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Blind crystal structure prediction of a novel second polymorph of 1-hydroxy-7-azabenzotriazole

DOI: 10.1107/S0108768106012584 DOI Help
PMID: 16840814 PMID Help

Authors: Harriott Nowell (Diamond Light Source) , Christopher S. Frampton (Pharmorphix Ltd) , Julie Waite (Pharmorphix Ltd) , Sarah L. Price (University College London)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Acta Crystallographica Section B Structural Science , VOL 62 , PAGES 642-650

State: Published (Approved)
Published: August 2006

Abstract: The commercially available peptide coupling reagent 1-hydroxy-7-azabenzotriazole has been shown to crystallize in two polymorphic forms. The two polymorphs differ in their hydrogen-bonding motif, with form I having an R-2(2)(10) dimer motif and form II having a C(5) chain motif. The previously unreported form II was used as an informal blind test of computational crystal structure prediction for flexible molecules. The crystal structure of form II has been successfully predicted blind from lattice-energy minimization calculations following a series of searches using a large number of rigid conformers. The structure for form II was the third lowest in energy with form I found as the global minimum, with the energy calculated as the sum of the ab initio intramolecular energy penalty for conformational distortion and the intermolecular lattice energy which is calculated from a distributed multipole representation of the charge density. The predicted structure was sufficiently close to the experimental structure that it could be used as a starting model for crystal structure refinement. A subsequent limited polymorph screen failed to yield a third polymorphic form, but demonstrated that alcohol solvents are implicated in the formation of the form I dimer structure.

Journal Keywords: Conformational Polymorphism; Crystal Structure Prediction; Polymorph Screening

Subject Areas: Chemistry


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