Troubleshooting unstable molecules in chemical space.

A key challenge in automated chemical compound space explorations is ensuring veracity in minimum energy geometries-to preserve intended bonding connectivities. We discuss an iterative high-throughput workflow for connectivity preserving geometry optimizations exploiting the nearness between quantum mechanical models. The methodology is benchmarked on the QM9 dataset comprising DFT-level properties of 133 885 small molecules, wherein 3054 have questionable geometric stability.