Depurinating acylfulvene-DNA adducts: characterizing cellular chemical reactions of a selective antitumor agent

Acylfulvenes (AFs) are a class of semisynthetic agents with high toxicity toward certain tumor cells, and for one analogue, hydroxymethylacylfulvene (HMAF), clinical trials are in progress. DNA alkylation by AFs, mediated by bioreductive activation, is believed to contribute to cytotoxicity, but the structures and chemical properties of corresponding DNA adducts are unknown. This study provides the first structural characterization of AF-specific DNA adducts. In the presence of a reductive enzyme, alkenal/one oxidoreductase (AOR), AF selectively alkylates dAdo and dGuo in reactions with a monomeric nucleoside, as well as in reactions with naked or cellular DNA, with 3-alkyl-dAdo as the apparently most abundant AF-DNA adduct. Characterization of this adduct was facilitated by independent chemical synthesis of the corresponding 3-alkyl-Ade adduct. In addition, in naked or cellular DNA, evidence was obtained for the formation of an additional type of adduct resulting from direct conjugate addition of Ade to AF followed by hydrolytic cyclopropane ring-opening, indicating the potential for a competing reaction pathway involving direct DNA alkylation. The major AF-dAdo and AF-dGuo adducts are unstable under physiologically relevant conditions and depurinate to release an alkylated nucleobase in a process that has a half-life of 8.5 h for 3-alkyladenine and less than approximately 2 h for dGuo adducts. DNA alkylation further leads to single-stranded DNA cleavage, occurring exclusively at dGuo and dAdo sites, in a nonsequence-specific manner. In AF-treated cells that were transfected with either AOR or control vectors, the DNA adducts identified match those from in vitro studies. Moreover, a positive correlation was observed between DNA adduct levels and cell sensitivity to AF. The potential contributing roles of AOR-mediated bioactivation and adduct stability to the cytotoxicity of AF are discussed.     

Elastic and inelastic electron tunneling spectroscopy of a new rectifying monolayer

Rectification of electrical current was observed in a Langmuir-Schaefer monolayer of fullerene-bis[ethylthio-tetrakis(3,4-dibutyl-2-thiophene-5-ethenyl)-5-bromo-3,4-dibutyl-2-thiophene] malonate, Au electrodes at room temperature (there are two regimes of asymmetry, at lower bias, i.e., between 0 and +/-2 V, and at higher bias), and also between Pb and Al electrodes at 4.2 K. The latter experiment was coupled with second harmonic detection of the second derivative of the current with respect to voltage (d2I/dV2). The d2I/dV2 spectrum shows intramolecular vibrations, and also two antisymmetric broad bands, centered at +/-0.65 V, due to resonant electron tunneling between the Fermi level(s) of the electrodes and the lowest unoccupied molecular orbital of the molecule.     

Approach on quantitative structure-activity relationship for design of a pH neutral carrier containing tertiary amino group

The quantitative structure-activity relationship (QSAR) for neutral carriers used to prepare hydrogen ion sensors has been studied. A series of synthesized carrier compounds were taken as the training set. Five molecular structure parameters of the compounds were calculated by using CNDO/2 algorithm and used as feature variables in constructing QSAR model. The lower and upper limits of the linear pH response range were taken as the activity measure. The corresponding model equations were derived from the stepwise regression procedure. With the established QSAR model, a new pH carrier, (4-hydroxybenzyl) didodecylamine (XIII) was proposed and synthesized. The PVC membrane pH electrode based on carrier XIII with a wide pH linear response range of 2.0-12.5 was prepared. Having a theoretical Nernstian response slope of 57.2 ± 0.3 mV/pH (n = 5 at 25 °C) without a super-Nernstian phenomenon, the sensor had low resistance, short response time, high selectivity and good reproducibility. Moreover, the sensor was successfully applied to detecting the pH value of serum samples.     

Photocatalysis effect of nanometer TiO2 and TiO2-coated ceramic plate on Hepatitis B virus

The photocatalysis effect of nanometer TiO2 particles and TiO2-coated ceramic plate on Hepatitis B virus surface antigen (HBsAg) was investigated. The ELISA (enzyme-linked immunosorbent assay) standard method was used to assess the efficiency of TiO2 material to destroy the HBsAg. The research has shown that the suspension of TiO2 (0.5g/L) can destroy most of the HBsAg under the irradiation of mercury lamp, with the light intensity of 0.6mW/cm(2) at 365nm wavelength, or under the sunlight irradiation for a few hours. TiO2-coated ceramic plates can also destroy the HBsAg under the irradiation of mercury lamp, with the light intensity of 0.05mW/cm(2) at 365nm wavelength or under the room daylight for a few hours.     

