D-π-A conjugated molecules for optoelectronic applications.

Dipolar chromophores consisting of electron donor (D) and electron acceptor (A) groups connected through a conjugated π-bridge have been actively studied and integrated in optoelectronic and electronic devices. Generally, such π-conjugated molecules provide substantial delocalization of π-electrons over the molecules. Here, a brief overview of recent research on D-π-A dipolar chromophores including their syntheses and several promising applications is reported, especially in nonlinear optical devices and organic photovoltaics. Structure/property relationships are discussed in order to exploit the potentials by tuning the π-electron density, polarizability, and HOMO-LUMO band gap of the chromophores. Some of the examples may well set the stage for chip-scale integration of optoelectronics as well as the realization of an important array of new device technologies.

Alkylated fullerene derivatives for solution-processable organic thin-film transistors and bulkheterojunction solar cells.

In this paper, we report synthesis and characterization of alkylated fullerene derivatives for solution-processable organic thin film transistors and solar cells. Their physical, thermal, and semiconducting properties have been studied. Organic thin-film transistors fabricated from C60TH-Oc exhibit electron mobilities as high as 3.2 x 10(-2) cm2 V(-1) s(-1) with 32 V of a threshold voltage. The best power conversion efficiency (PCE) was observed in a layered structure P3HT:C60TH-Oc (PCE = 0.44%), which was a twice value of P3HT:C60TH-Dd (PCE = 0.23%).

Methylation of the JMJD2B epigenetic regulator differentially affects its ability to coactivate the ETV1 and JUN transcription factors.

OBJECTIVES: Jumonji C domain-containing (JMJD) 2B (JMJD2B) is a transcriptional cofactor and histone demethylase that is involved in prostate cancer formation. However, how its function is regulated by posttranslational modification has remained elusive. Hence, we examined if JMJD2B would be regulated by lysine methylation. METHODS: Through in vitro methylation assays and Western blotting with methyl-lysine specific antibodies, we analyzed lysine methylation within JMJD2B. Identified methylated lysine residues were mutated to arginine residues and the respective impact on JMJD2B transcriptional activity measured with a reporter gene assay in human LNCaP prostate cancer cells. RESULTS: We discovered that JMJD2B is methylated on up to six different lysine residues. Further, we identified the suppressor of variegation 3-9/enhancer of zeste/trithorax (SET) domain-containing protein 7/9 (SET7/9) as the methyltransferase being responsible for this posttranslational modification. Mutating the methylation sites in JMJD2B to arginine residues led to diminished coactivation of the Ju-nana (JUN) transcription factor, which is a known oncogenic protein in prostate tumors. In contrast, methylation of JMJD2B had no impact on its ability to coactivate another transcription factor associated with prostate cancer, the DNA-binding protein E26 transformation-specific (ETS) variant 1 (ETV1). Consistent with a potential joint action of JMJD2B, SET7/9 and JUN in prostate cancer, the expression of JMJD2B in human prostate tumors was positively correlated with both SET7/9 and JUN levels. CONCLUSIONS: The identified SET7/9-mediated methylation of JMJD2B appears to impact its cooperation with selected interacting transcription factors in prostate cancer cells. Given the implicated roles of JMJD2B beyond prostate tumorigenesis, SET7/9-mediated methylation of JMJD2B possibly also influences the development of other cancers, while its impairment might have relevance for obesity or a global developmental delay that can be elicited by reduced JMJD2B activity.

SET7/9-mediated methylation affects oncogenic functions of histone demethylase JMJD2A.

The histone demethylase JMJD2A/KDM4A facilitates prostate cancer development, yet how JMJD2A function is regulated has remained elusive. Here, we demonstrate that SET7/9-mediated methylation on 6 lysine residues modulated JMJD2A. Joint mutation of these lysine residues suppressed JMJD2A's ability to stimulate the MMP1 matrix metallopeptidase promoter upon recruitment by the ETV1 transcription factor. Mutation of just 3 methylation sites (K505, K506, and K507) to arginine residues (3xR mutation) was sufficient to maximally reduce JMJD2A transcriptional activity and also decreased its binding to ETV1. Introduction of the 3xR mutation into DU145 prostate cancer cells reduced in vitro growth and invasion and also severely compromised tumorigenesis. Consistently, the 3xR genotype caused transcriptome changes related to cell proliferation and invasion pathways, including downregulation of MMP1 and the NPM3 nucleophosmin/nucleoplasmin gene. NPM3 downregulation phenocopied and its overexpression rescued, to a large degree, the 3xR mutation in DU145 cells, suggesting that NPM3 was a seminal downstream effector of methylated JMJD2A. Moreover, we found that NPM3 was overexpressed in prostate cancer and might be indicative of disease aggressiveness. SET7/9-mediated lysine methylation of JMJD2A may aggravate prostate tumorigenesis in a manner dependent on NPM3, implying that the SET7/9→JMJD2A→NPM3 axis could be targeted for therapy.

