Self-Assembled Metal-Organic Framework Stabilized Organic Cocrystals for Biological Phototherapy.

Organic self-assembled co-crystals have garnered considerable attention due to their facile synthesis and intriguing properties, but supramolecular interactions restrict their stability in aqueous solution, which is especially important for biological applications. Herein, we report on the first biological application of aqueous dispersible self-assembled organic co-crystals via the construction of metal-organic framework (MOF) -stabilized co-crystals. In particular, we built an electron-deficient MOF with naphthalene diimide (NDI) as the ligand and biocompatible Ca2+ as the metal nodes. An electron donor molecule, pyrene, was encapsulated to form the host-guest MOF self-assembled co-crystal. We observed that such MOF structure leads to uniquely high-density ordered arrangement and the close intermolecular distance (3.47 Å) of the charge transfer pairs. Hence, the concomitant superior charge transfer interaction between pyrene/NDI can be attained and the resultant photothermal conversion efficiency of Py@Ca-NDI in aqueous solution can thus reach up to 41.8 %, which, to the best of our knowledge, is the highest value among the reported organic co-crystal materials; it is also much higher than that of the FDA approved photothermal agent ICG as well as most of the reported MOFs. Based on this realization, as a proof of concept, we demonstrated that such a self-assembled organic co-crystal platform can be used in biological applications that are exemplified via highly effective long wavelength light photothermal therapy.

An electrochemical DNA biosensor fabricated from graphene decorated with graphitic nanospheres.

Graphene decorated with graphitic nanospheres functionalized with pyrene butyric acid (PBA) is used for the first time to fabricate a DNA biosensor. The electrode was formed by attaching a DNA probe onto PBA, which had been stacked onto a graphene material decorated with graphene nanospheres (GNSs). The nanomaterial was drop-coated onto a carbon screen-printed electrode (SPE) to create the GNS-PBA modified electrode (GNS-PBA/SPE). A simple method was used to produce GNS by annealing graphene oxide (GO) solution at high temperature. Field emission scanning electron micrographs confirmed the presence of a spherical shape of GNS with a diameter range of 40-80 nm. A stable and uniform PBA-modified GNS (GNS-PBA) was obtained with a facile ultrasonication step. Thus allowing aminated DNA probes of genetically modified (GM) soybean to be attached to the nanomaterials to form the DNA biosensor. The GNS-PBA/SPE exhibited excellent electrical conductivity via cyclic voltammetry (CV) and differential pulse voltammetry (DPV) tests using potassium ferricyanide (K3[Fe(CN)6]) as the electroactive probe. By employing an anthraquinone monosulfonic acid (AQMS) redox intercalator as the DNA hybridization indicator, the biosensor response was evaluated using the DPV electrochemical method. A good linear relationship between AQMS oxidation peak current and target DNA concentrations from 1.0 × 10-16 to 1.0 × 10-8 M with a limit of detection (LOD) of less than 1.0 × 10-16 M was obtained. Selectivity experiments revealed that the voltammetric GM DNA biosensor could discriminate complementary sequences of GM soybean from non-complementary sequences and hence good recoveries were obtained for real GM soybean sample analysis. The main advantage of using GNS is an improvement of the DNA biosensor analytical performance.

PN-Containing Pyrene Derivatives: Synthesis, Structure, and Photophysical Properties.

A straightforward method for the preparation of non-K region fused phosphorus- and nitrogen-containing (PN)-heterocyclic pyrenes has been accomplished. Their structural, photophysical, and electrochemical properties have been fully investigated. The described compounds exhibit intriguing redox properties and show strong photoluminescence with a wide range of tunable emission colors, with λem ranging from blue at 459 nm to red at 622 nm in CH2Cl2 solution.

Rapid and visual detection of berberine hydrochloride based on a water-soluble pyrene derivative.

In this study, a rapid method for the detection of berberine hydrochloride (BRH) was developed based on a water-soluble pyrenyl probe, 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS). This method features low cost, good selectivity, high sensitivity and a fast response. The sensing mechanism of this probe is attributed to the formation of a complex between HPTS and BRH induced by electrostatic interaction and π-π stacking. To the best of our knowledge, this is the first fluorescent sensor for BRH based on organic materials that has low cost and a visual response. The detection limit of this method was as low as 1.24 µM and the linear response range is 2-50 µM. This method also allowed rapid detection of BRH real samples.

