Data mining of iron(II) and iron(III) bond-valence parameters, and their relevance for macromolecular crystallography.

The bond-valence model is a reliable way to validate assumed oxidation states based on structural data. It has successfully been employed for analyzing metal-binding sites in macromolecule structures. However, inconsistent results for heme-based structures suggest that some widely used bond-valence R parameters may need to be adjusted in certain cases.

Hydrogen bonding at C=Se acceptors in selenoureas, selenoamides and selones.

In recent years there has been considerable interest in chalcogen and hydrogen bonding involving Se atoms, but a general understanding of their nature and behaviour has yet to emerge. In the present work, the hydrogen-bonding ability and nature of Se atoms in selenourea derivatives, selenoamides and selones has been explored using analysis of the Cambridge Structural Database and ab initio calculations. In the CSD there are 70 C=Se structures forming hydrogen bonds, all of them selenourea derivatives or selenoamides.

The Cambridge Structural Database in retrospect and prospect.

The Cambridge Crystallographic Data Centre (CCDC) was established in 1965 to record numerical, chemical and bibliographic data relating to published organic and metal-organic crystal structures. The Cambridge Structural Database (CSD) now stores data for nearly 700,000 structures and is a comprehensive and fully retrospective historical archive of small-molecule crystallography. Nearly 40,000 new structures are added each year.

Hydrogen-bond landscapes, geometry and energetics of squaric acid and its mono- and dianions: a Cambridge Structural Database, IsoStar and computational study.

As part of a programme of work to extend central-group coverage in the Cambridge Crystallographic Data Centre's (CCDC) IsoStar knowledge base of intermolecular interactions, we have studied the hydrogen-bonding abilities of squaric acid (H2SQ) and its mono- and dianions (HSQ(-) and SQ(2-)) using the Cambridge Structural Database (CSD) along with dispersion-corrected density functional theory (DFT-D) calculations for a range of hydrogen-bonded dimers. The -OH and -C=O groups of H2SQ, HSQ(-) and SQ(2-) are potent donors and acceptors, as indicated by their hydrogen-bond geometries in available crystal structures in the CSD, and by the attractive energies calculated for their dimers with acetone and methanol, which were used as model acceptors and donors. The two anions have sufficient examples in the CSD for their addition as new central groups in IsoStar.

Role of chloroform and dichloromethane solvent molecules in crystal packing: an interaction propensity study.

Using the Cambridge Structural Database (CSD), it is shown that the acidic C-H donors of chloroform and dichloromethane, respectively, form hydrogen bonds with N, O, S, halides or carbon-bound halogens in 82% and 77% of structures in which such interactions can occur. This hydrogen-bond potency is retained to a significant degree even in the presence of the more conventional O-H and N-H donors. The hydrogen-bond propensities exhibited by the C-H protons in CHCl3 and CH2Cl2 are similar to those of the acetylenic C-C≡C-H proton.

The versatile role of the ethynyl group in crystal packing: an interaction propensity study.

It is well documented that the ethynyl group can act as a hydrogen-bond donor via its acidic C-H, and as a hydrogen-bond acceptor via the triple-bond π-density. Using the Cambridge Structural Database (CSD), it is shown that C-C≡C-H forms hydrogen bonds to N, O, S or halogens in 74% of structures in which these bonds can form. Additionally, the ethynyl group forms C-H···π interactions with itself or with phenyl groups in 23% of structures and accepts hydrogen bonds from O-H, N-H or C(aromatic)-H in 47% of structures where such bonds are possible.

New software for statistical analysis of Cambridge Structural Database data.

A collection of new software tools is presented for the analysis of geometrical, chemical and crystallographic data from the Cambridge Structural Database (CSD). This software supersedes the program Vista. The new functionality is integrated into the program Mercury in order to provide statistical, charting and plotting options alongside three-dimensional structural visualization and analysis.

Geometry and conformation of cyclopropane derivatives having σ-acceptor and σ-donor substituents: a theoretical and crystal structure database study.

The structures of cyclopropane rings which carry σ-acceptor or σ-donor substituents have been studied using density-functional theory (DFT), and mean bond lengths and conformational parameters retrieved from the Cambridge Structural Database. It is confirmed that σ-acceptor substituents, e.g.

The hydrogen bond environments of 1H-tetrazole and tetrazolate rings: the structural basis for tetrazole-carboxylic acid bioisosterism.

Bioisosterism involving replacement of a carboxylic acid substituent by 1H-tetrazole, yielding deprotonated carboxylate and tetrazolate under physiological conditions, is a well-known synthetic strategy in medicinal chemistry. To improve our overall understanding of bioisosterism, we have used this example to study the geometrical and energetic aspects of the functional group replacement. Specifically, we use crystal structure informatics and high-level ab initio calculations to study the hydrogen bond (H-bond) energy landscapes of the protonated and deprotonated bioisosteric pairs.

Conformation and geometry of cyclopropane rings having π-acceptor substituents: a theoretical and database study.

