A series
of sterically congested quinone methides (QMs) exhibit
photoinduced antiproliferative activity against some human cancer
cell lines. To elucidate the structure–reactivity relationship
and details of mechanisms of the photogeneration of sterically congested
QMs, we chose phenylphenol derivatives 1–3 as QM precursors and investigated their photodehydration
processes in aqueous solutions using ultrafast spectroscopy and theoretical
computations. We found that meta derivatives 1 and 2 undergo water-mediated excited-state
proton transfer (ESPT) from the phenol OH, followed by expulsion
of the OH– to form QMs. By comparison, para derivative 3 proceeds via water-mediated ESPT from
H2O to benzyl alcohol coupled with dehydration as the first
step, delivering a cation intermediate, which further deprotonates
to yield QM. Such results would help chemists understand more about
the meta effects in photochemistry and about ESPT
and would help synthetic chemists design sterically congested QM precursors
with extraordinary reactivities and expand applications of QMs in
biological and medical systems.