Inhibitors of farnesyltransferase (FT), a key enzyme in the post-translational modifications of Ras proteins, have been extensively studied as novel anticancer agents in the preclinical stages, some of which are currently in clinical development. Previously, it has been reported that a novel FT inhibitor LB42907 inhibits Ras farnesylation in the nanomolar range in vitro. The aim of this study was to assess the antitumor efficacy of LB42907 in vitro and in vivo. Anchorage-independent growth of various human tumor cell lines was potently inhibited by treatment with LB42907, comparable to other FT inhibitors in clinical development. In the nude mouse, oral administration of LB42907 demonstrated potent antitumor activity in several human tumor xenograft models including bladder, lung and pancreas origin. Interestingly, significant tumor regression in EJ (bladder) and A549 (lung) xenografts was induced by LB42907 treatment. The effectiveness of LB42907 was also investigated in simultaneous combination with paclitaxel, vincristine, cisplatin or gemcitabine against NCI-H460, A549, and HCT116 cells in vitro using median-effect analysis. LB42907 markedly synergized with most anticancer drugs tested in this study in NCI-H460 cell. In contrast, LB42907 displayed antagonism or partial synergism with these drugs in A549 and HCT116 cells, depending on the class of combined drugs and/ or the level of cytotoxicity. Our results demonstrate that LB42907 is an effective antitumor agent in vitro and in vivo and combination of LB42907 with other chemotherapeutic drugs results in synergistic or antagonistic effects mainly in a cell line-dependent manner. Further preclinical study is warranted.

Bacillus halodurans O-methyltransferase (BhOMT) is an S-adenosylmethionine dependent methyltransferase. In our previous study, three dimensional structure of the BhOMT has been determined by comparative homology modeling and automated docking study showed that two hydroxyl groups at 3'- and 4'-position in Bring and structural rigidity of C-ring resulting from the double bond characters between C2 and C3 of flavonoid, were key factors for interaction with BhOMT. In the present study, BhOMT was cloned and expressed. Binding assay was performed on purified BhOMT using fluorescence experiments and binding affinity of luteolin, quercetin, fisetin, and myricetin were measured in the range of $10^7$. Fluorescence quenching experiments indicated that divalent cation plays a critical role on the metal-mediated electrostatic interactions between flavonoid and substrate binding site of BhOMT. Fluorescence study confirmed successfully the data obtained from the docking study and these results imply that hydroxyl group at 7-position of luteolin, quercetin, fisetin, and myricetin forms a stable hydrogen bonding with K211 and carboxyl oxygen of C-ring forms a stable hydrogen bonding with R170. Hydroxyl group at 3'-and 4'-position in the B-ring also has strong $Ca^{2+}$ mediated electrostatic interactions with BhOMT.

A trisaccharide, 6d-Altro-Hepp$\alpha$ (1$\rightarrow$3) GlcNAc$\beta$ (1$\rightarrow$3) Gal$\alpha$ (1$\rightarrow$$OCH_2CH_2N_3$, as an O-antigenic repeating unit of Campylobacter jejuni serotypes O:23 and O:36, was synthesized. Coupling of the 6d-altro-Hepp$\alpha$ (1$\rightarrow$3) GlcNAc$\beta$ (1$\rightarrow$SEt donor with Gal$\alpha$ (1${\rightarrow}OCH_2CH_2Cl$ acceptor in the presence of NIS-TfOH promoter afforded the trisaccharide having the $\beta$ (1$\rightarrow$3) Gal linkage. $\beta$ -Stereospecificity and the desired regioselectivity for the 3-OH Gal are obtained. Subsequent hydrogenation, acetylation, azide displacement, hydrazinolysis, Nacetylation, and finally deacetylation furnished the title trisaccharide hapten for further glycoconjugation.

Phosphomolybdic acid supported on silica gel (PMA-$SiO_2$) is an efficient catalyst for the activation of TMSCN for the facile cyanosilylation of various aldehydes. Cyano transfer from TMSCN to aldehyde proceeds smoothly at rt in presence of 0.8 mol % of PMA-$SiO_2$ leading to a range of cyanosilylether in excellent yield (mostly over 93%) within short reaction time (30 min). The catalyst can be recovered and reused several times without loss of activity.

