Deciphering the driving forces in crystal packing by analysis of electrostatic energies and contact enrichment ratios.

Hirshfeld surface analysis is a widely used tool for identifying the types of intermolecular contacts that contribute most significantly to crystal packing stabilization. One useful metric for analyzing these contacts is the contact enrichment descriptor, which indicates the types of contacts that are over- or under-represented. In this statistical study, enrichment ratios were combined with electrostatic energy (Eelec) data for a variety of compound families. To compute the electrostatic interaction energy between atoms, charge density models from the ELMAM2 database of multipolar atoms were used. As expected, strong hydrogen bonds such as O/N-H...N and O/N-H...O typically display large enrichment values and have the most negative (i.e. favorable) electrostatic energies. Conversely, contacts that are repulsive from an electrostatic perspective are usually the most under-represented. Analyzing the enrichment ratio and electrostatic energy indicators was shown to help identify which favorable contacts are the most competitive with each other. For weaker interactions, such as hydrophobic contacts, the behavior is less clear cut and can depend on other factors such as the chemical content of the molecule. The anticorrelation between contact enrichment and Eelec is generally lost for weaker contacts. However, we observed that C...C contacts are often enriched in crystal structures containing heterocycles, despite the low electrostatic attraction. For molecules with only weak hydrogen bond donors/acceptors and hydrophobic groups, the correlation between contact enrichment and Eelec is still evident for the strongest of these interactions. However, there are some exceptions where the most favorable contacts from an electrostatic perspective are not the most over-represented. This can occur in cases where the shape of the molecule is complex or elongated, favoring dispersion forces and shape complementarity in the packing.

Crystal structure, Hirshfeld surface analysis and contact enrichment ratios of 1-(2,7-di-methyl-imidazo[1,2-a]pyridin-3-yl)-2-(1,3-di-thio-lan-2-yl-idene)ethanone monohydrate.

In the title hydrated hybrid compound C14H14N2OS2·H2O, the planar imidazo[1,2-a]pyridine ring system is linked to the 1,3-di-thiol-ane moiety by an enone bridge. The atoms of the C-C bond in the 1,3-di-thiol-ane ring are disordered over two positions with occupancies of 0.579 (14) and 0.421 (14) and both disordered rings adopt a half-chair conformation. The oxygen atom of the enone bridge is involved in a weak intra-molecular C-H⋯O hydrogen bond, which generates an S(6) graph-set motif. In the crystal, the hybrid mol-ecules are associated in R 2 2(14) dimeric units by weak C-H⋯O inter-actions. O-H⋯O hydrogen bonds link the water mol-ecules, forming infinite self-assembled chains along the b-axis direction to which the dimers are connected via O-H⋯N hydrogen bonding. Analysis of inter-molecular contacts using Hirshfeld surface analysis and contact enrichment ratio descriptors indicate that hydrogen bonds induced by water mol-ecules are the main driving force in the crystal packing formation.

Atom interaction propensities of oxygenated chemical functions in crystal packings.

The crystal contacts of several families of hydrocarbon compounds substituted with one or several types of oxygenated chemical groups were analyzed statistically using the Hirshfeld surface methodology. The propensity of contacts to occur between two chemical types is described with the contact enrichment descriptor. The systematic large enrichment ratios of some interactions like the O-H⋯O hydrogen bonds suggests that these contacts are a driving force in the crystal packing formation. The same statement holds for the weaker C-H⋯O hydrogen bonds in ethers, esters and ketones, in the absence of polar H atoms. The over-represented contacts in crystals of oxygenated hydrocarbons are generally of two types: electrostatic attractions (hydrogen bonds) and hydrophobic interactions. While Cl⋯O interactions are generally avoided, in a minority of chloro-oxygenated hydrocarbons, significant halogen bonding does occur. General tendencies can often be derived for many contact types, but outlier compounds are instructive as they display peculiar or rare features. The methodology also allows the detection of outliers which can be structures with errors. For instance, a significant number of hydroxylated molecules displaying over-represented non-favorable oxygen-oxygen contacts turned out to have wrongly oriented hydroxyl groups. Beyond crystal packings with a single molecule in the asymmetric unit, the behavior of water in monohydrate compounds and of crystals with Z' = 2 (dimers) are also investigated. It was found in several cases that, in the presence of several oxygenated chemical groups, cross-interactions between different chemical groups (e.g. water/alcohols; alcohols/phenols) are often favored in the crystal packings. While some trends in accordance with common chemical principles are retrieved, some unexpected results can however appear. For example, in crystals of alcohol-phenol compounds, the strong O-H⋯O hydrogen bonds between two phenol groups turn out to be extremely rare, while cross contacts between phenols and alcohols have enriched occurrences.

