Helicity-encoded molecular strands: Efficient access by the hydrazone route and structural features

Control over the folding of molecular strands may be achieved by appropriate choice of the constituting subunits, in particular for chains of specific heterocycles such as sequences of directly connected pyridine (py) and pyrimidine (pym) rings, which are known to fold into extended helical structures. Since the hydrazone (hyz) group represents an isomorphic analogue of a py site, the condensation of hydrazine and carboxaldehyde derivatives of pym offers a very efficient approach to strands incorporating hyz instead of py units and constituted by sequences of alternating hyz and pym groups. A series of such strands of different lengths, up to ten hyz units, i.e., 1-7, were synthesized. Their spectral properties indicate that they fold indeed into helical shapes. Extensive characterization was performed in solution by H-1-NMR spectroscopy and in the solid state by determination of the crystal structures of eight such strands. They all display the expected helical geometry with up to 3(1)/(3) turns and direct stacking contacts. The efficiency and flexibility of the synthetic approach as well as its wide potential for generation of diversity through lateral decoration make the (hyz-pym) subunit a particularly attractive helicity codon.