Effect of esters based on terpenoids and GABA on fluidity of phospholipid membranes.

The influence of esters based on gamma-aminobutyric acid (GABA) and mono-/bicyclic terpenoids on membrane structure was investigated. The mechanism of action for terpenoid esters on phospholipids of artificial membranes and lipids isolated from the rat stratum corneum was studied by fluorescence and FT-IR spectroscopy. We report here, that inclusion of monocyclic terpenoid esters in phospholipid liposomes leads to growth of excimer to monomer ratio (IE/IM) indicating a decrease of membrane microviscosity. Another mechanism of influence on biomembranes was proposed for ester of bicyclic borneol - in this case a high ratio of vibronic peak intensities (I1/I3) was revealed. The addition of terpenoid esters appears in the FT-IR spectra as intensity reduction of absorption bands associated with C = O, P = O and P-O-С groups of lecithin phospholipids. Similar results were obtained after esters addition to lipids isolated from stratum corneum indicating a decrease of hydrogen bonds number between polar groups of lipids. Thus, the influence of terpenoid esters on molecular organization of the lipid matrix substantiates the feasibility of their use after transdermal delivery in vivo.

Interactions between highly galloylated persimmon tannins and pectins.

The interactions between pectins of different degrees of esterification (DE) and highly galloylated persimmon tannins with average degrees of polymerisation (DP26 and DP5) were investigated by UV-Vis spectrophotometry, dynamic light scattering, transmission electron microscopy, isothermal titration calorimetry and pyrene fluorescence methods Pectins displayed strong effects on the self-aggregation of persimmon tannins and improved the homogeneity of condensed tannin aggregates. The interaction between tannins and pectins may result from hydrogen bonding and hydrophobic interactions; by contrast, electrostatic interactions, which involve charged molecules in general, played no dominant role. In addition, the presence of gallate moieties in the high-polymerisation proanthocyanidin could enhance affinity with highly methylated pectins. Stronger association was observed with the high-polymerisation tannins (DP26) with high-methoxyl pectin (DE74) (Ka=(8.50±3.0)×103M-1) than with low-methylated pectin (DE30) (Ka=(3.62±1.92)×103M-1). The present results are expected to promote the application of the formed complexes as functional ingredients in food.

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid bearing a base discriminating fluorescence nucleobase 8-(pyrene-1-yl)-ethynyladenine.

A combination of fluorophore and nucleobase through a π-conjugated rigid linker integrates the base pairing and the fluorescence change into a single event. Such base discriminating fluorophore can change its fluorescence as a direct response to the base pairing event and therefore have advantages over tethered labels or base surrogates lacking the hydrogen-bonding ability. 8-(Pyrene-1-yl)ethynyl-adenine (APyE) has been extensively used as fluorescence labels in DNA and LNA, but it showed little discrimination between different nucleobases. Herein we investigated the synthesis, base pairing ability and optical properties of APyE in pyrrolidinyl peptide nucleic acid - a DNA mimic that shows much stronger affinity and specificity towards DNA than natural oligonucleotides. The APyE in PNA pairs specifically with thymine in the DNA strand, and resulted in 1.5-5.2-fold enhanced and blue-shifted fluorescence emission. Fluorescence quenching was observed in the presence of mismatched base or abasic site directly opposite to the APyE. The behavior of APyE in acpcPNA is distinctively different from DNA whereby a fluorescence was increased selectively upon duplex formation with complementary DNA and therefore emphasizing the unique advantages of using PNA as alternative oligonucleotide probes. Applications as color-shifting probe for detection of trinucleotide repeats in DNA were demonstrated, and the performance of the probe was further improved by combination with reduced graphene oxide as an external nanoquencher.

Bis(pyrene)-Doped Cationic Dipeptide Nanoparticles for Two-Photon-Activated Photodynamic Therapy.

