Charge-density-dependent selective radical suppression in carboxymethyl cellulose

Carboxymethyl cellulose (CMC) is a widely used biocompatible polysaccharide reported to exhibit antioxidant and radical scavenging activities, although its mechanism remains unclear. Herein, we clarified the function of CMC by quantifying its radical scavenging behavior in three radical-generating systems-H₂O₂ photolysis (•OH), 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) photolysis (•OOR/•OR/•OH), and K₂S₂O₈ thermolysis (SO₄•^-)-using electron spin resonance spin trapping. At a fixed polymer concentration (5 mg mL^-1), •OH scavenging was independent of the degree of substitution (DS), consistent with diffusion-controlled reactivity. In contrast, suppression of AAPH-derived radicals increased monotonically with DS, as reflected by decreasing half-maximal scavenging concentration (IC₅₀; 7.3 → 1.5 mg mL^-1) and increasing apparent rate constant (k_app = 1/IC₅₀; 0.14 → 0.66 mL mg^-1). SO₄•^- scavenging was weak and slightly decreased at high DS owing to electrostatic exclusion. These findings establish that CMC acts as a DS-dependent reaction field rather than a nonspecific scavenger. Polyglucuronic acid reproduced behavior of CMC with DS ≈ 1, indicating that chain-averaged charge density, rather than backbone structure or chain length, governs radical suppression. This charge density engineering concept provides a generalizable route to tune the radical selectivity of polysaccharide-based antioxidants.