Vivienne J. Griffith

Unusual 1C4 conformation of a methylglucose residue in crystalline permethyl-β-cyclodextrin monohydrate

The severely distorted conformation adopted by the uncomplexed TRIMEB molecule in the solid state is attended by ring-inversion of one of the seven methylglucose residues.

X-ray structure and thermal analysis of a 1∶1 complex between (S)-naproxen and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin

An inclusion complex between TRIMEB and (S)-naproxen has been crystallised and characterised by physicochemical methods including X-ray analysis. The complex crystallises in the orthorhombic crystal system, space groupP212121, witha=15.179(4),b=21.407(5),c=27.67(1) Å andZ=4. The structure was solved using published coordinates for the skeleton atoms of TRIMEB in an isomorphous complex. Refinement by full-matrix least-squares analysis yieldedR=0.0571 for 6573 unique observed reflections. Hydrophobic forces are responsible for the inclusion of the drug, which has its methoxy group buried in the cavity of the host and its propionic acid moiety protruding from the O(2), O(3) side of the TRIMEB molecule. Both host and guest undergo conformational changes on complexation relative to their conformations observed in the TRIMEB monohydrate and naproxen crystal structures respectively. Complex units pack in a screw-channel mode in a head-to-tail fashion with their axes almost parallel to theb-axis.

Synthesis and X-ray crystal structure of β-cyclodextrin diclofenac sodiu undecahydrate, a β-CD complex with a unique crystal packing arrangement

The title complex crystallizes in the hexagonal system forming infinite helical host channels residing on crystallographic screw hexads.

X-ray structures of 1:1 complexes of (L)-menthol with β-cyclodextrin and permethylated β-cyclodextrin

Abstract Inclusion complexes of (L)-menthol with β-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TRIMEB) have been crystallised and their structures determined by single crystal X-ray diffraction methods. The menthol-β-cyclodextrin complex crystallises in the monoclinic system, space group P21, Z = 4, Dx = 1.380 g cm−3, a = 15.342(3) A, b = 32.54(2) A, c = 15.324(3) A and β = 102.44(2)°. The structure was solved by isomorphous replacement and was refined to a final R-value of 0.108 for 5469 observed reflections. This is a dimeric β-cyclodextrin complex which packs in screw channel mode and the guest is oriented differently in the two crystallographically independent host molecules. The menthol-TRIMEB complex crystallises in the orthorhombic system, space group P212121, Z = 4, Dx = 1.256 g cm−3, a = 11.060(3) A, b = 26.138(6) A and c = 29.669(6) A. The structure was solved by direct methods and refined to a final R-value of 0.105 for 4387 observed reflections. In contrast to what was found ...

X-ray structure and thermal analysis of a 1∶1 complex between sulfathiazole andβ-cyclodextrin

An inclusion complex with the formula (β-cyclodextrin) (sulfathiazole) 8.3 H2O has been crystallized and characterized by physicochemical methods including single crystal X-ray analysis. The complex crystallizes in the monoclinic system, space group P21, witha=15.264(4),b= 16.500(6),c=15.559(5) Å,β=117.29(3)o andZ=2. The structure was solved using published co-ordinates forβ-cyclodextrin in an isomorphous complex. Refinement by block-diagonal leastsquares yieldedR=0.061 for 4706 unique observed reflections. Inclusion of sulfathiazole produces a slight ellipticity in the host conformation, but the guest adopts a conformation similar to that observed in its polymorphs. The guest is held in the macrocyclic cavity predominantly by hydrophobic forces, with the phenyl ring near the host primary hydroxyl side and the thiazole ring near the secondary hydroxyl side. The complex packs in layers parallel to theac-plane. Layers are linked by hydrogen bonding to water molecules which are located outside the cyclodextrin cavity. An extensive network of hydrogen bonds mediated chiefly by water molecules stabilizes the crystal structure.

X-RAY STRUCTURES AND THERMAL ANALYSES OF NEW CD/DRUG INCLUSION COMPOUNDS

Single crystal X-ray methods, thermogravimetry and differential scanning calorimetry have been used to characterize several cyclodextrin/drug complexes in order to reconcile crystal packing features with behaviour on heating.

Desorption of Water from CD/DRUG Inclusion Complexes

Thermogravimetric and differential scanning calorimetric traces were recorded for several crystalline hydrated cyclodextrin complexes containing drug substances (salts of diclofenac, meclofenamate sodium, (L)-menthol) as guests. It was possible to reconcile observed thermal events for complex dehydration with three dimensional hydration patterns deduced from available X-ray crystal structures of the complexes. For complexes containing drug salts, strong retention of water molecules is attributed to their coordination to metal ions.

Structure and kinetics of novel cyclophane inclusion compounds

A novel cyclophane host compound, 3, featuring a macrocyclic structure with two hydroquinone dimethyl ether and two 1,1-diphenylcyclohexane construction elements assembled via benzylic ether linkages has been synthesised and its inclusion compounds with toluene, 4, and cyclohexanone, 5, have been characterised by thermal analysis and X-ray crystallography. The conformation of the cyclophane is markedly different in the two inclusion compounds. The kinetics of desolvation of 5 are deceleratory and yield an activation energy of 182 kJ mol–1.