At present, one of main problems for photodynamic therapy (PDT) is how to improve the treatment depth. Two-photon activated (TPA) developed recently provide a possible solution for it. In this work, we report the energy-transferring assembled cationic dipeptide nanoparticles for two-photon activated photodynamic therapy (TPA-PDT). In the nanoparticles, the coencapsulated two-photon fluorescent dye bis(pyrene) (BP) is an energy donor, and a photosensitizer rose bengal (RB) is an acceptor based on an intraparticle fluorescence resonance energy transfer (FRET) mechanism. BP in the nanoparticles can be excited by one- or two- photon laser. And then, the energy of BP was transferred to RB, which highly enhanced the generation of singlet oxygen. The cellular experiments indicated that this nanosystem can induce the cytotoxicity under one- and two-photon irradiation, which allows further applications of FRET-based biomaterials for TPA-PDT.

Mechanistic investigation into sunlight-facilitated photodegradation of pyrene in seawater with oil dispersants.

This study investigated the effects of 3 model oil dispersants (Corexit EC9500A, Corexit EC9527A and SPC 1000) on photodegradation of pyrene under simulated sunlight. Both Corexit dispersants enhanced photodegradation of pyrene, while SPC1000 slightly inhibited the reaction. Span 80 and Tween 85 were the key ingredients causing the effects, though the underlying mechanisms differed. Span 80 enriches pyrene in the upper layer of water column, whereas Tween 85 induces a photosensitization process. Two reactive oxygen species, 1O2 and O2-, were found responsible for pyrene photodegradation, though the presence of EC9500A suppressed the 1O2 pathway. In terms of photodegradation products, EC9500A enhanced generation of polyaromatic intermediates, i.e., phenaleno[1,9-cd][1,2]dioxine, 1-hydroxypyrene, and 1,8-pyrenequinone, but did not alter the classical photodegradation pathway. The Corexit dispersants were more prone to photochemical decomposition, with multiple by-products detected. The information aids in our understanding of the effects of dispersants on photochemical weathering of oil compositions.

Molecular detection and in vitro antioxidant activity of S-allyl-L-cysteine (SAC) extracted from Allium sativum.

It is well known that Allium sativum has potential applications to clinical treatment of various cancers due to its remarkable ability in eliminating free radicals and increasing metabolism. An allyl-substituted cysteine derivative - S-allyl-L-cysteine (SAC) was separated and identified from Allium sativum. The extracted SAC was reacted with 1-pyrenemethanol to obtain pyrene-labelled SAC (Py-SAC) to give SAC fluorescence properties. Molecular detection of Py-SAC was conducted by steady-state fluorescence spectroscopy and time-resolved fluorescence method to quantitatively measure concentrations of Py-SAC solutions. The ability of removing 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radical using Py-SAC was determined through oxygen radical absorbance capacity (ORAC). Results showed the activity of Py-SAC and Vitamin C (VC) with ORAC as index, the concentrations of Py-SAC and VC were 58.43 mg/L and 5.72 mg/L respectively to scavenge DPPH, and 8.16 mg/L and 1.67 mg/L to scavenge •OH respectively. Compared with VC, the clearance rates of Py-SAC to scavenge DPPH were much higher, Py-SAC could inhibit hydroxyl radical. The ability of removing radical showed a dose-dependent relationship within the scope of the drug concentration.

Isolation and identification of Bacillus megaterium YB3 from an effluent contaminated site efficiently degrades pyrene.

Industrial effluents contaminated sites may serve as repositories of ecologically adapted efficient pyrene degrading bacteria. In the present study, six bacterial isolates from industrial effluents were purified using serial enrichment technique and their pyrene degrading potential on pyrene supplemented mineral salt medium was assessed. 16S rRNA sequence analysis showed that they belong to four bacterial genera, namely Acinetobacter, Bacillus, Microbacterium, and Ochrobactrum. Among these isolates, Bacillus megaterium YB3 showed considerably good growth and was further evaluated for its pyrene-degrading efficiency. B. megaterium YB3 could degrade 72.44% of 500 mg L(-1) pyrene within 7 days. GC-MS analysis of ethyl acetate extracted fractions detected two relatively less toxic metabolic intermediates of the pyrene degradation pathway. B. megaterium YB3 also tested positive for catechol 1, 2-dioxygenase and aromatic-ring-hydroxylating dioxygenase indole-indigo conversion assays. Considering the ability and efficiency of B. megaterium YB3 to degrade high pyrene content, the strain can be used as a tool to develop bioremediation technologies for the effective biodegradation of pyrene and possibly other PAHs in the environment.

