Conformation ethers

Figure 4 Polyoxyethylene alkyl ether conformation a in aqueous solution, b in oil.

Thuery, P., Nierlich, M., Bryan, J.C. et al. 1997. Crown ether conformations in 1,3-calix[4]arene bis(crown ether) Crystal structures of a cesium complex and solvent adducts and molecular dynamics simulations. J. Chem. Soc. Dalton Trans. 1997 (22) 4191 4202. 

Structure and vibrational spectra of vinyl ether conformers. The comparison of B3LYP and MP2 predictions ... 

These special stereochemical properties arise from the steric influence of the diortho iodines upon the diphenyl ether conformation. Minimal steric interaction between the 3,5-iodines and the 2, 6 -hydrogens is maintained when one ring is coplanar with, and the other perpendicular to, the plane of the two C-0 ether bonds. This gives rise to two skewed conformations (Figure 2) which can be described by the torsion angles < > (C5-C4-041-C11) and (J)1 (C4-041-C1,-C6 ) of 0°/90° and 90°/0° for /cj>1, respectively. Only the skewed conformer = 90°/0° has been ob-... 

Figure 2. Two examples of the skewed (/f = 90°/0°) fright) and antiskewed = 0°/90°) (left) diphenyl ether conformation of thyroxine. In each case the molecule is viewed perpendicular and parallel to the inner ring plane.

Figure 7. Superposition of a skewed (dark) diphenyl ether conformation on a twist-skewed (light) conformation, (a) Overlap of inner ring as common structural feature and (b) the outer phenyl ring.

All proteins require adiiododiphenyl ether nucleus. The implications of these data are that TBG and nuclear proteins prefer a twist-skewed diphenyl ether conformation whereas TBPA prefers a skewed diphenyl ether. 

Analysis of the TBPA-Ti complex (39,40) indicates that the binding site for the hormone is located deep inside the channel. The hormone makes extensive interactions with the protein side chains that project into the channel. The 4 -hydroxyl of Ti interacts with a patch of hydroxy-amino acids of the protein while each of the iodines makes contact with a number of hydro-phobic protein residues. The T amino acid side chain functional groups are in appropriate positions to interact with glutamic acid and lysine residues. Thus, this channel provides a favorable environment for each of the characteristic substituents of the thyroid hormone (40). However, because of the Ti orientation disorder in the protein complex, this structural model is not a sensitive measure of the observed correlations between diphenyl ether conformations and binding affinity data. 

The differences in binding orders between TBPA and TBG suggest that different structural features may play a key role in receptor interactions. It has been shown (4,28) that TBG also preferentially binds to a tetraiodo-4 -phenoxide ion, but since Ti is the strongest binder, this suggests a different side chain stereochemistry. Here we can assume that it is the twist-skewed diphenyl ether conformation which orients the Tside chain for optimal receptor-hormone interactions. In the case of the nuclear proteins optimal binding is observed for a distally oriented 3 -I and a 4 -hydroxyl. Side chain requirements appear to be similar to those of TBG (28,31). 

C. H. Marzabadi, J. E. Anderson, J. Gonzalez-Outeirino, P. R. J. Gaffney, C. G. H. White, D. A. Tocher, and L. J. Todaro, Why are silyl ethers conformationally different from alkyl ethers Chair-chair conformational equilibria in silyloxycyclohexanes and their dependence on the substituents on silicon. The wider roles of eclipsing, of 1,3-repulsive steric interactions, and of attractive steric interactions, J. Am. Chem. Soc., 125 (2003) 15163—15173. 

Li ---18C6 represents an outer-sphere complex and [Li 18C6 ] represents a complex in which the solvation and the crown ether conformation are in an intermediate state on the way to the final ground state, [Li-18C6]. The exchange process is characterized by 2 = L45 x 10 s and = 6.3 x 10 s" at 298.2... 

Both Rb and Cs are too large to be accommodated into the 18-crown-6 cavity. Therefore, they occupy a site somewhat distant from the plane of the ether oxygens. Rb is situated by 1.19 AandCs" even by 1.44 A above this plane, which leads to a less favorable interaction with the ligand donor atoms, thus explaining the diminished stabilities of the [18]crown-6 complexes with these ions. The crown ether conformation does not alter in comparison to the complex. Coordination of the metal ion is completed by contacts with the bridging SCN" ions, thus resulting in the formation of a 2 2 dimeric structure (Fig. 28)... 

Z Brzozka, B Lammennk, D N Remhoudt, E Ghidim, and R Ungaro, Transduction of selective recogmtion by preorgamzed lonophores, K+ selectivity of the different l,3-diethoxycalix[4]arene crown ether conformers, J Chem Soc Perkin Trans 2 (1993) 1037-1040 J A J Brumnk, J R Haak, J G Bomer, D N Remhoudt, M A McKervey, and S J Hams, Chemically modified field-effect transistors, a sodium ion selective sensor based on calix[4]arene receptor molecules, Chm Acta, 254 (1991) 75-80... 

Several explanations are proposed to explain the switch in stereoselectivity from exo-61a to exo-61h using different Lewis acids, such as different orientation of the vinyl ether (s-cis vs. s-trans), or change in the mechanism (concerted vs. stepwise) [93d]. Apparently, bulky aluminum Lewis acids, such as ATPh induce nitroalkenes to react with chiral dienophiles via the s-trans vinyl ether conformation (Figure 16.3), whereas SnCU induces nitroalkenes to react... 

---