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Multiphoton excitation promises opportunities for opening new photochemical reaction pathways and controlling photoproduct distributions. We demonstrate photonic control of the 6π photocyclization of ortho -terphenyl to make 4 a ,4 b -dihydrotriphenylene (DHT). Using pump-repump-probe spectroscopy we show that 1 + 1' excitation to a high-lying reactant electronic state generates a metastable species characterized by a red absorption feature that accompanies a repump-induced depletion in the one-photon trans -dihydro product ( trans -DHT); signatures of the new photoproduct are clearer for a structural analogue of the reactant that is sterically inhibited against one-photon cyclization. Quantum-chemical computations support assignment of this species to cis -DHT, which is accessible photochemically along a disrotatory coordinate from high-lying electronic states reached by 1 + 1' excitation. We use time-resolved spectroscopy to track photochemical dynamics producing cis -DHT. In total, we demonstrate that selective multiphoton excitation opens a new photoreaction channel in these photocyclizing reactants by taking advantage of state-dependent correlations between reactant and product electronic states.

A 2D CuNi metal-organic framework (MOF) named CuxNi3-x(HHTP)2 was synthesized with 2,3,6,7,10,11-hexahydroxytriphenylene (HHTP) as the linker and was used as a sensitive scaffold to adsorb aptamer strands for the electrochemical detection of living C6 glioma cells and one of their biomarkers, epidermal growth factor receptor (EGFR). Different from conventional MOFs, the CuxNi3-x(HHTP)2 MOF comprises long-range delocalized electrons, a graphene-analog nanostructure, multiple metal states (Cu0/Cu+/Cu2+ and Ni2+/Ni3+), and abundant oxygen vacancies. With these features, the CuxNi3-x(HHTP)2 MOF anchored a large amount of C6 cell-targeted aptamer strands via coordination among metal centers, oligonucleotides, π-π stacking, and van der Waals force. The CuxNi3-x(HHTP)2-based cytosensor showed a low limit of detection (LOD) of 21 cells mL-1 toward C6 glioma cells within a wide range from 50 cells mL-1 to 1 × 105 cells mL-1. Moreover, the proposed aptasensor displayed high selectivity, good stability, acceptable reproducibility, and a low LOD of 0.72 fg mL-1 for detecting EGFR with the concentration ranging from 1 fg mL-1 to 1 ng mL-1. The aptasensor based on the CuxNi3-x(HHTP)2 MOF exhibited superior sensing performance over those based on its monometallic analogues such as Cu3(HHTP)2 MOF and Ni3(HHTP)2 MOF. Hence, this sensing strategy based on a bimetallic semiconducting MOF shows great potential for cancer diagnosis.

6-Nitrochrysene (6-NC) is a potent mutagen in bacteria and carcinogenic in animals. It is the most potent carcinogen ever tested in newborn mouse assay. DNA lesions resulting from 6-NC modification are likely to induce mutations if they are not removed by cellular defense pathways prior to DNA replication. Earlier studies showed that 6-NC-derived C8-2'-deoxyadenosine adduct, N-(dA-8-yl)-6-AC, is very slowly repaired in human cells. In this study, we have investigated replication of N-(dA-8-yl)-6-AC in human embryonic kidney (HEK 293T) cells and the roles of translesion synthesis (TLS) DNA polymerases in bypassing it. Replication of a plasmid containing a single site-specific N-(dA-8-yl)-6-AC adduct in HEK 293 T cells showed that human DNA polymerase (hPol) η and hPol κ played important roles in bypassing the adduct, since TLS efficiency was reduced to 26 % in the absence of these two polymerases compared to 83 % in polymerase-competent HEK 293T cells. The progeny from HEK 293T cells provided 12.7 % mutants predominantly containing A→T transversions. Mutation frequency (MF) was increased to 17.8 % in hPol η-deficient cells, whereas it was decreased to 3.3 % and 3.9 % when the adduct containing plasmid was replicated in hPol κ- and hPol ζ-deficient cells, respectively. The greatest reduction in MF by more than 90 % (to MF 1.2 %) was observed in hPol ζ-knockout cells in which hPol κ was knocked down. Taken together, these results suggest that hPol κ and hPol ζ are involved in the error-prone TLS of N-(dA-8-yl)-6-AC, while hPol η performs error-free bypass., (Copyright © 2020 Elsevier B.V. All rights reserved.)

At the moment, there are no U.S. Food and Drug Administration (U.S. FDA)-approved drugs for the treatment of COVID-19, although several antiviral drugs are available for repurposing. Many of these drugs suffer from polymorphic transformations with changes in the drug's safety and efficacy; many are poorly soluble, poorly bioavailable drugs. Current tools to reformulate antiviral APIs into safer and more bioavailable forms include pharmaceutical salts and cocrystals, even though it is difficult to classify solid forms into these regulatory-wise mutually exclusive categories. Pure liquid salt forms of APIs, ionic liquids that incorporate APIs into their structures (API-ILs) present all the advantages that salt forms provide from a pharmaceutical standpoint, without being subject to solid-state matter problems. In this perspective article, the myths and the most voiced concerns holding back implementation of API-ILs are examined, and two case studies of API-ILs antivirals (the amphoteric acyclovir and GSK2838232) are presented in detail, with a focus on drug property improvement. We advocate that the industry should consider the advantages of API-ILs which could be the genesis of disruptive innovation and believe that in order for the industry to grow and develop, the industry should be comfortable with a certain element of risk because progress often only comes from trying something different.

