Interactions of elongated dinuclear metallo-cylinders with DNA three-way and four-way junctions

Non-canonical DNA structures play important roles in processing of the genetic code. Three-way (3WJ) and four-way (4WJ) junctions are dynamic, multi-stranded structures containing an open cavity at the centre. We have previously demonstrated that supramolecular dinuclear metallo-cylinders bind well inside 3WJ cavities, having an optimally complementary size and shape match, cationic charge to bind the DNA anion, as well as the ability to π‑stack with the branchpoint nucleobases. Herein, we show that a longer metallo-cylinder with a similar but extended central π surface binds to both 3WJ and 4WJ structures with good selectivity over double-stranded DNA. Experimental investigations, informed by molecular dynamics (MD) simulations, reveal that whilst this longer cylinder can bind 3WJs as the previously studied cylinders, the extended π surface of the cylinder now also facilitates 4WJ binding. The simulations capture two metastable 4WJ conformations -one resembling a 3WJ, and another where the extended length enables the cylinder to angle into and stabilise a rhombus-shaped 4WJ cavity. The ability to tune the structure of supramolecular assemblies is important for targeting different DNA structures with varying specificity, and in this work, we demonstrate the usefulness of overall length as a parameter for modulating DNA binding.