The complexation of oligonucleotides and antisense drugs with a cationic surfactant, cetylpyridinium chloride (CPC), has been studied using electrochemistry at a micrometer sized liquid/liquid interface. This method can be used to investigate the effect of chemical and structural modifications on the complexation behaviour of oligonucleotides. For the interaction between CPC and oligonucleotides the effect of phosphorothioate derivatisation upon binding characteristics has been examined. Phosphoromonothioate modification causes the onset of binding to occur at a lower free surfactant concentration. Calorimetric studies show that surfactants are strongly bound to oligonucleotides and the binding is driven by entropy. The enthalpy change for the formation of oligonucleotide-surfactant complex is negative in all cases at 25 degrees C indicating exothermic reaction.