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 nuclei c acids, generally through modification of the interaction of nucleic acids with proteins and, thus, can be of significant therapeutic benef it against selected cells or organisms. We have investigated by T-m an d viscosity studies and by CD and H-1 NMR spectra the interactions of tetracationic azoniacyclophanes, CPnn, where nn is the number of methy lene groups (from 3 to 6) in the linking chains, with DNA and RNA poly mers of the same sequence. All the compounds stabilize the DNA polymer s, but, in a surprising result, the compounds either stabilize RNA dup lexes or alternatively cause base-pair opening in RNA duplexes dependi ng on the size of the cyclophane and the solution conditions. With RNA polymers containing A-U base pairs, the largest cyclophane, CP66, spe cifically binds the adenine bases into its cavity and can cause comple te denaturation of the RNA at high concentrations. The NMR shift chang es' 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 betwee n the same macrocycle and several adenine derivatives (Schneider, H.-J .; Platter, T.; Palm, B.; Pfingstag, U.; Rudiger, V.; Theis, I. J. Am. Chem. Sec. 1992, 114, 7704-7708) and reflect the NMR anisotropy effec ts 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 t he nucleic acids.