Isoform-specific responses of metallothioneins in a marine pollution biomonitor, the green-lipped mussel Perna viridis, towards different stress stimulations.

Metallothioneins (MTs) are commonly used as biomarker for metal pollution assessment in marine ecosystems. Using integrated genomic and proteomic analyses, this study characterized two types of MT isoform in the digestive gland of a common biomonitor, the green-lipped mussel Perna viridis, towards the challenges of a metal (cadmium; Cd) and a non-metal oxidant (hydrogen peroxide; H2 O2 ) respectively. The two isoforms differed in their deduced protein sequences, with 73 amino acids for MT10-I and 72 for MT10-II (a novel type), but both consisted of a high percentage (27.4 to 29.2%) of cysteine. Two-dimensional gel and Western blot showed that the MT proteins were present in multiple isoform spots, and they were further validated to be MT10-I and MT10-II using MS analysis coupled with unrestricted modifications searching. Expression of mRNA revealed that MT10-I responded promptly to Cd but had a lagged induction to H2 O2 treatments, while MT10-II was exclusively induced by Cd treatment over the course of exposure. Expression of the MT proteins also showed a delayed response to H2 O2 , compared to Cd treatments. This study uncovered the potential different functional roles of various MTs isoforms in P. viridis and thus advances the resolution of using MTs as biomarkers in future applications.

Development of anti-influenza A compounds: a pilot study.

1. There is no effective anti-H5N1 avian influenza agent. 2. A chemical compound­ BFDBSC­can inhibit H5N1 virus infection in cell cultures, and such inhibition might be attributable to its halogenated benzoyl residues. 3. This pilot study assessed anti- H5N1 activity and toxicity of four chemical compounds with halogenated benzoyl residues in cell culture system. 4. Two compounds­FPBFDBSC and BFB-gallate­ showed higher antiviral effectsthan BFDBSC, whearas the other two­BFB-borneol and BFB-menthol­showed lower antiviral effects. These compounds did not show toxicity. 5. The halogenated benzoyl residues may play a key role in anti-H5N1 effects. However, all these compounds showed poor solubility, which may limit their utility

Formation dynamics of excitons and temporal behaviors of Fano resonance due to the exciton-impurity-phonon configuration interaction in ZnO.

Formation dynamics of free and neutral donor bound excitons (FX and D(0)X) in a high quality ZnO single crystal are studied by means of time-resolved photoluminescence (TRPL) at various temperatures. At low-temperatures, FX and D(0)X formation times are determined to be ~5 and ~10 ps, respectively, by fitting the rise process with the Boltzmann sigmoidal function. Temporal information of FX- and D(0)X-longitudinal optical (LO) phonon coupling is also acquired by measuring TRPL spectra of the first-order LO phonon-assisted FX and D(0)X transitions. In particular, interesting time evolution of luminescence intensity in the Fano resonance region due to the configuration interaction of exciton-impurity-phonon is explored.

Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition.

BACKGROUND: Gold(III) porphyrin 1a is a new class of anticancer drug, which inhibits cell proliferation of wide range of human cancer cell lines and induces apoptosis in human nasopharyngeal carcinoma cells. However, the underlying signalling mechanism by which gold(III) porphyrin 1a modifies the intracellular apoptosis pathways in tumour cells has not been explained in detail in neuroblastoma cells. METHODS: Cell proliferation and apoptosis were determined by measuring 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Annexin V binding, respectively. Western blot assay was used to detect proteins involved in apoptotic and Akt pathways. In vivo tumour growth was assessed by inoculating tumour cells to nude mice subcutaneously, and gold(III) porphyrin 1a was administrated intravenously. RESULTS: This study assessed the antitumour effect and mechanism of gold(III) porphyrin 1a on neuroblastoma in vitro and in vivo. Gold(III) porphyrin 1a displayed a growth inhibition and induction of apoptosis in neuroblastoma cells effectively in vitro, which was accompanied with release of cytochrome c and Smac/DIABLO and caspases activation. Further studies indicated that gold(III) porphyrin 1a inhibited X-linked inhibitor of apoptosis (XIAP). However, we found that gold(III) porphyrin 1a can induce a survival signal, Akt activation within minutes and could last for at least 24 h. To further confirm association between activation of Akt and the effectiveness of gold(III) porphyrin 1a, neuroblastoma cells were treated with API-2, an Akt-specific inhibitor. API-2 sensitised cells to gold(III) porphyrin 1a-induced apoptosis and growth inhibition. CONCLUSION: These results suggested that Akt may be considered as a molecular 'brake' that neuroblastoma cells rely on to slow down gold(III) porphyrin 1a-induced apoptosis and antiproliferation. Gold(III) porphyrin 1a is a mitochondrial apoptotic stimulus but also activates Akt, suggesting an involvement of Akt in mediating the effectiveness to growth inhibition and apoptosis by gold(III) porphyrin 1a and that inhibition of Akt can enhance the anticancer activity of gold(III) porphyrin 1a in neuroblastoma.