Cyclodextrin supramolecular inclusion-enhanced pyrene excimer switching for time-resolved fluorescence detection of biothiols in serum.

We report here an efficient pyrene excimer signaling-based time-resolved fluorescent sensor for the measurement of biothiols (cysteine (Cys), homocysteine (Hcy), glutathione (GSH)) in human serum based on thymine-Hg(2+)-thymine (T-Hg(2+)-T) coordination chemistry and the inclusion interaction of cyclodextrin. The sensing mechanism of the approach is based on the competitive ligation of Hg(2+) ions by Hcy/Cys/GSH and T-T mismatches in a bis-pyrene-labeled DNA strand with the self-complementary 5' and 3' ends. The introduction of γ-cyclodextrin can provide cooperation for the molecular level space proximity of the two labeled pyrene molecules, moreover the hydrophobic cavity of γ-cyclodextrin can also offer protection for the pyrene dimer's emission from the quenching effect of environmental conditions and enhance the fluorescence intensity of the pyrene excimer. When the biothiols are not presented, the sensing ensemble is in the "off" state due to the long distance between the two labeled pyrene molecules resulted from the formation of a more stable T-Hg(2+)-T structure. While in the presence of biothiols, Hg(2+) interacts very strongly with thiol groups and the T-Hg(2+)-T structure is dehybridized, and then the pyrene excimer will be formed due to the self-complementary 5' and 3' ends of the DNA probe and the cooperation interaction of γ-cyclodextrin to pyrene dimer, thus resulting in switching the sensing ensemble to the "on" state. In the optimum conditions described, the linear concentration range of 1.0-100 µM with the limit of detection (LOD) of 0.36 µM for GSH was obtained. Moreover, due to the much longer lifetime of the pyrene excimer fluorescence than those of the ubiquitous endogenous fluorescent components, the time-resolved fluorescence technique has been successfully used for application in complicated biological samples.

The effect of structural compositions on the biosorption of phenanthrene and pyrene by tea leaf residue fractions as model biosorbents.

To enhance the removal efficiency of polycyclic aromatic hydrocarbons (PAHs) by natural biosorbent, sorption of phenanthrene and pyrene onto raw and modified tea leaves as a model biomass were investigated. Tea leaves were treated using Soxhlet extraction, saponification, and acid hydrolysis to yield six fractions. The structures of tea leaf fractions were characterized by elemental analysis, Fourier transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). The amorphous cellulose components regulated the sorption kinetics, capacity, and mechanism of biomass fractions. The adsorption kinetics fit well to pseudo-second-order model and isotherms followed the Freundlich equation. By the consumption of the amorphous cellulose under acid hydrolysis, both the aliphatic moieties and aromatic domains contributed to total sorption, thus sorption capacities of the de-sugared fractions were dramatically increased (5­20-fold for phenanthrene and 8­36-fold for pyrene). All de-sugared fractions exhibited non-linear sorption due to strong specific interaction between PAHs and exposed aromatic domains of biosorbent, while presenting a relative slow rate because of the condensed domain in de-sugared samples. The availability of strong sorption phases (aromatic domains) in the biomass fractions were controlled by polar polysaccharide components, which were supported by the FTIR, CHN, and SEM data.

Development of dansyl-modified oligonucleotide probes responding to structural changes in a duplex.

We have synthesized a nonnucleoside amidite block of dansyl fluorophore to prepare dansyl-modified oligonucleotides (ONTs). The fluorescence intensities of dansyl-ONT specifically increased by the presence of adjacent guanosine residues but, significantly reduced in a dansyl-flipping duplex. These changes were caused by solvatochromism effect due to the number of guanine which is hydrophobic functional group and the external environment of dansyl group. The fluorescence intensities could be plotted as a function of the ONTs concentrations and the increase in the fluorescence was observed to equimolar concentrations of target DNA. This duplex exhibited higher melting temperature relative to the corresponding duplexes containing other base pairs. Similar changes in fluorescence could be detected upon hybridization with complementary RNAs. Thus, the dansyl-modified ONTs provide sequence specific fluorescent probe of DNA and RNA.

