Assessment of Computational Tools for Predicting Supramolecular Synthons

Chemistry

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