Lithium isotope effects and magnetic interactions in flavin-ascorbyl radical pairs.

Abstract

For decades, lithium carbonate has been a cornerstone treatment for bipolar disorder and related conditions, yet its mechanism of action remains poorly understood. Previous studies have suggested that the two stable isotopes, 6Li and 7Li, with nuclear spins of 1 and 3/2, respectively, can produce distinct biological effects. Because nuclear spin can subtly alter the course of specific chemical reactions, these studies have motivated the exploration of whether lithium's isotopes might act through a spin-dependent mechanism. Here, we investigate the Radical Pair Mechanism in the flavin-ascorbyl system using DFT and spin-dynamics calculations. The ascorbyl radical, derived from vitamin C, is both abundant in the brain and long-lived, making it a more credible partner for flavin. We propose that lithium's nuclear spin modulates triplet yields in flavin-ascorbyl radical pairs, offering a quantum-based explanation for isotope-dependent effects. Whether these spin interactions play a clinical role remains to be determined, but the possibility is exciting and points toward a promising line of inquiry.