A (3+1)-hybrid-type G-quadruplex was substituted within its central tetrad by a
single 2'-fluoro-modified guanosine. Driven by the anti-favoring nucleoside
analogue, a novel quadruplex fold with inversion of a single G-tract and
conversion of a propeller loop into a lateral loop emerges. In addition, scalar
couplings across hydrogen bonds demonstrate the formation of intra- and
inter-residual Fâ â â H8-C8 pseudo-hydrogen bonds within the modified
quadruplexes. Alternative folding can be rationalized by the impact of fluorine
on intermediate species on the basis of a kinetic partitioning mechanism.
Apparently, chemical or other environmental perturbations are able to redirect
folding of a quadruplex, possibly modulating its regulatory role in
physiological processes.
