1 research outputs found
Structure Dependence of Pyridine and Benzene Derivatives on Interactions with Model Membranes
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
of these small molecules or ions can assist in diffusion across membranes
or reach a membrane-bound target. This study explores how minor differences
in small molecules (isoniazid, benzhydrazide, isonicotinamide, nicotinamide,
picolinamide, and benzamide) can affect their interactions with model
membranes. Langmuir monolayer studies of dipalmitoylphosphatidylcholine
(DPPC) or dipalmitoylphosphatidylethanolamine (DPPE), in the presence
of the molecules listed, show that isoniazid and isonicotinamide affect
the DPPE monolayer at lower concentrations than the DPPC monolayer,
demonstrating a preference for one phospholipid over the other. The
Langmuir monolayer studies also suggest that nitrogen content and
stereochemistry of the small molecule can affect the phospholipid
monolayers differently. To determine the molecular interactions of
the simple N-containing aromatic pyridines with a membrane-like interface, <sup>1</sup>H one-dimensional NMR and <sup>1</sup>H–<sup>1</sup>H two-dimensional NMR techniques were utilized to obtain information
about the position and orientation of the molecules of interest within
aerosol-OT (AOT) reverse micelles. These studies show that all six
of the molecules reside near the AOT sulfonate headgroups and ester
linkages in similar positions, but nicotinamide and picolinamide tilt
at the water–AOT interface to varying degrees. Combined, these
studies demonstrate that small structural changes of small N-containing
molecules can affect their specific interactions with membrane-like
interfaces and specificity toward different membrane components