Calix[n]arenes and nucleic acids

Abstract

This chapter focusses on DNA calixarene interactions, starting from early investigations on ion paring, and ending with an increasing number of recent applications. Molecular recognition of nuclear acid derivatives by calixarenes in solution is shown to occur mainly by electrostatic interactions with the DNA backbone, by major groove binding or by intercalation. At the air-water interface, amphiphilic calixarenes can self-assemble into monolayers, which present their ionic groups on the upper rim into the aqueous phase, in a subtle interplay of hydrogen bonds towards phosphate diester groups and nucleic bases. Conjugates of nucleic acids and calixarenes are candidates for the formation of well-defined supramolecular structures; thus, powerful hydrogen-bonded dimers evolve, and calixarenes can also replace hairpin regions in DNA double strands facilitating triplex formation. 1,3-alternating calixarenes can be equipped with four guanosines and generate nanotubes via G-quartet formation. Attachment of nucleosides at the lower rim produced hybrid compounds which interfere with DNA replication. Introduction of heteroatoms leads to heterocalixarenes such as calix[4]pyrroles, which have been used as nucleotide-selective carriers and nucleotide-sensing ion-selective electrodes. Replacement of the bridging CH2 groups in regular calixarenes by metal ions affords so-called metallacalixarenes; these compounds appear somewhat related to cisplatin and display significantly altered interaction modes with DNA. A large chapter summarizes important applications of calixarenes, above all in DNA transfection, followed by oligonucleotide cleavage and HPLC chromatography. Finally, very new biochemical applications occurred in recent years, pointing to a potential new area of calixarene chemistry.