Acetonitrile as solvent for protein interaction analysis

Dimethyl sulfoxide (DMSO) is routinely used to dissolve hydrophobic and aromatic substances in drug screening. The dissolved substances are then diluted, e.g., 100-fold, into aqueous media containing their target molecules. Such a practice may be suitable for biological evaluation of the drug substances. However, structural evaluation using spectroscopic techniques, in particular far UV measurements, may be hampered by strong absorbance of DMSO. Here, I have tested acetonitrile (ACN) that is almost exclusively used for reverse phase chromatography of proteins and small organic molecules. Using a small aromatic/hydrophobic molecule, dodecyl-gallate, and bovine serum albumin as a model system, a side-by-side comparison was made for DMSO and ACN with regard to dissolution capability and far UV circular dichroism (CD) performance.