Interactions with cell membranes are vital to the efficacy of drug uptake. Phenylbiguanide is an antimalarial precursor drug that has been shown in 2D 1HNOESY NMR studies to be placed on the interface of the reverse micellar system, where the phenyl moiety sits in the non-polar interface and the biguanide moiety rests in the water pool1. In these systems deuterium oxide is needed in the water pool as a lock for NMR studies that compromises the water pool. This causes a decrease in signal intensity of the NH peak and is not truly similar to a real water pool. The current study investigates using deuterated cyclohexane as a NMR lock enabling the examination of water interaction near the interface in the water pool. Dynamic light scattering spectroscopy of the d-cyclohexane (20% v/v), 2,2,4-trimethyl pentane, sodium dioctyl suflosuccinate (AOT, 0.75 M), and phenylbiguanide (0.08 M) system show no compromise of the reverse micelle radius known as the wo which is the ratio of water to AOT molecules. 1HNMR studies confirmed that the water chemical shift moves exactly as expected when the environment of the water changes upon the production of the reverse micelles of wo size 0-5 and that the deuterated cyclohexane in 0-5% volume does not alter this expected movement2. These conditions allow for observations of the NH peak at 6.72 ppm in the 1HNMR that have increased over 100% and is a broad but well defined peak unlike previously seen when using deuterium oxide. Lastly, the 2D 1HNOESY spectrum had the well-defined cross peaks of phenyl protons Ha (7.44 ppm), Hb (7.20 ppm), and Hc (6.92 ppm) with the methylene protons (9,9’; 1.25 ppm) of AOT, an intense NH (6.72 ppm)-H2O (4.41 ppm) cross peak as well as two additional cross peaks. Water molecules can bridge the interface of these systems and a weak cross peak of Ha and H2O was observed, which indicates the penetration of water into the interface. Lastly, a weak cross peak of NH with AOT was observed which indicated that the molecule is placed near the interface while the Hb and Hc phenyl protons are in the vicinity of the hydrophobic parts of the AOT molecule. These studies document that the antimalarial drug molecule readily interacts with the interface by partially penetrating while part of the molecule remains interacting with the water associated with and near the interface. 1Samart, N., Beuning, C., et. al.; Langmuir, 2014, 30 (29), pp 8697-8706 2Stahla, M. et. al; Langmuir, 2008, 24 (12), pp 6027–6035

Interactions of drugs with model membrane systems: Focusing on the interactions near the water interface

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.