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-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin

Abstract

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)-beta-cyclodextrin (TMbetaCD) and (R)-(1) with hexakis(2,3,6-tri-O-methyl)-alpha-cyclodextrin (TMalphaCD). The crystal structure of TMbetaCD/(S)-(1) from synchrotron radiation data at 100 K, determined for the first time, proves that TMbetaCD crystallizes with only the (S)-enantiomer from the racemic mixture. Comparison with the 100 K structure of TMalphaCD/(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 TMalphaCD/(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 TMbetaCD/(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 TMbetaCD/(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 TMalphaCD/(R)-(1) compared with that of TMbetaCD/(S)-(1) ( approximately 6800 and approximately 935 M(-1), respectively), determined by NMR in aqueous solution, and the ability of TMalphaCD to selectively precipitate (R)-(1) from racemic (1) in much higher yield than TMbetaCD precipitates (S)-(1).

Crystallization of Supramolecular Complexes as an Alternative Route for the Separation of Racemic p‐X‐phenylethanol

“…The corresponding crystallographic parameters are reported in Tab. 2, and constitute original sets, with reference to all other structures containing TMb-CD [19,20]. Furthermore, the monoclinic P2 1 space group was highly unexpected since all structures published so far correspond to the orthorhombic P2 1 2 1 2 1 space group.…”

X-ray Structure and Thermal Properties of a 1:1 Inclusion Complex Between Permethylated β-Cyclodextrin and Psoralen

“…Following the first report of a TRIMEB inclusion complex with unit cell dimensions a , 11; b , 26; c , 29 A; space group P2 1 2 1 2 1 [12], several analogues have been identified. The guests in this series, like the present psoralen, tend to be relatively small, predominantly lipophilic molecules (methylcyclohexane [18], (S)-1,7-dioxaspiro(5.5)undecane [19], clofibric acid [20]). The other known isostructural series of TRIMEB complexes, with a , 15; b , 21; c , 28 A; also crystallizing in space group P2 1 2 1 2 1 , includes those with guests such as flurbiprofen, ibuprofen and naproxen [11,21].…”

Clathrates with mixed guests

“…We have previously shown that H1 successfully forms inclusion compounds with 1,4-dioxane [1] and acetone [2]. Here we report on the structures of H1•DMF and H1•DMA where DMF = N,Ndimethylformamide and DMA = N,N-dimethylacetamide.…”

“…-(1,4)-linked D-glucopyranosyl residues have a hydrophobic, relatively rigid cavity able to host a plethora of molecules. Being chiral compounds, CDs can, in principle, discriminate between enantiomers (guests) forming preferentially with one of the two a more stable inclusion complex [1,2]. X-ray crystallography can provide details of the factors that lead to chiral recognition.…”