Conformational analysis of jet cooled tryptophan analogs by molecular mechanics: Comparison with experiment

Abstract

The possibility of predicting the geometries of jet cooled conformers of tryptophan analogs via molecular mechanics, employing MM2 (1987), was studied by carrying out computations on six different analog molecules. For three of the analogs, tryptamine in particular, the computationally predicted gas phase conformer geometries could be compared with experimentally determined geometries obtained from jet cooled samples. Some conformer geometries agreed qualitatively with experiment but the match did not extend to all cases. Most notably, the MM2 calculations failed to predict the eclipsed conformers of tryptamine that were deduced experimentally via analysis of rotational constants. They similarly failed to predict a planar geometry conformation found for 3-indole acetic acid. These two disagreements prompted a reconsideration of the possible geometries that yield the best match to the experimentally determined rotational constants for various jet cooled conformers. For tryptamine conformers D/E it was found that likely geometries might in fact be more than 30° from eclipsed structures. Some differences were also found for the Cα–Cβ and Cβ–Cγ dihedral angle values assigned to tryptamine conformers A/B and conformer F. Nonetheless, the overall agreement of the MM2 calculations with the refined tryptamine conformer geometries remains no more than qualitative. Reanalysis of the possible geometries of conformer A of 3-indole acetic acid that are consistent with the experimental rotational constants yielded agreement with the previous planar geometry assignment. It was also possible to use the molecular mechanics data to predict relative conformer populations and from this relative peak sizes of 0–0 transitions in the jet cooled excitation spectra. Considering all six cases, the match with experiment is again at best partial. The agreement is not good enough for reliable association of definite computed geometries with particular peaks in an experimental excitation spectrum.