The acetylene black (AB) was dispersed into water in the presence of dihexadecyl hydrogen phosphate (DHP) via ultrasonication, resulting in a stable and well-distributed AB/DHP suspension. After evaporation of water, an AB/DHP composite film-modified electrode was prepared. The electrochemical responses of $K_3$[Fe$(CN)_6$] at the unmodified electrode, DHP film-modified electrode and AB/DHP film-modified electrode were investigated. It is found that the AB/DHP film-modified electrode possesses larger surface area and electron transfer rate constant. Furthermore, the electrochemical behaviors of 1-naphthylacetic acid (NAA) were examined. At the AB/DHP film-modified electrode, the oxidation peak current of NAA remarkably increases. Based on this, a sensitive and convenient electrochemical method was proposed for the determination of NAA. The linear range is in the range from $4.0 {\times} 10^{-8}\;to\;5.0 {\times} 10^{-6}$ mol $L^{-1}$, and the detection limit is $1.0 {\times} 10^{-8}$ mol $L^{-1}$. Finally, this new sensing method was employed to determine NAA in several soil samples.

Novel $CO_2$-soluble 8-hydroxyquinoline (8-HQ) chelating agents were synthesized and evaluated for solubility and metal ion extraction ability in supercritical $CO_2\;(Sc-CO_2)$. Among them, secondary amide-containing 8- HQ derivatives cannot be dispersed well into Sc-$CO_2$, but tertiary amide-containing derivatives can dissolve completely in Sc-$CO_2$ even at low CO2 pressures, perhaps owing to the predominant intermolecular interaction between the chelating agent and the $CO_2$ molecule. Based on 8-HQ chelating agent solubility data, we investigated the extraction of metal ions ($Co^{2+}$, $Cu^{2+}$, $Sr^{2+}$, $Cd^{2+}$, and $Zn^{2+}$) using two highly $CO_2$-soluble 8-HQ derivatives (4d, 4e) in Sc-$CO_2$. The extraction efficiency of tertiary amide-containing 8-HQ ligands, both fluorinated and non-fluorinated forms, was dramatically increased in the presence of diethyl amine (organic base). We suggest that diethyl amine could play an important synergistic role in the stronger metal binding ability of 8-HQ through an in situ deprotonation reaction in Sc-$CO_2$ medium.

Stable crystalline 1-Benzyl-4-aza-1-azonia-bicyclo[2.2.2]octane tribromide (BABOT), can be readily synthesized from the reaction of the corresponding bromide with $HNO_3$ and aqueous KBr. Selective Oxidation of a variety of dialkyl and alkyl Aryl sulfides to the corresponding sulfoxides in high yield was achieved by this reagent in solution ($CH_3CN/H_2O$) and solvent free conditions. The reaction proceeds under neutral and mild conditions and can be carried out easily at room temperature with regeneration of BABOT. In this method purification of products is straightforward and no over oxidation to sulfone was noted.

Theoretical studies on the un-catalyzed and catalyzed aminations of ketene with $NH_3$ and $(NH_3)_2$, respectively, were studied using MP2 and hybrid density functional theory of B3LYP at the 6-31+G(d,p) and 6- 311+G(3df,2p) basis sets in the gas phase and in benzene and acetonitrile solvents. In the gas phase reaction, the un-catalyzed mechanism was the same as those previously reported by others. The catalyzed mechanism, however, was more complicated than expected requiring three transition states for the complete description of the C=O addition pathways. In the un-catalyzed amination, rate determining step was the breakdown of enol amide but in the catalyzed reaction, it was changed to the formation of enol amide, which was contradictory to the previous findings. Starting from the gas-phase structures, all structures were re-optimized using the CPCM method in solvent medium. In a high dielectric medium, acetonitrile, a zwitterions formed from the reaction of $CH_2$=C=O with $(NH_3)_2$, I(d), exists as a genuine minimum but other zwitterions, I(m) in acetonitrile and I(d) in benzene become unstable when ZPE corrected energies are used. Structural and energetic changes induced by solvation were considered in detail. Lowering of the activation energy by introducing additional $NH_3$ molecule amounted to ca. −20 $\sim$ −25 kcal/mol, which made catalyzed reaction more facile than un-catalyzed one.

