Evaluating hydrogen-bond propensity, hydrogen-bond coordination and hydrogen-bond energy as tools for predicting the outcome of attempted co-crystallisations

Two different structure-informatics based methods and one approach based on hydrogen-bond interaction energies were evaluated for their abilities to predict the experimental outcomes of attempted co-crystallisations between two known drug molecules, Nevirapine and Diclofenac, and a series of potential co-formers. The hydrogen-bond propensity (HBP) tool gave the correct result in 26 out of 30 cases, whereas a hydrogen-bond coordination (HBC) method predicted the correct outcome in 22 out of 30 cases. Finally, calculated hydrogen-bond energies (HBE) using a simple electrostatic model, gave the correct result in 23 out of 30 experiments. In those cases, where the crystal structure of a co-crystal of either Nevirapine or Diclofenac was known, we also examined how well the three methods predicted which primary hydrogen-bond interactions were present in the crystal structure. HBP correctly predicted 6 out of 6 cases, HBC could not predict any of the synthon formations correctly, and HBE successfully predicted 1 out of 6 cases.