How to analytically quantify a chemical's potential to intercalate DNA?
Our lab uses a thiazole orange exclusion assay to measure how well our polyintercalating peptides* bind DNA. The assay works by mixing thiazole orange with DNA so it becomes fluorescent. Then we measure fluorescence while titrating in peptide and the loss of flourescence indicates binding. This is because thiazole orange is only fluorescent when intercalated into DNA, and as the competing compound displaces it, the free thiazole no longer fluoresces. Note that this assay is not foolproof, polycationic compounds can condense DNA without intercalating, but this conformation change still forces the thiazole out and reduces the fluorescence, so loss of fluorescence implies binding, not necessarily intercalation. This method works for RNA too, but you'll need more thiazole to see signal because there are usually fewer double helices to intercalate into.

Another method is to measure viscosity, because intercalators make the DNA longer and the solution becomes more viscous, but you either need a very sensitive method to measure the change or a very concentrated DNA solution, and the viscosity can probably also be changed by condensing the DNA.

Another possible method MIGHT be fluorescent anisotropy, if your intercalator is fluorescent. It would spin rapidly outside the DNA, but slow down once it binds the double helix. However, conformational changes in the DNA can change its rotation speed and confound the results.


That paper doesn't really mention the assay, it's just to show off the peptides so you understand what I'm talking about a little more. Those peptides also bind by electrostatic interaction and condense DNA, so it's not a pure measurement of intercalation.