Synthesis and Evaluation of Powerful Antioxidant Dendrimers Derived from D-Mannitol and Syringaldehyde

Antioxidants play a crucial role in preventing oxidative damage and are therefore integral to various sectors, including healthcare, food preservation, cosmetics, and industrial applications. Their capacity to enhance overall health and improve the quality and shelf life of products in these domains underscores their significance. Two powerful antioxidant dendrimers were synthesized using D-mannitol as the core and syringaldehyde as the antioxidant-producing phenolic unit. The generation 1 (G1) dendrimer features 12 syringic units on its surface, while the generation 2 (G2) dendrimer has 24. Antioxidant capacities were assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the β-carotene bleaching assays. Based on IC50 values, the G2 (0.7 μM) and G1 (1.36 μM) dendrimers show 371- and 191-fold higher antioxidant activity, respectively, compared to the starting compound, syringaldehyde (260 μM). They are also 1251- and 647-times more effective than butylated hydroxytoluene (BHT) (880 μM). Overall, G2 is twice as potent as G1. The dendrimers also provide strong protection against β-carotene bleaching. At concentrations between 3.75 and 60 μM, G2 preserves 75% to 88% of β-carotene after 16 h at 45 °C, while G1 maintains 51% to 84%. In comparison, syringaldehyde and BHT provide significantly less protection, with ranges of 21% to 47% and 22% to 36%, respectively. Their greatly enhanced antioxidant capabilities are due to the numerous free-radical-scavenging sites created by phenolic hydroxyl groups, which have electron-donating groups at the <i>ortho</i> and <i>para</i> positions. In cell viability assays using macrophages, G1 caused a decrease in cell viability at ≥31 µM. Conversely, G2 exhibited a gradual reduction in cell viability across the concentration range of 0.1 µM to 111 µM, with viability declining from 11.1% to 96.3%, indicating that the larger G2 is more cytotoxic than the smaller G1.