Polycyclic aromatic hydrocarbons (PAHs) have been a major concern because of their carcinogenicity, mutagenicity, teratogenicity and wide distribution in the environment. Over 90% of PAHs in the environment exist on soil surface/sediment. Benzo[a]pyrene (BaP) is one of the predominant PAHs in soil. Thus, it is critically important to understand the patterns of BaP accumulation and transformation peculiarities in soil for the risk assessment. The studies were conducted in model experiment with Haplic Chernozem spiked with various doses of BaP (20, 200, 400 and 800 µg kg -1 ) equivalent to 1, 10, 20 and 40 levels of maximum permissible concentrations. The unique properties of Haplic Chernozem were studied allow to accumulate and transform BaP as well as barley plants ability to absorb of some BaP concentration. Extraction of BaP from the soil was carried out by the saponification method. The qualitative and quantitative determination of BaP and other polycyclic aromatic hydrocarbons (PAHs) was performed by high-performance liquid chromatography with fluorescence detection (Agilent 1260 Germany, 2014). BaP accumulation in soil depended on the applied BaP concentrations in Haplic Chernozem. Studying the features of PAHs transformation in the soil of a model experiment 1 year after the compound application showed the BaP content in the soil decreased up to 11-40%. Two years after the BaP application the content in the soil decreased up to 15-44% from the initial BaP content in the soil. The percentage of BaP concentration reduction in Haplic Chernozem increased with an increase in the dose of the applied xenobiotic. An increase in the dose of the applied pollutant to the soil of the model experiment contributed to an increase in all PAHs, which indicated a rapid BaP transformation in Haplic Chernozem. The PAHs content in the soils of model experiment in the first year of the research formed the following descending series: pyrene > chrysene > fluoranthene > phenanthrene. In the second year of research the phenanthrene content became higher than the fluoranthene content. The content of these compounds exceeded 20% of the total PAHs content in the soil samples in the first and second years of the model experiment. The features of PAHs accumulation and transformation in soils under artificial pollution showed the degradation of large-nuclear PAHs, starting from 5-ring polyarenes, and their structural reorganization into the less-nuclear polyarenes, such as 4-, 3-, and 2-ring PAHs. During the 2 years of the model experiment the BaP concentration in the soil decreased up to 15-44% from the initial BaP content in the soil.

A new 2,7,10,15-tetraethynyldibenzo[g,p]chrysene ligand ( 1 ) and two tetranuclear gold(I) derivatives containing PPh 3 ( 3 ) and PMe 3 ( 4 ) phosphines were synthesized and characterized by 1 H and 31 P NMR, IR spectroscopy, and high-resolution mass spectrometry. The compounds were studied in order to analyze the effect of the introduction of gold(I) on the supramolecular aggregation and photophysical properties. Absorption and emission spectra displayed broad bands due to the establishment of π π interactions as an indication of intermolecular contacts and the formation of aggregates. A decrease of the recorded quantum yield (QY) of the gold(I) derivatives was observed compared to the uncomplexed ligand. The introduction of the complexes into poly methyl methacrylate (PMMA) and Zeonex 480R matrixes was analyzed, and an increase of the measured QY of 4 in Zeonex was observed. No phosphorescent emission was detected.

The formation of polycyclic aromatic hydrocarbons (PAHs) is a strong global concern due to their harmful effects. To help the reduction of their emissions, a crucial understanding of their formation and a deep exploration of their growth mechanism is required. In the present work, the formation of benzo(a)pyrene was investigated computationally employing chrysene and benz(a)anthracene as starting materials. It was assumed a type of methyl addition/cyclization (MAC) was the valid growth mechanism in this case. Consequently, the reactions implied addition reactions, ring closures, hydrogen abstractions and intramolecular hydrogen shifts. These steps of the mechanism were computed to explore benzo(a)pyene formation. The corresponding energies of the chemical species were determined via hybrid density funcional theory (DFT), B3LYP/6-31+G(d,p) and M06-2X/6-311++G(d,p). Results showed that the two reaction routes had very similar trends energetically, the difference between the energy levels of the corresponding molecules was just 6.13 kJ/mol on average. The most stable structure was obtained in the benzo(a)anthracene pathway.

Ebola virus (EBOV) causes a deadly hemorrhagic fever in humans and non-human primates. There is currently no FDA-approved vaccine or medication to counter this disease. Here, we report on the design, synthesis and anti-viral activities of two classes of compounds which show high potency against EBOV in both in vitro cell culture assays and in vivo mouse models Ebola viral disease. These compounds incorporate the structural features of cationic amphiphilic drugs (CAD), i.e they possess both a hydrophobic domain and a hydrophilic domain consisting of an ionizable amine functional group. These structural features enable easily diffusion into cells but once inside an acidic compartment their amine groups became protonated, ionized and remain trapped inside the acidic compartments such as late endosomes and lysosomes. These compounds, by virtue of their lysomotrophic functions, blocked EBOV entry. However, unlike other drugs containing a CAD moiety including chloroquine and amodiaquine, compounds reported in this study display faster kinetics of accumulation in the lysosomes, robust expansion of late endosome/lysosomes, relatively more potent suppression of lysosome fusion with other vesicular compartments and inhibition of cathepsins activities, all of which play a vital role in anti-EBOV activity. Furthermore, the diazachrysene 2 (ZSML08) that showed most potent activity against EBOV in in vitro cell culture assays also showed significant survival benefit with 100% protection in mouse models of Ebola virus disease, at a low dose of 10 mg/kg/day. Lastly, toxicity studies in vivo using zebrafish models suggest no developmental defects or toxicity associated with these compounds. Overall, these studies describe two new pharmacophores that by virtue of being potent lysosomotrophs, display potent anti-EBOV activities both in vitro and in vivo animal models of EBOV disease., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

GSK3532795, formerly known as BMS-955176 (1), is a potent, orally active, second-generation HIV-1 maturation inhibitor (MI) that advanced through phase IIb clinical trials. The careful design, selection, and evaluation of substituents appended to the C-3 and C-17 positions of the natural product betulinic acid (3) was critical in attaining a molecule with the desired virological and pharmacokinetic profile. Herein, we highlight the key insights made in the discovery program and detail the evolution of the structure-activity relationships (SARs) that led to the design of the specific C-17 amine moiety in 1. These modifications ultimately enabled the discovery of 1 as a second-generation MI that combines broad coverage of polymorphic viruses (EC 50 <15 nM toward a panel of common polymorphisms representative of 96.5% HIV-1 subtype B virus) with a favorable pharmacokinetic profile in preclinical species.