Methylation of the epigenetic JMJD2D protein by SET7/9 promotes prostate tumorigenesis.

How the function of the JMJD2D epigenetic regulator is regulated or whether it plays a role in prostate cancer has remained elusive. We found that JMJD2D was overexpressed in prostate tumors, stimulated prostate cancer cell growth and became methylated by SET7/9 on K427. Mutation of this lysine residue in JMJD2D reduced the ability of DU145 prostate cancer cells to grow, invade and form tumors and elicited extensive transcriptomic changes. This included downregulation of CBLC, a ubiquitin ligase gene with hitherto unknown functions in prostate cancer, and upregulation of PLAGL1, a transcription factor with reported tumor suppressive characteristics in the prostate. Bioinformatic analyses indicated that CBLC expression was elevated in prostate tumors. Further, downregulation of CBLC largely phenocopied the effects of the K427 mutation on DU145 cells. In sum, these data have unveiled a novel mode of regulation of JMJD2D through lysine methylation, illustrated how this can affect oncogenic properties by influencing expression of the CBLC gene, and established a pro-tumorigenic role for CBLC in the prostate. A corollary is that JMJD2D and CBLC inhibitors could have therapeutic benefits in the treatment of prostate and possibly other cancers.

The JMJD2A demethylase regulates apoptosis and proliferation in colon cancer cells.

JMJD2A is a transcriptional cofactor and enzyme that catalyzes demethylation of histone H3 lysines 9 and 36 and is overexpressed in human tumors, but its role in oncogenesis remains unclear. Here, we show that JMJD2A interacts with the tumor suppressor p53 both in vitro and in HCT116 colon cancer cells. Chromatin immunoprecipitation assays demonstrated that JMJD2A was recruited together with p53 to the promoter of the p21 cell cycle inhibitor upon stimulation with the DNA damaging agent, adriamycin. Downregulation of JMJD2A resulted in increased expression of p21 and of the pro-apoptotic Puma protein, whereas levels of the anti-apoptotic Bcl-2 protein were decreased. Furthermore, JMJD2A knock-down led to reduced HCT116, DLD-1 and HT-29 colon cancer cell proliferation, while overexpression of JMJD2A enhanced HCT116 proliferation in low serum media. Finally, JMJD2A depletion induced apoptosis in HCT116 cells and this effect was less pronounced in the absence of p53. Collectively, these data indicate that JMJD2A is a novel promoter of colon cancer cell proliferation and survival, which mediates its effects in p53-dependent and -independent ways. JMJD2A may therefore be a valid target to sensitize tumor cells to chemotherapy-induced cell death and growth suppression.

Crosslinkable nonlinear optical dendrimers synthesized by Diels-Alder reaction.

Crosslinkable NLO dendrimers based on azobenzene-type chromophores were synthesized by a Diels-Alder reaction. Their thermal and optical properties were investigated before and after poling at a high temperature. We found that the dendrimers retained good thermal stability up to 260 degrees C after curing at 130 degrees C for 10 min based on thermal analysis. Through in-situ poling and curing processes, the highest NLO activity of the dendrimers was d33 = 1.7 x 10(-6) esu at 1064 nm, which was determined by a Maker fringe experiment.

Synthesis and characterization of anthracene derivative for organic field-effect transistor fabrication.

Here we report on the synthesis and characterization of anthracene derivative for solution processable organic field-effect transistors. The transistor devices with bottom-contact geometry provided a maximum field-effect mobility of 3.74 x 10(-4) cm2 V(-1) s(-1) as well as current on/off ratio of 5.05 x 10(4) and low threshold voltage. Structural information in the solid state is obtained by thermal analysis and two-dimensional wide angle X-ray scattering (2D-WAXS). From the 2D-WAXS, it is clear that the planes of anthracene rings and benzene ring of the molecule are different in solid state. We assume similar arrangement in the thin-film which limit the effective hopping and thus charge mobility.

Synthesis and photophysical properties of two-photon absorbing spirofluorene derivatives.

