Spectroscopy, binding to liposomes and production of singlet oxygen by porphyrazines with modularly variable water solubility

Three novel classes of porphyrazine-like structures were synthesized to form modular structures in which lipophilicity and water solubility can be tuned. Subtle modification of solubility is an important criterion in selecting a compound for biological photosensitization. The general structure takes the form H2[pz(AnB4-n)], where the core is a porphyrazine (pz) group, A is a pyrrole ring with two sulfide linkages (SR moieties) and B is a pyrrole fused with a 4,7-bis(isopropyloxy)benzo group, with n=4, 3 and 2. These molecules possess their longest wavelength absorption band between 700 and 810 nm, hence laser beams of higher tissue penetration depth could be used to illuminate them in photodynamic therapy (PDT). Armed with absorption bands in the far-red and near-infrared (near-IR), and a capability to tune the solubility, these molecules could make for better sensitizers because of optimized uptake by lipidic membranes and better optical properties. We tested several derivatives of the A4, A3B and A2B2 structures for their singlet oxygen quantum yields in methanol and in liposomes, using 9,10-dimethyl anthracene (DMA) as a singlet oxygen target. Singlet oxygen quantum yields in liposomes ranged from 0.01 to 0.44, with the A2B2 group showing the most promise. In the binding assay to find the equilibrium binding constant, Kb, we detected fluorescence changes due to a change in environment. Peripheral long-chain moieties (the R group in the SR moieties) dominate lipid binding. These moieties range in the hydrophobicity that they induce from C8H17 and benzene, which rendered the molecule totally insoluble in water, to polyethylene glycol (PEG) and carboxylate groups, which imparted water solubility. Each molecule had between 4 and 8 such identical chains. Chains bearing an ether or ester link resulted in measurable equilibrium constants, with a higher Kb for ether substituents. Results for Kb ranged from 0.23 to 26.52 (mg mL(-1))(-1). A delicate balance exists between water solubility and good partitioning to membranes. In general, a higher oxygen-to-carbon ratio in the chains improves binding. Fewer chains and a centrally coordinated zinc ion further improve binding and singlet oxygen production.     

Novel sulfonated hydrophilic indium(III) and gallium(III) phthalocyanine photosensitizers: preparation and investigation of photophysicochemical properties

The new tetra-non-peripherally benzenesulfonic acid-substituted hydrophilic gallium chloride and indium chloride phthalocyanine complexes have been synthesized by cyclotetramerization of 4-(2,3-dicyanophenyl)benzenesulfonic acid (1). The newly synthesized phthalocyanines have been characterized by Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, mass and UV–vis spectroscopy techniques. The water-soluble gallium(III) phthalocyanine derivative (2) was aggregated in aqueous media but was fully disaggregated in the presence of a surfactant Triton X-100. The incorporation of sulfonate moieties of the phthalocyanine macrocycle provides hydrophilic character to the new compounds, which is useful for drug administration and serves as crucial in PDT application. So, the photochemical properties (singlet oxygen quantum yields and photodegradation quantum yields) and photophysical properties (fluorescence behavior) of the complexes were reported in different solutions (DMSO and water). The results of spectral measurements showed that both np-GaPc (2) and np-InPc (3) can be used as sensitizers in PDT because of their singlet oxygen efficiencies.     

Effect of fuel choice on conductivity and morphological properties of samarium doped ceria electrolytes for IT-SOFC

The present investigation is emphasized on the effect of various combustion agents on the crystal properties, surface microstructure, and oxygen ion conductivity of 20% mole-Sm doped ceria (Ce_0.80Sm_0.20O_1.90/SDC20) ceramics as solid electrolyte for IT-SOFCs. The most widely used combustion agents for engineering ceramic production as ethylene glycol, diethylene glycol, triethylene glycol, L-alanine, L-valine, glycine, citric acid monohydrate, urea, and EDTA-citric acid were compared in terms of SDC20 properties. X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TGA), and electrochemical impedance spectroscopy (EIS) were used to determine the microstructure properties, crystal structure and ionic conductivity of SDC20 powder. XRD pattern of the ceramics revealed the formation of single-phase fluorite structure. According to the results of electrochemical analysis, the maximum total ionic conductivity was observed in SDC20 electrolyte synthesized using triethylene glycol as the fuel among all the synthesized electrolytes (5.72 x 10^–2 S.cm^–1).     

Formation and characterization of water-soluble hetero capsules derived from multiple ionic interactions

We now report the formation and characterization of water-soluble hetero-capsules 1·2 resulting from the ionic interactions between positively charged flexible aniline hydrochloride 1 and negatively charged phosphonate 2 having rigid homooxacalix[3]arene units. The formation of the molecular capsules was studied by NOESY, DOSY NMR spectroscopy and ESI-Mass spectrometry. The water solubility of the capsules is improved by the introduction of mono- or triethylene glycol substituents in the homooxacalix[3]arene-based phosphonate units 2.     

