W. D. Sam Motherwell

Retrieval of Crystallographically-Derived Molecular Geometry Information

The crystallographically determined bond length, valence angle, and torsion angle information in the Cambridge Structural Database (CSD) has many uses. However, accessing it by means of conventional substructure searching requires nontrivial user intervention. In consequence, these valuable data have been underutilized and have not been directly accessible to client applications. The situation has been remedied by development of a new program (Mogul) for automated retrieval of molecular geometry data from the CSD. The program uses a system of keys to encode the chemical environments of fragments (bonds, valence angles, and acyclic torsions) from CSD structures. Fragments with identical keys are deemed to be chemically identical and are grouped together, and the distribution of the appropriate geometrical parameter (bond length, valence angle, or torsion angle) is computed and stored. Use of a search tree indexed on key values, together with a novel similarity calculation, then enables the distribution matching any given query fragment (or the distributions most closely matching, if an adequate exact match is unavailable) to be found easily and with no user intervention. Validation experiments indicate that, with rare exceptions, search results afford precise and unbiased estimates of molecular geometrical preferences. Such estimates may be used, for example, to validate the geometries of libraries of modeled molecules or of newly determined crystal structures or to assist structure solution from low-resolution (e.g. powder diffraction) X-ray data.

Organic crystal hydrates: what are the important factors for formation

A database study of 34 770 accurate organic crystal structures reveals that the most important factor determining a higher frequency of hydrates is the sum of the average donor and acceptor counts for the functional groups. Different parameter forms for donor/acceptor properties were investigated for correlation with formation of hydrates, and are discussed. We did not find that the donor/acceptor ratio or the molecular weight significantly affects the hydrate formation. We also examined a wide range of calculated molecular properties and found that increasing polar surface is correlated with increasing hydrate formation. The water environment pattern of donor and acceptor hydrogen bonds in the crystal is influenced by the donor/acceptor ratio of the molecule.

Hydrogen bond competition between chemical groups: new methodology and the Cambridge Structural Database

Abstract The probabilities of formation of intermolecular hydrogen bond interactions between chemical groups have been studied using new methodology to extract information from the Cambridge Structural Database (CSD). Data for 41052 crystal structures containing at least one strong hydrogen bond donor have been analysed using the RPluto program, assigning 108 chemical group codes to atoms, and creating tables of hydrogen contacts for subsequent analysis using the Access relational database software. This has enabled the study of competition effects where there are specified limited numbers of chemical groups in a structure, which is often difficult with the standard CSD search program, ConQuest. There are sufficiently high numbers of certain combinations of groups to make significant observations of the preference of a given donor for choices of acceptor atoms. For example, COOH…COOH contacts are frequently disrupted by groups such as keto carbonyl, whereas CONH…CONH is very robust and is seldom disrupted. There are a surprising number of structures that do not present any intermolecular hydrogen bond interactions, often due to intramolecular hydrogen bonding taking preference. There is a tendency to use as many groups as possible to build intermolecular hydrogen bond networks. An estimate is made of the relative strengths of self-association interactions which are, in decreasing order, CONH, COOH, alcoholic OH and phenolic OH. The frequency of preferred contacts in some cases allows one to predict the most probable contacts for a given molecule with a specific combination and ratio of chemical groups.

Structure solution and refinement of tetracaine hydrochloride from X-ray powder diffraction data

The previously unknown crystal structure of the local anaesthetic tetracaine hydrochloride (C15H25N2O2+Cl−) has been solved from synchrotron X-ray powder diffraction data using a direct-space global optimisation method in which the position and conformation of a structural model is adjusted. The C15H25N2O2+ moiety and the chloride counterion were treated as independent units during the structure solution process. This complex structure has been solved despite the nine torsional degrees of freedom in the cation. A restrained Rietveld refinement of the initial solution gives an excellent fit to the data, with Rwp = 0.0956 and RF2 = 0.1638, and reveals the presence of a significant degree of preferred crystallite orientation in the sample. The crystal structure shows efficient packing involving parallel sheets made up of molecules lying parallel to one another, head-to-tail, in chains. Hydrogen bonds are observed between adjacent molecules and an extensive pattern of N+–Cl− contacts is apparent.

Conformational variability of molecules in different crystal environments: a database study.

A methodology is described for analysing the Cambridge Structural Database (CSD) in terms of molecular conformations. Molecular species that have more than a single occurrence across the complete CSD are identified, either as the sole crystal component or co-crystallized with other components. Cluster analysis, based on a root-mean-square fit of coordinates and chemical connectivity, is performed to identify conformational variance for each molecule. Results are analysed in terms of the number of discrete conformations observed versus the number of crystal environments and number of acyclic torsion angles in the molecule. Special subsets of environments are also analysed, namely polymorphs, co-crystals and solvates. In general, conformational diversity increases with an increasing number of different crystal environments and with an increasing number of flexible torsion angles. Overall, molecules with one or more acyclic flexible torsion angle are observed to exist in more than one conformation in ca 40% of cases. There is evidence that solvated molecules exhibit more conformational flexibility on average, compared with polymorphs and co-crystals.

Tormat: a program for the automated structural alignment of molecular conformations

A method is described which enables automated superimposition of molecular conformations by the matching of chemical graphs, allowing for topological symmetry in the molecular structure. This algorithm is implemented in the program Tormat. The implemented method makes allowance for enantiomer inversion, explicit and implicit treatment of H atoms, and partial structure alignment.

Space group selection for crystal structure prediction of solvates

The most populated space groups for a selection of solvates of chiral and achiral molecules with common solvents are presented to assist crystal structure prediction calculations on these complex systems.

Hydrogen bonding preference of equatorial versus axial hydroxyl groups in pyran and cyclohexane rings in organic crystals

In a study of the hydrogen bonding counts in crystalline pyranose monosaccharides, we noticed that equatorial hydroxyls formed more hydrogen bonds, on average, than axial groups. A survey of the Cambridge Structural Database was extended to all pyran and cyclohexane rings which have at least one hydroxyl substituent. There is a definite tendency for equatorial hydroxyls to be involved in two hydrogen bonds, whereas axial are more likely to form only one. The sterically accessible surface of the hydroxyl oxygens was calculated, and shows a positive correlation with the number of hydrogen bonds. The axial groups in general have a lower accessible surface than equatorial groups, and are closer to the molecular centre of mass, giving less opportunity for forming hydrogen bonds in the closely packed crystal structures.

The probable number of hydrogen-bonded contacts for chemical groups in organic crystal structures

A new database has been created for chemical groups and their hydrogen-bonded contacts for 41055 organic crystals. The accessible surface of an atom and the ratio between the number of donors and acceptors in a compound have been found to be useful parameters to predict the probable number of contacts for that atom.

2-(p-Nitro­phenoxy)­tetra­hydro­pyran

The title compound, C11H13NO4 forms supramolecular sheets parallel to (001) via C—H⋯O hydrogen bonds. Sheets stack along the c axis via additional C—H⋯O interactions.