Calculated molecular electrostatic potential difference (ΔMEP) of acceptor atoms in a multi component system will lead to different supramolecular architectures.
Co-crystallization technology was employed as a way of solving two problems hampering the usefulness of 4,4′,5,5′-tetranitro-2,2′biimidazole (TNBI) as a viable energetic material, namely hygroscopicity and corrosiveness (high acidity). Co-crystal screening was carried out with 15 co-formers containing nitrogen or oxygen as the primary hydrogen-bond acceptor site. Formation of co-crystals was confirmed by IR spectroscopy and DSC, and suitable co-crystals were then analysed via single-crystal X-ray diffraction. In each case, the formation of a co-crystal was driven by the formation of multiple N–H···N or N–H···O hydrogen bonds between TNBI and the co-former. The N-oxide based acceptors produce better energetic materials due to a more optimal oxygen balance. Hygroscopicity evaluations and corrosion tests revealed that the unavailability of N–H protons in the co-crystals of TNBI reduce hygroscopicity and suppress the chemical acidity of the free parent compound thereby making it substantially easier to handle, store, and transport.
The importance of using structural mimics for mapping out the structural landscape of a poorly soluble active pharmaceutical ingredient was investigated using erlotinib as an example. A mimic was synthesized by preserving the main molecular functionalities responsible for creating the most probable structural arrangements in the solid state. Calculated molecular electrostatic potentials on both erlotinib and the mimic showed very comparable values indicating that the latter would be able to form hydrogen bonds of similar probability and strength as those of erlotinib. In order to establish the binding preference in cocrystallization experiments, the mimic molecule was co-crystallized with US Food and Drug Administration approved dicarboxylic acids. The crystal structures of the mimic and of four co-crystals thereof were obtained. The mimic forms hydrogen bonds in a way that closely resembles those found in the crystal structure of erlotinib. The four co-crystals display self-consistent hydrogen-bond interactions. Thermal and solubility data for the co-crystals demonstrate that by making systematic and controllable changes to the solid forms of the mimic, it is also possible to alter the behaviour and properties of the new solid forms. The use of a suitable structural mimic can allow for a systematic structural examination of a compound that is otherwise not amenable to such investigations by facilitating the elucidation and mapping out of a closely related structural landscape.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.