New spirofluorene-based quadrupolar two-photon absorbing dyes having triphenylamine and N,N-dibutylaniline as electron donors at the end of molcules were designed and synthesized. The third-order nonlinear optical properties of these compounds were studied using a two-photon excited fluorescence method. They were found to have high two-photon absorption cross-section owing to extended conjugation of the spirofluorene moiety. The effect of varying the donor strength could be discerned by comparing the two compounds. They were successfully used as a photosensitizers for two-photon initiated polymerization of three-dimensional micro-objects.

Ultrafast exciton dissociation followed by nongeminate charge recombination in PCDTBT:PCBM photovoltaic blends.

The precise mechanism and dynamics of charge generation and recombination in bulk heterojunction polymer:fullerene blend films typically used in organic photovoltaic devices have been intensively studied by many research groups, but nonetheless remain debated. In particular the role of interfacial charge-transfer (CT) states in the generation of free charge carriers, an important step for the understanding of device function, is still under active discussion. In this article we present direct optical probes of the exciton dynamics in pristine films of a prototypic polycarbazole-based photovoltaic donor polymer, namely poly[N-11''-henicosanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (PCDTBT), as well as the charge generation and recombination dynamics in as-cast and annealed photovoltaic blend films using methanofullerene (PC(61)BM) as electron acceptor. In contrast to earlier studies we use broadband (500-1100 nm) transient absorption spectroscopy including the previously unobserved but very important time range between 2 ns and 1 ms, which allows us not only to observe the entire charge carrier recombination dynamics but also to quantify the existing decay channels. We determine that ultrafast exciton dissociation occurs in blends and leads to two separate pools of products, namely Coulombically bound charge-transfer (CT) states and unbound (free) charge carriers. The recombination dynamics are analyzed within the framework of a previously reported model for poly(3-hexylthiophene):PCBM (Howard, I. A. J. Am. Chem. Soc. 2010, 132, 14866) based on concomitant geminate recombination of CT states and nongeminate recombination of free charge carriers. The results reveal that only ~11% of the initial photoexcitations generate interfacial CT states that recombine exclusively by fast nanosecond geminate recombination and thus do not contribute to the photocurrent, whereas ~89% of excitons create free charge carriers on an ultrafast time scale that then contribute to the extracted photocurrent. Despite the high yield of free charges the power conversion efficiency of devices remains moderate at about 3.0%. This is largely a consequence of the low fill factor of devices. We relate the low fill factor to significant energetic disorder present in the pristine polymer and in the polymer:fullerene blends. In the former we observed a significant spectral relaxation of exciton emission (fluorescence) and in the latter of the polaron-induced ground-state bleaching, implying that the density of states (DOS) for both excitons and charge carriers is significantly broadened by energetic disorder in pristine PCDTBT and in its blend with PCBM. This disorder leads to charge trapping in solar cells, which in turn causes higher carrier concentrations and more significant nongeminate recombination. The nongeminate recombination has a significant impact on the IV curves of devices, namely its competition with charge carrier extraction causes a stronger bias dependence of the photocurrent of devices, in turn leading to the poor device fill factor. In addition our results demonstrate the importance of ultrafast free carrier generation and suppression of interfacial CT-state formation and question the applicability of the often used Braun-Onsager model to describe the bias dependence of the photocurrent in polymer:fullerene organic photovoltaic devices.

Expression and functional characterization of three squalene synthase genes associated with saponin biosynthesis in Panax ginseng.

Squalene synthase (SQS) catalyzes the biosynthesis of squalene by condensing two molecules of farnesyl pyrophosphate (FPP), a key precursor in sterol and triterpene biosynthesis. Previously, we reported that PgSS1 overexpression results in the enhanced biosynthesis of both phytosterols and triterpene saponins in Panax ginseng. Here, cDNAs encoding two new SQS homologs (PgSS2 and PgSS3) from a P. ginseng expressed sequence tag (EST) library are described. Functional complementation analysis revealed that ectopic expression of PgSS1, PgSS2 and PgSS3 in the yeast erg9 mutant strain 2C1 lacking SQS activity restored ergosterol prototrophy. The recombinant mutant yeast produced squalene, squalene epoxide and ergosterol. PgSS1 (mRNA) was highly transcribed in all organs, whereas PgSS2 and PgSS3 (mRNAs) were only transcribed in specific organs. All three genes were activated positively by an elicitor (methyl jasmonate), but their transcriptional patterns were different. In situ hybridization analysis revealed that both PgSS1 and PgSS3 transcripts were preferentially accumulated near conducting tissue in the petiole. The PgSS1 and PgSS3 promoters were isolated, and the tissue- and organ-specific regulation of PgSS genes was examined. Transgenic ginseng was constructed by introducing PgSS1 and PgSS3 promoters fused to the ß-glucuronidase (GUS) gene. GUS expression driven by the PgSS1 promoter was found in both roots and shoots, but PgSS3-driven GUS was only found in shoots. These results suggest that the three SQS genes are differently expressed and that all three SQS enzymes are involved in squalene production in P. ginseng.

Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/ß-catenin in SW480 human colon cancer cells.

BACKGROUND: Polysaccharides extracted from the Phellinus linteus (PL) mushroom are known to possess anti-tumor effects. However, the molecular mechanisms responsible for the anti-tumor properties of PL remain to be explored. Experiments were carried out to unravel the anticancer effects of PL. METHODS: The anti-cancer effects of PL were examined in SW480 colon cancer cells by evaluating cell proliferation, invasion and matrix metallo-proteinase (MMP) activity. The anti-angiogenic effects of PL were examined by assessing human umbilical vein endothelial cell (HUVEC) proliferation and capillary tube formation. The in vivo effect of PL was evaluated in an athymic nude mouse SW480 tumor engraft model. RESULTS: PL (125-1000 µg/mL) significantly inhibited cell proliferation and decreased ß-catenin expression in SW480 cells. Expression of cyclin D1, one of the downstream-regulated genes of ß-catenin, and T-cell factor/lymphocyte enhancer binding factor (TCF/LEF) transcription activity were also significantly reduced by PL treatment. PL inhibited in vitro invasion and motility as well as the activity of MMP-9. In addition, PL treatment inhibited HUVEC proliferation and capillary tube formation. Tumor growth of SW480 cells implanted into nude mice was significantly decreased as a consequence of PL treatment, and tumor tissues from treated animals showed an increase in the apoptotic index and a decrease in ß-catenin expression. Moreover, the proliferation index and microvessel density were significantly decreased. CONCLUSIONS: These data suggest that PL suppresses tumor growth, invasion, and angiogenesis through the inhibition of Wnt/ß-catenin signaling in certain colon cancer cells.

Detection of DNA-hybridization using a near-field scanning microwave microscope.

A near-field scanning microwave microscope (NSMM) is used to detect sequence-specific hybridization between surface-immobilized and free DNA single strands. Hybridization between target (free) and capture (immobilized) sequences leads to changes in the reflection coefficient (S11) which are measured by the NSMM. These changes are caused by hybridization-induced modification of the dielectric constant profile of the DNA film. NSMM instrumentation does not require labeling of target sequences with fluorophores or other tagging groups. The physical basis of reflection coefficient changes underpinning the NSMM approach is discussed.

Efficient Inverted Solar Cells Using Benzotriazole-Based Small Molecule and Polymers.

We synthesized medium-band-gap donor-acceptor (D-A) -type conjugated polymers (PBTZCZ-L and PBTZCZ-H) consisting of a benzotriazole building block as an acceptor and a carbazole unit as a donor. In comparison with the polymers, a small conjugated molecule (BTZCZ-2) was developed, and its structural, thermal, optical, and photovoltaic properties were investigated. The power conversion efficiency (PCE) of the BTZCZ-2-based solar cell devices was less than 0.5%, considerably lower than those of polymer-based devices with conventional device structures. However, inverted solar cell devices configured with glass/ITO/ZnO:PEIE/BTZCZ-2:PC71BM/MoO3/Ag showed a tremendously improved efficiency (PCE: 5.05%, Jsc: 9.95 mA/cm2, Voc: 0.89 V, and FF: 57.0%). We believe that this is attributed to high energy transfer and excellent film morphologies.

Histone demethylase JARID1B/KDM5B is a corepressor of TIEG1/KLF10.

JARID1B/KDM5B (jumonji AT-rich interactive domain 1B/lysine-specific demethylase 5B) is an enzyme that efficiently removes methyl residues from trimethylated lysine 4 on histone H3, a pivotal mark for active chromatin. TIEG1/KLF10 (transforming growth factor-ß inducible early gene-1/Krüppel-like transcription factor 10) is a zinc-finger transcription factor that is involved in bone metabolism and exerts antiproliferative activity. Here, we found that TIEG1 interacts with JARID1B. In particular, the repression domains of TIEG1 bind to the C-terminus of JARID1B. Moreover, overexpression of JARID1B augments TIEG1 to repress transcription of Smad7, an inhibitor of the TGF-ß (transforming growth factor-ß) signaling pathway. Conversely, JARID1B knock-down leads to increased Smad7 mRNA levels. Thus, TIEG1 and JARID1B may cooperate to suppress tumorigenesis by enhancing TGF-ß signaling. Notably, both TIEG1 and JARID1B are downregulated in melanomas, suggesting that they indeed cooperate physiologically. In conclusion, JARID1B is the first TIEG1 corepressor identified, explaining how TIEG1 represses transcription through inducing histone H3 lysine 4 demethylation, which may be important for TIEG1 function in both normal and cancer cells.

