Radical cations vs. cations: a comparative study of retinyl cation and retinol radical cation

The reactivity of cationic and radical cationic intermediates has been extensively studied using both theoretical and experimental approaches. In the present study, the structurally related retinyl cation (Ret⁺) and retinol radical cation (retinol^·+) were employed as models to compare the intrinsic reactivities of cations and radical cations within a common structural framework. Using laser flash photolysis (LFP) technique, these intermediates (λ_max = 580-590 nm) were generated and their reactivities toward a variety of substrates were examined, including substrates undergoing exclusively electron-transfer reactions (e.g., ABTS^2- and vitamin E), nucleophilic addition (e.g., Cl^- and Br^- anions), deprotonation (e.g., DBU), and multiple concurrent pathways (e.g., phenols, and aniline derivatives). Our results showed that all tested substrates reacted more rapidly with retinol^·+ than with Ret⁺. The rate enhancement was up to 3 orders of magnitude for substrates such as ABTS^2-, vitamin E, and hydroquinone. For example, in methanol, the rate constants for the reactions of Ret⁺ and retinol^·+ with ABTS^2- were < 4.4 × 10⁷ and 2.14 × 10¹⁰ M^- 1 s^- 1, respectively. The enhanced reactivity of retinol^·+ was attributed to its higher reduction potential, which enabled an additional electron-transfer pathway alongside the nucleophilic addition and deprotonation pathways. Density functional theory (DFT) calculations further supported the greater electron affinity of retinol^·+ relative to Ret⁺. Overall, the present findings indicated that radical cations generally exhibit higher reactivity than their corresponding cations. Finally, the potential photocytotoxicity of retinoids, which are widely used in cosmetic formulations, is discussed.