Proteomic analysis of mouse liver for the evaluation of effects of Scutellariae radix by liquid chromatography with tandem mass spectrometry

Scutellariae radix or Scutellaria baicalensis is a medicinal plant that contains major flavonoids such as baicalein, baicalin, wogonin and wogonosides. The present work describes the development of an approach using proteomic analysis of mouse liver to study the effects of prolonged exposure to substances present in chemically standardized Scutellariae radix extracts. Histopathological examination of the mouse liver was compared with the proteome data. The botanical extracts were prepared using pressurized liquid extraction (PLE). A method without isotope labeling was developed, using proteolytic digestion with one- and two-dimensional liquid chromatography with tandem mass spectrometry, and was used to characterize the extent of differential protein expression in mouse liver in response to external factors such as extracts from Scutellariae radix. From the histopathological examination and proteome data, significant changes in the mouse livers were not observed for the low-dose group. The Scutellariae radix extracts at high dose were observed to cause damage at the bile duct and expression change of a number of proteins including some involved in catabolism of triglyceride-rich particles, carbohydrate metabolism, regulators of cell signaling processes, and enzymes involved in biotransformation. Thus, proteomic analysis of liver samples from mice treated with botanical extracts is a promising approach to provide information on any potential toxicity effects of the extracts. The present method also provides another means for comparing proteomes in biological samples such as liver lysates from mice subjected to different treatments.     

Sensitivity in Supramolecular Architectures of Polyaromatic Salts Containing Two Singly‐Pimerized Bipyridines

Three novel supramolecular arrays of zigzag polyaromatic salts are reported. Both the conformation and disposition of the dications are subjected to various noncovalent interactions. Thus, the presence or absence of the π‐π interacting enclathrated molecules, the efficient packing and the involved hydrogen bonding interactions of anions, as well as the increased hydrophobic property of the dications themselves exert influence.     

Improved synthesis of functionalized 5,6-dihydro-pyrimido[4,5-b][1,4]oxazepines

Novel synthetic approaches toward 5,6-dihydro-pyrimido[4,5-b][1,4]oxazepines were reported that led to successful introduction of poorly reactive anilines and various 2-hydroxybenzaldehydes to this therapeutically relevant scaffold. More extensive SAR studies on this scaffold hence became possible.     

Linear scaling computation of the Fock matrix. VII. Parallel computation of the Coulomb matrix

We present parallelization of a quantum-chemical tree-code for linear scaling computation of the Coulomb matrix. Equal time partition is used to load balance computation of the Coulomb matrix. Equal time partition is a measurement based algorithm for domain decomposition that exploits small variation of the density between self-consistent-field cycles to achieve load balance. Efficiency of the equal time partition is illustrated by several tests involving both finite and periodic systems. It is found that equal time partition is able to deliver 91%-98% efficiency with 128 processors in the most time consuming part of the Coulomb matrix calculation. The current parallel quantum chemical tree code is able to deliver 63%-81% overall efficiency on 128 processors with fine grained parallelism (less than two heavy atoms per processor).     

Ligand-assisted reduction of osmium tetroxide with molecular hydrogen via a [3+2] mechanism

Osmium tetroxide is reduced by molecular hydrogen in the presence of ligands in both polar and nonpolar solvents. In CHCl3 containing pyridine (py) or 1,10-phenanthroline (phen), OsO4 is reduced by H2 to the known Os(VI) dimers L2Os(O)2(mu-O)2Os(O)2L2 (L2 = py2, phen). However, in the absence of ligands in CHCl3 and other nonpolar solvents, OsO4 is unreactive toward H2 over a week at ambient temperatures. In basic aqueous media, H2 reduces OsO4(OH)n(n-) (n = 0, 1, 2) to the isolable Os(VI) complex, OsO2(OH)4(2-), at rates close to that found in py/CHCl3. Depending on the pH, the aqueous reactions are exergonic by deltaG = -20 to -27 kcal mol(-1), based on electrochemical data. The second-order rate constants for the aqueous reactions are larger as the number of coordinated hydroxide ligands increases, k(OsO4) = 1.6(2) x 10(-2) M(-1) s(-1) < k(OsO4(OH)-) = 3.8(4) x 10(-2) M(-1) s(-1) < k(OsO4(OH)2(2-)) = 3.8(4) x 10(-1) M(-1) s(-1). The observation of primary deuterium kinetic isotope effects, k(H2)/k(D2) = 3.1(3) for OsO4 and 3.6(4) for OsO4(OH)-, indicates that the rate-determining step in each case involves H-H bond cleavage. Density functional calculations and thermochemical arguments favor a concerted [3+2] addition of H2 across two oxo groups of OsO4(L)n and argue against H* or H- abstraction from H2 or [2+2] addition of H2 across one Os=O bond. The [3+2] mechanism is analogous to that of alkene addition to OsO4(L)n to form diolates, for which acceleration by added ligands has been extensively documented. The observation that ligands also accelerate H2 addition to OsO4(L)n highlights the analogy between these two reactions.     

Ultrathin polymer film formation by collision-induced cross-linking of adsorbed organic molecules with hyperthermal protons

A new synthetic approach for the formation of ultrathin polymer films with customizable properties was developed. In this approach, the kinematic nature of proton collisions with simple organic molecules condensed on a substrate is exploited to break C-H bonds preferentially. The subsequent recombination of carbon radicals gives a cross-linked polymer thin film, and the selectivity of C-H cleavage preserves the chemical functionalities of the precursor molecules. The nature and validity of the method are exemplified with theoretical results from ab initio molecular dynamics calculations and experimental evidence from a variety of characterization techniques. Its applicability is demonstrated by the synthesis of ultrathin polymer films with precursor molecules such as dotriacontane, docosanoic acid, poly(acrylic acid) oligomer, and polyisoprene. The approach is fundamentally different from conventional chemical synthesis as it involves an unusual mix of physical and chemical processes including charge exchange, projectile penetration, kinematics, collision-induced dissociation, inelastic energy transfer, chain transfer, and chain cross-linking.