Biguanides are drugs used in the treatment of diseases as antidiabetic, antihyperglycemic, and antimalarial agents, and some of them are used in combination therapy. In this study we examine the interaction of positively charged biguanides including the antimalarial drug derivative, 1-phenylbiguanide, with membrane model systems using multinuclear NMR spectroscopy. The membrane model system used is the reverse micelle formed by a negative charged surfactant, sodium bis(2-ethylhexyl)sulfosuccinate (NaAOT). The changes of proton chemical shift of 1-phenylbiguanide by 1H-NMR spectroscopy were used to investigate the location of 1-phenylbiguanide. The phenyl group of 1-phenylbiguanide (Ha small change and Hb and Hc big change) peaks show upfield chemical shifts as pH increases from 1.21 to 12.28. The Ha peaks show downfield chemical shifts and Hb show upfield chemical shifts as the size of the reverse micelle varies from w0 = 6, 8, 10, 14, and 16. These chemical shift changes suggest that the 1-phenylbiguanide is located at the membrane interface and that it partially penentrates into the interface, or the differences in the shifting would not be as pronounced. We conclude that 1-phenylbiguanide interacts with the interface in the reverse micelles consistent with the Coulombic attractions, but that some of the drug penetrates into the interface.References (1) Crans, D. C.; Rithner, C. D.; Baruah, B.; Gourley, B. L.; Levinger, N. E. J. Amer. Chem. Soc. 2006, 128, 4437.(2) Crans, D. C.; Trujillo, A. M.;  Bonetti, S.; Rithner, C. D.; Baruah, B.; Levinger, N. E. J. Org. Chem. 2008, 73, 9633.(3) Cuccovia, I. M.; Dias, L. G.; Maximiano, F. A.; Chaimovich, H. Langmuir. 2001, 17, 1060.(4) Chatkon, A.; Chatterjee, P.B.; Sedgwick, M.A.; Haller, K.J.; Crans, D.C. Eur. J. Inorg. Chem. 2013 , 1859.

Interaction of a biguanide antimalarial drug with the model membrane system: AOT reverse micelles

247th National Meeting (2014)

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