Kinetic Studies of the Mitosene Quinone Methide

CHARACTERIZING QUINONE METHIDES BY SPECTRAL GLOBAL FITTING 

FIGURE 7.16 Trapping of the phosphate of 5 -dGMP by the pyrido [1,2-a] indole quinone methide. The 13C-NMR shows most trapping with ring retention, labeled pyrido, with trace amounts of ring expansion, labeled azepino.  

SCHEME 7.18 Formation and fate of the pyrrolo[l,2-a]indole (w — 0) and the pyrido[l,2-a] indole-based ( = 1) quinone methides. 

The rate constants associated with the conversion of the pyrrolo[ 1,2-c/Jindole hydroquinone to its quinone methide were fit to the rate law equation (7.1), see Fig. 7.17 for rate data and the fit. The solid line in Fig. 7.17 was generated with Eq. 7.1 where k0 = 0.09min-1 and k 1.5 x 105M min The mechanism consistent with the pH-rate profile is the spontaneous elimination of acetate (kf) process) and the proton assisted elimination of acetate (kx process) from the electron-rich hydroquinone. The k0 process is independent of pH and exhibits a zero slope while the kx process exhibits a — 1 slope consistent with acid catalysis. 

The rate constants associated with the acid-catalyzed conversion of the pyrido[ 1,2- ]indole hydroquinone to its quinone methide were too large to measure. We did manage to measure two rate constants at pH 7 and 8, both with a value of 0.36 min-1. Based on the pH-rate profile obtained the pyrrolo 1,2-a indole hydroquinone, these 

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