Materials precursor score: modelling chemists' intuition for the synthetic accessibility of porous organic cage precursors
File(s)acs.jcim.1c00375.pdf (3.04 MB)
Published version
Author(s)
Type
Journal Article
Abstract
Computation is increasingly being used to try to accelerate the discovery of new materials. One specific example of this is porous molecular materials, specifically porous organic cages, where the porosity of the materials predominantly comes from the internal cavities of the molecules themselves. The computational discovery of novel structures with useful properties is currently hindered by the difficulty in transitioning from a computational prediction to synthetic realisation. Attempts at experimental validation are often time-consuming, expensive and, frequently, the key bottleneck of material discovery. In this work, we developed a computational screening workflow for porous molecules that includes consideration of the synthetic difficulty of material precursors, aimed at easing the transition between computational prediction and experimental realisation. We trained a machine learning model by first collecting data on 12,553 molecules categorised either as `easy-to-synthesise' or `difficult-to-synthesise' by expert chemists with years of experience in organic synthesis. We used an approach to address the class imbalance present in our dataset, producing a binary classifier able to categorise easy-to-synthesise molecules with few false positives. We then used our model during computational screening for porous organic molecules to bias towards precursors whose easier synthesis requirements would make them promising candidates for experimental realisation and material development. We found that even by limiting precursors to those that are easier-to-synthesise, we are still able to identify cages with favourable, and even some rare, properties.
Date Issued
2021-09-27
Date Acceptance
2021-07-26
Citation
Journal of Chemical Information and Modeling, 2021, 61 (9), pp.4342-4356
ISSN
1549-9596
Publisher
American Chemical Society
Start Page
4342
End Page
4356
Journal / Book Title
Journal of Chemical Information and Modeling
Volume
61
Issue
9
Copyright Statement
© 2021 The Authors. Published by American Chemical Society. This work is published under CC BY-NC-ND 4.0 International licence.
Sponsor
The Royal Society
Identifier
https://pubs.acs.org/doi/full/10.1021/acs.jcim.1c00375
Grant Number
URF\R1\191432
Subjects
Science & Technology
Life Sciences & Biomedicine
Physical Sciences
Technology
Chemistry, Medicinal
Chemistry, Multidisciplinary
Computer Science, Information Systems
Computer Science, Interdisciplinary Applications
Pharmacology & Pharmacy
Chemistry
Computer Science
RANDOM FOREST
DISCOVERY
DRUG
PERSPECTIVE
SELECTIVITY
COMPLEXITY
MOLECULES
Chemistry Techniques, Synthetic
Intuition
Machine Learning
Porosity
Intuition
Porosity
Chemistry Techniques, Synthetic
Machine Learning
Medicinal & Biomolecular Chemistry
0304 Medicinal and Biomolecular Chemistry
0307 Theoretical and Computational Chemistry
0802 Computation Theory and Mathematics
Publication Status
Published
Date Publish Online
2021-08-13