Effects of Water-Miscible Organic Solvents on Thermal Stability of DNA Oligonucleotides

A water-miscible organic solvent is commonly used to obtain homogenous solutions in studying the interaction between DNA and ligands that have poor water solubility. The amount of an organic solvent used is empirically kept to a minimum because the organic solvent can destabilize DNA by disrupting hydrogen bonds. However, guidance on what percentage of organic solvent is safe to use without affecting DNA stability is lacking in the literature. This study surveys the effect of five common organic solvents (methanol, ethanol, DMSO, DMF, and acetonitrile) on the thermal stability of duplex DNA oligonucleotides using UV denaturation. The thermodynamic parameters are derived from DNA melting curves. Our results reveal that the rank in order of increasing destabilization effects on DNA oligonucleotides is methanol \u3c ethanol \u3c DMSO \u3c DMF \u3c acetonitrile. Circular dichroism studies suggest the DNA conformation remains unchanged under the experimental conditions.