UNRAVELLING THE ELECTRICAL CONDUCTANCE OF INDIVIDUAL Z-FORM OLIGONUCLEOTIDES: A SINGLE-MOLECULE STUDY

Nucleic acids have emerged as new materials with promising applications in nanotechnology, molecular electronics, and biosensing, but their electronic properties, especially at the single-molecule level, are largely underexplored. The Z-form is an exotic left-handed helical oligonucleotide conformation that may be involved in critical biological processes such as the regulation of gene expression and epigenetic processes. In this work, we measure the electrical conductance of individual GC- rich DNA:RNA molecules in physiological buffer and TFE solvent, corresponding to the natural (right-handed helix) A-form typical in DNA:RNA hybrids and the (left-handed) Z-form conforma- tions, respectively. We perform single-molecule conductance measurements using the STM-assisted break-junction method in the so-called ’blinking’ approach, recording the spontaneous formation of single-biomolecule junctions and performing statistical analysis of the signals. We also perform Circular Dichroism experiments and ab initio calculations to rationalize the measured molecular conductivity with a simple structural and electronic model. Our results show that the electrical conductivity of the Z-form is similar to that of the B-form and one order of magnitude lower than that of the more compact A-form. The longer molecular length and higher energy for the HOMO of the Z-form account for the differences in single-molecule conductance observed experimentally.