Issue 39, 2023

“Freedom of design” in chemical compound space: towards rational in silico design of molecules with targeted quantum-mechanical properties

Abstract

The rational design of molecules with targeted quantum-mechanical (QM) properties requires an advanced understanding of the structure–property/property–property relationships (SPR/PPR) that exist across chemical compound space (CCS). In this work, we analyze these fundamental relationships in the sector of CCS spanned by small (primarily organic) molecules using the recently developed QM7-X dataset, a systematic, extensive, and tightly converged collection of 42 QM properties corresponding to ≈4.2M equilibrium and non-equilibrium molecular structures containing up to seven heavy/non-hydrogen atoms (including C, N, O, S, and Cl). By characterizing and enumerating progressively more complex manifolds of molecular property space—the corresponding high-dimensional space defined by the properties of each molecule in this sector of CCS—our analysis reveals that one has a substantial degree of flexibility or “freedom of design” when searching for a single molecule with a desired pair of properties or a set of distinct molecules sharing an array of properties. To explore how this intrinsic flexibility manifests in the molecular design process, we used multi-objective optimization to search for molecules with simultaneously large polarizabilities and HOMO–LUMO gaps; analysis of the resulting Pareto fronts identified non-trivial paths through CCS consisting of sequential structural and/or compositional changes that yield molecules with optimal combinations of these properties.

Graphical abstract: “Freedom of design” in chemical compound space: towards rational in silico design of molecules with targeted quantum-mechanical properties

Supplementary files

Article information

Article type
Edge Article
Submitted
13 jul 2023
Accepted
17 aug 2023
First published
18 aug 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 10702-10717

“Freedom of design” in chemical compound space: towards rational in silico design of molecules with targeted quantum-mechanical properties

L. Medrano Sandonas, J. Hoja, B. G. Ernst, Á. Vázquez-Mayagoitia, R. A. DiStasio and A. Tkatchenko, Chem. Sci., 2023, 14, 10702 DOI: 10.1039/D3SC03598K

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