Bridging the Plausibility-Validity Gap by Fine-Tuning a Reasoning-Enhanced LLM for Chemical Synthesis and Discovery
Year: 2025
Type: conference-paper
Abstract: Large Language Models frequently generate outputs that appear scientifically reasonable yet violate fundamental principles—a phenomenon we characterize as the “plausibility-validity gap.” This challenge proves especially acute in chemistry, where superficial correctness masks deeper errors in molecular structure, reaction mechanisms, and synthetic pathways. We present a systematic approach combining a reasoning-centric model architecture (Magistral Small) with Low-Rank Adaptation fine-tuning on a dual-domain dataset covering molecular properties and chemical transformations. Evaluation reveals substantial improvements: the fine-tuned system achieves 96.3 % format adherence, 97.4 % chemical validity, and 74.4 % synthesis feasibility. Comparative analysis shows our approach outperforms specialized translation models like MolT5 (97.4 % vs 77.2 % validity) while achieving performance comparable to complex tool-augmented systems like ChemCrow (9.0/10 vs 9.24/10 expert rating) through a more transparent, efficient methodology. Results demonstrate a learning hierarchy where syntactic correctness develops before chemical understanding, which precedes synthetic planning capability. This work establishes a reproducible framework for transforming generalist language models into dependable scientific tools while identifying critical areas including stereochemical precision, knowledge currency, and computational accessibility as key challenges for future advancement.
Authors: Malikussaid, Hilal Hudan Nuha, Isman Kurniawan
Institution: Telkom University
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W4416284254