Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, United States.
Chemical Sciences and Engineering Division, Argonne National Laboratory, Lemont, Illinois 60439, United States.
J Chem Inf Model. 2024 Feb 26;64(4):1277-1289. doi: 10.1021/acs.jcim.3c01583. Epub 2024 Feb 15.
Predicting the synthesizability of a new molecule remains an unsolved challenge that chemists have long tackled with heuristic approaches. Here, we report a new method for predicting synthesizability using a simple yet accurate thermochemical descriptor. We introduce , the energy difference between a molecule and its lowest energy constitutional isomer, as a synthesizability predictor that is accurate, physically meaningful, and first-principles based. We apply to 134,000 molecules in the QM9 data set and find that is accurate when used alone and reduces incorrect predictions of "synthesizable" by up to 52% when used to augment commonly used prediction methods. Our work illustrates how first-principles thermochemistry and heuristic approximations for molecular stability are complementary, opening a new direction for synthesizability prediction methods.
预测新分子的可合成性仍然是一个未解决的挑战，长期以来化学家一直使用启发式方法来解决这个问题。在这里，我们报告了一种使用简单而准确的热化学描述符来预测可合成性的新方法。我们引入 ，即分子与其最低能量构象异构体之间的能量差，作为一种可合成性预测因子，它具有准确性、物理意义和基于第一性原理。我们将 应用于 QM9 数据集的 134000 个分子，发现 单独使用时非常准确，并且当用于增强常用预测方法时，可将错误预测为“可合成”的分子减少多达 52%。我们的工作说明了第一性原理热化学和分子稳定性的启发式近似方法是互补的，为可合成性预测方法开辟了新的方向。