A microbial fuel cell (MFC) has been regarded as noble clean energy technology that can directly convert biomass to electricity. However, its low power density is a main limitation to be used as a new energy source. To overcome this limitation, we focused on the anode improvement in a mediator-type MFC using P. vulgaris as a biocatalyst. Fuel cell performance increased when the anode was coated with carbon black or polypyrrole. The best performance was observed when polypyrrole/carbon black (Ppy/CB) composite material was coated on a carbon paper electrode. Our obtained value of 452 mW $m^{-2}$ is the highest value among the reported ones for the similar system. The effects of amount of Ppy/CB, mediator concentration, and amount of P. vulgaris have also been examined.

We report a novel patterning method for a homo-polymeric poly(3-hexylthiophene) (P3HT) nanofilm particularly capable of strong adhesion to a $SiO_2$ surface. An oxidized silicon wafer substrate was micro-contact printed with n-octadecyltrichlorosilane (OTS) monolayer, and subsequently its negative pattern was selfassembled with three different amino-functionalized alkylsilanes, (3-aminopropyl)trimethoxysilane (APS), N- (2-aminoethyl)-3-aminopropyltrimethoxy silane (EDAS), and (3-trimethoxysilylpropyl) diethylenetriamine (DETAS). Then, P3HT nanofilms were selectively grown on the aminosilane pre-patterned areas via the vapor phase polymerization method. To evaluate the adhesion, patterning, and the film itself, the PEDOT nanofilms and SAMs were investigated with a $Scotch^{(R)}$ tape test, contact angle analyzer, ATR-FT-IR, and optical and atomic force microscopes. The evaluation showed that the newly developed all bottom-up process can offer a simple and inexpensive patterning method for P3HT nanofilms robustly adhered to an oxidized Si wafer surface by the mediation of $FeCl_3$ and amino-functionalized alkylsilane SAMs.

Benzyl arylether dendrimers with zinc porphyrin core and terminal vinyl groups have been synthesized and their photophysical properties and the influence of dendritic environments were investigated. Free base porphyrin-cored benzyl arylether dendrimers 1a-1c and 3a-3c, and their zinc derivatives 2a-2c and 4a-4c have been prepared. Absorption spectra are similar for all porphyrin-cored benzyl arylether dendrimers, except that absorption intensity at 280 nm increases in the higher generation of dendrimer. Fluorescence spectra are similar with two bands for all free base porphyrin dendrimers 1a-1c and 3a-3c, although fluorescence intensity ratio of shorter wavelength emission band to longer wavelength band varies with the generation of dendrimer. Emission efficiencies of 1a-1c and 3a-3c are lower than that of TTP. Emission efficiencies of 2a-2c and 4a-4c are higher than that of ZnTTP. Absorption and emission properties of 1a-1c, 2a-2c, 3a-3c, and 4a-4c were affected negligibly with dendritic environments.

Second-order rate constants have been determined spectrophotometrically for reactions of 2,4-dinitrophenyl 2- thiophenecarboxylate (2) with a series of alicyclic secondary amines in 80 mol % $H_2O$/20 mol % DMSO at 25.0 ${\pm}$ 0.1 ${^{\circ}C}$. The Brønsted-type plot exhibits a downward curvature, i.e., the slope decreases from 0.74 to 0.34 as the amine basicity increases. The $pK_a$ at the center of the Brønsted curvature, defined as $pK_a^o$, has been determined to be 9.1. Comparison of the Brønsted-type plot for the reactions of 2 with that for the corresponding reactions of 2,4-dinitrophenyl 2-furoate (1) suggests that reactions of 1 and 2 proceed through a common mechanism, although 2 is less reactive than 1. The curved Brønsted-type plot has been interpreted as a change in RDS of a stepwise mechanism. The replacement of the O atom in the furoyl ring by an S atom (1 $\rightarrow$ 2) does not alter the reaction mechanism but causes a decrease in reactivity. Dissection of the apparent second-order rate constants into the microscopic rate constants has revealed that the $k_2/k_{-1}$ ratio is not influenced upon changing the nonleaving group from furoyl to thiophenecarbonyl. However, $k_1$ has been calculated to be smaller for the reactions of 2 than for the corresponding reactions of 1, indicating that the C=O bond in the thiophenecarboxylate 2 is less electrophilic than that in the furoate 1. The smaller k1 for the reactions of 2 is fully responsible for the fact that 2 is less reactive than 1.

