In a world where antimicrobial resistance is an ever-looming problem, Ag+ is a promising and potent antimicrobial. The mechanism of antimicrobial activity for Ag+ is not well understood and is linked in part to interactions with DNA. Ag+ interacts with DNA in a relatively unique way, binding specifically to DNA bases as opposed to the negatively charged phosphate backbone. In addition to the implication of Ag+-base binding for antimicrobial activity, these interactions give exciting potential to a variety of other applications. Cytosine-Ag+-cytosine base pairings form with exceptional thermal stability as compared to Watson-Crick pairing, offering a building block for potential, robust Ag+-mediated DNA nanotechnology. Furthermore, the reorganization of single-stranded DNA secondary structure after the addition of Ag+ has shown to be important for formation of fluorescent silver clusters templated by DNA (AgN-DNA), which can tunably emit in the visible to near infrared region. Here we focus on understanding the structural impact and rules of Ag+-mediated base pairing in DNA and the formation and structure of AgN-DNA, with particular focus on involvement of Ag+. First, we aim to probe Ag+-DNA interactions by examining the binding of Ag+ to mixtures of homobase DNA oligonucleotides by electrospray ionization mass spectrometry. We report on the discovery of a guanine-Ag+-guanine pairing with exceptional thermal stability akin to the cytosine-Ag+-cytosine base pairing. Ag+-mediated homobase duplexes consisting of guanine and cytosine bases are observed from 6-20 base pairs long, suggesting a simple, elongated helical type structure. We use fluorescence resonance energy transfer (FRET) experiments with dye labelled cytosine homobase strands to determine strand orientation. We find that the strand orientation of the cytosine homobase Ag+-duplex is parallel, an important parameter for potential future Ag+-mediated DNA nanotechnology applications. We further use a quantum mechanics / molecular mechanics (QM/MM) approach to calculate the structure of a 20 base pair long Ag+-mediated cytosine duplex and find that the parallel strand orientation forms an ordered, helical duplex which is much more stable than the antiparallel duplex, agreeing with experimental results. Finally, we find striking similarities between CD spectra of AgN-DNA and Ag+-mediated homobase duplexes, suggesting that Ag+-mediated pairings may play an important role in establishing AgN-DNA structure.

From cations to clusters: Ag+-mediated DNA base pairings and fluorescent silver clusters

253rd National Meeting (2017)

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