Toward the Prediction of Organic Hydrate Crystal Structures

Lattice energy minimization studies on four ordered crystal structures of ice and 22 hydrates of approximately rigid organic molecules (along with 11 corresponding anhydrate structures) were used to establish a model potential scheme, based on the use of a distributed multipole electrostatic model, that can reasonably reproduce the crystal structures. Transferring the empirical repulsion−dispersion potentials for organic oxygen and polar hydrogen atoms to water appears more successful for modeling ice phases than using common water potentials derived from liquid properties. Lattice energy differences are reasonable but quite sensitive to the exact conformation of water and the organic molecule used in the rigid molecule modeling. This potential scheme was used to test a new approach of predicting the crystal structure of 5-azauracil monohydrate (an isolated site hydrate) based on seeking dense crystal packings of 66 5-azauracil···water hydrogen-bonded clusters, derived from an analysis of hydrate hydrogen bond geometries involving the carbonyl- and aza-group acceptors in the Cambridge Structural Database. The known structure was found within 5 kJ mol-1 of the global minimum in static lattice energy and as the third most stable structure, within 1 kJ mol-1, when thermal effects at ambient temperature were considered. Thus, although the computational prediction of whether an organic molecule will crystallize in a hydrated form poses many challenges, the prediction of plausible structures for hydrogen-bonded monohydrates is now possible

The Discovery of New Crystal Forms of 5-Fluorocytosine Consistent with the Results of Computational Crystal Structure Prediction

A computational search for low-energy crystal structures of 5-fluorocytosine was performed in conjunction with a manual crystallization screen to determine whether solid forms other than the known monohydrate structure could be discovered. The predicted low-energy structures were based on a hydrogen-bonded ribbon, which was observed in two newly determined anhydrous polymorphic crystal structures, a hemipentahydrate, and two solvates, as well as the known monohydrate. An alternative ribbon structure present in some less-stable predicted structures was found in a disordered monohydrate structure. The anhydrous crystal structure prediction was a success, by the criteria of the international crystal structure prediction blind tests. Thus we can rationalize the crystal structure behavior of 5-fluorocytosine as having a strongly preferred two-dimensional ribbon structure, which exhibits versatile methods of packing, leading to polymorphism and a number of closely related solvate structures

The Discovery of New Crystal Forms of 5-Fluorocytosine Consistent with the Results of Computational Crystal Structure Prediction

A computational search for low-energy crystal structures of 5-fluorocytosine was performed in conjunction with a manual crystallization screen to determine whether solid forms other than the known monohydrate structure could be discovered. The predicted low-energy structures were based on a hydrogen-bonded ribbon, which was observed in two newly determined anhydrous polymorphic crystal structures, a hemipentahydrate, and two solvates, as well as the known monohydrate. An alternative ribbon structure present in some less-stable predicted structures was found in a disordered monohydrate structure. The anhydrous crystal structure prediction was a success, by the criteria of the international crystal structure prediction blind tests. Thus we can rationalize the crystal structure behavior of 5-fluorocytosine as having a strongly preferred two-dimensional ribbon structure, which exhibits versatile methods of packing, leading to polymorphism and a number of closely related solvate structures

The Discovery of New Crystal Forms of 5-Fluorocytosine Consistent with the Results of Computational Crystal Structure Prediction

A computational search for low-energy crystal structures of 5-fluorocytosine was performed in conjunction with a manual crystallization screen to determine whether solid forms other than the known monohydrate structure could be discovered. The predicted low-energy structures were based on a hydrogen-bonded ribbon, which was observed in two newly determined anhydrous polymorphic crystal structures, a hemipentahydrate, and two solvates, as well as the known monohydrate. An alternative ribbon structure present in some less-stable predicted structures was found in a disordered monohydrate structure. The anhydrous crystal structure prediction was a success, by the criteria of the international crystal structure prediction blind tests. Thus we can rationalize the crystal structure behavior of 5-fluorocytosine as having a strongly preferred two-dimensional ribbon structure, which exhibits versatile methods of packing, leading to polymorphism and a number of closely related solvate structures

The Discovery of New Crystal Forms of 5-Fluorocytosine Consistent with the Results of Computational Crystal Structure Prediction

