High Throughput Sonication: Evaluation for Compound Solubilization

Kevin Oldenburg; Douglas Pooler; Kurt Scudder; Christopher Lipinski; Michele Kelly

Abstract

Dissolution of organic compounds in DMSO in HTS plate or tube format is a difficult problem as users move to higher compression plate formats. Precipitation of compounds from DMSO screening stocks is a recognized problem in the HTS materials management process. The adverse effect of freeze thaw cycles on DMSO stock solutions stored in plate format as a result of cherry picking operations has led to the gradual replacement of plate-based storage with tube-based storage so as to minimize the number of freeze thaw cycles. Compound solubility in DMSO is markedly decreased by uptake of small quantities of water. We attribute this effect to the non ideal properties of DMSO water mixtures such that cavity formation in solvent, a necessary step in dissolution, is more difficult in wet DMSO than in dry DMSO or in pure water. We report here that efficient compound dissolution is possible even in 384 well format by the use of in-well plate-based sonication. Surprisingly, compounds precipitated from DMSO stocks either by water uptake or repeated freeze thaw cycles can be re-dissolved by low energy sonication. Finally, we demonstrate that precipitation of compound from DMSO stock solutions is synergistically enhanced by water uptake into DMSO compound stock solutions as well as by increasing the number of freeze thaw cycles.

Keywords: Sonication, compound solubility, freeze-thaw cycle, water in DMSO, precipitation, solubilization

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