Development of hybridization-based probes that enable recognition of specific mixed-sequence double-stranded DNA (dsDNA) regions is of considerable interest due to their potential applications in molecular biology, biotechnology, and medicine. We have recently demonstrated that nucleic acid duplexes with +1 interstrand zipper arrangements of intercalator-functionalized nucleotides such as 2'-O-(pyren-1-yl)methyl RNA monomers are inherently activated for recognition of mixed-sequence dsDNA targets, including chromosomal DNA. In the present work, we follow up on our previous structure-activity relationship studies and explore if the dsDNA-recognition efficiency of these so-called Invader probes can be improved by using larger intercalators than pyrene. Oligodeoxyribonucleotides modified with 2'-O-(triphenylen-2-yl)methyl-uridine monomer X and 2'-O-(coronen-1-yl)methyl-uridine monomer Z form extraordinarily stabilized duplexes with complementary DNA (ΔT m 's per modification of up to 13 °C and 20 °C, respectively). Invader probes based on X- and Z-monomers are shown to recognize model dsDNA targets with exceptional binding specificity, but are less efficient than reference probes modified with 2'-O-(pyren-1-yl)methyl-uridine monomer Y. The insight from this study will inform further optimization of Invader probes.

Polyvinyl pyrrolidone (PVP) crowned chrysene nanoparticles (CHYNPs) were prepared by using a reprecipitation method. Dynamic light scattering (DLS) and scanning electron microscope (SEM) studies indicate that the monodispersed spherical nanoparticles bear a negative charge on their surfaces. The bathochromic spectral shift in the UV-visible and fluorescence spectrum of CHYNPs from chrysene (CHY) in acetone solution supports the J- type aggregation of nanoparticles. The aggregation-induced enhanced emission of CHYNPs at 486 and 522 nm decreases by increasing the concentration of the Ca 2 + ion solution. It can display an ON-OFF type fluorescence response with high selectivity towards Ca 2 + ions aqueous medium. Furthermore, the in situ generated PVP-CHYNPs-Ca 2 + ensemble could recover the quenched fluorescence upon the addition of fluoride anions resulting in an OFF-ON type sensor. The present method has a correlation coefficient R 2 = 0.988 with a detection limit of 1.22 μg/mL for Ca 2 + in the aqueous medium. The fluorescence changes of PVP crowned CHYNPs upon the addition of Ca 2 + and F - can be utilized as an INHIBIT logic gate at the molecular level, using Ca 2 + and F - chemical inputs and the fluorescence intensity signal as output., (Copyright © 2017 John Wiley & Sons, Ltd.)

This paper describes the synthesis of a trinuclear Cu(II) complex (4) containing a central 1,4,5,8,9,12-hexaazatriphenylene-hexacarboxylate (hat) core (3). Low, micromolar concentrations of the negatively charged parent ligand 3 and the neutral trinuclear complex 4 were found to photocleave negatively charged pUC19 plasmid DNA with high efficiency at neutral pH (350nm, 50min, 22°C). The interactions of complex 4 with double-helical DNA were studied in detail. Scavenger and colorimetric assays pointed to the formation of Cu(I), superoxide anion radicals, hydrogen peroxide, and hydroxyl radicals during photocleavage reactions. UV-visible absorption, circular dichroism, DNA thermal denaturation, and fluorescence data suggested that the Cu(II) complex contacts double-stranded DNA in an external fashion. The persistent association of ligand 3 and complex 4 with Na(I) and/or other cations in aqueous solution might facilitate electrostatic DNA interactions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The mechanisms of naphthacene and triphenylene discrimination using commercially available cellulose tris(4-methylbenzoate) (CMB) and cellulose tribenzoate (CB) chiral stationary phases were investigated using molecular mechanics calculations. Naphthacene and triphenylene could be separated by liquid chromatography on CMB and CB, with triphenylene being eluted earlier than naphthacene on both phases. However, the corresponding separation factor is much larger for CMB than for CB. The docking of these polycyclic aromatic hydrocarbons to the above polymers suggested that the most important sites of CMB and CB for interacting with these hydrocarbons are located at equivalent positions, featuring a space surrounded by main chain glucose units and benzoyl side chains. The difference of hydrocarbon stabilization energies with CMB and CB agreed well with the observed chromatographic separation factors., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We investigated the photophysical properties of difluoroboronated β-diketones (BF2DK) with chrysene and pyrene skeletons (ChB and PyB, respectively) in solution and in the solid state. Acetylchrysenes, as the key precursors to ChBs, were photochemically prepared from the corresponding (acetylphenyl)naphthylethenes by means of a modified photocyclization method. The absorption and emission spectra of the BF2DKs were obtained in chloroform and acetonitrile, and the quantum yields and lifetimes of the fluorescence were determined. Excimeric fluorescence from PyB was absent even in highly concentrated solution. Based on the Lippert-Mataga analysis of the absorption and fluorescence features, the photophysical properties of the ChBs were discussed in comparison with those of PyB. The fluorescence states of the studied BF2DKs are shown to be of a charge-transfer character. The fluorescence quantum yields decrease with increasing the solvent polarity due to the enhanced internal conversion process. The fluorescence quantum yields in the solid state of the studied BF2DKs were determined, and it was found that PyB is fluorescent, whereas the fluorescence quantum yields of the ChBs depend on the substituted position of the chrysene moiety.

Exposure to polycyclic aromatic hydrocarbons (PAHs) is the major human health hazard associated with the Deepwater Horizon oil spill. C2-Chrysenes are representative PAHs present in crude oil and could contaminate the food chain. We describe the metabolism of a C2-chrysene regioisomer, 6-ethylchrysene (6-EC), in human HepG2 cells. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC-MS/MS. 6-EC-tetraol isomers were identified as signature metabolites of the diol-epoxide pathway. O-Monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and N-acetyl-l-cysteine(NAC)-6-EC-ortho-quinone were discovered as signature metabolites of the ortho-quinone pathway. Potential dual metabolic activation of 6-EC involving the formation of bis-electrophiles, i.e., a mono-diol-epoxide and a mono-ortho-quinone within the same structure, bis-diol-epoxides, and bis-ortho-quinones was observed as well. The identification of 6-EC-tetraol, O-monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and NAC-6-EC-ortho-quinone supports potential metabolic activation of 6-EC by P450 and AKR enzymes followed by metabolic detoxification of the ortho-quinone through interception of its redox cycling capability by catechol-O-methyltransferase and sulfotransferase enzymes. The tetraols and catechol conjugates could be used as biomarkers of human exposure to 6-EC resulting from oil spills.

