Ligand Conformations Implications for Binding

For oxocrowns, information on conformation comes from both X-ray diffraction and CNMR studies. Unfortunately, for thiacrowns CNMR provides little insight into ligand conformation [76, 78]. Consequently X-ray diffraction has played a crudal role in the study of thiacrown conformations. Reasoning from such solid state data to behavior in solution must, of course, be conducted with caution. 

Comparison of oxa- and thia-crowns reveals some interesting contrasts. In the free state, most crown thioethers adopt peculiar inside-out conformations in 

Fusion of three aromatic residues to 9S3, as in (MeO)6-tribenzo-9S3, necessarily constrains the macrocycle conformationally. Klar and coworkers identified three likely conformations - termed crown , saddle , and pseudo-saddle - defined by the position of the phenylene moieties with respect to the plane of the three S atoms [83]. In the crown conformation, all three phenylene units lies on the same side of the S3 plane. In the saddle conformation, one phenylene ring lies in the S3 

In the solid state, 12S4 adopts a quadrangular structure (derived from the parent cycloalkane) with all four S atoms exodentate (Fig. 3) [80, 85]. In principle, two conformations for 12S4 are consistent with the quadrangular structure of the parent cycloalkane. In the conformation actually adopted the S atoms assume corner positions (cf. 1204) thus chelation to a metal ion necessitates a particularly radical - and therefore energetically costly - conformational rearrangement. 

Inclusion of two fused benzo groups causes dibenzo-18S6 to differ conforma-tionally from the unsubstituted parent compound [69]. All six donor atoms -indeed, the entire ligand except for the benzo groups - lies essentially in a plane (Table 1). The benzo groups lie centrosymmetrically disposed on opposite sides of the Sg plane at an angle of 83° (cf dibenzo-1806, 124°). The two non-benzo S atoms adopt anti placements about their bonds to the adjacent carbon atoms they also assume an exodentate orientation with respect to the crown cavity. 

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