Interaction of a Biguanide Compound with Membrane Model Interface Systems: Probing the Properties of Antimalaria and Antidiabetic Compounds

• Published in: Langmuir Vol. 30; no. 29; pp. 8697 - 8706
• Main Authors: Samart, Nuttaporn, Beuning, Cheryle N, Haller, Kenneth J, Rithner, Chris D, Crans, Debbie C
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 29.07.2014
• Subjects: Antimalarials - chemistry; Biguanides - chemistry; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Hypoglycemic Agents - chemistry; Kinetics; Membranes, Artificial; Micelles; Permeability; Prodrugs - chemistry; Protons; Surface Properties; Water - chemistry
• ISSN: 0743-7463; 1520-5827
• DOI: 10.1021/la501600s

Since membrane penetration is important for drug efficacy, how antimalarial precursor material 1-phenylbiguanide (PBG) interacts with an interface was characterized using a reverse micelle (RM) model system. 1H NMR studies show that PBG partitions across the membrane interface. Specifically, the 1H NMR studies showed that the 1-phenylbiguanide compound in an aqueous environment changed when placed near an interface. PBG is known to affect hydrogen bonding in water, and as the size of the RMs changes, the water organization in the water pool is changed. The NOESY spectrum of PBG in AOT RM contains cross-peak signals between the PBG protons and AOT protons, which is consistent with the penetration of the PBG into the interface. At the same time, there is a cross peak between the biguanide moiety and the HOD signal. This shows that these NH protons are near the HOD protons, placing the biguanide functional group in the water pool. Preliminary differential FTIR spectroscopic studies confirmed this location. In summary, we found that PBG interacts with different regions of the interface, with the phenyl group penetrating the hydrophobic interface while the biguanide remains in the water pool.