Regardless of DNA-binding mode, strong interactions with DNA require an electrostatic component. Electrostatic interactions are especially important for DNA-binding nuclear proteins or polyamines, which bind to the major groove or sugar-phosphate backbone of DNA. But the structure of COSAN markedly differs from the structure of known DNA-binding molecules. COSAN has a bulky, globular, and rigid structure with delocalized negative charge. For comparison, Figure shows the structures of COSAN, the intercalator ethidium bromide (EB), the minor groove-binder 4′,6-diamidino-2phenylindole (DAPI), and the major grove/backbone-binder spermine, a polyamine. Perhaps due to its unique structure, COSAN interactions with DNA remain, however, controversial. On the one hand, studies on interactions between COSAN and DNA have reported that this metallacarborane intercalates into DNA. On the other hand, research on COSAN conjugated with the intercalator naphthalimide or with oligonucleotides have failed to support these claims. In fact, COSAN conjugation to naphthalimide decreased its affinity to DNA and altered its binding mode to groove binding, as shown by minor changes in the DNA melting temperature and circular dichroism spectrum. Furthermore, COSAN-containing oligonucleotides maintain their ability to hybridize with complementary strands, forming duplexes with structures similar to those of the corresponding COSAN-free duplexes. COSAN also shows low toxicity to mammalian cells, whereas intercalators are often highly toxic. In short, the data on COSAN-DNA interactions are still inconclusive.