Retinylisoflavonoid as a novel membrane antioxidant.

We report a novel molecular dyad as an antioxidant, retinylisoflavonoid, with a retinal analogue C(22)-aldehyde and the isoflavonoid daidzein covalently linked. Its physicochemical properties, pK(a) (pK(a1) = 8.45, pK(a2) = 11.42), oxidation potential (1.03 V vs NHE), and Log(10) partition (Log P = 1.96), as well as the Trolox equivalent antioxidant capacity (TEAC = 0.4), have been characterized. Spectroscopic and quantum chemical investigations have revealed the following unique structural characters: (i) Either free in solution or included in liposomal membranes, the C(22)-aldehyde moiety of retinylisoflavonoid is coplanar with the B-ring of daidzein owing to the strong intramolecular hydrogen bonding C(14')=O···HO-B4'. Accordingly, the C(22)-aldehyde moiety extends its π-conjugation significantly to the B-ring. (ii) The inherent amphiphilicity of retinylisoflavonoid allows the C(22)-aldehyde moiety embedded in the lipid phase of the liposomes, whereas the daidzein counterpart stays at the membrane surface, in effect facilitating interior-to-surface radical communication. As the result, the antilipooxidation activity of retinylisoflavonoid is improved significantly in protecting membrane lipids compared to the parent compounds alone or in combination, and importantly, the performance is more prominent under higher-level oxidative stress. This work provides an advanced case study of new antioxidant development based on optimized electronic and molecular structures.