Computational Chemical Prediction for the Position of Hydrogen-Deuterium Exchange in Hydroxyindole Derivatives

We report an easy computational procedure for qualitative prediction of hydrogen-deuterium exchange position in hydroxyindole derivatives. The efficiency of the procedure was confirmed with experimental results (Figure 1). Hydrogen-deuterium exchange took place at the carbon atom having the big charge (Figure 2), namely, that next to the hydroxy function. The predicted positions were in good agreement with the observations, though there is an exception when steric hindrance should be considered to explain the results. Atomic charges in basic molecule skeleton obtained by using the molecular orbital calculation enable prediction for the position of hydrogen-deuterium exchange in hydroxyindole derivatives.

Fig. 1. The observed deuterium-labeled positions of hydroxyindole derivatives.

Fig. 2. The atomic charges of model molecules calculated by Merz-Singh-Kollman's method.