Quantum Mechanics Enables "Freedom of Design" in Molecular Property Space

Abstract

Rational design of molecules with targeted properties requires understanding quantum-mechanical (QM) structure-property/property-property relationships (SPR/PPR) across chemical compound space. We analyze these relationships using the QM7-X dataset---which includes multiple QM properties for ~4.2 M equilibrium and non-equilibrium structures of small (primarily organic) molecules. Instead of providing simple SPR/PPR that strictly follow physicochemical intuition, our analysis uncovers substantial flexibility in molecular property space (MPS) when searching for a single molecule with a desired pair of QM properties or distinct molecules with a targeted set of QM properties. As proof-of-concept, we used Pareto multi-property optimization to search for the most promising (i.e., highly polarizable and electrically stable) molecules for polymeric battery materials; without prior knowledge of this complex manifold of MPS, Pareto front analysis reflected this intrinsic flexibility and identified small directed structural/compositional changes that simultaneously optimize these properties. Our analysis of such extensive QM property data provides compelling evidence for an intrinsic “freedom of design” in MPS, and indicates that rational design of molecules with a diverse array of targeted QM properties is quite feasible.

Data-driven tailoring of molecular dipole polarizability and frontier orbital energies in chemical compound space

“…To draw more general conclusions about the relationship between the properties in question, we analyse the two-dimensional (2D) property space defined by HOMO–LUMO gap and polarizability for a selected subset of QM7-X molecules 8 (see Section 6.2). HOMO–LUMO gap values were taken from the dataset, while polarizability values were recalculated using the computational setup explained in Section 6.1.…”

“…[4][5][6][7] Given the complexity of a multi-property design task, it is essential to first have a solid grasp of the physical relationships between the various target properties. 8 Within this context, two fundamental quantum-mechanical (QM) electronic properties are the optical gap and the molecular dipole polarizability (a). Optical gap is an experimental property that measures the energy corresponding to the lowest observed optical transition.…”

“… 4–7 Given the complexity of a multi-property design task, it is essential to first have a solid grasp of the physical relationships between the various target properties. 8 …”

Aquamarine: Quantum-Mechanical Exploration of Conformers and Solvent Effects in Large Drug-like Molecules

“…The AQM dataset is provided in two HDF5 files in a ZENODO.ORG data repository 76 . The QM structural and property data of the 59, 783 conformations corresponding to 1, 653 molecules in both gas phase and implicit water were stored in the AQM-gas.hdf5 and AQM-sol.hdf5 files, respectively.…”

Molecule Structure Pedagogy with the Objectivity of Music

“…The correlation modeling and mapping method is widely used in chemical compound space projection. 15 A scientific correlation modeling can also be constructed between music and chemistry through a similar approach, which is a possible pattern to help students learn chemistry. This paper explored the correlation mapping between molecule representations and chord progressions and generates new music through 20 common amino acids using music data sets and artificial intelligence (AI).…”