Umbelliferone Decorated Water-soluble Zinc(II) Phthalocyanines – In Vitro Phototoxic Antimicrobial Anti-cancer Agents

In this contribution we report on the synthesis, characterization and application of water-soluble zinc(II) phthalocyanines, which are decorated with four or eight umbelliferone moieties for photodynamic therapy (PDT). These compounds are linked peripherally to zinc(II) phthalocyanine by a triethylene glycol linker attached to pyridines, leading to cationic pyridinium units, able to increase the water solubility of the system. Beside their photophysical properties they were analyzed concerning their cellular distribution in human hepatocyte carcinoma (HepG2) cells as well as their phototoxicity towards HepG2 cells, Gram-positive (S. aureus strain 3150/12 and B. subtilis strain DB104) and Gram-negative bacteria (E. coli strain UTI89 and E. coli strain Nissle 1917). At low light doses and concentrations, they exhibit superb antimicrobial activity against Gram-positive bacteria as well as anti-tumor activity against HepG2. They are even capable to inactivate Gram-negative bacteria, whereas the dark toxicity remains low. These unique water-soluble compounds can be regarded as all-in-one type photosensitizers with broad applications ranges in the future.     

A high yielding template-directed synthesis of the first fluorenone-containing [2]catenane

A new crownophane containing both 2,7-dioxyfluorenone and 1,5-dioxynaphthalene moieties bridged by triethylene glycol units has been synthesized and used as a highly efficient template for the preparation of the first fluorenone-containing [2]catenane incorporating a cyclobis(paraquat-p-phenylene) tetracation as a second macrocyclic component.     

Water-soluble xanthobilirubinic acids?

Abstract  Xanthobilirubinic acid, a model dipyrrinone for one-half of the bilirubin molecule in photochemical and metabolism studies, is more polar than bilirubin and insoluble in water and in chloroform. Replacing the β-alkyl substituents on the lactam ring of xanthobilirubinic acid with methyl-capped ethylene glycol, diethylene glycol, and triethylene glycol (PEG) groups steadily increased the water solubility of the pigment so that the last is completely soluble in both water and chloroform. Synthesized by base-catalyzed condensation of the corresponding methyl-capped 3,4-diPEG-pyrrolin-2-one with 3,5-dimethyl-4(2-ethoxycarbonylethyl)-2-formyl-1H-pyrrole, these new PEGylated analogs of xanthobilirubinic acid are yellow-colored dipyrrinones that form intermolecular hydrogen-bonded dimers in chloroform solution but are monomeric in methanol and water, as revealed by ¹H NMR spectroscopy and vapor pressure osmometry. Methyl xanthobilirubinate has served as a synthetic precursor to bilirubinoids; its amphiphilic PEGylated analogs suggest a route to water-soluble bilirubinoids and biliverdinoids. Graphical abstract        

Synthesis and studies of homopolycyanurates based on 2-carbazol-4,6-dichloro-s-triazine

Eight homopolycyanurates have been synthesized by interfacial polycondensation of 2-carbazol-4,6-dichloro-s-triazine with 1,7-dihydroxynaphthalene, 1,4-dihydroxyanthraquinone, ethylene glycol, diethylene glycol, triethylene glycol, 1,2-propanediol, 1,4-butanediol and 1,8-dihydroxyanthraquinone. All the homopolycyanurates synthesized were characterized for their solubility, density, viscosity, IR, NMR spectral and thermogravimetric parameters.     

双光子诱导产生单重态氧的三重态光敏剂的研究

自2001年以来,双光子敏化产生单重态氧的三重态光敏剂的研究取得了一定的进展。双光子三重态光敏剂对肿瘤组织的近红外激光和红外激光的光动力治疗作用具有广阔的应用前景。本文重点分析了近些年已报道的双光子三重态光敏剂种类,如疏水性、水溶性等不同的敏化剂;介绍了可以根据分子的激发态性质、利用化学手段对双光子三重态敏化剂的性质以及光敏产生单重态氧的量子产率进行调控;概括了双光子三重态敏化剂的相对和绝对双光子横截面的测量方法;总结了双光子三重态敏化剂发展中面临的一些关键问题,并展望了双光子三重态敏化剂的发展方向。     

Cyclodextrin dimers as cleavable carriers of photodynamic sensitizers.

Several phthalocyanines carrying hydrophobic components have been synthesized and shown to bind to a group of cyclodextrin dimers with a carbon-carbon double bond in the linker. The complexes are soluble in water. On irradiation in the presence of oxygen, the singlet oxygen produced cleaves the olefinic linkers in the complexes, resulting in precipitation of the sensitizers. This process concentrates the sensitizers in the light beam, a process that has useful potential in photodynamic therapy.     

