Formation and Nanomechanical Properties of Silver-Mediated Guanine DNA Duplexes in Aqueous Solution

High Resolution Image Download MS PowerPoint Slide Silver cations can mediate base pairing of guanine (G) DNA oligomers, yielding linear parallel G–Ag + –G duplexes with enhanced stabilities compared to those of canonical DNA duplexes. To enable their use in programmable DNA nanotechnologies, it is critical to understand solution-state formation and the nanomechanical stiffness of G–Ag + –G duplexes. Using temperature-controlled circular dichroism (CD) spectroscopy, we find that heating mixtures of G oligomers and silver salt above 50 °C fully destabilizes G-quadruplex structures and converts oligomers to G–Ag + –G duplexes. Electrospray ionization mass spectrometry supports that G–Ag + –G duplexes form at stoichiometries of 1 Ag + per base pair, and CD spectroscopy suggests that as the Ag + /base stoichiometry increases further, G–Ag + –G duplexes undergo additional morphological changes. Using liquid-phase atomic force microscopy, we find that this excess Ag + enables assembly of long fiberlike structures with ∼2.5 nm heights equivalent to a single DNA duplex but with lengths that far exceed a single duplex. Finally, using the conditions established to form single G–Ag + –G duplexes, we use a surface forces apparatus (SFA) to compare the solution-phase stiffness of single G–Ag + –G duplexes with dG-dC Watson–Crick–Franklin duplexes. SFA shows that G–Ag + –G duplexes are 1.3 times stiffer than dG-dC duplexes, confirming gas-phase ion mobility spectrometry measurements and computational predictions. These findings may guide the development of structural DNA nanotechnologies that rely on silver-mediated base pairing.