A Cationic Cyclophane That Forms a Base-Pair Open Complex with RNA Duplexes

It is now well-established that synthetic organic cations can
interact with the helical conformations of
DNA and RNA and can stabilize these structures. Such interactions
can also perturb the function of nucleic acids,
generally through modification of the interaction of nucleic acids with
proteins and, thus, can be of significant
therapeutic benefit against selected cells or organisms. We have
investigated by Tm and viscosity studies and by
CD
and 1H NMR spectra the interactions of tetracationic
azoniacyclophanes, CPnn, where nn is the number of
methylene
groups (from 3 to 6) in the linking chains, with DNA and RNA polymers
of the same sequence. All the compounds
stabilize the DNA polymers, but, in a surprising result, the compounds
either stabilize RNA duplexes or alternatively
cause base-pair opening in RNA duplexes depending on the size of the
cyclophane and the solution conditions.
With RNA polymers containing A−U base pairs, the largest
cyclophane, CP66, specifically binds the adenine bases
into its cavity and can cause complete denaturation of the RNA at high
concentrations. The NMR shift changes
observed both for CP66 and the adenine base in the polymer predict an
inclusion complex with the base in the cavity
of CP66. These shift values can be related to those measured
earlier with complexes between the same macrocycle
and several adenine derivatives (Schneider, H.-J.; Blatter, T.; Palm,
B.; Pfingstag, U.; Rüdiger, V.; Theis, I. J.
Am.
Chem. Soc. 1992, 114, 7704−7708) and
reflect the NMR anisotropy effects of the aromatic units both in host
and
guest. The different effects of the compounds on DNA and RNA are
caused by significant differences in their
interactions with the duplex and single-stranded states of the nucleic
acids.