NMR Insights into Nanoscale Molecular Interactions between Nucleic Acids and Pristine Graphene in Aqueous Solution

Delivery of oligonucleotide therapeutics to the sites of biological action is challenged by their large size and charge. Graphene can serve as a nanocarrier for their transport, but the nature of their molecular interactions with pristine graphene in water is still poorly understood. Here, we investigated the binding of short synthetic DNAs and their building blocks with graphene in water using NMR by following their signals upon exposure to graphene. Individual nucleobases displayed strong affinity toward graphene: adenine > guanine > cytosine > thymine. Single-stranded DNAs showed ≈2-3 times weaker binding affinities, with strong influence from nucleobase composition, length, and structural complexity. DNA duplexes were similarly able to interact with graphene, and without any structural disruption. Incorporation of polyaromatic pyrene "anchors" into nucleic acid sequences considerably reinforced their affinity to graphene and allowed graphene to not only distinguish <i>purine-rich</i> from <i>pyrimidine-rich</i> sequences more distinctly but also better discriminate single-stranded from double-stranded DNA.