An INHIBIT logic gate from a thiophene derivative using iron and zinc ions as the input: tuning the efficiency on moving from naphthalene to anthracene to pyrene for the green luminescent detection of the intracellular iron.

A pyrene-thiophene conjugate has been used for the efficient detection of intracellular irons through the generation of bright green luminescence. Amongst three different probes being reported, it is observed that the efficiency for the naked eye green luminescent detection of iron increases on moving from naphthalene to anthracene to pyrene. The developed technique may be very useful to monitor iron and zinc supplementation as single micronutrients in living systems through the construction of an INHIBIT logic gate.

Far infrared (terahertz) spectroscopy of a series of polycyclic aromatic hydrocarbons and application to structure interpretation of asphaltenes and related compounds.

A series of 33 different polycyclic aromatic hydrocarbons (PAHs) were studied by far infrared spectroscopy (terahertz spectroscopy) in the spectral range comprised between 600 and 50 cm(-1). In addition to common PAHs like naphthalene, anthracene, phenanthrene, fluoranthene, picene, pyrene, benzo[α]pyrene, and perylene, also quite unusual PAHs were studied like tetracene, pentacene, acenaphtene, acenaphtylene, triphenylene, and decacyclene. A series of alkylated naphthalenes and anthracenes were studied as well as methypyrene. Partially or totally hydrogenated PAHs were also object of the present investigation, ranging from tetrahydronaphthalene (tetralin) to decahydronaphthalene (decalin), 9,10-dihydroanthracene, 9,10-dihydrophenanthrene, hexahydropyrene, and dodecahydrotriphenylene. Finally, the large and quite rare PAHs coronene, quaterrylene, hexabenzocoronene, and dicoronylene were studied by far infrared spectroscopy. The resulting reference spectra were used in the interpretation of the chemical structure of asphaltenes (as extracted from a heavy petroleum fraction and from bitumen), the chemical structures of other petroleum fractions known as DAE (distillate aromatic extract) and RAE (residual aromatic extract), and a possible interpretation of components of the chemical structure of anthracite coal. Asphaltenes, heavy petroleum fractions, and coal were proposed as model compounds for the interpretation of the emission spectra of certain proto-planetary nebulae (PPNe) with a good matching in the mid infrared between the band pattern of the PPNe emission spectra and the spectra of these oil fractions or coal. Although this study was finalized in an astrochemical context, it may find application also in the petroleum and coal chemistry.

Identification and molecular interpretation of the effects of drug incorporation on the self-emulsification process using spectroscopic, micropolarimetric and microscopic measurements.

Addition of a drug to a self-emulsifying drug delivery system (SEDDS) can affect the emulsification process after administration, leading to variation in the emulsion droplet size formed and potentially its clinical behavior (Mercuri et al., Pharm. Res., 2011, 28, 1540-1551). However, the mechanisms involved and, in particular, the location of the drug within the system are poorly understood. Here, we have investigated the location of a model drug, ibuprofen, in the emulsions formed from a simple anhydrous SEDDS (soybean oil, Tween 80 and Span 80), using a range of physical characterization techniques. (1)H NMR studies showed an interaction between the drug and the polyoxyethylene chains of the surfactant Tween 80. Micropolarity assessment of the emulsion droplet interfacial region, using the chemical probes pyrene and Reichardt's dye, confirmed this interaction, and suggested that the drug was altering the microenvironment around the surfactants, and hence the behavior of the SEDDS with water during emulsification. Both dielectric spectroscopy and polarized light microscopy highlighted the differential behavior with water of placebo and drug-loaded SEDDS, also seen in the initial visual observational studies on the emulsification performance of the SEDDS. (1)H NMR studies with three other NSAIDs indicate that this effect is not confined to ibuprofen alone. The study has therefore indicated that the drug's influence on the emulsification process may be related to interactions within the microenvironment of the surfactant layer. Furthermore, such interactions may be usefully identified and characterized using a combination of micropolarity, spectroscopic and microscopic methods.

