomers.

Photocurrent response after enzymatic treatment of DNA duplexes immobilized on gold electrodes: electrochemical discrimination of 5-methylcytosine modification in DNA

We demonstrate a photoelectrochemical approach to the detection of the methylation status of cytosine bases in DNA. We prepared anthraquinone (AQ) photosensitizer-tethered oligodeoxynucleotide (ODN) duplexes bearing 5-methylcytosine (mC) or the corresponding cytosine (C) at a restriction site of the ODN strand immobilized on gold electrodes, and measured their photocurrent responses arising from hole transport after enzymatic digestion. Treatment with HapII or HhaI of the duplexes bearing normal C led to strand cleavage, and the photosensitizer unit was eliminated from the ODN strand immobilized on the gold electrode, exclusively reducing the photocurrent density. With a similar treatment, the duplexes bearing mC showed higher photocurrent responses arising from hole transport through the duplex. This significant difference in the photocurrent response between mC and normal C residues in DNA on the gold electrodes is potentially applicable to the detection of mC modification in DNA.

Photosensitive Polymer from Ionic Self-Assembly of Azobenzene Dye and Poly(ionic liquid) and Its Alignment Characteristic toward Liquid Crystal Molecules

A new strategy based on ionic self-assembly technology was provided for design of photosensitive material as liquid crystals (LC) alignment layer. The complex material was constructed by the coupling of poly(ionic liquid) and photosensitive unit azobenzene dye methyl orange. The structure, phase behavior and photoresponse were examined by a variety of techniques including FTIR, NMR, thermal analysis, polarized optical microscopy, X-ray diffraction, small-angle X-ray scattering, and birefringence measurements. Highly ordered lamellar nanostructure and photosensitive character were confirmed. Under the irradiation of pulsed UV laser with certain fluences, a pronounced optical anisotropic surface with the preferred direction perpendicular to the pulsed polarization or regular periodic grooves microstructure surface parallel to the pulsed polarization was obtained. The anisotropic surface of oriented molecular chain or topography was demonstrated to result in the alignment of LC by the optical transmittance plot and polarizing microscopy images of LC cells with different rotation angles.

Polymeric Photosensitizer Prodrugs for Photodynamic Therapy

A targeting strategy based on the selective enzyme-mediated activation of polymeric photosensitizer prodrugs (PPP) within pathological tissue has led to the development of agents with the dual ability to detect and treat cancer. Herein, a detailed study of a simple model system for these prodrugs is described. We prepared "first-generation" PPP by directly tethering the photosensitizer (PS) pheophorbide a to poly-(L)-lysine via epsilon amide links and observed that by increasing the number of PS on a polymer chain, energy transfer between PS units improved leading to better quenching efficiency. Fragmentation of the PPP backbone by trypsin digestion gave rise to a pronounced fluorescence increase and to more efficient generation of reactive oxygen species upon light irradiation. In vitro tests using the T-24 bladder carcinoma cell line and ex vivo experiments using mouse intestines illustrated the remarkable and selective ability of these PPP to fluoresce and induce phototoxicity upon enzymatic activation. This work elucidated the basic physicochemical parameters, such as water solubility and quenching/activation behavior, required for the future elaboration of more adaptable "second-generation" PPP, in which the PS is tethered to a proteolytically stable polymer backbone via enzyme-specific peptide linkers. This polymer architecture offers great flexibility to tailor make the PPP to target any pathological tissue known to over-express a specific enzyme.

Supramolecular Assembly of Photofunctional Dendrimers for Biomedical Nano-Devices

Recently, dendrimers are attracting much attention for their development as biomedical nano-devices. In the present paper, we introduce dendrimer photosensitizers, composed of a focal photosensitizing unit surrounded by poly(benzyl ether) dendritic wedges, for photodynamic therapy (PDT). Ionic dendritic porphyrins (DPs) formed supramolecular polyion complex (PIC) micelles through the electrostatic interaction with oppositely charged block copolymers, and showed no self-quenching effect of the focal photosensitizing unit due to the large dendritic wedges. The DP-loaded PIC micelles showed selective accumulation to the ophthalmic neovascular lesion and effective photodynamic effect. For the effective light delivery, dendrimer phthalocyanine (DPc) has also been developed and examined for its photodynamic effect.

Tailoring Protease-Sensitive Photodynamic Agents to Specific Disease-Associated Enzymes

We have developed novel polymeric photosensitizer prodrugs (PPPs) for improved photodynamic therapy. In PPPs, multiple photosensitizer units are covalently coupled to a polymeric backbone via protease-cleavable peptide linkers. These initially non-photoactive compounds become fluorescent and phototoxic after specific enzymatic cleavage of the peptide linkers and subsequent release of the photosensitizer moieties. Tethering the photosensitizer via a short and easily modified amino acid sequence to the polymeric backbone allows for the targeting of a wide variety of proteases. Model compounds, sensitive to trypsin-mediated cleavage, with different pheophorbide a-peptide loading ratios and backbone net charges were evaluated with respect to their solubility, "self-quenching" capacity of fluorescence emission, and reactive oxygen species (ROS) generation. In addition, linker sequence impaired selectivity toward enzymatic cleavage was demonstrated either by incubating PPPs with different enzymes having trypsin-like activity or by introducing a single d-arginine mutant in the peptide sequence. In vitro cell culture tests confirmed dose-dependent higher phototoxicity of enzymatically activated PPPs compared to the nonactivated conjugate after irradiation with white light. These data suggest that similar compounds adapted to disease-associated proteases can be used for selective photodynamic therapy.

