ABSTRACT
The Dean Flow, a physics phenomenon that accounts for the impact of channel curvature on fluid dynamics, has great potential to be used in microfluidic synthesis of nanoparticles. This study explores the impact of the Dean Flow on the synthesis of ZIF-8 particles. Several variables that influence the Dean Equation (the mathematical expression of Dean Flow) are tested to validate the applicability of this expression in microfluidic synthesis, including the flow rate, radius of curvature, channel cross sectional area, and reagent concentration. It is demonstrated that the current standard of reporting, providing only the flow rate and crucially not the radius of curvature, is an incomplete description that will invariably lead to irreproducible syntheses across different laboratories. An alternative standard of reporting is presented and it is demonstrated how the sleek and simple math of the Dean Equation can be used to precisely tune the final dimensions of high quality, monodisperse ZIF-8 nanoparticles between 40 and 700 nm.
ABSTRACT
In 2014, a published report of the high-throughput screen of>42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, we selected NEU-0001101 (1) for hit-to-lead optimization. Through our preliminary compound synthesis and SAR studies, we have confirmed the previously reported activity of 1 in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 1. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 1, while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery.
