Peptide Conformations. 28.1 Relayed Heteronuclear Correlation Spectroscopy and Conformational Analysis of Cyclic Hexapeptides Containing the Active Sequence of Somatostatin

Homo- and heteronuclear two-dimensional NMR techniques have been used to assign the *H and 13C NMR spectra of the cyclic hexapeptides cyclo[Phe-D-Trp-Lys(Z)-Thr-Xxx-Pro] (1, Xxx = Gly; 2, Xxx = Phe) in Me2SO. Unequivocal assignments of Trp and Phe carbon resonances in 2 could only be obtained by heteronuclear relayed spectroscopy. Conformational analysis of 2 proves a βII’ turn of the Phe7-CO←HN-Thr and a βVI turn for Thr-CO←HN-Phe7 including a cis peptide bond between Phe and Pro. Substitution of Phe by Gly results in a dramatic change in the conformation: two species are observed in slow equilibrium (70:30). The major isomer involves a trans Gly-Pro bond. The technique of relayed heteronuclear correlation spectroscopy and a new, improved pulse sequence are described, which yield an increase in sensitivity of 21/2 to 2 depending on the chemical shift of the protons. This gain is also essential in many nonpeptide applications, e.g., to natural products, to rare materials, or in case of low solubility. The relative merits of various techniques to establish the sequences of carbon nuclei in the molecular backbone are discussedThe scrambling reaction between Mn2(CO)10 and Re2(CO)10 to form MnRe(CO)10 proceeds cleanly to a stable equilibrium in decalin at 170-190 'C. Studies of the initial rates show that two paths are followed, the major one being evident over the whole range of temperatures and partial pressures of CO above the solutions. The kinetics suggest that it involves prior aggregation to form Mn2Re2(CO)20 which undergoes stepwise loss of CO to form the clusters Mn2Re2(CO)20_' (n =≥ 4). All these clusters can be envisaged to be quasitetrahedral and to contain one Mn-Mn and one Re-Re bond together with n Mn-Re bonds and 4 - n Mn(μ-CO)Re bonds. When the requisite number of CO ligands have been removed the Mn-Mn and Re-Re bonds are lost, either by CO insertion or by redistribution of the M-M and M(μ-CO)M bonds within the cluster. Further CO insertion leads to Mn2Re2(CO)20 containing two Mn-Re bonds, and this readily fragments to form MnRe(CO)10. At low partial pressures of CO the rate-determining step is the formation of Mn2Re2(CO)20 or Mn2Re2(CO)19 and the activation parameters are AH* = 22 ' 3 kcal mol-1 and ΔS* = -20 ' 6 cal K'1 mol-1. The other path is most evident at 190 'C under small partial pressures of CO, and it appears to involve prior loss of CO from the decacarbonyls before aggregation. The kinetics suggest that scrambling occuss mainly via the tetranuclear intermediate Mn2Re2(CO)16.