Hydrophobic effect of alkyl substituents on DNA intercalation of a dye.

Naphthalene imides carrying alkyl chains of different length were synthesized to evaluate the hydrophobic effect on DNA interaction with small molecules. These dyes bind to DNA with moderately high affinity of 10(4)-10(5) M-1 and raise the melting temperature of the DNA duplex by 8-18 degrees C at a 0.2 molar ratio of dye to DNA-p (phosphate unit). However, both the DNA binding affinity and DNA duplex stability decrease with an increase in the hydrophobicity (logP) of the dye. These results demonstrate that the interaction of the hydrophobic alkyl chain of the dye with the DNA groove destabilizes the DNA structure, presumably by removing the structure-stabilizing water from the DNA groove.