Structure-activity relationships of flavonoids for vascular relaxation in porcine coronary artery.

Flavonoids are polyphenolic compounds that are widespread in the plant kingdom, and structure-activity relationships (SAR) for vascular relaxation effects were examined for 17 of them using porcine coronary arteries. Density functional theory was employed to calculate the chemical parameters of these compounds. The order of potency for vascular relaxation was as follows: flavones (apigenin and luteolin) >or= flavonols (kaempferol and quercetin)>isoflavones (genistein and daidzein)>flavanon(ol)es (naringenin)>chalcones (phloretin)>anthocyanidins (pelargonidin)>flavan(ol)es ((+)-catechin and (-)-epicatechin). SAR analysis revealed that for good relaxation activity, the 5-OH, 7-OH, 4'-OH, C2=C3 and C4=O functionalities were essential. Comparison of rutin with quercetin, genistin with genistein, and puerarin with daidzein demonstrated that the presence of a glycosylation group greatly reduced relaxation effect. Total energy and molecular volume were also predictive of their relaxation activities. Our findings indicated that the most effective relaxing agents are apigenin, luteolin, kaempferol and genistein. These flavonoids possess the key chemical structures demonstrated in our SAR analysis.

ß-catenin downregulates Dicer to promote ovarian cancer metastasis.

Ovarian cancer is a nearly uniform lethal disease and its highly aggressive metastatic phenotype portends a poor prognosis. Lack of a well-controlled, relevant experimental model has been a major obstacle to identifying key molecules causing metastasis. Here we describe the creation of a new isogenic model of spontaneous human ovarian cancer metastasis exhibiting opposite phenotypes-highly metastatic (HM) and non-metastatic (NM)-both in vitro and in vivo. HM was unique in its ability to metastasize consistently to the peritoneum, mimicking the major dissemination route of human ovarian cancer. In contrast, NM failed to form detectable metastases, although it was equally tumorigenic. Using comparative label-free quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS), we identified ß-catenin, which we demonstrated for the first time as having a direct role in the pathogenesis of ovarian cancer metastasis. Our studies also revealed a previously unrecognized role of ß-catenin in the downregulation of multiple microRNAs (miRNAs) through attenuating miRNA biogenesis by targeting Dicer, a key component of the miRNA-processing machinery. One such downregulated miRNAs was miR-29s involved in epithelial-to-mesenchymal transition and subsequent stem cell traits. Silencing ß-catenin or overexpressing Dicer or miR-29 mimics in HM significantly reduced the ability of these cells to migrate. ß-catenin-knockdown cells also failed to metastasize in an orthotopic model of ovarian cancer. Meta-analysis revealed an increase in CTNNB1 and a decrease in DICER1 expression levels in the high-risk group. These results uncover ß-catenin as a critical factor in promoting ovarian cancer aggressiveness and a new mechanism linking between ß-catenin and miRNA downregulation underlying this process.

Kinetics of electron transfer between cytochrome c and iron hexacyanides. Evidence for two electron-transfer sites.

The electron-transfer reaction between ferrocytochrome c and ferricyanide has been studied by the method of photoexcitation. The observed transfer rate shows saturation behaviour at high ferricyanide concentration. Data analysis indicates that there are two binding sites of vastly different affinities at which electron transfer occurs. The binding constant for the strong binding site decreases from 1600 M-1 to 80 M-1 as the ionic strength increases from 15 mM to 140 mM. At 20 degrees C, the intramolecular electron-transfer rate for this site is 4.65 X 10(4) s-1, which gives an electron-transfer distance of approx. 9.7 A according to Hopfield's model.

