Molecular mechanism and thermodynamics study of plasmid DNA and cationic surfactants interactions.
The molecular mechanism and thermodynamics of the interactions between plasmid DNA and cationic surfactants were investigated by isothermal titration calorimetry (ITC), dynamic light scattering, surface tension measurements, and UV spectroscopy. The cationic surfactants studied include benzyldimethyldodecylammonium chloride, benzyldimethyltetradecylammonium chloride, cetylpyridinium chloride, and cetyltrimethylammonium chloride. The results indicate a critical aggregation concentration (cac) of a surfactant: above the cac the surfactant forms aggregates with plasmid DNA; below the cac, however, there is no detectable interaction between DNA and surfactant. Surfactants with longer hydrocarbon chains have smaller cac, indicating that hydrophobic interaction plays a key role in DNA-surfactant complexation. Moreover, an increase in ionic strength (I) increases the cac but decreases the critical micellization concentration (cmc). These opposite effects lead to a critical ionic strength (I(c)) at which cac = cmc; when I < I(c), cac < cmc; when I > I(c), DNA does not form complexes with surfactant micelles. In the interaction DNA exhibits a pseudophase property as the cac is a constant over a wide range of DNA concentrations. ITC data showed that the reaction is solely driven by entropy because both deltaH(o) (approximately 2-6 kJ mol(-1)) and deltaS(o) (approximately 70-110 J K(-1) mol(-1)) have positive values. In the complex, the molar ratio of DNA phosphate to surfactant is in the range of 0.63-1.05. The reaction forms sub-micrometer-sized primary particles; those aggregate at high surfactant concentrations. Taken together, the results led to an inference that there is no interaction between surfactant monomers and DNA molecules and demonstrated that DNA-cationic surfactant interactions are mediated by the hydrophobic interactions of surfactant molecules and counterion binding of DNA phosphates to the cationic surfactant aggregates.
Biologics and Vaccines, Pharmaceutical Research and Development, Merck Research Laboratories, Merck & Co., Inc., West Point, Pennsylvania 19486, USA. demin_zhu@merck.com
De-Min
DM
Zhu
Robert K
RK
Evans
D000818:Animals; D002412:Cations; D002417:Cattle; D003587:Cytomegalovirus / Q000235:genetics; D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000737:chemistry; D006801:Humans; D008823:Micelles; D010710:Phosphates / Q000737:chemistry; D010957:Plasmids / Q000737:chemistry* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013501:Surface-Active Agents / Q000737:chemistry*; D013696:Temperature; D013816:Thermodynamics
D002412:Cations; D008823:Micelles; D010710:Phosphates; D013501:Surface-Active Agents; D013006:Growth Hormone; D004247:DNA