Formation and characterization of the tetranuclear scandium nitride: Sc4N4

The scandium dimer reacts with dinitrogen in solid argon to form the previously characterized planar cyclic Sc(mu-N)2Sc molecule, with the N-N bond being completely cleaved. The cyclic Sc(mu-N)2Sc molecules dimerize on annealing to form a cubic Sc4N4 cluster with tetrahedral symmetry, which is a fundamental building block for ScN nanoparticles and crystals.     

Infrared spectra of chlorinated ethylene cations: C2Cl4+, C2HCl3+, 1,1-C2H2Cl2+, and trans-C2H2Cl2+ in solid argon

Infrared spectra of chlorinated ethylene cations: C2Cl4+, C2HCl3+, 1,1-C2H2Cl2+, and trans-C2H2Cl2+ isolated in solid argon are presented. These cations were produced by co-deposition of chlorinated ethylene/Ar mixtures with high-frequency-discharged Ar at 4 K. Photosensitive absorptions are assigned to different vibrational modes of the cations on the basis of observed chlorine isotopic shifts and quantum chemical frequency calculations. With the removal of one electron from the HOMO of chlorinated ethylene neutrals that is C=C bonding and C-Cl antibonding in character, the observed C-Cl stretching vibrational frequencies of the cations are blue-shifted relative to those of the chlorinated ethylene neutrals. The results also show that the cations can be regarded as "isolated" with the vibrational frequencies only slightly shifted when compared to the available gas-phase values.     

From molecule to bulk material: optical properties of hydrogen-bonded dimers [C12H12N4O2AgPF6]2 and [C28H28N6O3AgPF6]2 depend on the arrangement of the oxime moieties

The dependence of the optical properties of [C(12)H(12)N(4)O(2)AgPF(6)](2) (dimer-1) and [C(28)H(28)N(6)O(3)AgPF(6)](2) (dimer-2) on the arrangement of the oxime moieties in the molecule and in bulk crystals was investigated by means of time-dependent density functional theory. Dimer-1 with simple pyridine oxime ligands and a wavy arrangement has a smaller dipole moment and larger transition energy between the two states, and thus smaller third-order polarizabilities and two-photon absorption cross sections. Dimer-2 with extended pyridine oxime ligands and a ladder arrangement has a larger dipole moment and smaller transition energy between the two states, and thus larger third-order polarizabilities and two-photon absorption cross sections. The lowest energy absorption band is red-shifted for dimer-2 as compared with dimer-1, due to more pronounced pi-pi delocalization interactions and weaker hydrogen bonding in dimer-2. The electronic absorption spectra, frequency-dependent third-order polarizabilities, and two-photon absorption cross sections involve significant contributions from charge transfers from pi/pi* orbitals of the pyridine oxime ligands but no contribution from PF(6) (-) ions or H(2)O molecules in the wavelength range studied for the monomers and dimers of the C(12)H(12)N(4)O(2)AgPF(6) and C(28)H(28)N(6)O(3)AgPF(6) molecules. The third-order susceptibilities and two-photon absorption coefficients of bulk solids were estimated on the basis of the optical properties of the corresponding dimers, and the bulk material constructed from dimer-2 has the larger optical parameters of the two.     

Shape- and phase-controlled synthesis of monodisperse, single-crystalline ternary chalcogenide colloids through a convenient solution synthesis strategy

Colloidal, monodisperse, single-crystalline pyramidal CuInS2 and rectangular AgInS2 nanocrystals were successfully synthesized through a convenient and improved solvothermal process that uses hexadecylamine as a capping reagent. The crystal phase, morphology, crystal lattice, and chemical composition of the as-prepared products were characterized by using X-ray diffraction, transmission electron microscopy (TEM), high-resolution TEM, and energy dispersive X-ray spectroscopy. Results revealed that the as-synthesized CuInS2 colloid is in the tetragonal phase (size: 13-17 nm) and the AgInS2 in the orthorhombic structure (size: 17+/-0.5 nm). A possible shape evolution and crystal growth mechanism has been suggested for the formation of pyramidal CuInS2 and rectangular AgInS2 colloids. Control experiments indicated that the morphology- and/or phase-change of CuInS2 and orthorhombic AgInS2 colloids are temperature- and/or time-dependent. CuInS2 colloids absorb well in the range of visible light at room-temperature, indicating its potential application as a solar absorber. Two photoluminescence (PL) subbands at 1.938 and 2.384 eV in the PL spectra of CuInS2 colloids revealed that the recombination of the closest and the second closest donor-acceptor pairs within the CuInS2 lattice, in which the donor defect (Cui) occupies an interstitial position and the acceptor defect (VIn) resides at an adjacent cation site. In addition, the synthesis strategy developed in this study is convenient and inexpensive, and could also be used as a general process for the synthesis of other pure or doped ternary chalcogenides that require a controlled size (or shape). This process could be extended to the synthesis of other functional nanomaterials.