Explanation for main features of structure-genotoxicity relationships of aromatic amines by theoretical studies of their activation pathways in CYP1A2

Aromatic and heteroaromatic amines (ArNH(2)) represent a class of potential mutagens that after being metabolically activated covalently modify DNA. Activation of ArNH(2) in many cases starts with N-hydroxylation by P450 enzymes, primarily CYP1A2. Poor understanding of structure-mutagenicity relationships of ArNH(2) limits their use in drug discovery programs. Key factors that facilitate activation of ArNH(2) are revealed by exploring their reaction intermediates in CYP1A2 using DFT calculations. On the basis of these calculations and extensive analysis of structure-mutagenicity data, we suggest that mutagenic metabolites are generated by ferric peroxo intermediate, (CYP1A2)Fe(III)-OO(-), in a three-step heterolytic mechanism. First, the distal oxygen of the oxidant abstracts proton from H-bonded ArNH(2). The subsequent proximal protonation of the resulting (CYP1A2)Fe(III)-OOH weakens both the O-O and the O-H bonds of the oxidant. Heterolytic cleavage of the O-O bond leads to N-hydroxylation of ArNH(-) via S(N)2 mechanism, whereas cleavage of the O-H bond results in release of hydroperoxy radical. Thus, our proposed reaction offers a mechanistic explanation for previous observations that metabolism of aromatic amines could cause oxidative stress. The primary drivers for mutagenic potency of ArNH(2) are (i) binding affinity of ArNH(2) in the productive binding mode within the CYP1A2 substrate cavity, (ii) resonance stabilization of the anionic forms of ArNH(2), and (iii) exothermicity of proton-assisted heterolytic cleavage of N-O bonds of hydroxylamines and their bioconjugates. This leads to a strategy for designing mutagenicity free ArNH(2): Structural alterations in ArNH(2), which disrupt geometric compatibility with CYP1A2, hinder proton abstraction, or strongly destabilize the nitrenium ion, in this order of priority, prevent genotoxicity.     

Dimensionality control of vapochromic hydrogen-bonded proton-transfer assemblies composed of a bis(hydrazone)iron(II) complex

We describe the novel synthesis of a bis(hydrazone)iron(II) complex in protonated [Fe(Hpbph)(2)]Cl(2) (1) and deprotonated [Fe(pbph)(2)] (2) forms and several hydrogen-bonded proton-transfer (HBPT) assemblies having different dimensionalities of hydrogen-bonded network structures, [Fe(Hpbph)(2)](CA)·2CH(3)OH (3), [Fe(Hpbph)(2)](HCA)(2)·2THF (4), and [Fe(Hpbph)(2)](CA)(H(2)CA)(2)·2CH(3)CN (5) (Hpbph = 2-(diphenylphosphino)benzaldehyde-2-pyridylhydrazone), consisting of a deprotonated Fe(II)-hydrazone complex (2) as a proton acceptor (A) and chloranilic acid (H(2)CA) as a proton donor (D). The deprotonated complex 2 exhibited two-step reversible protonation reactions to form the double-protonated form 1, and the acid-dissociation constants were determined to be 7.6 and 10.3 in methanol solution. Utilizing this proton-accepting ability of 2, we succeeded in synthesizing HBPT assemblies 3, 4, and 5 from the reactions in CH(3)OH, THF, and CH(3)CN, respectively, with the same D/A ratio of H(2)CA/[Fe(pbph)(2)] = 10:1. These assemblies were found to have one-dimensional (1-D), two-dimensional (2-D), and three-dimensional (3-D) hydrogen-bonded networks with D/A ratios of 1:1, 2:1, and 3:1 for 3, 4, and 5, respectively. In 3, a 1-D hydrogen-bonded chain composed of the alternate arrangement of [Fe(Hpbph)(2)](2+) and CA(2-), {···[Fe(Hpbph)(2)](2+)···CA(2-)···}(∞), was surrounded by solvated methanol molecules to form isolated 1-D hydrogen-bonded chains. In the HBPT assembly 4, a 2-D hydrogen-bonded sheet was formed from two types of hydrogen-bonded chains, {···[Fe(Hpbph)(2)](2+)···HCA(-)···HCA(-)···}(∞) and {···HCA(-)···HCA(-)···}(∞), and solvated THF molecules did not form any hydrogen bonds. In 5, two orthogonal hydrogen-bonded chains constructed from the neutral chloranilic acid molecules, {···CA(2-)···2(H(2)CA)···}(∞), were formed in addition to the 1-D hydrogen-bonded chain similar to that in 3, resulting in the formation of a rigid 3-D hydrogen-bonded network structure. By controlling the dimensionality of the hydrogen bond network, we found that the 2-D HBPT assembly 4 is sufficiently flexible to exhibit interesting vapochromic behavior in response to various organic vapors.     