Linkage and branch analysis of high-mannose oligosaccharides using closed-ring labeling of 8-aminopyrene-1,3,6-trisulfonate and p-aminobenzoic ethyl ester and negative ion trap mass spectrometry.

A strategy based on negative ion electrospray ionization tandem mass spectrometry and closed-ring labeling with both 8-aminopyrene-1,3,6-trisulfonate (APTS) and p-aminobenzoic acid ethyl ester (ABEE) was developed for linkage and branch determination of high-mannose oligosaccharides. X-type cross-ring fragment ions obtained from APTS-labeled oligosaccharides by charge remote fragmentation provided information on linkages near the non-reducing terminus. In contrast, A-type cross-ring fragment ions observed from ABEE-labeled oligosaccharides yielded information on linkages near the reducing terminus. This complementary information provided by APTS- and ABEE-labeled oligosaccharides was utilized to delineate the structures of the high-mannose oligosaccharides. As a demonstration of this approach, the linkages and branches of high-mannose oligosaccharides Man(5)GlcNAc(2), Man(6)GlcNAc(2), Man(8)GlcNAc(2), and Man(9)GlcNAc(2) cleaved from the ribonuclease B were assigned from MS(2) spectra of ABEE- and APTS-labeled derivatives.

Interfacial and self-assembly properties of bolaamphiphilic compounds derived from a multifunctional oil.

The self-assembly characteristics in aqueous solutions of cationic bolaamphiphiles with systematic changes in their chemical structure is described with respect to their interfacial properties within water and at the air/water interface. Six cationic bolaamphiphiles were synthesized from multifunctional vernonia oil with the following variations: (a) two different alkyl chain lengths connecting the head groups, (b) polar ester or hydrogen bonding amide groups within the hydrophobic domain, and (c) an acetylcholine cationic head group with different conjugation sites to the alkyl chain. Surface tension measurements were used for determining critical aggregation concentration (CAC) values and air/water interfacial parameters such as 'effectiveness', surface excess concentration and area occupied by one molecule in the air/water interface. Fluorescent studies with pyrene were used to characterize CAC properties within the aqueous volume and transmission electron microscopy (TEM) for determining the aggregate structure's size, homogeneity and morphology. A bolaamphiphile molecular structure vs. interfacial property relationship was derived from this data which could be used to determine the molecular structure properties needed to generate interfacial forces to form either spherical vesicles or fibrous networks. The effects of the aliphatic chain length, head group orientation and functional groups within the hydrophobic domain on CAC, surface tension properties and self-aggregate morphology are described. Most bolaamphiphiles studied had CAC values in the 10-190 µM range, while two out of the six were found to assemble into MLM spherical vesicles with diameters ranging up to 120 nm suitable for drug delivery applications. Others formed a gelatinous network of fibers or multi-lamellar vesicles.

Pyrenes and pyrendiones from Uvaria lucida.

A chemical investigation of the chloroform extract of the roots of Uvaria ludida Benth. (Annonaceae), an important African traditional medicine, led to the isolation of six new compounds; three pyrenes, 2-hydroxy-1,8-dimethoxypyrene (1), 8-methoxy-1,2-methylenedioxypyrene (2), and 7-hydroxy-8-methoxy-1,2-methylenedioxypyrene (3), two pyrenediones, 2-hydroxy-1,8-pyrenedione (4) and 2-methoxy-1,8-pyrenedione (5), and a sesquiterpene, (-)-10-oxo-isodauc-3-en-15-oic acid (6), together with eight known compounds (7-14). The structural elucidation by spectroscopic studies of the compounds isolated is described. While pyrenes did not exhibit strong cytotoxicity against human promyelocytic leukemia HL-60 cells, pyrenediones showed strong cytotoxicity. The IC(50) of 4 was 70 ng mL(-1), which was close to that of etoposide (IC(50) = 60 ng mL(-1)).