Although concentrations of alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) in oil-contaminated sediments are higher than those of unsubstituted PAHs, only little attention has been given to metabolism and ecotoxicity of alkyl-PAHs. In this study we demonstrated that metabolism of alkyl-PAHs primarily forms polycyclic aromatic acids (PAAs). We generalize this to other alkyl-PAHs, based on literature and the present study of the metabolism of 1-methylphenanthrene, 3,6-dimethylphenanthrene, and 1-, 2-, 3-, and 6-methylchrysene related to their unsubstituted parent PAHs. Also, we observed that body burdens and production of PAAs was related to the position of the methyl group, showing the same isomer specific preferences as for microbial degradation of alkyl-PAHs. We detected a high production of PAAs, and larger metabolism of alkyl-PAHs than their unsubstituted parent PAHs. We therefore propose that carboxylic acid metabolites of alkyl-PAHs have the potential of constituting a new class of contaminants in marine waters that needs attention in relation to ecological risk assessments.

Degradation of chrysene, a four ringed highly carcinogenic polycyclic aromatic hydrocarbon (PAH) has been demonstrated by bacterial mixed culture Biorem-CGBD comprising Achromobacter xylosoxidans, Pseudomonas sp. and Sphingomonas sp., isolated from crude oil polluted saline sites at Bhavnagar coast, Gujarat, India. A full factorial Central Composite Design (CCD) using Response Surface Methodology (RSM) was applied to construct response surfaces, predicting 41.93% of maximum chrysene degradation with an experimental validation of 66.45% chrysene degradation on 15th day, using a combination of 0.175, 0.175 and 0.385 mL of OD600 = 1 inoculum of A. xylosoxidans, Pseudomonas sp. and Sphingomonas sp., respectively and a regression coefficient (R2) of 0.9485 indicating reproducibility of the experiment. It was observed that chrysene degradation can be successfully enhanced using RSM, making mixed culture Biorem-CGBD a potential bioremediation target for PAH contaminated saline sites.

Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and logKow values provided a rough estimation of structure-activity relationships for alkyl-PAHs, but Kow alone did not provide a complete explanation of the chronic toxicity of alkyl PAHs., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In this contribution, we finely tuned the singlet-triplet energy gap (ΔEST) of AIE-active materials to modulate their fluorescence, phosphorescence and delay fluorescence via rational molecular design and investigated the possible ways to harvest their triplet energy in OLEDs. Noteworthily, two molecules o-TPA-3TPE-o-PhCN and o-TPA-3TPE-p-PhCN with larger ΔEST values (0.59 eV and 0.45 eV, respectively) emitted efficient long-lived low temperature phosphorescence in their glassy solutions and exhibited efficient crystallization-induced room temperature phosphorescence (RTP). Meanwhile, it was the first time to observe a novel crystallization-induced delay fluorescence phenomenon in another AIE-active molecule p-TPA-3TPE-p-PhCN owing to its very small ΔEST value (0.21 eV). It was also found that molecules with various ΔEST values showed significantly different temperature sensitivity. Non-doped electroluminescent (EL) devices using these molecules as light-emitting layers were fabricated, exhibiting external quantum efficiencies (EQE) higher than theoretical values of purely singlet emitter type devices. Particularly, p-TPA-3TPE-p-PhCN showed outstanding device performances with high luminance and efficiencies up to 36,900 cd m(-2), 11.2 lm W(-1), 12.8 cd A(-1) and 4.37%, respectively, considering that its solid-state quantum yield was only 42%. All the above observations suggested that tuning the ΔEST values of AIE materials is a powerful methodology to generate many more interesting and meaningful optoelectronic properties.

A series of triphenylenes with oligoethoxy chains of various length, TP6EOnM with n = 2, 3, 4, has been synthesised and purified by HPLC. The self-association of these disc-shaped molecules in dilute aqueous solutions (∼10(-7) to ∼4 × 10(-4) M) has been studied by UV-visible absorption spectroscopy. The free energy of association decreases as the length of the chains increases. As a result, for a given concentration, the average size of aggregate diminishes as the chain length increases. While the absorption properties of the monomer are identical for the three molecules, the extinction coefficients of solutions of the three triphenylenes at a given concentration are significantly different and are directly linked to the average size of the aggregates. The change of epsilon values upon aggregation could explain the trend generally observed with dyes for solar cells substituted with chains of increasing length showing increasing extinction coefficient values.

A tandem one-pot method for the direct synthesis of polysubstituted triphenylene 2,3-dicarboxylic esters with different substitution patterns was developed by enyne metathesis of diarylacetylene, followed by Diels-Alder, aromatization and a cyclization cascade.

In vitro biotransformation assays are currently being explored to improve estimates of bioconcentration factors of potentially bioaccumulative organic chemicals in fish. The present study compares thin-film and solvent-delivery dosing techniques as well as single versus multiple chemical dosing for measuring biotransformation rates of selected polycyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) liver S9. The findings show that biotransformation rates of very hydrophobic substances can be accurately measured in thin-film sorbent-dosing assays from concentration-time profiles in the incubation medium but not from those in the sorbent phase because of low chemical film-to-incubation-medium mass-transfer rates at the incubation temperature of 13.5 °C required for trout liver assays. Biotransformation rates determined by thin-film dosing were greater than those determined by solvent-delivery dosing for chrysene (octanol-water partition coefficient [KOW ] =10(5.60) ) and benzo[a]pyrene (KOW  =10(6.04) ), whereas there were no statistical differences in pyrene (KOW  =10(5.18) ) biotransformation rates between the 2 methods. In sorbent delivery-based assays, simultaneous multiple-chemical dosing produced biotransformation rates that were not statistically different from those measured in single-chemical dosing experiments for pyrene and benzo[a]pyrene but not for chrysene. In solvent-delivery experiments, multiple-chemical dosing produced biotransformation rates that were much smaller than those in single-chemical dosing experiments for all test chemicals. While thin-film sorbent-phase and solvent delivery-based dosing methods are both suitable methods for measuring biotransformation rates of substances of intermediate hydrophobicity, thin-film sorbent-phase dosing may be more suitable for superhydrophobic chemicals., (© 2014 SETAC.)

