Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and ¹³C NMR Chemical Shift Tensors

An understanding of the role of intermolecular interactions in crystal formation is essential to control the generation of diverse crystalline forms which is an important concern for pharmaceutical industry. Very recently, we reported a new approach to interpret the relationships between intermolecular hydrogen bonding, redistribution of electron density in the system, and NMR chemical shifts (Babinský et al. <i>J. Phys. Chem. A</i>, <b>2013</b>, <i>117</i>, 497). Here, we employ this approach to characterize a full set of crystal interactions in a sample of anhydrous theobromine as reflected in ¹³C NMR chemical shift tensors (CSTs). The important intermolecular contacts are identified by comparing the DFT-calculated NMR CSTs for an isolated theobromine molecule and for clusters composed of several molecules as selected from the available X-ray diffraction data. Furthermore, electron deformation density (EDD) and shielding deformation density (SDD) in the proximity of the nuclei involved in the proposed interactions are calculated and visualized. In addition to the recently reported observations for hydrogen bonding, we focus here particularly on the stacking interactions. Although the principal relations between the EDD and CST for hydrogen bonding (HB) and stacking interactions are similar, the real-space consequences are rather different. Whereas the C–H···X hydrogen bonding influences predominantly and significantly the in-plane principal component of the ¹³C CST perpendicular to the HB path and the CO···H hydrogen bonding modulates both in-plane components of the carbonyl ¹³C CST, the stacking modulates the out-of-plane electron density resulting in weak deshielding (2–8 ppm) of both in-plane principal components of the CST and weak shielding (∼ 5 ppm) of the out-of-plane component. The hydrogen-bonding and stacking interactions may add to or subtract from one another to produce total values observed experimentally. On the example of theobromine, we demonstrate the power of this approach to identify and classify the intermolecular forces that govern the packing motifs in crystals and modulate the NMR CSTs

Interpretation of Crystal Effects on NMR Chemical Shift Tensors: Electron and Shielding Deformation Densities

The relationship between the NMR observables and the supramolecular structure of any system is not straightforward. In this work we examine the influence of the crystal packing for three purine derivatives (hypoxanthine, theobromine, and 6-(2-methoxy)­benzylaminopurine) on the principal components of the NMR chemical shift tensors (CSTs). We employ density functional calculations to obtain various molecular properties (the ground-state electron density, the magnitudes and orientations of the components of NMR chemical shift tensor, and the spatial distribution of the isotropic magnetic shielding) for the isolated molecules and for the molecules embedded in supramolecular clusters modeling the crystal environment and evaluate their differences. The concept has enabled us to rationalize the effect of the crystal packing on the NMR CSTs in terms of the redistribution of the ground-state electron density induced by intermolecular interactions in the solid state

Supramolecular Shuttle Based on Inclusion Complex between Cucurbit[6]uril and Bispyridinium Ethylene

Cucurbit[6]uril (CB6) and bispyridinium ethylene form a stable inclusion complex. A rotaxane derived from this complex was prepared in which a CB6 wheel shuttles along an axle in an NMR time-resolved regime

Cooperative Binding of Cucurbit[<i>n</i>]urils and β‑Cyclodextrin to Heteroditopic Imidazolium-Based Guests

Imidazolium-based guests containing two distinct binding epitopes are capable of binding β-cyclodextrin and cucurbit­[6/7]­uril (CB) simultaneously to form heteroternary 1:1:1 inclusion complexes. In the final configuration, the hosts occupy binding sites disfavored in the binary complexes because of the chemically induced reorganization of the intermediate 1:1 aggregate. In addition, the reported guests are capable of binding two CBs to form either 1:2 or 1:1:1 ternary assemblies despite consisting of a single cationic moiety. Whereas the adamantane site binds CB solely via hydrophobic interactions, the CB unit at the butyl site is stabilized by a combination of hydrophobic and ion–dipole interactions

Cooperative Binding of Cucurbit[<i>n</i>]urils and β‑Cyclodextrin to Heteroditopic Imidazolium-Based Guests

Imidazolium-based guests containing two distinct binding epitopes are capable of binding β-cyclodextrin and cucurbit­[6/7]­uril (CB) simultaneously to form heteroternary 1:1:1 inclusion complexes. In the final configuration, the hosts occupy binding sites disfavored in the binary complexes because of the chemically induced reorganization of the intermediate 1:1 aggregate. In addition, the reported guests are capable of binding two CBs to form either 1:2 or 1:1:1 ternary assemblies despite consisting of a single cationic moiety. Whereas the adamantane site binds CB solely via hydrophobic interactions, the CB unit at the butyl site is stabilized by a combination of hydrophobic and ion–dipole interactions