A computational search for low-energy crystal structures of 5-fluorocytosine was performed in conjunction with a manual crystallization screen to determine whether solid forms other than the known monohydrate structure could be discovered. The predicted low-energy structures were based on a hydrogen-bonded ribbon, which was observed in two newly determined anhydrous polymorphic crystal structures, a hemipentahydrate, and two solvates, as well as the known monohydrate. An alternative ribbon structure present in some less-stable predicted structures was found in a disordered monohydrate structure. The anhydrous crystal structure prediction was a success, by the criteria of the international crystal structure prediction blind tests. Thus we can rationalize the crystal structure behavior of 5-fluorocytosine as having a strongly preferred two-dimensional ribbon structure, which exhibits versatile methods of packing, leading to polymorphism and a number of closely related solvate structures

The Discovery of New Crystal Forms of 5-Fluorocytosine Consistent with the Results of Computational Crystal Structure Prediction

A computational search for low-energy crystal structures of 5-fluorocytosine was performed in conjunction with a manual crystallization screen to determine whether solid forms other than the known monohydrate structure could be discovered. The predicted low-energy structures were based on a hydrogen-bonded ribbon, which was observed in two newly determined anhydrous polymorphic crystal structures, a hemipentahydrate, and two solvates, as well as the known monohydrate. An alternative ribbon structure present in some less-stable predicted structures was found in a disordered monohydrate structure. The anhydrous crystal structure prediction was a success, by the criteria of the international crystal structure prediction blind tests. Thus we can rationalize the crystal structure behavior of 5-fluorocytosine as having a strongly preferred two-dimensional ribbon structure, which exhibits versatile methods of packing, leading to polymorphism and a number of closely related solvate structures

The Discovery of New Crystal Forms of 5-Fluorocytosine Consistent with the Results of Computational Crystal Structure Prediction

A computational search for low-energy crystal structures of 5-fluorocytosine was performed in conjunction with a manual crystallization screen to determine whether solid forms other than the known monohydrate structure could be discovered. The predicted low-energy structures were based on a hydrogen-bonded ribbon, which was observed in two newly determined anhydrous polymorphic crystal structures, a hemipentahydrate, and two solvates, as well as the known monohydrate. An alternative ribbon structure present in some less-stable predicted structures was found in a disordered monohydrate structure. The anhydrous crystal structure prediction was a success, by the criteria of the international crystal structure prediction blind tests. Thus we can rationalize the crystal structure behavior of 5-fluorocytosine as having a strongly preferred two-dimensional ribbon structure, which exhibits versatile methods of packing, leading to polymorphism and a number of closely related solvate structures

The Discovery of New Crystal Forms of 5-Fluorocytosine Consistent with the Results of Computational Crystal Structure Prediction

A computational search for low-energy crystal structures of 5-fluorocytosine was performed in conjunction with a manual crystallization screen to determine whether solid forms other than the known monohydrate structure could be discovered. The predicted low-energy structures were based on a hydrogen-bonded ribbon, which was observed in two newly determined anhydrous polymorphic crystal structures, a hemipentahydrate, and two solvates, as well as the known monohydrate. An alternative ribbon structure present in some less-stable predicted structures was found in a disordered monohydrate structure. The anhydrous crystal structure prediction was a success, by the criteria of the international crystal structure prediction blind tests. Thus we can rationalize the crystal structure behavior of 5-fluorocytosine as having a strongly preferred two-dimensional ribbon structure, which exhibits versatile methods of packing, leading to polymorphism and a number of closely related solvate structures

The Discovery of New Crystal Forms of 5-Fluorocytosine Consistent with the Results of Computational Crystal Structure Prediction

A computational search for low-energy crystal structures of 5-fluorocytosine was performed in conjunction with a manual crystallization screen to determine whether solid forms other than the known monohydrate structure could be discovered. The predicted low-energy structures were based on a hydrogen-bonded ribbon, which was observed in two newly determined anhydrous polymorphic crystal structures, a hemipentahydrate, and two solvates, as well as the known monohydrate. An alternative ribbon structure present in some less-stable predicted structures was found in a disordered monohydrate structure. The anhydrous crystal structure prediction was a success, by the criteria of the international crystal structure prediction blind tests. Thus we can rationalize the crystal structure behavior of 5-fluorocytosine as having a strongly preferred two-dimensional ribbon structure, which exhibits versatile methods of packing, leading to polymorphism and a number of closely related solvate structures

A New Polymorph of 5-Fluorouracil Found Following Computational Crystal Structure Predictions

A new polymorph of 5-fluorouracil has been obtained following a manual polymorph screen inspired by a computational crystal structure prediction search. It corresponds to the structure that was predicted to be the global minimum in lattice energy. The difficulty of crystallizing this simple structure with a rational hydrogen-bonding motif can be rationalized from the differential solvation of the functional groups