Synthesis and evaluation of a molecularly imprinted polymer selective to 2,4,6-trichlorophenol

Molecularly imprinted polymers (MIPs) selective for the phenolic contaminant 2,4,6-trichlorophenol (2,4,6-TCP) were prepared and evaluated in three porogens of differing character (hexane, acetonitrile, dichloromethane). Rebinding of 2,4,6-TCP was found to be most effective in dichloromethane (imprinting factor: 13.2). Competitive binding studies performed against a range of close structural analogues showed a high preference for the target molecule, although partial recognition towards 2,4-dichlorophenol was also observed. Specificity was found to be dependent upon the presence of ring chlorine on the target, which suggested that these atoms participate in secondary binding interactions that are essential for successful recognition in the polymer cavity

Identification of Differential Protein Binding Affinities in an Atropisomeric Pharmaceutical Compound by Noncovalent Mass Spectrometry, Equilibrium Dialysis, and Nuclear Magnetic Resonance

Atropisomerism of pharmaceutical compounds is a challenging area for drug discovery programs (Angew. Chem., Int. Ed. 2009, 48, 6398−6401). Strategies for dealing with these compounds include raising the energy barrier to atropisomerization in order to develop the drug as a single isomer (Tetrahedron 2004, 60, 4337−4347) or reducing the barrier to rotation and developing a mixture of rapidly interconverting isomers (Chirality 1996, 8, 364−371). Commonly, however, the atropisomers will be differentiated in terms of their affinity for a given protein target, and it is therefore important to rapidly identify the most active component prior to further compound development. We present equilibrium dialysis and saturation transfer difference NMR (STD-NMR) as techniques for assessing relative affinities of an atropisomeric mixture against antiapoptotic protein targets Bcl-2 and Bcl-x_L. These techniques require no prior separation of the mixture of compounds and are therefore rapid and simple approaches. We also explore the use of noncovalent mass spectrometry for determining <i>K</i>_D values of individual atropisomers separated from the equilibrium mixture and compare the results to solution-phase measurements. Results from equilibrium dialysis, STD-NMR, and noncovalent mass spectrometry are all in excellent agreement and provide complementary information on differential binding, amplification of the strongest binders, and <i>K</i>_D values

Synthesis and evaluation of a molecularly imprinted polymer selective to 2,4,6-trichloroanisole

In the wine industry 2,4,6-trichloroanisole (TCA) has been identified as the primary contaminant responsible for 'cork taint'. A molecularly imprinted polymer (MIP) selective for TCA was prepared in three porogens (hexane, acetonitrile, and dichloromethane) of varying polarities using non-covalent molecular imprinting techniques. Target rebinding to the MIP was found to be most effective in its porogenic solvent and highest in dichloromethane (imprinting factor = 3.65). Competitive binding assays performed against a range of close structural analogues demonstrated a preference for the target molecule

Rights Without Remedies: The Court Party Theory and the Demise of the Court Challenges Program

The author argues that the Court Challenges Program’s 2006 cancellation was based on claims that judicial review is undemocratic, including those made by three academics, Rainer Knopff, F.L. Morton and Ian Brodie; the Court Party Theorists (the “CPT”). Through a study of Charter equality cases, this paper examines the CPT’s arguments regarding judicial activism, interest groups and interveners and finds they are largely unsupported by statistical evidence. Further, the debate about judicial review and democracy obscures judicial review’s important auditing function over the legislature’s constitutional adherence. This audit depends on individuals’ capacity to pursue Charter litigation, an ability compromised by the access to justice crisis. The author examines this crisis and the efforts to fill the funding gap left by the CCP’s cancellation and concludes that a publicly-funded program like the CCP is best-placed to ensure that the Charter remains a relevant tool for enforcing fundamental human rights in Canada.MAS