Electron transfer between cytochrome c and metal hexacyanide complexes. Effect of thermodynamic driving force on the electron transfer rate.

The electron transfer reactions between ferrocytochrome c and three isomorphic hexacyanide complexes, [Fe(CN)6]3-, [Os(CN)6]3- and [Ru(CN)6]3-, have been studied using the method of photoexcitation. The transfer rates for [Os(CN)6]3- and [Ru(CN)6]3- are, respectively, about 45- and 200-times higher than that of [Fe(CN)6]3-. A reorganization energy of approx. 0.8 eV was found for the cytochrome c-hexacyanide system when the data were analyzed according to the theory of Marcus.

Autophagy-induced RelB/p52 activation mediates tumour-associated macrophage repolarisation and suppression of hepatocellular carcinoma by natural compound baicalin.

The plasticity of tumour-associated macrophages (TAMs) has implicated an influential role in hepatocellular carcinoma (HCC). Repolarisation of TAM towards M1 phenotype characterises an immune-competent microenvironment that favours tumour regression. To investigate the role and mechanism of TAM repolarisation in suppression of HCC by a natural compound baicalin, Orthotopic HCC implantation model was used to investigate the effect of baicalin on HCC; liposome-clodronate was introduced to suppress macrophage populations in mice; bone marrow-derived monocytes (BMDMs) were induced to unpolarised, M1-like, M2-like macrophages and TAM using different conditioned medium. We observed that oral administration of baicalin (50 mg/kg) completely blocked orthotopic growth of implanted HCC. Suppression of HCC by baicalin was diminished when mice macrophage was removed by clodronate treatment. Baicalin induced repolarisation of TAM to M1-like phenotype without specific toxicity to either phenotype of macrophages. Baicalin initiated TAM reprogramming to M1-like macrophage, and promoted pro-inflammatory cytokines production. Co-culturing of HCC cells with baicalin-treated TAMs resulted in reduced proliferation and motility in HCC. Baicalin had minimal effect on derivation of macrophage polarisation factors by HCC cells, while directly induced repolarisation of TAM and M2-like macrophage. This effect was associated with elevated autophagy, and transcriptional activation of RelB/p52 pathway. Suppression of autophagy or RelB abolished skewing of baicalin-treated TAM. Autophagic degradation of TRAF2 in baicalin-treated TAM might be responsible for RelB/p52 activation. Our findings unveil the essential role of TAM repolarisation in suppressive effect of baicalin on HCC, which requires autophagy-associated activation of RelB/p52.

Amidation of saturated C-H bonds catalyzed by electron-deficient ruthenium and manganese porphyrins. A highly catalytic nitrogen atom transfer process.

Amidation of a variety of hydrocarbons with PhI=NTs catalyzed by ruthenium and manganese meso-tetrakis(pentafluorophenyl)porphyrins 1 and 2 afforded N-substituted amides in up to 92% yields with good to excellent substrate conversions. By employing catalyst 2, exceptionally high turnovers (up to 2600) were achieved, and the amidations can be effected by directly using PhI(OAc)(2)/NH(2)R as amidating reagents; in the case of R = COCF(3) a direct amination was realized in up to 90% yield.

Luminescence and photocatalytic properties of a platinum(II)-quaterpyridine complex incorporated in Nafion membrane.

The non-emissive platinum(II)-quaterpyridine complex shows strong photoluminescence at room temperature upon incorporation into Nafion membrane; this complex is stabilized toward photochemical decomposition in Nafion even in the presence of oxygen, and can be used as a sensitizer to generate singlet oxygen to oxidize alkenes.

Efficient multiphoton-absorption-induced luminescence in single-crystalline ZnO at room temperature.

At room temperature, multiphoton absorption- (MPA-) induced photoluminescence in ZnO strongly driven by a femtosecond (fs) near-infrared laser is studied. Two-photon absorption and three-photon absorption are proved to be responsible for the intense luminescence, when the wavelength of the fs excitation laser is above and below the half-bandgap of ZnO, respectively. Strong MPA absorption in ZnO is unambiguously evidenced by the interferometric autocorrelation measurements of the luminescence signal.