The present study examines concentrations and risks of polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs (NPAHs), steranes, and hopanes in lake trout collected in Lake Michigan. A total of 74 fish were collected in 2 seasons at 3 offshore sites. The total PAH concentration (Σ9 PAH) in whole fish ranged from 223 pg/g to 1704 pg/g wet weight, and PAH concentrations and profiles were similar across season, site, and sex. The total NPAH (Σ9 NPAH) concentrations ranged from 0.2 pg/g to 31 pg/g wet weight, and carcinogenic compounds, including 1-nitropyrene and 6-nitrochrysene, were detected. In the fall, NPAH concentrations were low at the Illinois site (0.2-0.5 pg/g wet wt), and site profiles differed considerably; in the spring, concentrations and profiles were similar across sites, possibly reflecting changes in fish behavior. In the fall, the total sterane (Σ5 Sterane) and total hopane (Σ2 Hopane) levels reached 808 pg/g and 141 pg/g wet weight, respectively, but concentrations in the spring were 10 times lower. Concentrations in eggs (fall only) were on the same order of magnitude as those in whole fish. These results demonstrate the presence of target semivolatile organic compounds in a top predator fish, and are consistent with PAH biodilution observed previously. Using the available toxicity information for PAHs and NPAHs, the expected cancer risk from consumption of lake trout sampled are low. However, NPAHs contributed a significant portion of the toxic equivalencies in some samples. The present study provides the first measurements of NPAHs in freshwater fish, and results suggest that additional assessment is warranted., (© 2014 SETAC.)

Enterovirus 71 (EV71) can cause severe disease and even lead to death in children, and an effective antiviral drug is currently unavailable. The anti-EV71 effect of chrysin (5,7-dihydroxyflavone), a natural flavonoid commonly found in many plants, was tested in this report. By using the predicting program Autodock 4.0 and an in vitro protease inhibition assay, we found that chrysin could suppress viral 3Cpro activity. Replication of viral RNA and production of viral capsid protein and the infectious virion were strongly inhibited by chrysin, without noticeable cytotoxicity. Cytopathic effects on cells were also prevented. Diisopropyl chrysin-7-yl phosphate (CPI), the phosphate ester for chrysin, was generated through a simplified Atheron-Todd reaction to achieve stronger anti-viral activity. CPI was also able to bind with and inhibit viral 3Cpro activity in vitro. As expected, CPI demonstrated more potent antiviral activity against EV71.

We prepared three discotic liquid crystals (DLCs) based on a triphenylene (TP) disc functionalized with twelve alkyl peripheries. The synthesis of the discogens was performed by a click reaction using Cu(OAc)2 as the catalyst, with six triazolyl groups connecting the TP core with twelve alkyl chains. According to thermal data from differential scanning calorimetry (DSC), discogen , which has the shortest hexyl peripheries, exhibited two LC phases, and and , with decyl and tetradecyl peripheries, respectively, displayed three LC phases as a function of the temperature. Structural analyses using small- and wide-angle X-ray scattering (SAXS and WAXS) techniques revealed ordered and disordered hexagonal columnar LC phases in all the discogens. On the other hand, an unconventional micellar phase with P42/mnm symmetry consisting of thirty micelles was found only in and , when the temperature increased. The thermally induced transformation from the columnar to the micellar phase can be explained by increased chain entropy at higher temperatures. The complex micellar packing in the noncubic phase is attributed to the softness of the DLC micelles because the micellar corona consists of flexible alkyl chains. The discogen design concept in this study (i.e., the introduction of multibranched alkyl peripheries to the discotic mesogens via click chemistry) resulted in unconventional columnar-to-micellar transformation in conventional TP DLCs.

Previous studies in rats, mice, and in vitro systems showed that 6-NC can be metabolically activated by two major pathways: (1) the formation of N-hydroxy-6-aminochrysene by nitroreduction to yield three major adducts, N-(dG-8-yl)-6-AC, 5-(dG-N(2)-yl)-6-AC, and N-(dA-8-yl)-6-AC, and (2) the formation of trans-1,2-dihydroxy-1,2-dihydro-6-hydroxylaminochrysene (1,2-DHD-6-NHOH-C) by a combination of nitroreduction and ring oxidation pathways to yield N-(dG-8-yl)-1,2-DHD-6-AC, 5-(dG-N(2)-yl)-1,2-DHD-6-AC and N-(dA-8-yl)-1,2-DHD-6-AC. These DNA lesions are likely to cause mutations if they are not removed by cellular defense mechanisms before DNA replication occurs. Here, we compared for the first time, in HeLa cell extracts in vitro, the relative nucleotide excision repair (NER) efficiencies of DNA lesions derived from simple nitroreduction and from a combination of nitroreduction and ring oxidation pathways. We show that the N-(dG-8-yl)-1,2-DHD-6-AC adduct is more resistant to NER than the N-(dG-8-yl)-6-AC adduct by a factor of ∼2. Furthermore, the N-(dA-8-yl)-6-AC is much more resistant to repair since its NER efficiency is ∼8-fold lower than that of the N-(dG-8-yl)-6-AC adduct. On the basis of our previous study and the present investigation, lesions derived from 6-NC and benzo[a]pyrene can be ranked from the most to the least resistant lesion as follows: N-(dA-8-yl)-6-AC > N-(dG-8-yl)-1,2-DHD-6-AC > 5-(dG-N(2)-yl)-6-AC ≃ N-(dG-8-yl)-6-AC ≃ (+)-7R,8S,9S,10S-benzo[a]pyrene diol epoxide-derived trans-anti-benzo[a]pyrene-N(2)-dG adduct. The slow repair of the various lesions derived from 6-NC and thus their potential persistence in mammalian tissue could in part account for the powerful carcinogenicity of 6-NC as compared to B[a]P in the rat mammary gland.

