The first combined experimental and theoretical study on the ionization and lipophilic properties of peptide nucleic acid (PNA) derivatives, including eleven PNA monomers and two PNA decamers, is described. The acidity constants (pK_a) of individual acidic and basic centers of PNA monomers were measured by automated potentiometric pH titrations in water/methanol solution, and these values were found to be in agreement with those obtained by MoKa software. These results indicate that single nucleobases do not change their pK_a values when included in PNA monomers and oligomers. In addition, immobilized artificial membrane chromatography was employed to evaluate the lipophilic properties of PNA monomers and oligomers, which showed the PNA derivatives had poor affinity towards membrane phospholipids, and confirmed their scarce cell penetrating ability. Overall, our study not only is of potential relevance to evaluate the pharmacokinetic properties of PNA, but also constitutes a reliable basis to properly modify PNA to obtain mimics with enhanced cell penetration properties.

描述了肽核酸 (PNA) 衍生物（包括十一种 PNA 单体和两种 PNA 十聚体）的电离和亲脂特性的首次结合实验和理论研究。PNA 单体的单个酸性和碱性中心的酸度常数 (pK _a ) 通过水/甲醇溶液中的自动电位 pH 滴定测量，发现这些值与 MoKa 软件获得的值一致。这些结果表明，单碱基不改变自己的pK_一当包含在 PNA 单体和低聚物中时的值。此外，采用固定化人工膜层析法评估PNA单体和低聚物的亲脂性，表明PNA衍生物对膜磷脂的亲和力较差，证实了它们缺乏细胞穿透能力。总体而言，我们的研究不仅与评估 PNA 的药代动力学特性具有潜在相关性，而且还构成了适当修改 PNA 以获得具有增强细胞渗透特性的模拟物的可靠基础。