The activity of the catalytic system composed of Fe$(acetylacetonate)_3$ (Fe$(acac)_3$), triphenylphosphine, and diethylaluminum chloride for the dimerization of bicyclo[2.2.1]hepta-2,5-diene (2,5-norbornadiene, NBD) to produce hexacyclic endo-endo dimer (hexacyclo[$7.2.1.0^{2,8}.1^{3,7}.1^{5,13}.0^{4,6}$]tetradec-10-ene, Hnn) was significantly enhanced by the presence of $AlCl_3$, especially at the molar ratios of NBD/Fe$(acac)_3$ of 500. XPS analysis of the catalytic systems clearly demonstrates that $AlCl_3$ facilitates the reduction of Fe$(acac)_3$ to form active species, Fe(II) and Fe(0) species. The layer separation was observed when [BMIm]Cl was used along with $AlCl_3$, but catalyst recycle was not very successful.

A stable twist boat conformation of thiane S-oxide 1a in solid state and in solution was unambiguously determined by single crystal X-ray crystallography and solution NMR analyses. On the contrary, the thiane Sdioxide 2 which was obtained from the oxidation of corresponding thiane S-oxide 1a was confirmed to adopt a regular chair conformation.

Using DFT B3LYP/6-31+G(d,p)//B3LYP/6-31G(d,p) calculation method, stable molecular structures were optimized for the p-tert-butylcalix[4]arene functionalized at lower rim by cage-annulated crown ether (1) in two different conformers and their potassium-ion complexes. Cone conformer of free host 1 was slightly more stable than partial-cone conformer. For two different kinds of complexation mode, the potassium ion in benzene-rings (bz) pocket showed comparable complexation efficiency with the cation in cage-annulated crown-ether (cr) for the cone and partial-cone conformers of 1. The complex (1${\bullet}K^+$) in the cr-binding mode for the partial-cone conformer was more stable than the cone conformer for B3LYP/6-31G(d,p) geometry optimization. However, $1_{(cone)}{\bullet}K^+$(cr) showed lower single-point energy than the $1_{(pc)}{\bullet}K^+$(cr) for B3LYP/6- 31+G(d,p) calculation method.

Highly efficient synthesis of substituted benzo[1,4]oxazin-3-ones and pyrido[1,4]oxazin-2-ones under microwave irradiation via Smiles rearrangement is reported. Substituted benzo[1,4]oxazin-3-ones and pyrido[1,4]oxazin-2-ones were obtained by treatment of substituted 2-chlorophenols or 2-chloropyridols with N-substituted 2-chloroacetamide in the presence of potassium carbonate in MeCN and subsequent exposure to cesium carbonate in DMF. All the reactions which take 2-10 hours under conventional condition were completed successfully within a few minutes under microwave irradiation giving moderate to excellent yields.

Artemisinin, the effective ingredient of Chinese herb Artemisia annua L (Qinghao in Chinese), has been proved to be effective to antimalarial. Herein, a reliable, sensitive and convenient electrochemical method was developed for the determination of artemisinin utilizing the excellent properties of multi-wall carbon nanotube (MWNT). The electrochemical behavior of artemisinin was investigated. It is found that the reduction peak current of artemisinin remarkably increases and the peak potential shifts positively by 240 mV at the MWNT film-modified electrode. These phenomena indicate that the MWNT film exhibits efficient catalytic activity to the electrochemical reduction of artemisinin. The effects of pH value, amount of MWNT, scan rate and accumulation time were examined. The limit of detection (S/N = 3) is as low as 10 $\mu$ g $L^{-1}$. Finally, this newly developed method was used to determine the content of artemisinin in Artemisia annua L.

Polymer materials are very difficult to decompose for the purpose of chemical analysis. Nondestructive analysis without pretreatment provides a suitable solution that will overcome this obstacle. In this study, CRM candidate samples that contained toxic elements such as As, Cd, Cr and Zn in a polypropylene (PP) were analyzed using instrumental neutron activation analysis (INAA). The analytical results were obtained from ten samples selected by random sampling at two different concentration levels (low and high). Particular attention was paid to reducing analytical errors and evaluating the associated uncertainty.