Bulged DNA structures are of general biological significance because of the important role in a number of biochemical processes. Compounds capable of targeting bulged DNA sequences can be used as probes for studying their role in nucleic acid function or could even have significant therapeutic potential. The interaction of metallosupramolecular helicates [Fe2 L3 ](4+) (L = C25 H20 N4 ) with DNA duplexes containing bulges has been studied by measurement of the DNA melting temperature and gel electrophoresis. This study was aimed at exploring binding affinity of the helicates to DNA bulges of various sizes and nucleotide sequences. The studies reported herein reveal that both enantiomers of [Fe2 L3 ](4+) bind to DNA bulges containing at least two unpaired nucleotides. In addition, these helicates exhibit a considerably enhanced affinity to duplexes containing unpaired pyrimidine bases in the bulge and/or pyrimidine bases flanking the bulge on both sides. We suggest that the bulge creates the structural motif, such as the triangular prismatic pocket formed by the unpaired bulge bases, to accommodate the [Fe2 L3 ](4+) helicate molecule, and is likely responsible for the affinity of duplexes with a varying number of bulge bases. Our results reveal that DNA bulges represent another example of unusual DNA structures recognized by dinuclear iron(II) supramolecular helicates [Fe2 L3 ](4+) . This article is protected by copyright. All rights reserved.