Physical binding energies using the electron localization function in 4-hydroxyphenylboronic acid co-crystals with aza donors

Binding energies are traditionally simulated using cluster models by computation of each synthon for each individual co-crystal former. However, our investigation of the binding strengths using the electron localization function (ELF) reveals that these can be determined directly from the crystal supercell computations. We propose a new modeling protocol for the computation of physical binding energies directly from bulk simulations using ELF analysis. In this work, we establish a correlation between ELF values and binding energies calculated for co-crystals of 4-hydroxyphenylboronic acid (4HPBA) with four different aza donors using density functional theory with varying descriptions of dispersion. Boronic acids are gaining significant interest in the field of crystal engineering, but theoretical studies on their use in materials are still very limited. Here, we present a systematic investigation of the non-covalent interactions in experimentally realized co-crystals. Prior diffraction studies on these complexes have shown the competitive nature between the boronic acid functional group and the para-substituted phenolic group forming heteromeric interactions with aza donors. We determine the stability of the co-crystals by simulating their lattice energies, and the different dispersion descriptions show similar trends in lattice energies and lattice parameters. Our study bolsters the experimental observation of the boronic acid group as a competitive co-crystal former in addition to the well-studied phenolic group. Further research on correlating ELF values for physical binding could potentially transform this approach to a viable alternative for the computation of binding energies.