Exploring Architectural Decoupling of Molecular Span from Molar Mass: A Staged In Silico Design Strategy for a Polyolefin Antioxidant Candidate
Year: 2026
Type: preprint
Abstract: Polyolefin stabilizer design balances restricted mobility against functional-site density, structural simplicity and toxicological assessability.A staged in silico inverse-design workflow tested whether a mirrored two-arm phenolic architecture could partially decouple molecular span from molar mass while retaining a substantial conformational envelope below 1,000 g mol⁻¹.Of 10,300 IUPAC-evaluable PlastChem records, 599 (5.8%) matched the case-insensitive "bis" screen; 56 of these were antioxidant-labeled (0.54% of all 10,300 records), comprising 27 two-arm (48%), 11 three-arm (20%), and 18 other or unresolved (32%) records.Cheminformatics, radical-state and conformational calculations, physicochemical and migration assessment, and applicabilitydomain-qualified toxicological screening guided starting-compound, monomer and dimer evaluation.The natural-product-inspired dimer (C46H56O8; 736.95 g mol⁻¹) yielded 70 gas-phase conformers with maximum allatom internuclear spans (Lmol) of 13.05-16.84Å and maximum van der Waals-envelope spans (Dmax) of 15.45-19.24Å. GFN2-xTB/ALPB(n-hexane) optimization of an open, approximately U-shaped conformer selected for balanced phenolic-site accessibility preserved its overall geometry and balanced phenolic-site accessibility and yielded a frequency-confirmed local minimum with Lmol = 17.08 Å and Dmax = 19.48Å.A frequency-confirmed GFN-FF Irganox 1010 conformer gave Lmol = 17.51Å and Dmax = 19.91Å, providing a descriptive cross-method, single-conformer comparison.Predicted high hydrophobicity, low water solubility, and strong sorption motivated a reduced-mobility hypothesis.Under assigned transport and partition parameters, mass-conserving migration calculations predicted lower aqueous release for the dimer than the monomer but appreciable dimer release under lipophilic stress.Toxicological screening showed endpoint-specific signals without monotonic improvement across the three design stages, and applicability-domain coverage decreased for the dimer.By linking architectural selection with geometric, migration, and toxicological assessment, the workflow prioritizes the candidate for synthesis and experimental evaluation in polyethylene and polypropylene.
Source: ChemRxiv
Author: Kentaro Takasaki
Institution: Sophia University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7211890634