Conformational Analysis of Macrocyclic Ether Ligands. I. 1,4,7,10-Tetraoxacyclododecane and 1,4,7,10-Tetrathiacyclododecane

Crystallographic results retrieved from the Cambridge Structural Database (CSD) have been used to perform systematic conformational analyses of both free and metal-coordinated unsaturated 12-membered oxa and thia macrocycles. Conformational classifications established using symmetry-modified Jarvis-Patrick clustering are visualized in conformational space by principal component analysis (PCA) plots. These show that the relationship between cluster populations and relative molecular mechanics energies is modified by the coordination requirements of a metal ion. With oxa donors the [3333] conformer (oxygen in edge positions) predominates for metal-coordinated macrocycles, with the donor atoms in a square-planar arrangement, whilst the [48] conformer occurs bound in a cis-octahedral fashion to metal ions and the [66] conformer does not bind in an endo-dentate manner at all. The [3333] and [66] conformers are both common for free ligands, reflecting their similar molecular mechanics energies; the conformation is often determined by the hydrogen-bonding network. There are few thia examples: it is found that conformers with low molecular mechanics energies are unsuited to metal coordination and substantial reorganization is necessary for chelation. The differences in behaviour of oxa and thia macrocycles may be rationalized in terms of differing torsion-angle preferences for CXCC and XCCX units (X = O, S).