Chiral polycyclic aromatic hydrocarbons containing bis(1-adamantyl) groups at the peri-positions, named equatorenes, were synthesized in optically pure form starting from optically pure 4,5-bis(1-adamantyl)-8-methoxy-1-naphthol. A sequential Diels-Alder reaction of furan and arynes generated from 1,2-bromotriflates provided tricyclic and tetracyclic epoxides, and acid-catalyzed aromatization gave phenanthrol and chrysenol. Deoxygenation reactions involving the hydrogenolysis of triflates gave 1,8-bis(1-adamantyl)naphthalene, 1,10-bis(1-adamantyl)phenanthrene, and 1,12-bis(1-adamantyl)chrysene. 3,4-Bis(1-adamantyl)pyrene was synthesized from phenanthrol by Sonogashira coupling and Pt-catalyzed cyclization. Essentially no racemization occurred during the synthesis. X-ray analysis indicated the distorted naphthalene moiety possessing the peri-diadamantyl groups and the flat structure of the other benzene rings. UV-vis analysis of the equatorenes showed considerable redshifts compared with that of the corresponding achiral arenes. Electrochemical analysis of the naphthalene and pyrene indicated that the distortion decreased the highest occupied molecular orbital stability with no marked effect on the lowest unoccupied molecular orbital energy level, and the origin was discussed on the basis of calculation results.

Mycobacterium tuberculosis (Mtb), due to its unusual organization crosses different immune barriers and causes tuberculosis. The advent of multidrug resistance tuberculosis (MDR-TB) has attained alarming situation. Hence, computational drug design has been performed in this work to find potent molecules for this purpose. Isoniazid is a widely used frontline drug against tuberculosis. But reports justified the inactivity of isoniazid on acetylation by Arylamine N-acetyltransferase (NAT). 35 countries were highlighted to have isoniazid resistance from survey in 1998. Hence, Mtb NAT has been selected as the target in the present case and hundred compounds were screened in order to find potent NAT inhibitor to raise the efficacy of isoniazid. Molecular docking with Biosolveit LeadIT and Autodock 4.2 simulation was performed. The result showed 7- methylpicene-1, 2-diol to have -26.77 and -8.26 kcal/mol score in LeadIT and Autodock 4.2. The work validated 7- methylpicene-1, 2-diol to be a potent NAT inhibitor to supplement isoniazid.

Triphenylene twins are intriguing structures, and those bridged through their 3,6-positions by dipyrromethene units give a new class of macrocycles that can be viewed as rigid, expanded porphyrin derivatives in which coplanarity is enforced in a formally antiaromatic π system. Somewhat surprisingly, however, macrocyclization leads to significant overall stabilization of the dipyrromethene chromophores.

Each enantiomer of the diastereomeric pair of bay-region dibenz[a,h]anthracene 3,4-diol-1,2-epoxides in which the benzylic 4-hydroxyl group and epoxide oxygen are either cis (isomer 1) or trans (isomer 2) were evaluated for mutagenic activity. In strains TA 98 and TA 100 of Salmonella typhimurium, the diol epoxide with (1S,2R,3S,4R) absolute configuration [(-)-diol epoxide-1] had the highest mutagenic activity. In Chinese hamster V-79 cells, the diol epoxide with (1R,2S,3S,4R) absolute configuration [(+)-diol epoxide-2] had the highest mutagenic activity. The (1R,2S,3R,4S) diol epoxide [(+)-diol epoxide-1] also had appreciable activity, whereas the other two bay-region diol epoxide enantiomers had very low activity. In tumor studies, the (1R,2S,3S,4R) enantiomer was the only diol epoxide isomer tested that had strong activity as a tumor initiator on mouse skin and in causing lung and liver tumors when injected into newborn mice. This stereoisomer was about one-third as active as the parent hydrocarbon, dibenz[a,h]anthracene as a tumor initiator on mouse skin; it was several-fold more active than dibenz[a,h]anthracene as a lung and liver carcinogen when injected into newborn mice. (-)-(3R,4R)-3β,4α-dihydroxy-3,4-dihydro-dibenz[a,h]anthracene [(-)-3,4-dihydrodiol] was slightly more active than dibenz[a,h]anthracene as a tumor initiator on mouse skin, whereas (+)-(3S,4S)-3α,4β-dihydroxy-3,4-dihydro-dibenz[a,h]anthracene [(+)-3,4-dihydrodiol] had only very weak activity. The present investigation and previous studies with the corresponding four possible enantiopure bay-region diol epoxide enantiomers/diastereomers of benzo[a]pyrene, benz[a]anthracene, chrysene, benzo[c]phenanthrene, dibenz[c,h]acridine, dibenz[a,h]acridine and dibenz[a,h]anthracene indicate that the bay-region diol epoxide enantiomer with [R,S,S,R] absolute stereochemistry has high tumorigenic activity on mouse skin and in newborn mice.

The patch clamp technique in the whole cell configuration is potentially a powerful tool to investigate electroporation (electric-field-induced membrane permeabilization). Membrane polarization beyond certain threshold voltages leads to a steep conductance increase either indicating field-induced pore formation or being due to patch clamp artifacts (seal resistance breakdown). Protoplasts derived from tobacco culture cell lines (Bright Yellow-2, BY-2; Virginia bright Italian-0, VBI-0) were stained with the voltage-sensitive dye ANNINE-6. After establishing the whole cell patch clamp configuration 50-ms command voltage (Ucomm) steps ranging from -500 mV to +500 mV were applied while simultaneously exposing protoplasts to light at 475 nm wavelength. Pulse-induced currents and fluorescence intensity (known to be linearly related to the trans-membrane voltage, Um) were recorded. Plotting fluorescence intensity against Ucomm revealed saturation of the curve at values<-300 mV and >+300 mV and close correlation with theoretical Um values calculated on the basis of membrane pore formation. For BY-2 and VBI-0 protoplasts ANNINE-6 voltage sensitivity was calculated to be -0.0014 mV(-1) and -0.0012 mV(-1), respectively. Voltage ramp experiments revealed cation-selectivity of field-induced pores. Anions are conducted poorly independent of their size. In conclusion, the patch clamp technique is validated as a useful tool in electroporation research., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Herein, we report the development of a new method for the syntheses of substituted triphenylenes from the corresponding 1,2,4-trisubstituted arenes, which were themselves generated in a highly regioselective manner according to an intermolecular alkyne cyclotrimerization reaction that was catalyzed by a novel Co-TMTU complex. This highly regioselective reaction for the formation of 1,2,4-trisubstituted arenes will be a valuable addition to the plethora of tools already available to synthetic chemists and encourage further mechanistic studies of this important alkyne trimerization process.

