Photosensitized oxidative DNA damage: from hole injection to chemical product formation and strand cleavage

Oxidatively generated damage to DNA induced by a pyrenyl photosensitizer residue (Py) covalently attached to a guanine base in the DNA sequence context 5'-d(CAT[G1Py]CG2TCCTAC) in aerated solutions was monitored from the initial one-electron transfer, or hole injection step, to the formation of chemical end-products monitored by HPLC, mass spectrometry, and high-resolution gel electrophoresis. Hole injection into the DNA was initiated by two-photon excitation of the Py residue with 355 nm laser pulses, thus producing the radical cation Py*+ and hydrated electrons; the latter are trapped by O2, thus forming the superoxide anion O2*-. The decay of the Py*+ radical is correlated with the appearance of the G*+/G(-H)* radical on microsecond time scales, and O2*- combines with guanine radicals at G1 to form alkali-labile 2,5-diamino-4H-imidazolone lesions (Iz1Py). Product formation in the modified strand is smaller by a factor of 2.4 in double-stranded than in single-stranded DNA. In double-stranded DNA, hot piperidine-mediated cleavage at G2 occurs only after G1Py, an efficient hole trap, is oxidized thus generating tandem lesions. An upper limit of hole hopping rates, khh < 5 x 103 s-1 from G1*+-Py to G2 can be estimated from the known rates of the combination reaction of the G(-H)* and O2*- radicals. The formation of Iz products in the unmodified complementary strand compared to the modified strand in the duplex is approximately 10 times smaller. The formation of tandem lesions is observed even at low levels of irradiation corresponding to "single-hit" conditions when less than approximately 10% of the oligonucleotide strands are damaged. A plausible mechanism for this observation is discussed.     

Mechanisms of oxidation of guanine in DNA by carbonate radical anion, a decomposition product of nitrosoperoxycarbonate

Peroxynitrite is produced during inflammation and combines rapidly with carbon dioxide to yield the unstable nitrosoperoxycarbonate, which decomposes (in part) to CO(3) (.-) and (.)NO(2) radicals. The CO(3) (.-) radicals oxidize guanine bases in DNA through a one-electron transfer reaction process that ultimately results in the formation of stable guanine oxidation products. Here we have explored these mechanisms, starting with a spectroscopic study of the kinetics of electron transfer from 20-22mer double-stranded oligonucleotides to CO(3) (.-) radicals, together with the effects of base sequence on the formation of the end-products in runs of one, two, or three contiguous guanines. The distributions of these alkali-labile lesions were determined by gel electrophoresis methods. The cascade of events was initiated through the use of 308 nm XeCl excimer laser pulses to generate CO(3) (.-) radicals by an established method based on the photodissociation of persulfate to sulfate radicals and the oxidation of bicarbonate. Although the Saito model (Saito et al., J. Am. Chem. Soc. 1995, 117, 6406-6407) predicts relative ease of one-electron oxidations in DNA, following the trend 5'-GGG > 5'-GG > 5'-G, we found that the rate constants for CO(3) (.-)-mediated oxidation of guanines in these sequence contexts (k(5)) showed only small variation within a narrow range [(1.5-3.0)x10(7) M(-1) s(-1)]. In contrast, the distributions of the end-products are dependent on the base sequence context and are higher at the 5'-G in 5'-GG sequences and at the first two 5'-guanines in the 5'-GGG sequences. These effects are attributed to a combination of initial hole distributions among the contiguous guanines and the subsequent differences in chemical reaction yields at each guanine. The lack of dependence of k(5) on sequence context indicates that the one-electron oxidation of guanine in DNA by CO(3) (.-) radicals occurs by an inner-sphere mechanism.     

Synthetic 6-O-methylglucose-containing polysaccharides (sMGPs): design and synthesis

With the hope of mimicking the chemical and biological properties of natural 6-O-methyl-D-glucose-containing polysaccharides (MGPs), synthetic 6-O-methyl-D-glucose-containing polysaccharides (sMGPs) were designed and synthesized from alpha-, beta-, and gamma-cyclodextrins (CDs). The synthetic route proved to be flexible and general, to furnish a series of sMGPs ranging from 6-mer to 20-mer. A practical and scalable method was discovered selectively to cleave the CD derivatives and furnish the linear precursors to the glycosyl donors and acceptors. The Mukaiyama glycosidation was adopted to couple the glycosyl donors with the glycosyl acceptors. Unlike in the 3-O-methyl-D-mannose-containing polysaccharide (sMMP) series, the amount of the Mukaiyama acid required in the sMGP series increased with an increase of substrate size; that is, for large oligomers, more than one equivalent of the acid was required.     

