Abstract
<jats:p>Global concern over plastic additives has increased the need for stabilisers combining antioxidant function with reduced migration and improved environmental and human-health profiles. Here, an in silico workflow for inverse molecular design was applied to develop a natural-product-inspired dimeric phenolic antioxidant for polyolefins. PM6 calculations and predictive property screening were combined with CREST/GFN-FF conformational exploration and GFN2-xTB refinement. The resulting 70-conformer ensemble spanned compact folded and more open U-shaped geometries. A low-energy open conformer was selected because both phenolic O–H sites remained comparably accessible; GFN2-xTB/ALPB(hexane) optimisation preserved this topology and yielded a frequency-confirmed local minimum. Despite a molar mass of approximately 737 g mol-1, the candidate exhibited a maximum molecular dimension approaching that of the substantially heavier Irganox 1010. Its molecular size, hydrophobic surface character, very low predicted water solubility and strong predicted sorption support a reduced-migration design rationale. Environmental-fate and toxicological screening identified no dominant systemic concern within model applicability domains, although transformation products and local effects require experimental evaluation. The candidate is prioritised for synthesis and validation through antioxidant-performance, migration, ageing and safety studies.</jats:p>