Glycan-protein interactions are of utmost importance in several biological phenomena. Although the variety of carbohydrate residues in mammalian cells is limited to less than a dozen different sugars, their spatial topographical presentation in what is now associated as the "glycocodes" provides the fundamental keys for specific and high affinity "lock-in" recognition events associated with a wide range of pathologies. Toward deciphering our understanding of these glycocodes, chemists have developed new creative tools that included dendrimer chemistry in order to provide monodisperse multivalent glycoconjugates. This review provides a survey of the numerous aromatic architectures generated for the multivalent presentation of relevant carbohydrates using covalent attachment or supramolecular self-assemblies. The basic concepts toward their controlled syntheses will be described using modern synthetic procedures with a particular emphasis on powerful organometallic methodologies. The large variety of dendritic aromatic scaffolds, together with a brief survey of their unique biophysical and biological properties will be critically reviewed. The distinctiveness of the resulting multivalent glycoarchitectures, encompassing glycoclusters, glycodendrimers and molecularly defined self-assemblies, in forming well organized cross-linked lattices with multivalent carbohydrate binding proteins (lectins) together with their photophysical, medical, and imaging properties will also be briefly highlighted. The topic will be presented in increasing order of aromatic backbone complexities and will end with fullerenes together with self-assembled nanostructures, thus complementing the various scaffolds described in this special thematic issue dedicated to multivalent glycoscience.

Nanoaggregates of a supramolecular ensemble of triphenylene derivative 3 and Cu(2+) ions exhibit 'turn-on' response towards CN(-) ions in an aqueous medium and can detect the trace amount of inorganic cyanide ions (NaCN) in tap water and blood serum milieu.

Chrysene and pyrene are known toxic compounds recalcitrant to biodegradation. Here directed evolution allowed us to identify two new mutants of cytochrome P450 BM3 that are able to hydroxylate both compounds. Random mutagenesis has been used to generate libraries of mutants of P450 BM3 active toward polycyclic aromatic hydrocarbons (PAHs) PAHs. After two rounds of error-prone PCR and backcross with parental DNA, three mutants were identified for improved activity toward pyrene and for the first time a new activity toward chrysene in comparison to the wild type enzyme. The mutants show higher affinity and coupling efficiency for chrysene with faster rates of product formation compared to the wild type. Furthermore, the mutants are able to hydroxylate chrysene in different positions, producing four metabolites, 1-, 3-, 4-, and 6-hydroxychrysene, and to hydroxylate pyrene to 1-hydroxypyrene. The majority of the mutation sites are found to be far from the active site, demonstrating the power of directed evolution in identifying mutations difficult to predict with a rational design approach. The different product profiles obtained for the different P450 BM3 mutants indicate that substrate orientation in the catalytic pocket of the protein can be modified by protein engineering. The mutants can be used for metabolic engineering for safe and cost-effective sustainable production of hydroxylated PAHs for industrial purposes as well as for the assessment of their carcinogenic activity in mammals., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The arenium acid [mesitylene-H](+) has been shown to be an extraordinarily active H/D exchange catalyst for the perdeuteration of polycyclic aromatic hydrocarbons. The reactions take place under ambient conditions in C6D6 as an inexpensive deuterium source. High isolated yields and excellent degrees of deuterium incorporation were achieved using the substrates p-terphenyl, fluoranthene, pyrene, triphenylene, and corannulene.

We report experimental evidence indicating that the nature of the interaction established between HAT(CN)(6), a well-known strong electron acceptor aromatic compound, with mono- or polyatomic anions switches from the almost exclusive formation of reversible anion-π complexes, featuring a markedly charge transfer (CT) or formal electron-transfer (ET) character, to the quantitative and irreversible net production of the anion radical [HAT(CN)(6)](•-) and the dianion [HAT(CN)(6)](2-) species. The preferred mode of interaction is dictated by the electron donor abilities of the interacting anion. Thus, weaker Lewis basic anions such as Br(-) or I(-) are prone to form mainly anion-π complexes. On the contrary, stronger Lewis basic F(-) or (-)OH anions display a net ET process. The ET process can be either thermal or photoinduced depending on the HOMO/LUMO energy difference between the electron donor (anion) and the electron acceptor (HAT(CN)(6)). These ET processes possibly involve the intermediacy of anion-π complexes having strong ET character and producing an ion-pair radical complex. We hypothesize that the irreversible dissociation of the pair of radicals forming the solvent-caged complex is caused by the reduced stability (high reactivity) of the radical resulting from the anion.

We investigate the influence of temperature on the self-assembly of 2,6,11-tricarboxydecyloxy-3,7,10-triundecyloxy triphenylene (asym-TTT) adsorbed on HOPG using scanning tunneling microscopy (STM) at the liquid/solid interface. We show that the packing structures of 2D self-assembled asym-TTT can be precisely tuned by adjusting the substrate temperature. The temperature change from 20 °C to 35 °C induces two phase transitions and increment in the packing density from 0.161 to 0.179 molecules per nm(2). The density-functional theory (DFT) calculations reveal that their interaction energies are similar. In particular, the experimental findings further illustrate the preferential adsorption of guest molecules, such as phthalocyanine, only in the domain of more close packing structures.

Discotic liquid crystalline (DLC) charge transfer (CT) complexes, which combine visible light absorption with rapid charge transfer characteristics within the CT complex, can have a great potential for photovoltaic applications when they can be made to self-assemble in a bulk heterojunction arrangement with separate channels for electron and hole conduction. However, the morphology of some liquid crystalline CT complexes has been under debate for many years. In particular, the liquid crystalline CT complex built from the electron acceptor 2,4,7-trinitro-9-fluorenone (TNF) and discotic molecules has been reported to have the TNF "sandwiched" either between the discotic molecules within the same column or between the columns within the aliphatic tails of the discotic molecules. We present a detailed structural study of the prototypic 1:1 mixture of the discotic 2,3,6,7,10,11-hexakis(hexyloxy)triphenylene (HAT6) and TNF. Nuclear magnetic resonance (NMR) line widths and cross-polarization rates are consistent with the picosecond time scale anisotropic thermal motions of the HAT6 and TNF molecules previously observed. By computational integration of Rietveld refinement analyses of neutron diffraction patterns with density experiments and short-range structural constraints from heteronuclear 2D NMR, we determine that the TNF molecules are vertically oriented between HAT6 columns. The data provide the insight that a morphology of separate hole conducting channels of HAT6 molecules can be realized in the liquid crystalline CT complex.