Spectral features of LO phonon sidebands in luminescence of free excitons in GaN.

In the paper a combined experimental and theoretical investigation of the longitudinal optical phonon sidebands (PSBs) in the luminescence of free excitons in GaN at moderately high temperatures was reported. The spectral features, including line broadening, shift, and asymmetry of the one- and two-phonon PSBs, were revealed both experimentally and theoretically. It is found that the linewidth of the one-phonon PSB is surprisingly always larger than that of the two-phonon PSB in the interested temperature range. Moreover, the thermal broadening rates of the one- and two-phonon PSBs are considerably different. We adopted the Segall-Mahan theory [B. Segall and G. D. Mahan, Phys. Rev. 171, 935 (1968)] to compute the PSB spectra of the free excitons in GaN. Only one adjustable parameter, the effective mass of the holes, was used in the calculations. For the one-phonon PSB, an excellent agreement between theory and experiment is achieved when an adequate effective mass of the holes was used.

Aurophilic attraction and luminescence of binuclear gold(I) complexes with bridging phosphine ligands: ab initio study.

Electronic structure and spectroscopic properties of [Au2(dpm)2]2+ (dpm = bis(diphosphino)methane) were studied by ab initio calculations. The absorption and emission spectra of this binuclear gold(I) complex in acetonitrile and in the solid state were calculated by single excitation configuration interaction (CIS) method. In the calculations, the solvent effect was taken into account by the weakly solvated [Au2(dpm)2]2+ x (MeCN)2 complex. The ground state structures of [Au2(dpm)2]2+ and [Au2(dpm)2]2+ x (MeCN)2 were optimized by the second-order Møller-Plesset perturbation (MP2) method, while the emissive triplet excited state structures were optimized by the CIS calculations. The results reveal that coordination of acetonitrile to the gold atom in the 3[d(sigma*)s(sigma)] excited state causes a significant red shift in emission energy. The weak aurophilic attraction exists in the ground states of [Au2(dpm)2]2+ and [Au2(dpm)2]2+ x (MeCN)2, and is greatly enhanced in their 3[d(sigma*)s(sigma)] excited states. In acetonitrile, the 3Au(s(sigma)) --> 1Ag(d(sigma*)) transition (phosphorescence) of [Au2(dpm)2]2+ was calculated at 557 nm, in consistent with the observed emission of [Au2(dppm)2](ClO4)2 (dppm = bis(diphenylphosphino)methane) at 575 nm. A high energy emission at 331 nm is predicted for [Au2(dpm)2]2+ in the absence of the interaction between the gold atom and solvent molecule and/or neighboring anion in the excited state. The CIS calculations on the excited states also reveal that the two absorption bands at 278 and 218 nm recorded for [Au2(dcpm)2](ClO4)2 in acetonitrile can be attributed to the 1Ag(d(sigma*)) --> 1Au(p(sigma)) and 1Ag(d(sigma*)) --> 1Au((sp)sigma) transitions, respectively.

Ruthenium complexes with a terminal hydrazido ligand. Synthesis, spectroscopy, and X-ray crystal structure.

Bis(1,1-diphenylhydrazido(1-))ruthenium(IV) porphyrins, [Ru(IV)(Por)(NHNPh2)2] (Por = TPP, TTP, 4-Cl-TPP, 4-MeO-TPP), were prepared in approximately 60% yields through the reaction of dioxoruthenium(VI) porphyrins, [Ru(VI)(Por)O2], with 1,1-diphenylhydrazine in ethanol. This new type of ruthenium complex has been characterized by 1H NMR, IR, UV-vis, and FABMS with elemental analysis. The crystal structure of [Ru(IV)(TTP)(NHNPh2)2], which reveals an eta1-coordination mode for both hydrazido axial ligands, has been determined. The average Ru-NHNPh2 distance and Ru-N-N angle were found to be 1.911(3) A and 141.1(3) degrees, respectively. The porphyrin ring exhibits a ruffling distortion that is unprecedentedly large for ruthenium complexes with simple porphyrinato ligands (such as TTP). This is probably due to the steric effect of the axial hydrazido(1-) ligands.

Highly efficient asymmetric epoxidation of alkenes with a D(4)-symmetric chiral dichlororuthenium(IV) porphyrin catalyst.

