Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
Add more filters










Database
Language
Publication year range
1.
Chem Sci ; 8(1): 78-84, 2017 Jan 01.
Article in English | MEDLINE | ID: mdl-28451150

ABSTRACT

We report the synthesis of a bis(urea) gelator designed to specifically mimic the chemical structure of the highly polymorphic drug substance ROY. Crystallization of ROY from toluene gels of this gelator results in the formation of the metastable red form instead of the thermodynamic yellow polymorph. In contrast, all other gels and solution control experiments give the yellow form. Conformational and crystal structure prediction methods have been used to propose the structure of the gel and show that the templation of the red form by the targeted gel results from conformational matching of the gelator to the ROY substrate coupled with overgrowth of ROY onto the local periodic structure of the gel fibres.

2.
Acta Crystallogr B Struct Sci Cryst Eng Mater ; 72(Pt 4): 477-87, 2016 08 01.
Article in English | MEDLINE | ID: mdl-27484370

ABSTRACT

We present a re-parameterization of a popular intermolecular force field for describing intermolecular interactions in the organic solid state. Specifically we optimize the performance of the exp-6 force field when used in conjunction with atomic multipole electrostatics. We also parameterize force fields that are optimized for use with multipoles derived from polarized molecular electron densities, to account for induction effects in molecular crystals. Parameterization is performed against a set of 186 experimentally determined, low-temperature crystal structures and 53 measured sublimation enthalpies of hydrogen-bonding organic molecules. The resulting force fields are tested on a validation set of 129 crystal structures and show improved reproduction of the structures and lattice energies of a range of organic molecular crystals compared with the original force field with atomic partial charge electrostatics. Unit-cell dimensions of the validation set are typically reproduced to within 3% with the re-parameterized force fields. Lattice energies, which were all included during parameterization, are systematically underestimated when compared with measured sublimation enthalpies, with mean absolute errors of between 7.4 and 9.0%.

3.
J Am Chem Soc ; 135(25): 9307-10, 2013 Jun 26.
Article in English | MEDLINE | ID: mdl-23745577

ABSTRACT

We synthesize a series of imine cage molecules where increasing the chain length of the alkanediamine precursor results in an odd-even alternation between [2 + 3] and [4 + 6] cage macrocycles. A computational procedure is developed to predict the thermodynamically preferred product and the lowest energy conformer, hence rationalizing the observed alternation and the 3D cage structures, based on knowledge of the precursors alone.


Subject(s)
Imines/chemical synthesis , Crystallography, X-Ray , Cyclization , Imines/chemistry , Macromolecular Substances/chemical synthesis , Macromolecular Substances/chemistry , Models, Molecular , Molecular Structure , Thermodynamics
4.
Phys Chem Chem Phys ; 15(21): 8069-80, 2013 Jun 07.
Article in English | MEDLINE | ID: mdl-23503809

ABSTRACT

A protocol for the ab initio crystal structure determination of powdered solids at natural isotopic abundance by combining solid-state NMR spectroscopy, crystal structure prediction, and DFT chemical shift calculations was evaluated to determine the crystal structures of four small drug molecules: cocaine, flutamide, flufenamic acid, and theophylline. For cocaine, flutamide and flufenamic acid, we find that the assigned (1)H isotropic chemical shifts provide sufficient discrimination to determine the correct structures from a set of predicted structures using the root-mean-square deviation (rmsd) between experimentally determined and calculated chemical shifts. In most cases unassigned shifts could not be used to determine the structures. This method requires no prior knowledge of the crystal structure, and was used to determine the correct crystal structure to within an atomic rmsd of less than 0.12 Å with respect to the known reference structure. For theophylline, the NMR spectra are too simple to allow for unambiguous structure selection.


Subject(s)
Cocaine/chemistry , Flufenamic Acid/chemistry , Flutamide/chemistry , Magnetic Resonance Spectroscopy/methods , Theophylline/chemistry , Crystallography/methods , Models, Molecular , Powders , Quantum Theory
SELECTION OF CITATIONS
SEARCH DETAIL
...