In situ click chemistry: enzyme inhibitors made to their own specifications

The in situ click chemistry approach to lead discovery employs the biological target itself for assembling inhibitors from complementary building block reagents via irreversible connection chemistry. The present publication discusses the optimization of this target-guided strategy using acetylcholinesterase (AChE) as a test system. The application of liquid chromatography with mass spectroscopic detection in the selected ion mode for product identification greatly enhanced the sensitivity and reliability of this method. It enabled the testing of multicomponent mixtures, which may dramatically increase the in situ screening throughput. In addition to the previously reported in situ product syn-TZ2PA6, we discovered three new inhibitors, syn-TZ2PA5, syn-TA2PZ6, and syn-TA2PZ5, derived from tacrine and phenylphenanthridinium azides and acetylenes, in the reactions with Electrophorus electricus and mouse AChE. All in situ-generated compounds were extremely potent AChE inhibitors, because of the presence of multiple sites of interaction, which include the newly formed triazole nexus as a significant pharmacophore.     

Spectrophotometric method for the determination of manganese with phenylfluorone in the presence of Triton X-100 and cetylpyridinium chloride in pharmacological preparations and vegetable fertilizers

A simple and very sensitive method for the spectrophotometric determination of manganese in pharmacological preparations and vegetable fertilizers is proposed. The method is based on the formation of a blue coloured complex of Mn (II) with 9-phenyl-2,3,7-trihydroxy-6-fluorone (PF) in the presence of cetylpyridinium chloride (CP) and Triton X-100. Optimum concentrations of PF, CP, Triton X-100 and pH ensuring maximum absorbance were defined. The complex Mn(II)-PF-CP-Triton X-100 shows maximum absorbance at 591 nm with the molar absorptivity value 1.77x10(5 )L mol(-1 )cm(-1). The detection limit of the method is 0.004 microg mL(-1). The Beer's law is obeyed for manganese concentrations in the range 0.02-0.2 microg mL(-1). The effect of foreign ions was elucidated. The statistical evaluation of the method was carried out for six determination using 5 microg Mn and the following results were obtained: standard deviation 0.021, confidence interval 5.05+/-0.05 microg Mn. The method has been applied for the determination of manganese in pharmacological preparations (Biovital, Kinder Biovital) and vegetable fertilizers (Hydrovit 100, Florovit).     

Measurement of the reaction 2H(e,e') at 180 degrees close to the deuteron breakup threshold

Inclusive inelastic electron scattering off the deuteron under 180 degrees has been studied at the S-DALINAC close to the breakup threshold at momentum transfers q=0.27 fm;{-1} and 0.74 fm;{-1} with good energy resolution sufficient to map in detail the spin flip M1 response, which governs the starting reaction pn-->dgamma of big-bang nucleosynthesis over most of the relevant temperature region. Results from potential model calculations and (for q=0.27 fm;{-1}) from pionless nuclear effective field theory are in excellent agreement with the data.     

Charge form factor of the neutron at low momentum transfer from the 2H-->(e-->,e'n)1H reaction

We report new measurements of the neutron charge form factor at low momentum transfer using quasielastic electrodisintegration of the deuteron. Longitudinally polarized electrons at an energy of 850 MeV were scattered from an isotopically pure, highly polarized deuterium gas target. The scattered electrons and coincident neutrons were measured by the Bates Large Acceptance Spectrometer Toroid (BLAST) detector. The neutron form factor ratio GEn/GMn was extracted from the beam-target vector asymmetry AedV at four-momentum transfers Q2=0.14, 0.20, 0.29, and 0.42 (GeV/c)2.     

Complete Sets of Polarization Observables in Electromagnetic Deuteron Breakup

 For deuteron photo- and electrodisintegration the selection of complete sets of polarization observables is discussed in detail by applying a recently developed new criterion for the check of completeness of a chosen set of observables. The question of ambiguities and their resolution by considering additional observables is discussed for a numerical example, for which the role of experimental uncertainties is also investigated. Furthermore, by inversion of the expressions of the observables as Hermitean forms in the t-matrix elements a bilinear term of the form can be given as a complex linear form in the observables from which an explicit solution for in terms of observables can be obtained. These can also be used to select sets of observables for the explicit representation of the t-matrix. Received May 15, 1999; accepted for publication August 30, 1999     

Invariant Amplitudes for Coherent Electromagnetic Pseudoscalar Production from a Spin-One Target, II: Crossing, Multipoles, and Observables

 The formal properties of the recently derived set of linearly independent invariant amplitudes for the electromagnetic production of a pseudoscalar particle from a spin-one particle have been further exploited. The crossing properties are discussed in detail. Since not all of the amplitudes have simple crossing behaviour, we introduce an alternative set of basic amplitudes which are either symmetric or antisymmetric under crossing. The multipole decomposition is given, and the representation of the multipoles as integrals over the invariant functions weighted with Legendre polynomials is derived. Furthermore, differential cross section and polarization observables are expressed in terms of the corresponding invariant functions. Received July 5, 1999; accepted for publication September 19, 1999     

点击化学——释义与目标

化学,是一种致力于使功能与形式紧密结合于其中的构造艺术尝试.正因为分子的功能是最重要的,从药物的发现到新塑料、香水、染料等的发明,创造新的功能一直是化学所有努力的目标.     

General multipole expansion of polarization observables in deuteron electrodisintegration

Formal expressions are derived for the multipole expansion of the structure functions of a general polarization observable of exclusive electrodisintegration of the deuteron using a longitudinally polarized beam and/or an oriented target. This allows one to exhibit explicitly the angular dependence of the structure functions by expanding them in terms of the small rotation matrices d ^j _m'm(θ), whose coefficients are given in terms of the electromagnetic multipole matrix elements. Furthermore, explicit expressions for the coefficients of the angular distributions of the differential cross-section including multipoles up to L _max = 3 are listed in tabular form. Received: 19 November 2002 / Accepted: 7 May 2002