Cooperative Binding of Cucurbit[n]urils and ß-Cyclodextrin to Heteroditopic Imidazolium-Based Guests.

Imidazolium-based guests containing two distinct binding epitopes are capable of binding ß-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.

The influence of Mg2+ coordination on 13C and 15N chemical shifts in CKI1RD protein domain from experiment and molecular dynamics/density functional theory calculations.

Sequence dependence of (13) C and (15) N chemical shifts in the receiver domain of CKI1 protein from Arabidopsis thaliana, CKI1RD , and its complexed form, CKI1RD •Mg(2+), was studied by means of MD/DFT calculations. MD simulations of a 20-ns production run length were performed. Nine explicitly hydrated structures of increasing complexity were explored, up to a 40-amino-acid structure. The size of the model necessary depended on the type of nucleus, the type of amino acid and its sequence neighbors, other spatially close amino acids, and the orientation of amino acid NH groups and their surface/interior position. Using models covering a 10 and a 15 Å environment of Mg(2+), a semi-quantitative agreement has been obtained between experiment and theory for the V67-I73 sequence. The influence of Mg(2+) binding was described better by the 15 Å as compared to the 10 Å model. Thirteen chemical shifts were analyzed in terms of the effect of Mg(2+) insertion and geometry preparation. The effect of geometry was significant and opposite in sign to the effect of Mg(2+) binding. The strongest individual effects were found for (15) N of D70, S74, and V68, where the electrostatics dominated; for (13) Cß of D69 and (15) N of K76, where the influences were equal, and for (13) Cα of F72 and (13) Cß of K76, where the geometry adjustment dominated. A partial correlation between dominant geometry influence and torsion angle shifts upon the coordination has been observed.

Loss of loop adenines alters human telomere d[AG3(TTAG3)3] quadruplex folding.

Abasic (AP) lesions are the most frequent type of damages occurring in cellular DNA. Here we describe the conformational effects of AP sites substituted for 2'-deoxyadenosine in the first (ap7), second (ap13) or third (ap19) loop of the quadruplex formed in K(+) by the human telomere DNA 5'-d[AG3(TTAG3)3]. CD spectra and electrophoresis reveal that the presence of AP sites does not hinder the formation of intramolecular quadruplexes. NMR spectra show that the structural heterogeneity is substantially reduced in ap7 and ap19 as compared to that in the wild-type. These two (ap7 and ap19) sequences are shown to adopt the hybrid-1 and hybrid-2 quadruplex topology, respectively, with AP site located in a propeller-like loop. All three studied sequences transform easily into parallel quadruplex in dehydrating ethanol solution. Thus, the AP site in any loop region facilitates the formation of the propeller loop. Substitution of all adenines by AP sites stabilizes the parallel quadruplex even in the absence of ethanol. Whereas guanines are the major determinants of quadruplex stability, the presence or absence of loop adenines substantially influences quadruplex folding. The naturally occurring adenine-lacking sites in the human telomere DNA can change the quadruplex topology in vivo with potentially vital biological consequences.

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.

Intermolecular Interactions in Crystalline Theobromine as Reflected in Electron Deformation Density and (13)C 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. J. Phys. Chem. A, 2013, 117, 497). Here, we employ this approach to characterize a full set of crystal interactions in a sample of anhydrous theobromine as reflected in (13)C 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 (13)C CST perpendicular to the HB path and the C═O···H hydrogen bonding modulates both in-plane components of the carbonyl (13)C 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.

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.