A general scheme for estimation of aromatic stabilization energies of benzenoid hydrocarbons based on selected topological features has been presented. The reactions have been applied to benzene, naphthalene, anthracene, phenanthrene, pyrene, tetracene, benz[a]anthracene, chrysene, [4]-helicene, anthanthrene and coronene.

The binding behavior of triphenylene based copper ensemble prepared in situ has been investigated toward various anions (F(-), Cl(-), Br(-), I(-), CH(3)COO(-), H(2)PO(4)(-), NO(3)(-), OH(-), ClO(4)(-), CN(-), CO(3)(-) and SO(4)(-)) by UV-vis and fluorescence spectroscopy. Among various anions tested, 1-Cu(2+) ensemble shows selective and sensitive response towards cyanide ions and responds to CN(-) ions even in the presence of bovine serum albumin and in blood serum milieu. Further, as practical application of compound 1, we utilized the TLC strips coated with THF solution of 1 for the solid state detection of copper and cyanide ions.

We have performed electron energy-loss spectroscopy studies in order to investigate the electronic properties of chrysene molecular solids. The valence band electronic excitation spectra and the C 1s core level excitations have been measured for pristine and potassium doped chrysene. The core level studies show a fine structure which signals the presence of four close lying conduction bands close to the Fermi level. Upon potassium doping, these bands are filled with electrons, and we have reached a doping level of about K(2.7)chrysene. Furthermore, undoped chrysene is characterized by an optical gap of about 3.3 eV and five, relatively weak, excitonic features following the excitation onset. Doping induces major changes in the electronic excitation spectra, with a new, prominent low energy excitation at about 1.3 eV. The results of a Kramers-Kronig analysis indicate that this new feature can be assigned to a charge carrier plasmon in the doped material, and momentum dependent studies reveal a negative plasmon dispersion.

The formation of "Russian doll" complexes consisting of [n]cycloparaphenylenes was predicted using quantum chemistry tools. The electronic structures of multiple inclusion complexes containing up to four macrocycles were explored at the M06-2X/6-31G* level of theory. The binding energy between the macrocycles increases from the center to the periphery of the complex and can be >60 kcal mol(-1) for macrocycles containing 14 and 19 repeating units. It has been demonstrated that additional electrostatic interactions originating from the asymmetric electron density distribution observed when comparing the concave and convex macrocycle sides are responsible for the high binding energies in these Russian doll complexes. Oxidation or reduction of the Russian doll complexes creates polarons that are delocalized across the complexes. In the case of polaron cations, most of the polarons are localized at the macrocycle with the smallest ionization potential; for polaron anions, the negative charge is localized across the outer rings of the complex. Because anion polarons are more delocalized than cation polarons, the relaxation energies of the polaron anions were found to be smaller than those of the polaron cations.

Seeing stars: The two-dimensional patterns of the polycyclic heteroaromatic star molecules 1 on graphite vary with the side chain length. For n=12, frustrated self-assembly leads to hierarchically organized superstructures: up to 10 molecules form triangular aggregates which pack densely into hexagonal patterns with very large (15.5 nm) lattice constants., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Orient and conduct: Triphenylene-based discotic ionic liquid crystals (ILCs) with six imidazolium ion pendants can disperse pristine single-walled carbon nanotubes (SWNTs). When the ILC is columnarly assembled, doping with SWNTs results in macroscopic homeotropic columnar orientation. Combination of shear and annealing treatments gives rise to three different orientation states, which determine the anisotropy of electrical conduction., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We used scanning force microscopy (SFM) to study the binding and excited state reactions of the intercalating photoreagent Ru[(TAP)(2)PHEHAT](2+) (TAP = 1,4,5,8-tetraazaphenanthrene; PHEHAT = 1,10-phenanthrolino[5,6-b]1,4,5,8,9,12-hexaazatriphenylene) with DNA. In the ground state, this ruthenium complex combines a strong intercalative binding mode via the PHEHAT ligand, with TAP-mediated hydrogen bonding capabilities. After visible irradiation, SFM imaging of the photoproducts revealed both the structural implications of photocleavages and photoadduct formation. It is found that the rate of photocleaving is strongly increased when the complex can interact with DNA via hydrogen bonding. We demonstrated that the photoadduct increases DNA rigidity, and that the photo-biadduct can crosslink two separate DNA segments in supercoiled DNA. These mechanical and topological effects might have important implications in future therapeutic applications of this type of compounds.

The zinc complex of a new triphenylene based receptor is evaluated for its anti-oxidant activity which is better in comparison to that of commercially available anti-oxidants., (This journal is © The Royal Society of Chemistry 2012)

We address the calculation of charge carrier mobility of liquid-crystalline columnar semiconductors, a very promising class of materials in the field of organic electronics. We employ a simple coarse-grained theoretical approach and study in particular the temperature dependence of the mobility of the well-known triphenylene family of compounds, combining a molecular-level simulation for reproducing the structural changes and the Miller-Abrahams model for the evaluation of the transfer rates within the hopping regime. The effects of electric field, positional and energetic disorder are also considered. Simulations predict a low energetic disorder (~0.05 eV), slightly decreasing with temperature within the crystal, columnar and isotropic phases, and fluctuations of the square transfer integral of the order of 0.003 eV(2). The shape of the temperature-dependent mobility curve is however dominated by the variation of the transfer integral and barely affected by the disorder. Overall, this model reproduces semi-quantitatively all the features of experimentally measured mobilities, on one hand reinforcing the correctness of the hopping transport picture and of its interplay with system morphology, and on the other suggesting future applications for off-lattice modeling of organic electronics devices., (This journal is © the Owner Societies 2012)

An efficient, new, and scalable semisynthesis of glucan synthase inhibitors 1 and 2 from the fermentation product enfumafungin 3 is described. The highlights of the synthesis include a high-yielding ether bond-forming reaction between a bulky sulfamidate 17 and alcohol 4 and a remarkably chemoselective, improved palladium(II)-mediated Corey-Yu allylic oxidation at the highly congested C-12 position of the enfumafungin core. Multi-hundred gram quantities of the target drug candidates 1 and 2 were prepared, in 12 linear steps with 25% isolated yield and 13 linear steps with 22% isolated yield, respectively.