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, 6 Li and 7 Li, 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.