Impact and importance of electrostatic potential calculations for predicting structural patterns of hydrogen and halogen bonding

Abstract

The way in which differences in electrostatic potential values can govern how ditopic hydrogen/halogen-bond acceptors form supramolecular interactions in the solid state has been examined using two heterocycles, [1,2,3]triazalo-[3,5-α]quinoline and, [1,2,3]triazalo-[3,5-α]pyridine. In general, the “better” donor (as ranked by electrostatic potential values) preferentially binds to the acceptor atom that carries the higher electrostatic potential value but the outcome is crucially dependent on the magnitude of the potential-energy differences, and structural selectivity can be fine-tuned to generate specifically targeted supramolecular architectures. DFT calculations on [1,2,3]triazalo-[3,5-α]quinoline and [1,2,3]triazalo-[3,5-α]pyridine indicate that the differences in electrostatic potential between the competing sites on the molecules are 38 kJ mol⁻¹ and 26 kJ mol⁻¹, respectively. In order to establish how the nature of the electrostatic potential differences impact the structural landscape around these molecules both heterocycles were co-crystallized with twelve hydrogen-bond (HB) donors, five halogen-bond (XB) donors, and four mixed HB/XB donors. A total of 42 new co-crystals were obtained (as determined by IR spectroscopy), eight of which yielded crystals suitable for single-crystal X-ray diffraction. Results indicate that an electrostatic potential difference greater than 38 kJ mol⁻¹ leads to a pronounced intermolecular preference for the best acceptor but no selectivity is obtained with a smaller difference. This study shows that electrostatic factors play important roles for defining the structural landscape around molecules capable of engaging in a numerous and competing intermolecular interactions as long as the difference between potentially competing sites is large enough.