Caprylolactam has been investigated by FT-IR to establish the presence, nature, and relative stability of its multiple conformations in solution. Three independent IR studies have been interpreted as showing the presence of two cis and two trans forms in solution, based on 4 N-H stretch features. Previous work in this area is now outdated (pre-FTIR) and was limited in spectral range to the strongest IR features due to the low sensitivity and low concentrations to avoid hydrogen bond formation. Our investigations using FT-IR and computational methods have identified the source of the N-H stretch features as due to the presence of multiple conformations. While the FT-IR spectra of a proposed cis and known trans form were reproduced by Gaussian simulations, we were not able to locate any other minima in the potential energy surface. This effort to find alternative conformations has evolved to using modern conformational software, Conflex7®, designed for this type of application. Conflex7® located 17 possible conformations. Eight of the conformations, 3 cis and 5 trans, were determined to be thermally populated at room temperature and contribute to the observed peaks. Determination of these conformations is essential for any analysis and prediction of deuterium isotope effects in 13C NMR spectra in small lactams. These calculations require knowledge of all conformational states in solution that will contribute to the spectra. So far, this conformational heterogeneity, beyond the cis and trans forms, is not observed in NMR spectra of caprylolactam. Our objective focuses on establishing all the conformational factors that may contribute to predicting the shifts for trans peptide bond structures which can lead to more accurate modeling and predictions for larger peptides.

Multiple cis and trans conformations of caprylolactam and their role in deuterium isotope effect predictions in 13C NMR

253rd National Meeting (2017)

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