SC3: The Multi-Solvent Solubility Challenge and Benchmark
Authors: Vansh Ramani, Har Ashish Arora, Dhairya Kuchhal, Sergei Tatarin, Lev Krasnov, Sayan Ranu, Tarak Karmakar
Organizations: Indian Institute of Technology Delhi, India · Kurnakov Institute of General and Inorganic Chemistry RAS, Russia
Abstract
Solubility prediction is a standard benchmark in computational chemistry, yet multi-solvent models which reportedly approach the experimental-noise ceiling (i.e. the aleatoric limit) are not yet reliable enough to be deployed. We argue that this gap is partly artefactual: published benchmarks differ in curation policies, evaluate on count-weighted RMSE that hides failure on tail-heavy solvent distributions, and treat the widely cited 0.6-0.8 log S inter-laboratory figure as the aleatoric ceiling even though it reflects worst-case, not expected, disagreement. We introduce SC3, a multi-solvent solubility benchmark built on BigSolDB v2.1 with three contributions: (i) a reproducible curation pipeline yielding 101,535 measurements over 1,327 solutes and 206 solvents, with a recalibrated aleatoric floor of 0.106 log S-roughly 6 times tighter than the conventional figure; (ii) nested Gold/Silver/Bronze consensus tiers with per-point standard deviation, three leakage-checked splits, and a multi-solvent metric suite (PS-RMSE, Z-RMSE); and (iii) a 31-model benchmark across six families, whose best Bronze PS-RMSE sits at 5 times the aleatoric limit, and we observe this is a gap unclosed by any deep alternative tested. We perform three follow-on analyses: data scaling, transfer from quantum-chemistry solvation energies, and feature-level attribution, which demonstrates that calibrated per-point uncertainty is a reusable infrastructure for diagnosis beyond point prediction.
Accurate prediction of solubility remains a central challenge across materials science and sustainable chemistry. In particular due to emerging technologies like organic and hybrid photovoltaics, batteries, and catalysis, solvent usage is expected to increase significantly within the coming years. Therefore, substituting solvents with greener alternatives is vital. This is where machine learning can have substantial impact. However, the limited data on critical parameters of solubility significantly constraints machine learning efficacy. In this work, we transfer a pre-trained foundational model on QM9 targets to our application with minimal data requirements. Additionally, the pipeline integrates uncertainty quantification, allowing the user to gauge the confidence of the predictions. As baseline, we succeed in predicting the Hansen solubility parameters and Dielectric Constant for which extensive databases exist. Importantly, we achieve high model performance on additional targets, such as Gutmann Donor and Acceptor numbers, where the available data is extremely limited. Overall, we augment data on solubility descriptors by orders of magnitude with high quality predictions. For effective dissemination, we deploy easy-to-use, easily integrateable with high throughput labs, customizable tool for ranking and screening possible solvent substitutes. Finally, we rediscovered known green solvent alternatives and proposed new candidates proving its relevance for finding eco-friendly solvents.
Language models are playing an increasingly important role in laboratory science, performing tasks such as experiment planning, execution, and post-hoc analysis. However, precisely measuring their abilities is difficult, as scientific capabilities require a mixture of both problem-solving skills and domain-specific intuition. Existing evaluations rarely measure the capabilities required to make reliable decisions in a physical laboratory and often rely on public data that may have appeared in model training corpora. We introduce onepot-Bench 0, a proprietary benchmark suite for evaluating language models on synthetic chemistry capabilities relevant to wet-lab execution. onepot-Bench 0 comprises three complementary evaluations: ChemAbacus measures tool-free cheminformatics literacy and numerical reasoning; SynthRefusal characterizes safety and refusal behavior across a variety of benign, controlled, and designer-drug targets; and SynthBench evaluates reaction-outcome prediction and catalyst selection using private experimental data generated in our laboratory. Together, these evaluations probe basic competency, reliability, and deeper knowledge, all skills which are required for reliable performance in the lab.
SciCode is the standard measure of the scientific-coding ability of language models: research-level problems that demand both frontier scientific theory and its implementation as working numerical code. It is a component of the Artificial Analysis Intelligence Index and a standing evaluation in government and national-laboratory suites. Yet its scores have recently plateaued: the strongest 2026 models cluster tightly around 60% subproblem accuracy, and a successor model ties its predecessor. We trace this stagnation to defects in the benchmark itself. A per-problem, domain-expert audit of all 65 test problems uncovers 263 defects; 192 of them, spread across 91% of the main problems, cause correct, instruction-following solutions to be wrongly rejected---through non-reproducible gold answers, over-tight tolerances, or self-contradictory specifications. Critically, 78% of these score-suppressing defects require specialized physics or mathematics knowledge to detect, not mere clerical proofreading. We corrected every confirmable defect to produce SciCode-Verified. The corrections add only the specifications a well-posed problem requires, repair grading, and tighten the tests that were too lenient; every change is recorded with its justification and independently re-checked by a second domain expert. We re-evaluate twelve frontier model snapshots on the corrected benchmark and find a substantial recovery: subproblem accuracy rises from 45--60% to 84--98%, and main-problem accuracy from 9--27% to 69--92%. State-of-the-art models are far more proficient in scientific coding than SciCode has suggested---the bottleneck was not model capability, but the quality of the evaluation instrument. We release SciCode-Verified with its complete audit trail as the corrected public standard.