Inducible and selective alkylation of DNA was accomplished under neutr
al conditions by use of a silyl-protected phenol that served as a prec
ursor for a highly reactive quinone methide. As expected, addition of
fluoride triggered reaction of a model compound, methylsiloxy)-4-[(p-n
itrophenoxy)methyl]benzamide, and its oligodeoxynucleotide conjugate.
Surprisingly, the silyl phenol was also specifically yet more slowly a
ctivated by the environment of duplex DNA in the absence of fluoride.
This alternative process was associated with the hybridization of prob
e and target strands, and single-stranded DNA was unable to induce a s
imilar activation. Therefore, DNA appears to effect its own alkylation
by promoting the formation of an electrophilic and nondiffusible inte
rmediate.