Knowledge-based model of hydrogen-bonding propensity in organic crystals

Abstract

A new method is presented to predict which donors and acceptors form hydrogen bonds in a crystal structure, based on the statistical analysis of hydrogen bonds in the Cambridge Structural Database (CSD). The method is named the logit hydrogen-bonding propensity (LHP) model. The approach has a potential application in identifying both likely and unusual hydrogen bonding, which can help to rationalize stable and metastable crystalline forms, of relevance to drug development in the pharmaceutical industry. Whilst polymorph prediction techniques are widely used, the LHP model is knowledge-based and is not restricted by the computational issues of polymorph prediction, and as such may form a valuable precursor to polymorph screening. Model construction applies logistic regression, using training data obtained with a new survey method based on the CSD system. The survey categorizes the hydrogen bonds and extracts model parameter values using descriptive structural and chemical properties from three-dimensional organic crystal structures. LHP predictions from a fitted model are made using two-dimensional observables alone. In the initial cases analysed, the model is highly accurate, achieving ~ 90% correct classification of both observed hydrogen bonds and non-interacting donor-acceptor pairs. Extensive statistical validation shows the LHP model to be robust across a range of small-molecule organic crystal structures

The role of weak intermolecular C–H...F interactions in supramolecular assembly: Structural investigations on 3,5- dibenzylidene-piperidin-4-one and database analysis

“…Few attempts in this direction were earlier also made, to rank the effectiveness of HB groups and the quantities were referred by various names such as probabilities, relative success, propensity or competition function. [25][26][27][28][29][30] To investigate the efficacy of fluorine for making interactions, these parameters were calculated using Cambridge Structural Database (CSD) (Version 5.31). 15 All intra-molecular short-contacts were excluded.…”

Will they co-crystallize?

“…A knowledge-based method based on hydrogen bond propensity (HBP) analysis 27 of the CSD 28 to determine the likelihood of co-crystal formation by assessing the probability of the homo-and hetero-interactions has been shown to successfully identify some co-crystals of paracetamol.…”

Two Closely Related Organic Charge-Transfer Complexes Based on Tetrathiafulvalene and 9H-fluorenone Derivatives. Competition between Hydrogen Bonding and Stacking Interactions

“…The propensity of this group to generate R 2 2 (8) ring motifs [14,15] has been recognized since a long time, and indeed, it appears with a frequency of about 24% for the X-ray structures deposited in the CSD which bear a COOH fragment [16]. For 1, C2TNF molecules form centrosymmetric dimers and the hydrogen bonds may be considered as strong: the O12-H12···O13 i angle is 169.7°, and the H12···O13 i distance is 1.76 Å (symmetry code i: 1−x, 1−y, −z), resulting in a O12…O13 separation of 2.651(4) Å.…”