Facile synthesis of pegylated zinc(II) phthalocyanines via transesterification and their in vitro photodynamic activities

Treatment of 4,5-bis[4-(methoxycarbonyl)phenoxy]phthalonitrile and 4,5-bis[3,5-bis(methoxycarbonyl)phenoxy]phthalonitrile with an excess of 1,3-diiminoisoindoline in the presence of Zn(OAc)(2)·2H(2)O and 1,8-diazabicyclo[5.4.0]undec-7-ene in triethylene glycol monomethyl ether or polyethylene glycol monomethyl ether (with an average molecular weight of 550) led to "3 + 1" mixed cyclisation and transesterification in one pot, affording the corresponding di-β-substituted zinc(II) phthalocyanines in 7-23% yield. As shown by absorption spectroscopy, these compounds were essentially non-aggregated in N,N-dimethylformamide and could generate singlet oxygen effectively. The singlet oxygen quantum yields (Φ(Δ) = 0.53-0.57) were comparable with that of the unsubstituted zinc(II) phthalocyanine (Φ(Δ) = 0.56). These compounds in Cremophor EL emulsions also exhibited photocytotoxicity against HT29 human colorectal adenocarcinoma and HepG2 human hepatocarcinoma cells with IC(50) values in the range of 0.25-3.72 μM. The analogue with four triethylene glycol chains was the most potent photosensitiser and localised preferentially in the mitochondria of HT29 cells. The bis(polyethylene glycol)-counterpart could form surfactant-free nanoparticles both in water and in the culture medium. The hydrodynamic radii, as determined by dynamic laser light scattering, ranged from 6.3 to 79.8 nm depending on the preparation methods and conditions. The photocytotoxicity of these nanoparticles (IC(50) = 0.43-0.56 μM) was comparable with that of the Cremophor EL-formulated system (IC(50) = 0.34 μM).     

A novel water-soluble NHC-Pd polymer: an efficient and recyclable catalyst for the Suzuki coupling of aryl chlorides in water at room temperature

A novel water-soluble NHC-Pd polymer with triethylene glycol legs was developed as a water soluble and highly recyclable catalyst that shows high catalytic activity in the Suzuki-Miyaura coupling of aryl chlorides in high yields in water at room temperature.     

Single-molecule force spectroscopy measurements of "hydrophobic bond" between tethered hexadecane molecules

The hydrophobic effect is important for many biological and technological processes. Despite progress in theory, experimental data clarifying water structure and the interaction between hydrophobic solutes at the nanometer scale are scarce due to the very low solubility of hydrophobic species. This article describes an AFM single molecule force spectroscopy method to probe the interaction between molecules with low solubility and reports measurements of the strength and the length scale of the "hydrophobic bond" between hexadecane molecules. Hexadecane molecules are tethered by flexible poly(ethylene glycol) linkers to AFM probes and substrates, removing the aggregation state uncertainty of solution-based approaches as well as spurious surface effects. A shorter hydrophilic polymer layer is added to increase the accessibility of hydrophobic molecules for the force spectroscopy measurements. Statistical analysis of the rupture forces yields a barrier width of 0.24 nm, and a dissociation rate of 1.1 s(-1). The results of single molecule measurements are related to the theoretical predictions of the free energy of cavitation in water and to the empirical model of micellization of nonionic surfactants. It is estimated that approximately one-quarter of each molecule's surface is hydrated during forced dissociation, consistent with an extended (nonglobular) conformation of the hexadecane molecules in the dimer.     

竹红菌素作为激发态氧分子的光敏剂的研究

近年来,竹红菌素(Hypocrellin A and B,简称HA和HB)及其衍生物在光疗技术上的应用,尤其是在癌症和艾滋病的治疗上的应用,越来越引起人们的重视[1~8].     

Abraham Model Correlations for Triethylene Glycol Solvent Derived from Infinite Dilution Activity Coefficient,Partition Coefficient and Solubility Data Measured at 298.15 K

A gas chromatographic headspace analysis method was used to experimentally determine gas-to-liquid partition coefficients and infinite dilution activity coefficients for 29 liquid organic solutes dissolved in triethylene glycol at 298.15 K. Solubilities were also determined at 298.15 K for 23 crystalline nonelectrolyte organic compounds in triethylene glycol based on spectroscopic absorbance measurements. The experimental results of the headspace chromatographic and spectroscopic solubility measurements were converted to gas-to-triethylene glycol and water-to-triethylene glycol partition coefficients, and molar solubility ratios using standard thermodynamic relationships. Expressions were derived for solute transfer into triethylene glycol by combining our measured experimental values with published literature data. Mathematical correlations based on the Abraham model describe the observed partition coefficient and solubility data to within 0.16 log₁₀ units (or less).     

