Theoretical studies of damage to 3'-uridine monophosphate induced by electron attachment

Low-energy electrons (LEE) are well known to induce nucleic acid damage. However, the damage mechanisms related to charge state and structural features remain to be explored in detail. In the present work, we have investigated the N1-glycosidic and C3'-O(P) bond ruptures of 3'-UMP (UMP=uridine monophosphate) and the protonated form 3'-UMPH with -1 and zero charge, respectively, based on hybrid density functional theory (DFT) B3 LYP together with the 6-31+G(d,p) basis set. The glycosidic bond breakage reactions of the 3'UMP and 3'UMPH electron adducts are exothermic in both cases, with barrier heights of 19-20 kcal mol(-1) upon inclusion of bulk solvation. The effects of the charge state on the phosphate group are marginal, but the C2'-OH group destabilizes the transition structure of glycosidic bond rupture of 3'-UMPH in the gas phase by approximately 5.0 kcal mol(-1). This is in contrast with the C3'-O(P) bond ruptures induced by LEE in which the charge state on the phosphate influences the barrier heights and reaction energies considerably. The barrier towards C3'-O(P) bond dissociation in the 3'UMP electron adduct is higher in the gas phase than the one corresponding to glycosidic bond rupture and is dramatically influenced by the C2'-OH group and bulk salvation, which decreases the barrier to 14.7 kcal mol(-1). For the C3'-O(P) bond rupture of the 3'UMPH electron adduct, the reaction is exothermic and the barrier is even lower, 8.2 kcal mol(-1), which is in agreement with recent results for 3'-dTMPH and 5'-dTMPH (dTMPH=deoxythymidine monophosphate). Both the Mulliken atomic charges and unpaired-spin distribution play significant roles in the reactions.     

How close can you get? Studies of ultrafast light-induced processes in ruthenium-[60] fullerene dyads with short pyrazolino and pyrrolidino links

Two pyrazoline- and one pyrrolidine-bridged Ru(II)bipyridine-[60]fullerene dyads have been prepared and studied by ultrafast time-resolved spectroscopy. A silver-assisted synthesis route, in which Ag(I) removes the chlorides from the precursor complex Ru(bpy) 2Cl 2 facilitates successful coordination of the [60]fullerene-substituted third ligand. Upon light excitation of the ruthenium moiety, the emission was strongly quenched by the fullerene. The main quenching mechanism is an exceptionally fast direct energy transfer ( k obs > 1 x 10 (12) s (-1) in the pyrazoline-bridged dyads), resulting in population of the lowest excited triplet state of fullerene. No evidence for electron transfer was found, despite the extraordinarily short donor-acceptor distance that could kinetically favor that process. The observations have implications on the ongoing development of devices built from Ru-polypyridyl complexes and nanostructured carbon, such as C 60 or nanotubes.     

Hydrogen abstraction from deoxyribose by a neighbouring uracil-5-yl radical

Hydrogen abstraction from the C1' and C2' positions of deoxyadenosine by a neighbouring uracil-5-yl radical in the 5'-AU*-3' DNA sequence is explored using DFT. This hydrogen abstraction is the first step in a sequence leading to single or double strand break in DNA. The uracil-5-yl radical can be the result of photolysis or low-energy electron (LEE) attachment. If the radical is produced by photolysis the neighbouring adenine will become a cation radical and if it is produced by LEE the adenine will remain neutral. The hydrogen abstraction reactions for both cases were investigated. It is concluded that it is possible for the uracil-5-yl to abstract hydrogen from C1' and C2'. When adenine is neutral there is a preference for the C1' site and when the adenine is a radical cation the C2' site is the preferred. If adenine is positively charged, the rate-limiting step when abstracting hydrogen from C1' is the formation of an intermediate crosslink between uracil and adenine. This crosslink might be avoided in dsDNA, making C1' the preferred site for abstraction.     