Alkyl 4-chlorobenzoyloxycarbamates as highly effective nitrogen source reagents for the base-free, intermolecular aminohydroxylation reaction

Ethyl- (7), benzyl- (8), tert-butyl- (9), and fluorenylmethyl-4-chlorobenzoyloxycarbamates (10) have been prepared as storable and easy-to-prepare nitrogen sources for use in the intermolecular Sharpless aminohydroxylation reaction and its asymmetric variant. These reagents were found to be effective under base-free reaction conditions. The scope and limitations of these methods have been explored using a variety of alkenes, among which, trans-cinnamates, in particular, proved to be good substrates.     

New Approaches to Generalized Two‐Dimensional Correlation Spectroscopy and Its Applications

Abstract

This review is focused on the recent approaches to generalized 2D correlation spectroscopy, a technique widely used for the analysis of spectral data. A brief introduction of generalized 2D correlation spectroscopy is described first. Then the powerful combination of generalized 2D correlation spectroscopy and multivariate chemometircs techniques, such as the data reconstruction by principal component analysis (PCA), eigenvalue manipulation transformation (EMT), and self‐modeling curve resolution (SMCR) analysis are explored. Examples of successful applications of new approaches to generalized 2D correlation spectroscopy are highlighted.     

Direct Dynamic Evidence of Charge Separation in a Dye-Sensitized Solar Cell Obtained under Operando Conditions by Raman Spectroscopy

Interfaces play an important role in enhancing the energy conversion performance of dye-sensitized solar cells (DSCs). The interface effects have been studied by many techniques, but most of the studies only focused on one part of a DSC, rather than on a complete solar cell. Hence, monitoring the interface evolution of a DSC is still very challenging. Here, in situ/operando resonance Raman (RR) spectroscopic analyses were carried out to monitor the dynamics of the photovoltaic conversion processes in a DSC. We observed the creation of new species (i.e., polyiodide and iodine aggregates) in the photosensitization process. We also obtained molecular-scale dynamic evidence that the bands from the C=C and C=N bonds of 2,2′-bipyridyl (bpy), the S=C=N bonds of the NCS ligand, and photochemical products undergo reasonably strong intensity and frequency changes, which clearly demonstrates that they are involved in charge separation. Furthermore, RR spectroscopy can also be used to quickly evaluate the performance of DSCs.     

Transitioning Between Tableaux and Spider Bases for Specht Modules

Regarding the Specht modules associated to the two-row partition (n, n), we provide a combinatorial path model to study the transitioning matrix from the tableau basis to the A₁-web basis (i.e. cup diagrams), and prove that the entries in this matrix are positive in the upper-triangular portion with respect to a certain partial order.

     

Nozzle design study for a quasi-axisymmetric scramjet-powered vehicle at Mach 7.9 flight conditions

A nozzle shape optimization study for a quasi-axisymmetric scramjet has been performed for a Mach 7.9 operating condition with hydrogen fuel, aiming at the application of a hypersonic airbreathing vehicle. In this study, the nozzle geometry which is parameterized by a set of design variables, is optimized for the single objective of maximum net thrust using an in-house CFD solver for inviscid flowfields with a simple force prediction methodology. The combustion is modelled using a simple chemical reaction code. The effects of the nozzle design on the overall vehicle performance are discussed. For the present geometry, net thrust is achieved for the optimized vehicle design. The results of the nozzle-optimization study show that performance is limited by the nozzle area ratio that can be incorporated into the vehicle without leading to too large a base diameter of the vehicle and increasing the external drag of the vehicle. This study indicates that it is very difficult to achieve positive thrust at Mach 7.9 using the basic geometry investigated.     

Determination of cholesterol in human hair using gas chromatography-mass spectrometry

This work describes a sensitive method for determining cholesterol in human hair using GC-MS. In this study, we used a very small amount of hair, only 1 mg, to quantify cholesterol. We also can achieve more effective purification and a good recovery over 92% with solid-phase extraction using an Oasis HLB cartridge. The intra-day and inter-day precision and accuracy values were less than 7.08%. Cholesterol was determined to be in the range of 355-1693 microg/g in healthy human hair. We tested the concentration correlation between the serum and hair to examine the feasibility of using the hair cholesterol level as an index of the serum cholesterol level. The correlation between the serum cholesterol was 0.86 (r-value) in patients with hypercholesterolemia. This finding indicates that, in the clinical field, hair could replace serum in cholesterol level measurement.