Conformation pleated loop

The low-temperature H NMR spectra for calix[4]- and calix[5]arenes reveal that all four or five phenolic units are identical.225 This is compatible with a cone conformation with C4v and C5v symmetry, respectively.226,227 For calix[8]arenes the same pattern is interpreted by a / -symmetrical pleated loop conformation, with a regular up-and-down of the methylene bridges. Calix[7]arenes, however, show seven singlets for the OH protons and seven (overlapping pairs of doublets) for the methylene protons. This total lack of any symmetry element (C,) makes this conformation chiral.228... 

A regular (or still time-averaged) cone conformation is discussed for cahx[5]arenes while calix[8]arenes most probably adopt a pleated loop conformation with a regular up and down arrangement of the phenolic units. 

An early X-ray structure of 8 crystallized from pyridine indicated it to have a pleated loop conformation (see ref. 1, p. 70), and rather similar conformations have been observed for its complexes with calcium and uranyl cations. In a more recent study, however, the X-ray structure of a complex of 8 with eight pyridine molecules showed it to assume a twisted conformation, something approaching the pinched conformation suggested in the early 1980s before an X-ray structure had been obtained. Complexes of 8 " with various metal ions, including lanthanides, thorium, and molybdenum, also reveal a conformation different from a pleated loop and approximately described as a 1,2,3,4-alternate. 

Several examples of various 0CH20-bridged calix[8]arenes 15-19 (Fig. 7.14) were obtained by treatment of C[8] with CS2CO3 and BrCH2Cl [44]. Dynamic NMR studies and MM3 calculations indicated that the dioxocine subunits adopt a boat-chair conformation, which is well compatible with the geometrical requirements of a calix[8]arene pleated-loop conformation [44]. 

Fig. 7.26 X-ray structure of p-tert-butylcalix[8]arene in the pleated-loop conformation...

The most common conformations found for p-ferf-butylcalix[8]arene are the pleated-loop [92] (Fig. 7.26) and the chair-like (for an example of chair-like conformation, see Fig. 7.18) [93]. In particular, some reports [65] showed that the chair-like solid state conformation is preferred when the intramolecular hydrogen bonding at the lower rim is absent. 

The pleated loop conformation was also found in the solid state structures of a monopotassium salt of C[8] reported by Fronun [94a] and obtained by its treatment with K2CO3 in a two-phase H2O/THF system. The macrocycles are supramolecularly stacked one over the other to give a one-dimensional system with an inner coaxial channel (Fig. 7.27). A 10-molecule water cluster with a distorted cubane core is sandwiched between two cmisecutive calixarenes [94a]. 

Among the solid state structures of the larger calix[ ]arenes, Raston [96] and coworkers reported the first inclusion complex of p-tert-butylcalix[9]arene C[9] with o-carborane (Fig. 7.30). In this structure, the calix[9]arene macrocycle adopts a conformation composed by three 3/4-cone clefts and a pleated-loop portion. Perrin et al. [97] showed that p-tert-butylcalix[10]arene C[10] adopts in the solid state a pinched cone conformation stabilized by a circular H-bond between OH groups and very similar to that found for calix[6]arene macrocycle [98]. 

An intruiguing solid state structure of p-tcrt-butylcalix[16]arene C[16] has been reported by Perrin and coworkers [99]. The conformation adopted by caUx[16] arene macrocycle can be described as two superimposed Celtic tores with a large pleated-loop geometry. Each tore is coimected to the other one by a pseudo-calix[4] arene cone moiety. This conformation confirms the Gutsche s postulate [7a] stating that calixarenes incorporate as many cone-like and/or pleated-loop-like conformational segments as possible because they are "the best conformation stabilizing structures in the calixarene family". 

Calix[8]arenes may adopt 16 main (basic) conformations[41] and numerous intermediate or distorted conformations related to the main ones. There are two extreme conformations the double cone or inverted double cone conformation which may be characterized as a compact one and mimics two joined together in parallel or antiparallel cones of calix[4]arenes and, at the other end, there is an extended nearly planar circular conformation which may be called rosette or pleated loop . This extreme conformations are exemplified by these found for para-sulphonatocalix[8] arene (Fig. 38.26). 

Final proof for the inferred structure (1) for cyclosporin A and a first insight in the shape of the molecule resulted from X-ray analysis and high-resolution NMR spectra. The preparation of a crystallized derivative containing a heavy atom was achieved by an addition reaction using iodine and thallium(I) acetate. Instead of the expected iodoacetoxy derivative, the cyclic product (11) was obtained. Obviously, the reaction proceeded by a selective addition of iodine to the double bond of the MeBmt unit followed by an internal cyclization with the participation of the OH group. Iodocyclosporin A (11) reverted easily with Zn powder in acetic acid into genuine cyclosporin A by rranr-elimination. X-ray analysis [6] revealed that iodocyclosporin A assumes a rather rigid backbone conformation. The amino acids 1-6 adopt an antiparallel, markedly twisted /i-pleated sheet conformation, whereas the residues 7-11 form a loop. 

Generally, less than half of a globular protein is in an cr-helix or 8-pleated sheet (Figure 23.10). Most of the rest of the protein is still highly ordered but is difficult to describe. These polypeptide fragments are said to be in a coil conformation or a loop conformation. 

The folding of peptide backbones is quite unpredictable. It may assume many forms, such as sinusoidal, saddle, elongated loop, disk, pleated sheet, and helical, e.g., often containing water molecules in interior cavities. The conformation of cyclic peptides can change drastically upon complexation with alkali metal ions. However, there is evidence from crystal structure analyses that conformations of large cyclic peptides are independent of the polarity of solvent, even though the solvent may cocrystallize with the peptide. 

Helices and pleated sheets account for only about one-half of the structure of the average globular protein. The remaining polypeptide segments have what is called a coil or loop conformation. These nonrepetitive structures are not random they are just more difficult to describe. Globular proteins also have stretches, called reverse turns or j8 bends, where the polypeptide chain abruptly changes direction. These often connect successive strands of /3 sheets and almost always occur at the surface of proteins. 

Secondary structures are specified in terms of legnlar folding patterns called a helices, /3-pleated sheets, and coU or loop conformations. 

The backbone structure of an enzyme called ligase (Section 26.5) a /3-pleated sheet is indicated by a flat arrow pointing in the N — C direction, an a-helix by a flat helical ribbon, and a coil or loop conformation by a thin tube. 

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