The potential in bioethanol production from waste fiber sludges in pulp mill-based biorefineries

Industrial production of bioethanol from fibers that are unusable for pulp production in pulp mills offers an approach to product diversification and more efficient exploitation of the raw material. In an attempt to utilize fibers flowing to the biological waste treatment, selected fiber sludges from three different pulp mills were collected, chemically analyzed, enzymatically hydrolyzed, and fermented for bioethanol production. Another aim was to produce solid residues with higher heat values than those of the original fiber sludges to gain a better fuel for combustion. The glucan content ranged between 32 and 66% of the dry matter. The lignin content varied considerably (1-25%), as did the content of wood extractives (0.2-5.8%). Hydrolysates obtained using enzymatic hydrolysis were found to be readily fermentable using Saccharomyces cerevisiae. Hydrolysis resulted in improved heat values compared with corresponding untreated fiber sludges. Oligomeric xylan fragments in the solid residue obtained after enzymatic hydrolysis were identified using matrix-assisted laser desorption ionization-time of flight and their potential as a new product of a pulp mill-based biorefinery is discussed.     

Structure-based engineering of strictosidine synthase: auxiliary for alkaloid libraries

The highly substrate-specific strictosidine synthase (EC 4.3.3.2) catalyzes the biological Pictet-Spengler condensation between tryptamine and secologanin, leading to the synthesis of about 2000 monoterpenoid indole alkaloids in higher plants. The crystal structure of Rauvolfia serpentina strictosidine synthase (STR1) in complex with strictosidine has been elucidated here, allowing the rational site-directed mutation of the active center of STR1 and resulting in modulation of its substrate acceptance. Here, we report on the rational redesign of STR1 by generation of a Val208Ala mutant, further describing the influence on substrate acceptance and the enzyme-catalyzed synthesis of 10-methyl- and 10-methoxystrictosidines. Based on the addition of strictosidine to a crude strictosidine glucosidase preparation from Catharanthus cells, a combined chemoenzymatic approach to generating large alkaloid libraries for future pharmacological screenings is presented.     

Comparative study of DFT methods applied to small titanium/oxygen compounds

The performance of a number of different local and nonlocal density functional theory (DFT) methods has been investigated for some small titanium—oxygen systems. Equilibrium geometries, ionization potentials, dipole moments, atomization energies, and harmonic vibrational frequencies have been calculated for the TiO, TiO₂, and Ti₂ molecules, and the results are compared with experimental data and ab initio calculations. It is shown that most DFT methods perform much better than the ab initio Hartree—Fock (HF), second-order perturbation theory (MP2), and configuration interaction including single and double excitations (CISD) treatments. For good agreement with experimental data, gradient corrections to the exchange part of the DFT functional are needed, as well as some type of correction for the errors in the calculated energy splittings between different atomic states of titanium. Hybrid methods including a mixture of HF exchange with DFT exchange correlation do not perform as well as “pure” DFT methods for the studied systems. © 1996 John Wiley & Sons, Inc.     

Novel Vinylpyridine Based Cationic MIP Monoliths for Enantiomer Separation in CEC

Cationic vinylpyridine based molecularly imprinted polymer monoliths were, for the first time, applied to enantiomer separation using capillary electrochromatography. In order to map the synthesis conditions under which superporous monoliths are obtained, capillary columns were prepared by an in situ polymerization technique using varying monomer and porogen compositions. Both electrolyte pH and percentage of the organic modifier acetonitrile were found to affect the electrochromatographic behaviour on such columns. An interesting observation is that the electroosmotic flow changed direction from cathodic at high pH to anodic at low pH of the electrolyte, opening up the opportunity to manipulate the flow. This is attributed to the vinylpyridine based MIP becomes protonated and positively charged at low pH, whereas it is uncharged at high pH where instead negatively charged silanol groups drive the electroosmotic flow. Improved enantiomer resolution, as well as increased retention, was observed when the concentration of acetonitrile in the electrolyte decreased, indicating a significant element of hydrophobic effects in the molecular recognition of the imprinted enantiomer. Enantiomer separation of the non-steroidal anti-inflammatory drug ibuprofen was studied and efficiencies as high as 30,000 plates per meter with an asymmetry factor below 4 were obtained for the last eluting imprinted enantiomer. These values are better than that obtained generally using MIP based chromatography.     

Telomerization: Advances and Applications of a Versatile Reaction

A chameleonic reaction : The transition‐metal‐catalyzed telomerization of 1,3‐dienes with different nucleophiles leads to the synthesis of numerous products which can be applied in the cosmetic and pharmaceutical industry as well as in polymers and flavors. This Review shows the versatility of the telomerization based on recent research and industrial applications.