Assessment of water-soluble pi-extended squaraines as one- and two-photon singlet oxygen photosensitizers: design, synthesis, and characterization

Singlet oxygen sensitization by organic molecules is a topic of major interest in the development of both efficient photodynamic therapy (PDT) and aerobic oxidations under complete green chemistry conditions. We report on the design, synthesis, biology, and complete spectroscopic characterization (vis-NIR linear and two-photon absorption spectroscopy, singlet oxygen generation efficiencies for both one- and two-photon excitation, electrochemistry, intrinsic dark toxicity, cellular uptake, and subcellular localization) of three classes of innovative singlet oxygen sensitizers pertaining to the family of symmetric squaraine derivatives originating from pi-excessive heterocycles. The main advantage of pi-extended squaraine photosensitizers over the large number of other known photosensitizers is their exceedingly strong two-photon absorption enabling, together with sizable singlet oxygen sensitization capabilities, for their use at the clinical application relevant wavelength of 806 nm. We finally show encouraging results about the dark toxicity and cellular uptake capabilities of water-soluble squaraine photosensitizers, opening the way for clinical small animal PDT trials.     

Synthesis and properties of water-soluble silica nanoparticles

Methods for synthesis and optimum conditions of the formation of stable water-soluble silica nanoparticles are presented. The silica nanoparticles were synthesized by the hydrolytic polycondensation of tetraethoxysilane using two methods: under alkaline conditions (Stöber´s method) or in an acetic acid medium followed by the modification by grafting triethylene oxide moieties on the particle surface. The structure of the modified silica nanoparticles was confirmed by the data of IR and NMR spectroscopy. Polydispersity was evaluated by gel permeation chromatography and dynamic light scattering. The formation and stability of Langmuir monolayers of the silica nanoparticles modified by triethylene oxide moieties were studied.     

Full-color tunable photoluminescent ionic liquid crystals based on tripodal pyridinium, pyrimidinium, and quinolinium salts

Color-tunable luminescent ionic liquid crystals have been designed as a new series of luminescent materials. To achieve tuning of emission colors, intramolecular charge transfer (ICT) character has been incorporated into tripodal molecules. A series of the compounds has three chromophores in each molecule, incorporated with both electron-donating moieties such as alkylaminobenzene and alkoxybenzene, and electron-accepting moieties such as pyridinium, pyrimidinium, and quinolinium parts. These C(3)-symmetrical molecules self-assemble into liquid-crystalline (LC) columnar (Col) structures over wide temperature ranges through nanosegregation between ionic moieties and nonionic aliphatic chains. Photoluminescent (PL) emissions of these tripodal molecules are observed in the visible region both in the self-assembled condensed states and in solutions. For example, a pyrimidinium salt with didodecylaminobenzene moieties exhibits yellowish orange emission (λ(em) = 586 nm in a thin film). Multicolor PL emissions are successfully achieved by simple tuning of changing electron-donating and electron-accepting moieties of the compounds, covering the visible region from blue-green to red. It has been revealed that ICT processes in the excited states and weak intermolecular interactions play important roles in the determination of the PL properties of the materials, by measurements of UV-vis absorption and emission spectra, fluorescence lifetimes, and PL quantum yields.     

Controlled self-assembly triggered by olefin metathesis: cross-linked graphitic nanotubes from an amphiphilic hexa-peri-hexabenzocoronene

Acyclic diene metathesis (ADMET) in CH2Cl2 of a Gemini-shaped nonionic hexabenzocoronene amphiphile (2), bearing triethylene glycol chains with terminal allylic functionalities, resulted in spontaneous formation of graphitic nanotubes with a cross-linked surface. Without ADMET, 2 did not self-assemble to form a tubular structure due to a high solubility in CH2Cl2. Although 2 formed nanotubes in THF, ADMET on the surface of the preformed nanotubes in THF proceeded only sluggishly and resulted in partial disruption of the tubular structure. The cross-linked nanotubes showed a softening temperature (244 degrees C) higher than that of the uncross-linked version (195 degrees C) and preserved their hollow structure much longer upon heating.     

Threading of cyclodextrins onto a polyester of octanedicarboxylic acid and polyethylene glycol

A water-soluble polyester was synthesized from dimethyl octane-1,8-dicarboxylate and polyethylene glycol (M̄_n = 900). This polymer forms water-soluble inclusion compounds with α-, β- and hydroxypropyl-α-cyclodextrin as proven by surface tension measurements, ¹H NMR spectroscopy and titration microcalorimetry. Mainly the octamethylene segments were covered by the cyclodextrins. This inclusion can be used to increase the solubility and the critical micelle concentration of the polyester in water.