Nucleic acids are very intriguing “molecules” from a chemical perspective. Independently by the relevance of their biological role, a chemist may find many aspects worth of interest and study.

Nucleic acids show an impressive expression of shapes and architectures that imply and mean a richness of chemical behaviours. In fact, these “molecules” can form supramolecular ensemble like double and triple helix; specific sequences can adopt a rich variety of conformations (cruciform structures, bulge loop, hairpins, quadruplexes, etc.) spontaneously or by responding to external stimuli as the presence of potassium ions (to form telomeric G-quadruplexes); eventually, alternated purine-pyrimidine sequences can switch their helical sense (by catalysis of protonated spermine, a ubiquitous amine) from the low energy right-handed B-helix to the higher energy left-handed Z form. Quite interestingly, if the strands are long enough, different conformations (like Z tracts embedded in B sequences) can coexist on the same “molecule”.

Owing to the specificity of geometrical parameters, spatial disposition of phosphate and solvent exposition of bases, each conformation has specific chemico-physical properties, which entails different “reactivity” with interacting molecules (host). Also, dichotomous reactivity can be found when two different structural motives coexist on the same “molecule”. In all of these cases, hosted molecules can be useful as conformational probes and reporters of nucleic acids structures.

Thus, nucleic acids are “molecules” whose specificity goes well beyond base sequence, involving structures and supra-structures: the same nucleic acid sequence can live different “chemical lives”, be a different “chemical subject” depending on the spatial organization of the base/phosphate/sugar ensemble.