Enhanced binding of a hexacyclic amidine analogue of Hoechst 33258 to the minor groove of DNA: 1H NMR and UV melting studies with the decamer duplex d(GGTAATTACC)2

Abstract

NMR and UV melting studies with the decamer duplex d(GGTAATTACC) ₂ show that replacing the N-methylpiperazine ring of the DNA minor groove binding agent Hoechst 33258 with a hexacyclic amidine leads to both an increase in duplex stability (ΔT _m ≈ 7 °C) and enhanced A–T specific recognition; the amidine NH exchanges slowly with the solvent and has a small temperature coefficient (<3 ppb/°C) supporting its involvement in intermolecular hydrogen bonding, however, the data suggest that the ring is flipping rapidly even at 278 K even though the interaction appears to contribute significantly to complex stability.