Chemistry | |
Assessment of Computational Tools for Predicting Supramolecular Synthons | |
ChristerB. Aakerӧy1  John Desper1  Ann McLean1  AbhijeetS. Sinha1  Bhupinder Sandhu1  | |
[1] Department of Chemistry, Kansas State University, Manhattan, KS 66506, USA; | |
关键词: hydrogen-bond propensity; hydrogen-bond coordination; supramolecular synthon; hydrogen-bond energies; Cambridge Structural Database; molecular electrostatic potential; | |
DOI : 10.3390/chemistry3020043 | |
来源: DOAJ |
【 摘 要 】
The ability to predict the most likely supramolecular synthons in a crystalline solid is a valuable starting point for subsequently predicting the full crystal structure of a molecule with multiple competing molecular recognition sites. Energy and informatics-based prediction models based on molecular electrostatic potentials (MEPs), hydrogen-bond energies (HBE), hydrogen-bond propensity (HBP), and hydrogen-bond coordination (HBC) were applied to the crystal structures of twelve pyrazole-based molecules. HBE, the most successful method, correctly predicted 100% of the experimentally observed primary intermolecular-interactions, followed by HBP (87.5%), and HBC = MEPs (62.5%). A further HBC analysis suggested a risk of synthon crossover and synthon polymorphism in molecules with multiple binding sites. These easy-to-use models (based on just 2-D chemical structure) can offer a valuable risk assessment of potential formulation challenges.
【 授权许可】
Unknown