A dichlororuthenium(IV) complex of 5,10,15,20-tetrakis[(1S,4R,5R,8S)-1,2,3,4,5,6,7,8-octahydro-1,2:5,8-dimethanoanthrance-9-yl]porphyrin, [Ru(IV)(D(4)-Por)Cl(2)] (1), was prepared by heating [Ru(II)(D(4)-Por)(CO)(MeOH)] (2) in refluxing CCl(4). Complex 1 is characterized by (1)H NMR (paramagnetically shifted pyrrolic protons at delta(H) = -52.3 ppm), FAB-mass spectroscopies, and magnetic susceptibility measurement (mu(eff) = 3.1 mu(B)). The ruthenium complex exhibits remarkable catalytic activity toward enantioselective alkene epoxidation using 2,6-dichloropyridine N-oxide (Cl(2)pyNO) as terminal oxidant. The Ru(IV)-catalyzed styrene epoxidation is achieved within 2 h (versus 48 h for the 2-catalyzed reaction), and optically active styrene oxide was obtained in 69% ee and 84% yield (875 turnovers). Likewise, substituted styrenes and some conjugated cis-disubstituted alkenes (e.g., cis-beta-methylstyrene, cis-1-phenyl-3-penten-1-yne, 1,2-dihydronaphthalene, and 2,2-dimethylchromenes) are converted effectively to their organic epoxides in 50-80% ee under the Ru(IV)-catalyzed conditions, and more than 850 turnovers of epoxides have been attained. When subjecting 1 to four repetitive uses by recharging the reaction mixture with Cl(2)pyNO and styrene, styrene oxide was obtained in a total of 2190 turnovers and 69% ee. UV-vis and ESI-mass spectral analysis of the final reaction mixture revealed that a ruthenium-carbonyl species could have been formed during the catalytic reaction, leading to the apparent catalyst deactivation. We prepared a heterogeneous chiral ruthenium porphyrin catalyst by immobilizing 1 into sol-gel matrix. The heterogeneous catalyst is highly active toward asymmetric styrene epoxidation producing styrene oxide in 69% ee with up to 10,800 turnovers being achieved. The loss of activity of the Ru/sol-gel catalyst is ascribed to catalyst leaching and/or deactivation. On the basis of Hammett correlation (rho(+) = -1.62, R = 0.99) and product analysis, a dioxoruthenium(VI) porphyrin intermediate is not favored.

Substrate-Binding reactions of the 3[dsigma*psigma] excited state of binuclear gold(I) complexes with bridging bis(dicyclohexylphosphino)methane ligands: emission and time-resolved absorption spectroscopic studies.

The complexes [Au2(dcpm)2]-Y2 (dcpm = bis(dicyclohexylphosphino)methane; Y=ClO4 (1), PF6- (2), CF3SO3- (3), Au(CN)2- (4), Cl- (5), SCN (6) and I- (7)) were prepared, and the structures of 1 and 4-7 were determined by X-ray crystallography. Complexes 1-4 display intense phosphorescence with lambdamax at 360-368 nm in the solid state at room temperature as well as in glassy solutions at 77 K. The solid-state emission quantum yields of the powdered samples are 0.37 (1), 0.74 (2), 0.53 (3) and 0.12 (4). Crystalline solid 5 displays both high-energy UV (lambdamax = 366 nm) and low-energy visible emissions (lambdamax = 505 nm) at room temperature, whereas either 6 or 7 shows only an intense emission with lambdamax at 465 or 473 nm, respectively. All the complexes in degassed acetonitrile solutions exhibit an intense phosphorescence with lambdamax ranging from 490 to 530 nm. The high-energy UV emission is assigned to the intrinsic emission of the 3[dsigma*psigma] excited state of [Au2(dcpm)2]2+, whereas the visible emission is attributed to the adduct formation of the triplet excited state with the solvent/counterion. The quenching rate constants of the visible emission of [Au2(dcpm)2]2+ in acetonitrile by various anions are 6.08 x 10(5) (ClO4-), 9.18 x l0(5) (PF6 ), 1.55 x 10(7) (Cl-) and 4.06 x 10(9) (I-) mol(-1) dm3s(-1). The triplet-state difference absorption spectra of 1-4 in acetonitrile show an absorption band with lambdamax at 350 nm and a shoulder/absorption maxima at 395-420 nm; their relative intensities are dependent upon the halide ion present in solution. Substrate binding reactions of the 3[dsigma*psigma] excited state with halide (X-) to give [Au2(dcpm)2X]+* would account for the lower energy absorption maxima in the triplet-state difference absorption spectra. With iodide as the counterion, complex 7 undergoes a photoinduced electron-transfer reaction with I- to give the radical anion I2-.

