Structural elucidation of metabolites of ritonavir and indinavir by liquid chromatography-mass spectrometry

The structural elucidation of metabolites of ritonavir and indinavir, HIV-protease inhibitor drugs, by liquid chromatography-electrospray ionization mass spectrometry is described. Ritonavir and indinavir were biotransformed separately by incubation with transplant quality human liver microsomes. The incubation mixture was then analyzed by HPLC coupled to ion trap (ITMS) and triple quadrupole mass analyzers. The metabolites retained most of the structural features of the parent molecules. Baseline chromatographic resolution of isobaric species by gradient elution HPLC permitted rapid structural identification of these metabolites. Both drugs were biotransformed primarily by oxidative and hydrolytic pathways to numerous metabolites that retained many of the features of the parent molecules. Triple quadrupole and ion trap mass spectrometry were applied jointly to thoroughly detect and thoroughly characterize these metabolites. Furthermore, retention-time and data-dependent scanning assured acquisition of detailed MS-MS spectra for rapid detection of metabolic pathways of ritonavir and indinavir. Comparison of the ITMS and triple quadrupole data showed qualitative and quantitative differences in the mass spectral patterns, suggesting that these instruments should be used in parallel to ensure comprehensive metabolite detection and characterization by LC-MS.     

Ultrasensitive small molecule fluorogenic probe for human heparanase

Heparanase (HPA) is a critical enzyme involved in the remodeling of the extracellular matrix (ECM), and its elevated expression has been linked with diseases such as various types of cancer and inflammation. The detection of heparanase enzymatic activity holds tremendous value in the study of the cellular microenvironment, and search of molecular therapeutics targeting heparanase, however, no structurally defined probes are available for the detection of heparanase activity. Here we present the development of the first ultrasensitive fluorogenic small-molecule probe for heparanase enzymatic activity via tuning the electronic effect of the substrate. The probe exhibits a 756-fold fluorescence turn-on response in the presence of human heparanase, allowing one-step detection of heparanase activity in real-time with a picomolar detection limit. The high sensitivity and robustness of the probe are exemplified in a high-throughput screening assay for heparanase inhibitors.

Heparanase, a critical enzyme involved in the remodeling of the extracellular matrix, activates a disaccharide probe HADP to give a strong fluorescence signal.     

氧化物担载Ni（C5H5）2衍生催化剂的EXAFS表征

本文以二茂镍为母体化合物,以氧化铝和氧化硅为担体制备了担载镍催化剂。为了表征其结构特点,对这些催化剂热分解处理前后的样品在日本筑波高能物理研究所(Photon-Factory)的同步辐射加速器BL—10B EXAFS实验站进行了外延x-光精细结构谱测定(透射法)。以单散射球面波理论对实验结果进行了多参数拟合,同时对母体化合物也进行了平行测定和拟合,以验证数据及拟合方法的可靠性。研究结果表明,母体化合物的EXAFS结果与文献XRD相一致;母体化合物与担体表面发生了强烈的化学作用;镍组分在催化剂表面高度分散,氧化铝与Ni(C_5H_5)_2有更强的相互作用形成。Ni[(O)_s]_n(n≈4),近一半的镍原子周围有0.30 nm处的镍原子散射;氧化硅上除Ni[(CO)_s]_n(n≈3)外,在0.30 nm处有配位数为2的非成键Ni原子。     

苯胺在银和金电极上的表面增强拉曼光谱

聚苯胺作为性能较好的导电高聚物有很大的应用潜力,有关其聚合和导电机理的研究受到广泛重视。表面增强拉曼光谱(SERS)能现场(in situ)检测表面吸附分子、提     

Photoaddition reactions of trans dichloroethylene with benzenoid compounds: facile formation of tetracyclo[3.3.0.02,804,6]octanes and semibullvalenes

$\text{trans}$ 1,2-Dichloroethylene undergoes a stereospecific photoreaction with benzonitrile, the three tolunitriles, α,α,α-trifluorotoluene, fluorobenzene, and chlorobenzene to give substituted 6-$\text{exo}$ 7-$\text{endo}$ dichlorotricyclo[3,3,0,0_2,8]oct-3-enes which on treatment with base yield cyclised products or semibullvalenes: phenol yields dichlorobicyclo[3.2.1]oct-2-en-8-one with this ethylene photochemically.     

