Studies on the production feasibility of 64Cu by (n, p) reactions on Zn targets in Dhruva research reactor

⁶⁴Cu is an useful radionuclide for both PET imaging and targeted therapy, as it decays by three different modes, namely, electron capture (41%), ??^? (40%) and positron emission (19%). ⁶⁴Cu is generally produced by ⁶⁴Ni (p, n) reaction in a cyclotron for medical use. High specific activity ??no carrier added?? grade ⁶⁴Cu by ⁶⁴Zn (n, p) route is an alternative for research studies and was hence explored. 10?mg zinc foil target (48.63% in ⁶⁴Zn) was irradiated in the medium flux reactor Dhruva at a thermal neutron flux of ~5.6?×?10¹³ n?cm^?2?s^?1 for 3?days. The irradiated Zn foil was dissolved in 5?mL 10?M HCl and ⁶⁴Cu was separated by anion exchange chromatography (Dowex 1?×?8; 100?C200 mesh) at 3?M HCl conditions. ⁶⁴Cu radioactivity content and its radionuclide purity were ascertained by ??-ray spectrometry using HPGe detector coupled to a 4?K multichannel analyser system. Radiochemical separation yielded a radionuclidic purity of 99.9% ⁶⁴Cu.     

Mechanistic insights into the hydrolysis of organophosphorus compounds by paraoxonase‐1: exploring the limits of substrate tolerance in a promiscuous enzyme

We designed, synthesized, and screened a library of analogs of the organophosphate pesticide metabolite paraoxon against a recombinant variant of human serum paraoxonase‐1. Alterations of both the aryloxy leaving group and the retained alkyl chains of paraoxon analogs resulted in substantial changes to binding and hydrolysis, as measured directly by spectrophotometric methods or in competition experiments with paraoxon. Increases or decreases in the steric bulk of the retained groups generally reduced the rate of hydrolysis, while modifications of the leaving group modulated both binding and turnover. Studies on the hydrolysis of phosphoryl azide analogs as well as amino‐modified paraoxon analogs, the former being developed as photoaffinity labels, found enhanced tolerance of structural modifications when compared with O‐alkyl‐substituted molecules. Results from computational modeling predict a predominant active site binding mode for these molecules, which is consistent with several proposed catalytic mechanisms in the literature and from which a molecular‐level explanation of the experimental trends is attempted. Overall, the results of this study suggest that while paraoxonase‐1 is a promiscuous enzyme, there are substantial constraints in the active site pocket, which may relate to both the leaving group and the retained portion of paraoxon analogs. Copyright © 2012 John Wiley & Sons, Ltd.