用图神经网络预测溶剂连续变化下的反应产率,突破传统离散分类局限。
Learning Continuous Solvent Effects from Transient Flow Data: A Graph Neural Network Benchmark on Catechol Rearrangement
- 构建分子图与混合溶剂编码的混合GNN模型,实现连续溶剂空间建模。
- 在1227组实验数据上达到MSE 0.0039,较基线降低60%以上误差。
- 适合需要精准溶剂优化的合成化学与流程化学研究者。
预测有机合成中连续溶剂组成范围内的反应结果仍是重大挑战。传统机器学习常将溶剂视为离散类别变量,难以实现溶剂空间的系统插值与外推。本文提出 extbf{Catechol Benchmark},一个高通量瞬态流动化学数据集,包含1,227组实验产率数据,涵盖24种纯溶剂及其二元混合物,以连续体积分数(% B)参数化。在严格的留一溶剂与留一混合物测试协议下评估多种架构,结果表明经典表格方法(如梯度提升决策树)和大语言模型嵌入(如Qwen-7B)在定量预测上表现不佳,均方误差(MSE)分别为0.099和0.129。相比之下,我们提出一种融合图注意力网络(GATs)、微分反应指纹(DRFP)与可学习混合溶剂编码的混合GNN架构,实现**MSE 0.0039(±0.0003)**,相较竞争基线降低60%,优于表格集成模型超过25倍。消融实验证明,显式分子图消息传递与连续混合编码对泛化能力至关重要。完整数据集、评估协议与参考实现已开源,助力数据高效反应预测与连续溶剂表征学习。
原文摘要 · Abstract (English)
Predicting reaction outcomes across continuous solvent composition ranges remains a critical challenge in organic synthesis and process chemistry. Traditional machine learning approaches often treat solvent identity as a discrete categorical variable, which prevents systematic interpolation and extrapolation across the solvent space. This work introduces the \textbf{Catechol Benchmark}, a high-throughput transient flow chemistry dataset comprising 1,227 experimental yield measurements for the rearrangement of allyl-substituted catechol in 24 pure solvents and their binary mixtures, parameterized by continuous volume fractions ($\% B$). We evaluate various architectures under rigorous leave-one-solvent-out and leave-one-mixture-out protocols to test generalization to unseen chemical environments. Our results demonstrate that classical tabular methods (e.g., Gradient-Boosted Decision Trees) and large language model embeddings (e.g., Qwen-7B) struggle with quantitative precision, yielding Mean Squared Errors (MSE) of 0.099 and 0.129, respectively. In contrast, we propose a hybrid GNN-based architecture that integrates Graph Attention Networks (GATs) with Differential Reaction Fingerprints (DRFP) and learned mixture-aware solvent encodings. This approach achieves an \textbf{MSE of 0.0039} ($\pm$ 0.0003), representing a 60\% error reduction over competitive baselines and a $>25\times$ improvement over tabular ensembles. Ablation studies confirm that explicit molecular graph message-passing and continuous mixture encoding are essential for robust generalization. The complete dataset, evaluation protocols, and reference implementations are released to facilitate data-efficient reaction prediction and continuous solvent representation learning.
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