Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

The enantioselectivity of β-cyclodextrin (β-CD) towards L- and D-N-acetyltryptophan (NAcTrp) has been studied in aqueous solution and the crystalline state. NMR studies in solution show that β-CD forms complexes of very similar but not identical geometry with both L- and D-NAcTrp and exhibits stronger binding with L-NAcTrp. In the crystalline state, only β-CD-L-NAcTrp crystallizes readily from aqueous solutions as a dimeric complex (two hosts enclosing two guest molecules). In contrast, crystals of the complex β-CD-D-NAcTrp were never obtained, although numerous conditions were tried. In aqueous solution, the orientation of the guest in both complexes is different than in the β-CD-L-NAcTrp complex in the crystal. Overall, the study shows that subtle differences observed between the β-CD-L,D-NAcTrp complexes in aqueous solution are magnified at the onset of crystallization, as a consequence of accumulation of many soft host-guest interactions and of the imposed crystallographic order, thus resulting in very dissimilar propensity of each enantiomer to produce crystals with β-CD

Mucinous cystic neoplasms of the mesentery: a case report and review of the literature

<p>Abstract</p> <p>Background</p> <p>Mucinous cystic neoplasms arise in the ovary and various extra-ovarian sites. While their pathogenesis remains conjectural, their similarities suggest a common pathway of development. There have been rare reports involving the mesentery as a primary tumour site.</p> <p>Case presentation</p> <p>A cystic mass of uncertain origin was demonstrated radiologically in a 22 year old female with chronic abdominal pain. At laparotomy, the mass was fixed within the colonic mesentery. Histology demonstrated a benign mucinous cystadenoma.</p> <p>Methods and results</p> <p>We review the literature on mucinous cystic neoplasms of the mesentery and report on the pathogenesis, biologic behavior, diagnosis and treatment of similar extra-ovarian tumors. We propose an updated classification of mesenteric cysts and cystic tumors.</p> <p>Conclusion</p> <p>Mucinous cystic neoplasms of the mesentery present almost exclusively in women and must be considered in the differential diagnosis of mesenteric tumors. Only full histological examination of a mucinous cystic neoplasm can exclude a borderline or malignant component. An updated classification of mesenteric cysts and cystic tumors is proposed.</p

Release of the Prays oleae pheromone as a consequence of supramolecular structure: study of the \u3b2-cyclodextrin-(Z)-tetradec-7-en-1-al complex by X-ray crystallography and NMR spectroscopy in the solid state and in solution

The structure of the \u3b2-cyclodextrin-(Z)-tetradec-7-en-1-al complex in aqueous solution and in the solid state, as well as the release profile of the (Z)-tetradec-7-en-1-al (sex pheromone of the olive pest Prays oleae) from the solid complex was investigated, in an effort to correlate the supramolecular structure with the macroscopic property of spontaneous liberation of the pheromone. It was observed that in solution a 2 36 1 host 36 guest complex prevails, having the guest in a curled configuration. In the crystal structure of the complex, two \u3b2-CD molecules forming head-to-head dimers and packed in channels enclose one guest molecule whose methyl terminal aliphatic chain curls at the cis-double bond and runs along the intradimer interface. In the space between host molecules there is also entrapped an additional pheromone molecule, also visible in the IR spectra, which is heavily disordered. The guest inside the cavity is disordered over two sites and exhibits mobility, especially at the methyl and carbonyl end-groups, which is also confirmed by solid state NMR experiments. Thus, there are two types of guest molecules in the crystalline complex, one inside the \u3b2-CD cavity and another trapped and held loosely outside the cavity. The release behavior, studied by NMR, shows that the \u201coutside\u201d pheromone is liberated from the solid initially at a fast rate, which reaches very low levels when almost half of the guest molecules have been released. The other half, molecularly encapsulated in the \u3b2-CD cavity, is well stabilized.NRC publication: Ye

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

β-Cyclodextrin (β-CD) dimers have been prepared using the bioorthogonal Staudinger ligation for the first time. In addition to a known linker, methyl 2-(diphenylphosphanyl)terephthalate, a doubly active linker was specifically developed that enabled connection of two β-CD units in a single step and in aqueous/organic media, under mild conditions and with good yields. A three-carbon spacer between the β-CD torus and the azido group was required for facile dimer formation. The products, as studied by NMR spectroscopy, were found to adopt closed conformations by intramolecular self-inclusion. On the other hand, association via intermolecular binding was also observed in aqueous solution, confirmed by DOSY NMR experiments. Despite self-inclusion, the β-CD cavities were capable of guest encapsulation, as shown by titration experiments: the binding constant with 1-adamantylamine was similar to that of natural β-CD. Theoretical calculations for isolated molecules (PM3 level of theory) and in the presence of solvent [water, PM3(COSMO)] as well as DFT calculations suggested that the compounds prefer to adopt conformations which bring the phenyl groups either inside the β-CD cavity (inclusion) or over its narrow side (vicinal). Thus, Staudinger ligation could be the method of choice for linking CDs exhibiting (i) ease of preparation in aqueous media, in short steps, under mild conditions and in good yields, (ii) satisfactory aqueous solubility and independent binding capacity of the cavities

Non-covalent interactions in the crystallization of the enantiomers of 1,7-dioxaspiro[5.5]undecane (olive fly sex pheromone) by enantiospecific cyclodextrin hosts, hexakis(2,3,6-tri- O -methyl)-α\alpha-cyclodextrin and heptakis(2,3,6-tri- O -methyl)-β\beta-cyclodextrin

The enantiomers of racemic olive fly sex pheromone 1,7-dioxaspiro[5.5]undecane (1) have been isolated by crystallization with enantiospecific cyclodextrin hosts: (S)-(1) crystallizes with heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMβCD) and (R)-(1) with hexakis(2,3,6-tri-O-methyl)-α-cyclodextrin (TMαCD). The crystal structure of TMβCD/(S)-(1) from synchrotron radiation data at 100 K, determined for the first time, proves that TMβCD crystallizes with only the (S)-enantiomer from the racemic mixture. Comparison with the 100 K structure of TMαCD/(R)-(1) redetermined with synchrotron data has provided insight into the interactions between each of the hosts with the corresponding enantiomeric guests. Owing to the high resolution of the data and the unusually high quality of the crystals, localization of the H atoms has been achieved, a rare accomplishment for cyclodextrin X-ray structures. This made possible, apart from the geometry of the complexes, the detailed description of a five-membered-ring water cluster with very well ordered hydrogen bonding. The enantiospecificity exhibited by the described systems reveals the subtle differences of the weak intermolecular forces involved in the selective binding of the two optical antipodes by the two hosts. The binding geometry in the two complexes is different, but it is effected in both by numerous host–guest C—H...O interactions, resulting from induced fit of the hosts toward each of the enantiomeric guests. In TMαCD/(R)-(1) two of these H...O host–guest distances, directed toward the acetal O atoms defining the chirality of the guest, are much shorter than the rest and also shorter than all the H...O distances in TMβCD/(S)-(1). Moreover, (R)-(1) interacts not only with the enclosing host, but with other hosts in the crystal lattice, in contrast to (S)-(1) in the TMβCD/(S)-(1) complex which is isolated inside channels formed by the host molecules. The above differences are reflected in the much higher binding constant of TMαCD/(R)-(1) compared with that of TMβCD/(S)-(1) (∼6800 and ∼935 M−1, respectively), determined by NMR in aqueous solution, and the ability of TMαCD to selectively precipitate (R)-(1) from racemic (1) in much higher yield than TMβCD precipitates (S)-(1).</jats:p