Pyridine based small molecule drugs, vitamins, and cofactors are vital for many cellular processes, but little is known about their interactions with membrane interfaces. These specific membrane interactions can help the molecules diffuse across membranes or even reach their membrane bound target. This study explored how minor differences in pyridine based small molecules (isoniazid, benzhydrazide, isonicotinamide, benzamide, nicotinamide, and picolinamide) interact with model membranes to demine if small differences in structure can affect their membrane interactions. Compression isotherms of the first model membrane of this study, Langmuir monolayers of dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylethanolamine (DPPE), in the presence of the pyridine derivatives of interest was able to show that isoniazid and isonicotinamide affect the DPPE monolayer at lower concentrations than the DPPC monolayer and the nitrogen content and stereochemistry can affect the phospholipid monolayers differently. To obtain a molecular perspective of the interactions of the molecules mentioned above, 1H 1D NMR and 1H-1H 2D NMR techniques were utilized to obtain information about position and orientation of the pyridine based molecules of interest within the second model membrane, Aerosol-OT (AOT) reverse micelles. These studies were able to show that all six of the molecules resided near the AOT sulfonate headgroups and ester linkages in similar positions, but does show nicotinamide and picolinamide tilt at the water-AOT interface to varying degrees. Combined, these studies demonstrate that small structural changes of small molecules can affect their specific interactions with membrane-like interfaces and their interactions with specific phospholipids which may play a role in their diffusion across bilayers, and specificity toward specific cells.

Interactions of pyridine based aromatic hydrazides and amides with model membrane interfaces

256th National Meeting (2018)

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