Dual-Layer Geometric Pharmacology for Dental Medicine: Integrating Molecular GII_mol with Validated Drug-Target Q_LTE Interaction Data

We present the first dual-layer geometric pharmacological analysis of 15 common dental drugs, integrating two complementary GII (Geometric Instability Index) scales: Layer 1 (pilot): Molecular descriptor GII_mol and Q_LTE_mol computed from 2D molecular geometry for 15 dental small molecules (Dexamethasone, Clindamycin, Articaine, Celecoxib, Lidocaine, Mepivacaine, Naproxen, Ibuprofen, Diclofenac, Bupivacaine, Amoxicillin, Metronidazole, Doxycycline, Methylprednisolone, Chlorhexidine). Layer 2 (validated): Drug-target interaction Q_LTE_inter from the published Genesis Lo-Shu Quercetin dataset (DOI: 10.5281/zenodo.20100814) and validated GII_drug biologic immunogenicity framework (DOI: 10.5281/zenodo.20115927). Key findings: (1) A unified GII continuum is revealed spanning from ultra-compact small molecules (Dexamethasone GII=0.080) through Hub biologics (Etanercept GII=0.350) to Focused biologics (Infliximab GII=0.967). Chlorhexidine GII_mol=0.522 overlaps with the biologic Hub zone, geometrically explaining its systemic toxicity. (2) Doxycycline is identified as the L8/MMP-9 bridge drug (highest Vina=-6.25 AND MMP-9 Q_inter=7.51 from independent Layer 2 data). (3) Three geometrically-justified drug combinations are proposed: Doxycycline sub-MIC + Quercetin (L4+L5+L8 three-node coverage), Celecoxib + Quercetin (L5 COX-2 dual confirmation), and Dexamethasone + Clindamycin (L5-zone geometry-optimized implant protocol). All results are evidence-stratified (Level A validated vs. Level B hypothesis-generating). Part of the Genesis Geometric Medicine Framework v4.