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, ¹H one-dimensional NMR and ¹H–¹H 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.

中文翻译：

---

吡啶和苯衍生物与模型膜相互作用的结构依赖性

基于吡啶的小分子药物，维生素和辅因子对于许多细胞过程至关重要，但对其与膜界面的相互作用了解甚少。这些小分子或离子的这些特定的膜相互作用可以帮助跨膜扩散或到达膜结合的靶标。这项研究探索了小分子（异烟肼，苯甲酰肼，异烟酰胺，烟酰胺，吡啶甲酰胺和苯甲酰胺）中的微小差异如何影响它们与模型膜的相互作用。Langmuir单层对二棕榈酰磷脂酰胆碱（DPPC）或二棕榈酰磷脂酰乙醇胺（DPPE）的研究表明，在存在所列分子的情况下，异烟肼和异烟酰胺以比DPPC单层更低的浓度影响DPPE单层，这表明一个磷脂优于另一个磷脂。Langmuir单层研究还表明，小分子的氮含量和立体化学可以不同地影响磷脂单层。为了确定简单的含氮芳族吡啶与膜状界面的分子相互作用，¹高电平单维NMR和^1个H- ¹ H双维NMR技术被用来获得关于气溶胶OT（AOT）反胶束内的感兴趣的分子的位置和方向信息。这些研究表明，所有六个分子都位于相似位置的AOT磺酸根和酯键附近，但是烟酰胺和吡啶甲酰胺在水-AOT界面处有不同程度的倾斜。综合起来，这些研究表明，含氮小分子的微小结构变化会影响它们与膜状界面的特异性相互作用以及对不同膜成分的特异性。