The 3e' orbitals of cyclopropane have the correct symmetry to interact with low-lying unoccupied orbitals of π-acceptor substituents and maximum overlap occurs when the two orbital systems are parallel, i.e. when the π-acceptor bisects the ring in projection down the substituent bond.

Applications of the Cambridge Structural Database in chemical education.

The Cambridge Structural Database (CSD) is a vast and ever growing compendium of accurate three-dimensional structures that has massive chemical diversity across organic and metal-organic compounds. For these reasons, the CSD is finding significant uses in chemical education, and these applications are reviewed. As part of the teaching initiative of the Cambridge Crystallographic Data Centre (CCDC), a teaching subset of more than 500 CSD structures has been created that illustrate key chemical concepts, and a number of teaching modules have been devised that make use of this subset in a teaching environment.

Bond lengths in organic and metal-organic compounds revisited: X-H bond lengths from neutron diffraction data.

The number of structures in the Cambridge Structural Database (CSD) has increased by an order of magnitude since the preparation of two major compilations of standard bond lengths in mid-1985. It is now of interest to examine whether this huge increase in data availability has implications for the mean bond-length values published in the late 1980s. Those compilations reported mean X-H bond lengths derived from rather sparse information and for rather few chemical environments.

Universal prediction of intramolecular hydrogen bonds in organic crystals.

A complete exploration of intramolecular hydrogen bonds (IHBs) has been undertaken using a combination of statistical analyses of the Cambridge Structural Database and computation of ab initio interaction energies for prototypical hydrogen-bonded fragments. Notable correlations have been revealed between computed energies, hydrogen-bond geometries, donor and acceptor chemistry, and frequencies of occurrence. Significantly, we find that 95% of all observed IHBs correspond to the five-, six- or seven-membered rings.

Persistent hydrogen bonding in polymorphic crystal structures.

The significance of hydrogen bonding and its variability in polymorphic crystal structures is explored using new automated structural analysis methods. The concept of a chemically equivalent hydrogen bond is defined, which may be identified in pairs of structures, revealing those types of bonds that may persist, or not, in moving from one polymorphic form to another. Their frequency and nature are investigated in 882 polymorphic structures from the Cambridge Structural Database.

Orthogonal dipolar interactions between amide carbonyl groups.

Orthogonal dipolar interactions between amide C=O bond dipoles are commonly found in crystal structures of small molecules, proteins, and protein-ligand complexes. We herein present the experimental quantification of such interactions by employing a model system based on a molecular torsion balance. Application of a thermodynamic double-mutant cycle allows for the determination of the incremental energetic contributions attributed to the dipolar contact between 2 amide C=O groups.

Interaction geometries and energies of hydrogen bonds to C[double bond]O and C[double bond]S acceptors: a comparative study.

The occurrence, geometries and energies of hydrogen bonds from N-H and O-H donors to the S acceptors of thiourea derivatives, thioamides and thiones are compared with data for their O analogues - ureas, amides and ketones. Geometrical data derived from the Cambridge Structural Database indicate that hydrogen bonds to the C[double bond]S acceptors are much weaker than those to their C[double bond]O counterparts: van der Waals normalized hydrogen bonds to O are shorter than those to S by approximately 0.25 A.

Dipolar C[triple-bond]N...C[triple-bond]N interactions in organic crystal structures: database analysis and calculation of interaction energies.

The Cambridge Structural Database (CSD) has been used to study nonbonded interactions between dipolar cyano groups. The analysis shows that C[triple-bond]N..

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.

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

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.

Librarians, crystal structures and drug design.

There are now 355,000 published crystal structures of organic and metal-organic compounds, all of which have been acquired, validated, chemically annotated and organised for searching in the Cambridge Structural Database (CSD). The CSD is used in rational drug design and is beginning to answer important questions relevant to the formulation of pharmaceutical active ingredients. The value and credibility of this research are ultimately dependent on the accuracy and completeness of the underlying crystal-structure data.

Recurring main-chain anion-binding motifs in short polypeptides: nests.

A novel tripeptide motif called a nest has recently been described in proteins with the function of binding anionic, or partially anionic, atoms such as carbonyl O atoms. In the present work, a search for nests in small polypeptides stored in the Cambridge Structural Database is reported. 37 unique examples were found: over half form part of hydrogen-bond arrangements resembling those in proteins, such as Schellman/paperclip loop motifs, various types of beta-turn and Asx-turns or Ser/Thr-turns, while a third are in novel situations, some involving binding to anionic groups from other molecules within the crystal complex.

Research applications of the Cambridge Structural Database (CSD).

Crystal structure data are of fundamental importance in a wide spectrum of scientific activities. This tutorial review summarises the principal application areas, so far, for the data from more than 300,000 crystal structures of small organic and metal-organic compounds that are stored in the Cambridge Structural Database (CSD). Direct use of the accumulated data is valuable in establishing standard molecular dimensions, determining conformational preferences and in the study of intermolecular interactions, all of which are crucial in structural chemistry and rational drug design.