Enzyme mediated kinetic resolution of δ-hydroxy-α,β-unsaturated esters as a route to optically active δ-lactones

A novel synthetic route to optically active saturated and unsaturated δ-lactones based on enzymatic kinetic resolution and ring-closing metathesis reactions has been proposed. The influence of temperature, co-solvent, organic additives and the substrate structure on the catalytic behavior of selected hydrolases was studied. The substantial impact of the organic co-solvent and surfactant type on the enzymatic activity and enantioselectivity was observed providing enantiomerically pure δ-hydroxy-α,β-unsaturated esters. The established protocol combining enzymatic kinetic resolution with ring closing metathesis was successfully applied in the synthesis of the enantiomerically pure (6R)-phenyl-5,6-dihydro-2H-pyran-2-one which plays crucial role in the synthesis of the number of bioactive compounds.     

Optimal echo spacing for multi-echo imaging measurements of Bi-exponential T2 relaxation

Calculations, analytical solutions, and simulations were used to investigate the trade-off of echo spacing and receiver bandwidth for the characterization of bi-exponential transverse relaxation using a multi-echo imaging pulse sequence. The Cramer–Rao lower bound of the standard deviation of the four parameters of a two-pool model was computed for a wide range of component T₂ values and echo spacing. The results demonstrate that optimal echo spacing (TE_opt) is not generally the minimal available given other pulse sequence constraints. The TE_opt increases with increasing value of the short T₂ time constant and decreases as the ratio of the long and short time constant decreases. A simple model of TE_opt as a function of the two T₂ time constants and four empirically derived scalars is presented.     

Evaluation of tetracationic salts as gas‐phase ion‐pairing agents for the detection of trivalent anions in positive mode electrospray ionization mass spectrometry

In previous studies, new electrospray ionization mass spectrometry (ESI‐MS) approaches were developed for the highly sensitive detection of singly and doubly charged anions in positive mode ESI‐MS by using specially synthesized dicationic and tricationic ion‐pairing agents, respectively. By detecting the positively charged ion complex in the positive mode, limits of detection (LODs) for the anions can be lowered by several magnitudes. In this work, we used eighteen newly synthesized tetracationic ion‐pairing agents, constructed with different geometries, linkages and cation moieties, for the detection of eighteen triply charged anions of different structural motifs. The LODs for these anions were from ten to several thousand times lower in the positive selective ion monitoring (SIM) mode than in the negative mode. These tetracationic agents also were shown to be useful for the detection of ?1 and ?2 anions. In addition, the LODs for ?3 anions can be further lowered by monitoring the product fragments of the ion‐pairing complexes in the single reaction monitoring (SRM) mode. Copyright © 2010 John Wiley & Sons, Ltd.     

Real‐time measurement of peroxyacetyl nitrate using selected ion flow tube mass spectrometry

The on‐line detection of gaseous peroxyacetyl nitrate (PAN) using selected ion flow tube mass spectrometry (SIFT‐MS) has been investigated using a synthetic sample of PAN in air at a humidity of ～30%. Using the H₃O⁺ reagent ion, signals due to PAN at m/z 122, 77 and 95 have been identified. These correspond to protonated PAN, protonated peractetic acid and its water cluster, respectively. These products and their energetics have been probed through quantum mechanical calculations. The rate coefficient of H₃O⁺ has been estimated to be 4.5 × 10^?9 cm³ s^?1, leading to a PAN sensitivity of 138 cps/ppbv. This gives a limit of detection of 20 pptv in 10 s using the [M+H]⁺ ion of PAN at m/z 122. Copyright © 2010 John Wiley & Sons, Ltd.     

Influence of the solvent quality on the AhR mediated Procept assay measurement of dioxin and dioxin-like compounds

Polychlorodibenzo-p-dioxins, polychorodibenzofurans and “dioxin-like” polychlorinated biphenyls are widespread persistent organic pollutants sharing a similar toxicological pathway mediated by the aryl-hydrocarbon receptor (AhR). Since the confirmatory method for their measurement at trace levels in complex matrices (using isotopic dilution and gas chromatography-high resolution mass spectrometry) remains time and cost-consuming, growing efforts of the scientific community have been focused on the development of screening approaches, including AhR mediated assays. Unfortunately, AhR ligands are highly diverse and agonistic/antagonistic effects can be observed on procedural blanks and/or sample extracts. In this study, the influence of solvent grade quality on the response of a DNA-binding AhR mediated assay used for screening dioxins has been investigated. Our results demonstrated a very critical impact of this parameter with both strong agonistic and antagonistic effects observed for any tested solvent lot. A small silver nitrate silica column removed partly these interfering compounds and then can be recommended as final purification step. Some preferable grades can be identified and selected in order to guarantee the best possible performances. However, it appears necessary to test every new lot, even if a grade appeared previously compliant.     

Predicted binding rate of new cephalosporin antibiotics by a 3D-QSAR method: a new approach

Abstract  

Antibiotics are chemotherapeutic agents with activity against microorganisms, for example bacteria, fungi, or protozoa, used for the treatment of many types of diseases. Binding of antibiotics to serum proteins in human plasma is a major determinant of their pharmacodynamic and pharmacokinetic behavior and, consequently, can affect their systemic distribution in the body. Here, the predicted binding rates of ceftazidime and 13 other pharmacological agents classified as antibiotics to plasma proteins (percentage fraction bound; PFB) were evaluated by use of 3D-QSAR models. We attempted to establish the contribution of hydrogen bond donor/acceptor and hydrophobic properties supplied by electrostatic fields to the PFB. Significant cross-validated correlation q ² (0.5–0.7) and the fitted correlation r ² (0.7–0.97) coefficients revealed that these models have reasonable power to predict the design 19 new antibiotics using ceftazidime as template, these compounds being our suggestion for further studies.