R16 Topical Chromanol Lead Short Communication: 18-Pair 30 ns Matrix, 60 ns Robustness Panels, and Complete 200 ns Anchor-Triad Follow-up

R16 optimized the R15 chromanol fragment toward a topical lead hypothesis by increasing skin-window compatibility while preserving a compact chromanol core. We evaluated six chloro/dimethyl analogs across TGFB1, DCT, and TYR using Boltz-2 cofolding, an 18-pair 30 ns OpenMM stability matrix, two 60 ns robustness panels, and 100 ns plus 200 ns anchor-triad follow-up. The top cofold row was r16₀3ₜgfb1 (R15chromanolClₚos9, OCC1COc2cc (O) c (Cl) cc2C1) with affinity probability 0. 682. All 18 30 ns matrix entries were stable, the TGFB1 top-six 60 ns panel completed 6/6 stable, and the DCT/TYR representative 60 ns panel completed 3/3 stable. The 200 ns long-horizon anchor triad also completed 3/3 stable: TGFB1 R15chromanolClₚos9 max RMSD 0. 71 A, DCT R15chromanolClₚos9 max RMSD 1. 05 A, and TYR R15chromanolClₚos6 max RMSD 0. 80 A. These data support an in-silico topical optimization hypothesis, not clinical efficacy, confirmed binding, composition novelty, or freedom to operate. Keywords: chromanol, topical drug discovery, TGFB1, DCT, TYR, Boltz-2, OpenMM, in silico, prior-art gate