Diethynylbenzene-based liquid crystalline semiconductor for solution-processable organic thin-film transistors.

We report here the synthesis and characterization of novel diethynylbenzene-based liquid crystalline semiconductor (P1) for organic thin-film transistors (OTFTs). Compound P1 was synthesized by the Sonogashira coupling reaction between 2-bromo-5-(4-hexylthiophen-2-yl)thieno[3,2-b]thiophene and 1,4-bis(dodecyloxy)-2,5-diethynylbenzene. Top contact OTFTs were fabricated by spin casting with 2 wt% solution of P1 in chloroform and their best performance, which exhibited a hole mobility of 4.5 x 10(-5) cm2/Vs, was showed after annealing of the films at liquid crystalline temperature. Time-of-flight (TOF) mobility measured at liquid crystalline phase was observed to be 1.5 x 10(-6) cm2/Vs for both positive and negative carriers. These results indicate that the liquid crystallinity helps to improve the molecular packing and enhance charge mobility for P1. These advantages can be applicable to design and construct solution-processable OTFT materials for electronic applications.

Synthesis and properties of a solution-processable truxene derivative for OLED devices.

A soluble truxene derivative (TR1) attached with triphenylamine at the peripheral position was designed and synthesized. The structure and purity of TR1 were carefully characterized by 1H NMR, UV/vis and photoluminescent spectroscopy, mass spectroscopy, and thermal analyses. It exhibited good solubility in common organic solvents and good film forming properties. The maximum absorption and emission peaks in THF solution were shown at 358 nm and 415 nm, respectively. Bright blue emission was observed in both solution and solid states under UV excitation. The fluorescent quantum efficiency was 0.46. The best luminous efficiency was found to be 3.65 cd/A with CIE coordinates of (0.163, 0.260) in electroluminescence devices.

Degenerate multi-photon properties of spirofluorene derivatives.

Two- and three-photon absorption properties of the fluorene-based chromophores have been investigated. The two- and three-photon absorption cross-section are found to be increased with the strength of the electron donor groups in the order of N-ethylcarbazoyl (1), triphenylamino (2), and N,N-dibutylanilino (3) groups. This nonlinear absorption enhancement can be interpreted by the increase of intramolecular charge transfer facilitated by strong electron donors and the decreased detuning energy (deltaE). Furthermore, direct laser microfabrication by two-photon photopolymerization with compound 2 as a two-photon sensitizer was carried out. Laser exposure time-dependent lateral voxel size has also been studied.

Transduction of artificial transcriptional regulatory proteins into human cells.

Protein transduction (PT) is a method for delivering proteins into mammalian cells. PT is accomplished by linking a small peptide tag--called a PT domain (PTD)--to a protein of interest, which generates a functional fusion protein that can penetrate efficiently into mammalian cells. In order to study the functions of a transcription factor (TF) of interest, expression plasmids that encode the TF often are transfected into mammalian cells. However, the efficiency of DNA transfection is highly variable among different cell types and is usually very low in primary cells, stem cells and tumor cells. Zinc-finger transcription factors (ZF-TFs) can be tailor-made to target almost any gene in the human genome. However, the extremely low efficiency of DNA transfection into cancer cells, both in vivo and in vitro, limits the utility of ZF-TFs. Here, we report on an artificial ZF-TF that has been fused to a well-characterized PTD from the human immunodeficiency virus-1 (HIV-1) transcriptional activator protein, Tat. This ZF-TF targeted the endogenous promoter of the human VEGF-A gene. The PTD-attached ZF-TF was delivered efficiently into human cells in vitro. In addition, the VEGF-A-specific transcriptional repressor retarded the growth rate of tumor cells in a mouse xenograft experiment.

The complete chloroplast genome of Korean Gastrodia elata Blume.

The completed chloroplast genome of Gastrodia elata Blume (G. elata) from Korea was determined in this study. The cpDNA is 35,230 bp in length and lacked the large and small single copy (LSC and SSC) regions, due to the lost inverted repeat (IR). The overall AT content is 73.30%, and the cpDNA contains 20 protein-coding genes, 5 tRNA genes, and 3 rRNA genes. Remarkably, the Korean G. elata cp genome was 74 bp smaller than that of the Chinese G. elata. It revealed substantial sequence variants 495 SNPs and 75 InDels between the two G. elata genomes.