Computational de novo design of new drugs and materials requires rigorous and unbiased exploration of chemical compound space. However, large uncharted territories persist due to its size scaling combinatorially with molecular size. We report computed geometric, energetic, electronic, and thermodynamic properties for 134k stable small organic molecules made up of CHONF. These molecules correspond to the subset of all 133,885 species with up to nine heavy atoms (CONF) out of the GDB-17 chemical universe of 166 billion organic molecules. We report geometries minimal in energy, corresponding harmonic frequencies, dipole moments, polarizabilities, along with energies, enthalpies, and free energies of atomization. All properties were calculated at the B3LYP/6-31G(2df,p) level of quantum chemistry. Furthermore, for the predominant stoichiometry, C7H10O2, there are 6,095 constitutional isomers among the 134k molecules. We report energies, enthalpies, and free energies of atomization at the more accurate G4MP2 level of theory for all of them. As such, this data set provides quantum chemical properties for a relevant, consistent, and comprehensive chemical space of small organic molecules. This database may serve the benchmarking of existing methods, development of new methods, such as hybrid quantum mechanics/machine learning, and systematic identification of structure-property relationships.

Chemically accurate and comprehensive studies of the virtual space of all possible molecules are severely limited by the computational cost of quantum chemistry. We introduce a composite strategy that adds machine learning corrections to computationally inexpensive approximate legacy quantum methods. After training, highly accurate predictions of enthalpies, free energies, entropies, and electron correlation energies are possible, for significantly larger molecular sets than used for training. For thermochemical properties of up to 16k isomers of C7H10O2 we present numerical evidence that chemical accuracy can be reached. We also predict electron correlation energy in post Hartree-Fock methods, at the computational cost of Hartree-Fock, and we establish a qualitative relationship between molecular entropy and electron correlation. The transferability of our approach is demonstrated, using semiempirical quantum chemistry and machine learning models trained on 1 and 10% of 134k organic molecules, to reproduce enthalpies of all remaining molecules at density functional theory level of accuracy.

As the quantum chemistry (QC) community embraces machine learning (ML), the number of new methods and applications based on the combination of QC and ML is surging. In this Perspective, a view of the current state of affairs in this new and exciting research field is offered, challenges of using machine learning in quantum chemistry applications are described, and potential future developments are outlined. Specifically, examples of how machine learning is used to improve the accuracy and accelerate quantum chemical research are shown. Generalization and classification of existing techniques are provided to ease the navigation in the sea of literature and to guide researchers entering the field. The emphasis of this Perspective is on supervised machine learning.