Abstract: The binding interactions of a series of square-planar platinum(II)–phenanthroline complexes of the type [Pt(PL)(AL)]2+ [where PL = variously methyl-substituted 1,10-phenanthroline (phen) and AL = ethane-1,2-diamine (en)] were assessed with a G-quadruplex DNA (5′-TTG GGG GT-3′, G4DNA) and a double-stranded DNA (5′-CGC GAA TTC GCG-3′, dsDNA) sequence by ESI–MS. The results indicate a strong correlation between G4DNA affinity and increasing phenanthroline methyl substitution. Circular dichroism (CD) spectroscopy and molecular docking studies also support the finding that increased substitution of the phenanthroline ligand increased selectivity for G4DNA. Graphic abstract: ESI-MS was used to probe the interaction of a range of square-planar Pt(II)–phenanthroline complexes with double-stranded and G-quadruplex DNA. [Figure not available: see fulltext.].