2-Oxo-2H-chromen-4-yl propionate.

In the title compound, C12H10O4, the atoms of the 2-oxo-2H-chromene ring system and the non-H atoms of the 4-substituent all lie on a crystallographic mirror plane. The mol-ecular structure exhibits an intra-molecular C-H⋯O hydrogen bond, which generates an S(6) ring. In the crystal, mol-ecules form R 3 (2)(12) trimeric units via C-H⋯O inter-actions which propagate into layers parallel to the ac plane. These layers are linked by weak C-H⋯O inter-actions along the [010] direction, generating a three-dimensional network.

Experimental and database-transferred electron-density analysis and evaluation of electrostatic forces in coumarin-102 dye.

The electron-density distribution of a new crystal form of coumarin-102, a laser dye, has been investigated using the Hansen-Coppens multipolar atom model. The charge density was refined versus high-resolution X-ray diffraction data collected at 100 K and was also constructed by transferring the charge density from the Experimental Library of Multipolar Atom Model (ELMAM2). The topology of the refined charge density has been analysed within the Bader `Atoms In Molecules' theory framework. Deformation electron-density peak heights and topological features indicate that the chromen-2-one ring system has a delocalized π-electron cloud in resonance with the N (amino) atom. The molecular electrostatic potential was estimated from both experimental and transferred multipolar models; it reveals an asymmetric character of the charge distribution across the molecule. This polarization effect is due to a substantial charge delocalization within the molecule. The molecular dipole moments derived from the experimental and transferred multipolar models are also compared with the liquid and gas-phase dipole moments. The substantial molecular dipole moment enhancements observed in the crystal environment originate from the crystal field and from intermolecular charge transfer induced and controlled by C-H···O and C-H···N intermolecular hydrogen bonds. The atomic forces were integrated over the atomic basins and compared for the two electron-density models.

Ethyl 4-cyano-7-nitro-1,2,3,3a,4,5-hexa-hydro-pyrrolo-[1,2-a]quinoline-4-carboxyl-ate.

In the title compound, C(16)H(17)N(3)O(4), the six-membered N-containing ring adopts a half-chair conformation. One C atom of the five-membered ring is disordered over two sites, with occupancy factors of ca 0.67 and 0.33. The major pyrroline component adopts a half-chair conformation. Inter-molecular C-H⋯O hydrogen bonds forming centrosymmetric dimers are observed in the crystal.

2-[2-(4-Methoxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepin-4-yl]phenol.

In the structure of title compound, C(22)H(20)O(2)N(2), the 11-membered benzodiazepine ring system adopts a distorted boat conformation. The benzene ring of this system forms dihedral angles of 89.69 (12) and 48.82 (12)° with those of the phenol and methoxy-phenyl substituents, respectively. The dihedral angle between the benzene rings is 49.61 (11)°. An intra-molecular O-H⋯N hydrogen bond generates an S(6) ring.

1-(2-Methyl-imidazo[1,2-a]pyridin-3-yl)-3,3-bis-(methyl-sulfan-yl)prop-2-enone monohydrate.

The title compound, C(13)H(14)N(2)OS(2)·H(2)O, appears in the form of bimolecular aggregate in which mol-ecular components are linked by O-H⋯N hydrogen bonding. The nine-membered imidazo[1,2-a]pyridine system is almost planar, with a mean deviation of 0.026 (1) Å. An intra-molecular C-H⋯O hydrogen bond forms within the imidazo[1,2-a]pyridine system. The crystal packing is consolidated by O-H⋯O and C-H⋯O hydrogen bonds, forming a supra-molecular structure consisting of perpendicular infinite mol-ecular chains running along the a and c axes.