RING CONFORMATIONS OF PROLINE - SOLUTION STUDIES BASED ON LANTHANIDE NUCLEAR MAGNETIC-RESONANCE SHIFTS AND MOLECULAR MECHANICS

Previous studies of ring conformational equilibria of proline based on molecular mechanics computations show the presence of two shallow energy minima: A is a half chair with C7 up and Cs down with respect to the average plane of the ring and with the carboxyl group up; B is an envelope with C7 down. Evaluation of available X-ray data showed that in the solid state the reported conformations cluster about one or the other of these conformations of thetheoretical minimum energy. The present study concerns the conformational states of the proline ring in solution in CDC13 and is based on lanthanide NMR shift studies. The shift reagents Yb(fod)3 and Eu(fod)3 gave 25 usable shift values with Ac-L-Pro-OCH3 and 29 with Bz-Pro-OCH3.1 The shift results are consistent with a conformational mixture of roughly 60 partsof A and 40 of B. Assumption of a planar average ring conformation gives a poorer account of the data and the data are inconsistent with a ring having a single intermediate conformation derived from either A or B. In the present study the lanthanide shift data were processed by a molecular mechanics program modified so as to permit simultaneous adjustment of lanthanide parameters, substrate geometry, and conformer mole fractions. Minor adjustment of substrate geometry gave dramatic improvement in the agreement factor between observed and calculated induced shift values, and the observed values have been reproduced to within experimental error. We provide a probable explanation of the variable and unrealistically long lanthanide-oxygen distances commonly reported in LIS studies. This is a consequence of representing a physical system made up of many complexes in rapid equilibrium by one single mathematically averaged complex. The geometry of the substrate is reproduced well by the mathematical model, although this may not closely resemble any individual complex with respect tothe lanthanide position nor with respect to the properties of the magnetic tensor. © 1979, American Chemical Society. All rights reserved.