Anthraquinones, Cdc25B phosphatase inhibitors, isolated from the roots of Polygonum multiflorum Thunb

Three anthraquinones, Cdc25B phosphatase inhibitors, were isolated from the methanolic extract of the roots of Polygonum multiflorum Thunb. (Polygonaceae). Anthraquinones, physcion (1), emodin (2), and questin (3), inhibited the enzymatic activity of Cdc25B phosphatase with IC(50) values of 62.5, 30, and 34 microg mL(-1), respectively. Emodin (2) and questin (3) strongly inhibited the growth of human colon cancer cells, SW620 with GI(50) values of 6.1 and 0.9 microg mL(-1), respectively. Commercially available anthraquinones, chrysophanol (4), and rhein (5) also inhibited Cdc25B phosphatase with IC(50) values of 10.7 and 22.1 microg mL(-1), respectively.     

SIM(2)-invariant modifications of electrodynamic theory

In the Cohen–Glashow Very Special Relativity we exhibit possible modifications to the Maxwell theory and to the quantum electrodynamics Lagrangian in some generality, and discuss characteristic features depending on the modifications. Modified gauge transformations in SIM(2)-invariant theories are introduced and the related gauge fields, with two polarization states, can have nonzero mass. Also considered are SIM(2)-covariant modifications to the Proca-type field equations for a massive spin-1 particle.     

Enhanced Hydrogen Storage by Palladium Nanoparticles Fabricated in a Redox‐Active Metal–Organic Framework

Quick on the uptake : Palladium nanoparticles were fabricated simply by immersing {[Zn₃(ntb)₂(EtOH)₂]?4 EtOH}_n ( 1 ) in an MeCN solution of Pd(NO₃)₂ at room temperature, without any extra reducing agent. 3 wt % PdNPs@[ 1 ]^0.54+(NO₃^?)_0.54 significantly increase H₂ uptake capacities, both at 77 K and 1 bar and at 298 K and high pressures (see picture, red curve) compared to [Zn₃(ntb)₂]_n (black). ntb=4,4′,4′′‐nitrilotrisbenzoate.

     

A relationship between subpermanents and the arithmetic-geometric mean inequality

Using the arithmetic-geometric mean inequality, we give bounds for k-subpermanents of nonnegative n×n matrices F. In the case k=n, we exhibit an n²-set S whose arithmetic and geometric means constitute upper and lower bounds for per(F)/n!. We offer sharpened versions of these bounds when F has zero-valued entries.     

Downward self‐polarization of lead‐free (K0.5Na0.5)(Mn0.005Nb0.995)O3 ferroelectric thin films on Nb:SrTiO3 substrate

Spontaneously appearing macroscopic polarization (self‐polarization) in ferroelectrics without an electrode or an external electric field would enable the freedom to design many ferroelectric heterostructures and devices. The (K_0.5Na_0.5)(Mn_0.005Nb_0.995)O₃ (KNMN) thin film was grown on Nb:SrTiO₃ single‐crystal substrate and the resultant self‐polarization behavior due to strain relaxation was investigated. The lattice mismatch and difference in TEC between the KNMN thin film and the Nb:SrTiO₃ substrate creates a compressive strain. The compressive strain gradient may be the main cause for the observed downward self‐polarization. The downward self‐polarization of the KNMN thin film can be explained by the strong inhomogeneous compressive strain caused by strain relaxation. (© 2016 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Novel fabrication route for carbon-free and dense CuInSe2 (CIS) thin films via a non-vacuum process for solar cell application

Carbon-free CuInSe₂ (CIS) thin film with a dense microstructure has been prepared using a novel non-vacuum based fabrication route. Cu_xS_y and In₂Se₃ binary nanoparticles, approximately 10 nm in size, were synthesized by a low temperature colloidal process. The precursor film was deposited using the coating ink formulated with the binary nanoparticles and pyridine, and then annealed in the rapid thermal annealing (RTA) chamber at 540 °C for 15 min under selenium (Se) atmosphere. Scanning electron micrographs, X-ray diffraction patterns and Raman spectra showed a phase pure carbon-free and dense CIS thin film was prepared in this method. A solar cell device fabricated using this CIS thin film showed the following photovoltaic characteristics: V_OC = 350 mV, J_SC = 24.72 mA cm⁻², FF = 38.73% and η = 3.36% under standard AM 1.5 condition.