1‐(β‐d‐Erythrofuranos­yl)cytidine (β‐erythrocytidine)

1‐(β‐d ‐Erythrofuranosyl)cytidine, C₈H₁₁N₃O₄, (I), a derivative of β‐cytidine, (II), lacks an exocyclic hydroxy­methyl (–CH₂OH) substituent at C4′ and crystallizes in a global conformation different from that observed for (II). In (I), the β‐d ‐erythrofuranosyl ring assumes an E₃ conformation (C3′‐exo; S, i.e. south), and the N‐glycoside bond conformation is syn. In contrast, (II) contains a β‐d ‐ribofuranosyl ring in a ³T₂ conformation (N, i.e. north) and an anti‐N‐glycoside linkage. These crystallographic properties mimic those found in aqueous solution by NMR with respect to furan­ose conformation. Removal of the –CH₂OH group thus affects the global conformation of the aldofuranosyl ring. These results provide further support for S/syn–anti and N/anti correlations in pyrimidine nucleosides. The crystal structure of (I) was determined at 200 K.     

Liquefaction of corn stover and preparation of polyester from the liquefied polyol

This research investigated a novel process to prepare polyester from corn stover through liquefaction and crosslinking processes. First, corn stover was liquefied in organic solvents (90 wt% ethylene glycol and 10 wt% ethylene carbonate) with catalysts at moderate temperature under atmospheric pressure. The effect of liquefaction temperature, biomass content, and type of catalyst, such H₂SO₄, HCl, H₃PO₄, and ZnCl₂, was evaluated. Higher liquefaction yield was achieved in 2 wt% sulfuric acid, 1/4 (w/w) stover to liquefying reagent ratio; 160°C temperature, in 2h. The liquefied corn stover was rich in polyols, which can be directly used as feedstock for making polymers without further separation or purification. Second, polyester was made from the liquefied corn stover by crosslinking with multifunctional carboxylic acids and/or cyclic acid anhydrides. The tensile strength of polyester is about 5 MPa and the elongation is around 35%. The polyester is stable in cold water and organic solvents and readily biodegradable as indicated by 82% weight loss when buried in damp soil for 10 mo. The results indicate that this novel polyester could be used for the biodegradable garden mulch film production.     

Prompt-gamma activation analysis using thek 0 approach

Applying thek ₀ standardization method to prompt-gamma activation analysis (PGAA) offers similar benefits as in instrumental neutron activation analysis. It has been demonstrated that under constant flux conditionsk ₀-factors obtained by normalizing to a titanium comparator, measured separately, yield consistent analytical sensitivity ratios. The ratio method has been generalized by using stoichiometric compounds for the determination ofk ₀-factors. Since chlorine forms compounds with essentially everyelement and it also serves as a detector efficiency standard,k ₀ values have been determined relative to chlorine as an internal standard for several analytically important elements in two reactor facilities: the thermal guided beam at the BRR in Budapest and the cold-neutron beams at the NBSR at NIST.     

Indole esters as heterocyclic synthons. III. Preparation and reactions of furo[3,2-b]indoles

The preparation of furo[3,2-b]indoles via Dieckmann cyclization is described. The precursor diesters were obtained from 3-hydroxy-1H-indole-2-carboxylic acid esters and methyl or ethyl bromoacetate. Reactions of the furo[3,2-b]indole enolic esters prepared are discussed.     

The ground-state singlet potential surface for C2H4

Calculations with an extended polarized basis set and Møller-Plesset perturbation theory including triple substitution correlation corrections in the fourth-order treatment indicate that singlet ethylidene (CH₃CH:) is not a local minimum on the C₂H₄ potential energy surface. Rearrangement to ethylene occurs without actuation. Barriers for hydrogen scrambling and for 1,1-hydrogen elimination are estimated.