Water-soluble polycarbodiimides and their cytotoxic and antifungal properties

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.

Keywords: Polycarbodiimides; amphiphilic; antifungal; cytotoxic; water-soluble polymers.