Conformationally Gated Photoinduced Processes within Photosensitizer−Acceptor Dyads Based on Osmium(II) Complexes with Triarylpyridinio-Functionalized Terpyridyl Ligands: Insights from Theoretical Analysis

A theoretical analysis, based on density functional theory, has been carried out to study photoinduced processes within a recently experimentally characterized (Lainé, P. P.; Bedioui, F.; Loiseau, F.; Chiorboli, C.; Campagna, S. J. Am. Chem. Soc. 2006, http://dx.doi.org/10.1021/ja058357w.) series of Os(II) bis-tpy complexes (tpy = 2,2':6'2' '-terpyridine) functionalized by 2,4,6-triarylpyridinium groups, TP+. These dyad systems, designed to produce a charge-separated state (CSS) upon light excitation, are made up of a photosensitizer unit (P, the metal complex) and a tunable acceptor unit (A, the TP+). A full ab initio characterization of the electronic and structural properties of the lowest-lying triplet excited states, as well as of the CSS, allowed for a complete rationalization of the photoinduced processes taking place within the dyads. Among salient insights, theory allowed (i) substantiation of the inner P structural planarization as the relaxation mode of the MLCT states, (ii) confirmation of the existence of a ligand-centered triplet excited state (3LC) shown to essentially involve the nitro substituent of A (TP+-NO2) and lying very close in energy to the P-centered 3MLCT state, and (iii) a demonstration that the energy of the 3LC level is independent of intercomponent tilt angle (theta1). On this basis, the occurrence of a reversible electronic energy transfer between the 3MLCT and the 3LC states could be substantiated and shown to depend on the intramolecular conformation represented by theta1, which actually governs their electronic coupling (essentially via the degree of intercomponent conjugation). These computational issues were checked against experimental data already available and the results of a specifically undertaken photophysical study. Finally, CSS formation has been confirmed by studying the spin density patterns of reduced nitro-derivatized dyads. Taken together, these findings accurately account for the different excited-state behaviors of the dyads as a function of the level of structural restriction of their intercomponent conformation (and related amplitude for torsional fluctuations), thus providing theoretical evidence of conformationally gated photoinduced electron- and energy-transfer processes.

Liquid Crystal Photoalignment Using Soluble Photosensitive Polyimide

A novel soluble fluorinated polyimide containing a photosensitive chalcone unit in the main chain was investigated as a thermally stable photoalignment material for liquid crystals. A defect-free homogeneous alignment of liquid crystals was induced on the surface of a polymer film after exposure to linearly polarized UV light at an exposure energy of 7200 mJ/cm2. Spectroscopic analyses revealed that [2+2] cycloadditon between the chalcone moieties generated the surface anisotropy needed to induce an efficient alignment of liquid crystals.

Photoinduced Alignment Behavior of Poly(alkyl methacrylate)s Containing an Azobenzene Moiety in the Side Chain

ABSTRACT A series of poly(alkyl methacrylate)s having azobenzene and cyanobiphenyl moieties were synthesized and their optical properties were characterized. The effect of content of the photosensitive unit and the length of alkyl chain of a transparent unit on the photoresponsive alignment behavior was investigated. The azobenzene monomer (photoresponsive unit), the cyanobiphenyl monomer (mesogenic unit), and the alkyl methacrylate monomers with methyl, ethyl, n-butyl, hexyl or lauryl group (transparent unit) were copolymerized to yield transparent polymer films. Upon irradiation of LPL at 488 nm, a uniaxial optical anisotropy was generated due to the molecular alignment. The photoinduced alignment behavior was strongly dependent on the alkyl chain length and the intensity of the actinic light.

Highly selective photo-catalytic dimerization of α-methylstyrene by a novel palladium complex with photosensitizing ruthenium(ii) polypyridyl moiety

A novel dinuclear complex containing the photo-sensitizing Ru unit and a Pd center is effective toward selective catalytic dimerization of alpha-methylstyrene leading to 2,4-diphenyl-4-methyl-1-pentene under visible-light irradiated conditions.

Synthesis and properties of an efficient and switchable photosensitizing unit, [Ru(4,4′-diphenyl-2,2′-bipyridine)2(7-amino-dipyrido[3,2-a:2′,3′-c]phenazine)]2+, for a photo-induced energy transfer systemElectronic supplementary information (ESI) available: time-resolved emission decay curves of Ru(Ph)-NHCO-Os and Ru-NHCO-Os. See http://www.rsc.org/suppdata/dt/b2/b211225f/

A Ru(II) complex containing the 4,4′-diphenyl-2,2′-bipyridine (Ph2bpy) and 7-amino-dipyrido[3,2-a:2′,3′-c]phenazine (dppz-NH2) ligands was synthesized and found to be an excellent switchable photosensitizing unit suitable for photo-induced energy transfer, which has large light absorptivity, superior excited state properties and an amino functional unit for connecting acceptor units. [Os(tpy)2]2+ (tpy = 2,2′:6′,2″-terpyridine) unit was connected to the amino group of this photosensitizing unit by an amide bond to construct a heterodinuclear Ru(II)/Os(II) photo-induced energy transfer system. This system showed stronger Os(II) centered emission compared to the similar heterodinuclear Ru(II)/Os(II) complex containing 2,2′-bipy (bpy) instead of Ph2bpy. Analysis of the photophysical processes of these complexes indicated that the stronger Os(II) emission was ascribed not only to the higher absorptivity but also to the increased energy transfer efficiency from the Ru(II) to the Os(II) center. It also demonstrated that photosensitization by energy transfer to the Os(II) center was switched on and off reversibly by protonation/deprotonation of the dppz moiety.