Luminescent mu-ethynediyl and mu-butadiynediyl binuclear gold(I) complexes: observation of (3)(pi pi*) emissions from bridging C(n)(2-) units.

The synthesis and X-ray structural and spectroscopic characterization for LAuC triple bond CAuL x 4CHCl(3) and LAuC triple bond C--C triple bond CAuL x 2CH(2)Cl(2) (1 x 4CHCl(3) and 2 x 2CH(2)Cl(2), respectively; L = PCy(3), tricyclohexylphosphine) are reported. The bridging C(n)(2-) units are structurally characterized as acetylene or diacetylene units, with C triple bond C distances of 1.19(1) and 1.199(8) A for 1 x 4CHCl(3) and 2 x 2CH(2)Cl(2), respectively. An important consequence of bonding to Au(I) for the C(n)(2-) moieties is that the lowest-energy electronic excited states, which are essentially acetylenic (3)(pi pi*) in nature, acquire sufficient allowedness via Au spin-orbit coupling to appear prominently in both electronic absorption and emission spectra. The origin lines for both complexes are well-defined and are observed at 331 and 413 nm for 1 and 2, respectively. Sharp vibronic progressions corresponding to v(C triple bond C) are observed in both emission and absorption spectra. The acetylenic (3)(pi pi) excited state of 2 has a long lifetime (tau(0) = 10.8 mus) in dichloromethane at room temperature and is a powerful reductant (E degrees [Au(2)(+)/Au(2)] < or = -1.85 V vs SSCE).

Luminescent mononuclear and binuclear cyclometalated palladium(II) complexes of 6-phenyl-2,2 bipyridines: spectroscopic and structural comparisons with platinum(II) analogues.

The mononuclear cyclometalated Pd(II) complexes [Pd(L1)X] (HL1 = 6-phenyl-2,2'-bipyridine; X = Cl, la; Br, 1b; I, 1c), [Pd(L1)PPh3]+ (1d), [Pd(L2-5)Cl] [2a-5a, HL2-5 = 4-(aryl)-6-phenyl-2,2'-bipyridine; aryl = phenyl (2), 4-chlorophenyl (3), 4-tolyl (4), 4-methoxyphenyl (5)] and the binuclear derivatives [Pd2(L1-5)2(mu-dppm)]2+ (1e-5e, dppm = bis(diphenylphosphino)methane) and [Pd2(L1)2(mu-dppCs)]2+, (1f, dppC5 = 1,5-bis(diphenylphosphino)pentane) were prepared. The crystal structures of 1d(ClO4), 1e(ClO4)2 x DMF, and 2e(ClO4)2 have been determined by X-ray crystallography. The magnitude of the Pd-Pd distances in le and 2e (3.230(1) and 3.320(2) A, respectively) suggest minimal metal-metal interaction, although pi-stacking of the aromatic ligands (interplanar separations 3.34 and 3.35 A, respectively) is evident. All complexes display low-energy UV absorptions at lambda approximately 390 nm, which are tentatively assigned to 1MLCT transitions; red shifts resulting from Pd-Pd interactions in the binuclear species are not apparent. The complexes in this work are non-emissive at 298 K, but the cationic derivatives exhibit intense luminescence at 77 K. The structured emissions of 1d and 1f in MeOH/EtOH glass (lambdamax 467-586 nm) and all cationic species in the solid state (lambdamax 493-578 nm) are assigned to intraligand excited states. Complexes le-5e display dual emissions in MeOH/EtOH glass at 77 K, and the broad structureless bands at lambdamax 626-658 nm are attributed to pi-pi excimeric IL transitions. A comparison between the photophysical properties of Pd(II) and Pt(II) congeners is presented.