Abstract

We have successfully synthesized water-soluble neutral and polyelectrolyte helical polycarbodiimides and studied their biological properties. These polymers were prepared by decorating carbodiimide backbones with nonionic, hydrophilic functional groups such as dimethylamine, piperazine, and morpholine. Additionally, the 3° amines present in these functional groups were quaternized using methyl iodide as the alkylating agent to produce their ionic analogs. Polycarbodiimides were chosen as the base polymer used because of their facile chemical modification, pH tolerance in terms of both their helical conformations and degradation behaviors, and tunable helical inversion barriers. Hydrophilic side groups, such as morpholine, dimethylamine, and piperazine, can be used to balance the amphiphilic architecture of the polycarbodiimides along with lipophilic groups, such as alkyl side chains. A chiral R or S BINOL Ti(IV) isopropoxide catalyst was used to control the handedness of the polycarbodiimide helices in these studies. These ionic and neutral polycarbodiimides were subsequently studied for potential antimicrobial and cytotoxic properties. Poly[N-methyl-N’-2-morpholinoethylcarbodiimide], as an example, exhibited significant antifungal properties against Candida albicans. Also, Poly[N-methyl-N’-2-morpholinoethylcarbodiimide] showed significant inhibition of biofilm formation. This suggests that the polymer is a promising candidate for antifungal biomedical applications. Measuring cytotoxicity against urinary bladder cancer cells, poly[N-[3-(dimethylamino)propyl)]-N’-[3-(morpholino)propyl]carbodiimide] (S-cat) and poly[N-[3-(dimethylamino)propyl)]-N’-[3-(morpholino)propyl]carbodiimide]-MeI (S-cat) showed significantly low IC₅₀ values. The IC₅₀ values of poly[N-[3-(dimethylamino)propyl)]-N’-[3-(morpholino)propyl]carbodiimide] (S-cat) and Poly[N-[3-(dimethylamino)propyl)]-N’-[3-(morpholino)propyl]carbodiimide]-MeI (S-cat) are 3.50 μM and 1.27 μM, respectively. The significantly low cancer cell growth inhibition concentration implies the highest cytotoxicity of the polymers, suggesting potential applications as cancer therapeutics. These results also showed that the functionalization and chirality of polycarbodiimides modulate their anticancer and antifungal activity.

摘要

我们成功地合成了水溶性中性和聚电解质螺旋聚碳二亚胺，并研究了它们的生物学特性。这些聚合物是通过用非离子亲水官能团（如二甲胺、哌嗪和吗啉）修饰碳二亚胺骨架而制备的。此外，使用甲基碘作为烷基化剂将这些官能团中存在的 3° 胺季铵化，以产生它们的离子类似物。选择聚碳二亚胺作为使用的基础聚合物是因为它们易于化学改性、在其螺旋构象和降解行为方面的 pH 耐受性以及可调节的螺旋反转屏障。亲水侧基，例如吗啉、二甲胺和哌嗪，可用于平衡聚碳二亚胺的两亲结构和亲油基团，例如烷基侧链。手性在这些研究中， R或S BINOL Ti(IV) 异丙氧基催化剂用于控制聚碳二亚胺螺旋的旋向性。随后研究了这些离子和中性聚碳二亚胺的潜在抗菌和细胞毒性特性。例如，聚[ N-甲基-N' -2-吗啉代乙基碳二亚胺]对白色念珠菌具有显着的抗真菌特性。此外，聚[ N-甲基-N' -2-吗啉代乙基碳二亚胺]显示出对生物膜形成的显着抑制。这表明该聚合物是抗真菌生物医学应用的有希望的候选者。测量对膀胱癌细胞的细胞毒性，聚[ N-[3-(二甲氨基)丙基)]- N' -[3-(吗啉代)丙基]碳二亚胺] ( S- cat)和聚[ N- [3-(二甲氨基)丙基)]- N' -[3- (吗啉代)丙基]碳二亚胺]-MeI ( S -cat )显示出显着低的IC ₅₀值。聚[ N- [3-(二甲基氨基)丙基)]- N' -[3-(吗啉代)丙基]碳二亚胺]( S- cat)和聚[ N- [3-(二甲基氨基)丙基)的IC ₅₀值]- N' -[3-(吗啉代)丙基]碳二亚胺]-MeI ( S-cat) 分别为 3.50 μM 和 1.27 μM。显着低的癌细胞生长抑制浓度意味着聚合物的最高细胞毒性，表明其作为癌症治疗剂的潜在应用。这些结果还表明，聚碳二亚胺的功能化和手性调节了它们的抗癌和抗真菌活性。