SC3: New Multi-Solvent Solubility Benchmark Reveals Significant Gap Between Current Models and Experimental Limits
Researchers introduced SC3, a new benchmark for predicting how well chemicals dissolve in different solvents, containing over 101,000 measurements across 1,327 solutes and 206 solvents. The study recalibrates the theoretical limit of prediction accuracy (aleatoric floor) to 0.106 log S, roughly 6 times tighter than previously assumed, revealing that current best models still perform 5 times worse than this limit. This work addresses longstanding inconsistencies in solubility benchmarking and provides a more reliable foundation for developing computational chemistry models.
Researchers at arXiv have introduced SC3, a comprehensive multi-solvent solubility prediction benchmark built on BigSolDB v2.1, containing 101,535 measurements across 1,327 solutes and 206 solvents. The study identifies critical flaws in existing benchmarks, including inconsistent curation policies, evaluation metrics that mask poor performance on underrepresented solvents, and an inflated estimate of the theoretical prediction limit (aleatoric ceiling). The authors recalibrate this limit to 0.106 log S—approximately 6 times tighter than the widely cited 0.6-0.8 figure—based on expected rather than worst-case inter-laboratory disagreement. SC3 introduces three key contributions: a reproducible curation pipeline with consensus tiers (Gold/Silver/Bronze) and per-point uncertainty estimates, multiple evaluation metrics designed to catch failure modes, and a 31-model benchmark across six model families. Results show that even the best-performing models achieve only 5 times the aleatoric limit, indicating substantial room for improvement. The authors also conduct analyses on data scaling, transfer learning from quantum chemistry, and feature attribution, demonstrating how calibrated uncertainty estimates can guide model development.
What's missing
The paper does not discuss potential applications or real-world deployment scenarios for improved solubility prediction models, nor does it address computational costs or practical feasibility of the benchmark for different research groups.
What different sources said
- arXiv cs.LGCenter
SC3: The Multi-Solvent Solubility Challenge and Benchmark
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