DNA duplexes are stabilized by many interactions, one of which is stacking interactions between the nucleic acid bases.  These interactions are useful for designing small molecules that bind to DNA.  Intercalators have been shown to be valuable anti-cancer agents that stack between the DNA bases and exhibit stabilizing effects.  Naphthalimides have been an important family of intercalators since the early 1970's.  There is a continued need to design intercalators that will exhibit these stabilizing effects while being more selective toward DNA binding.  This work aims to investigate various 4-substituted naphthalimides.  These substituents include functional groups such as an amino, nitro, chloro, and bromo group at the 4-position.  In order to help explain substituent interactions in DNA-intercalator binding, multiple DNA duplexes as well as some RNA duplexes were melted in the presence of a 4-substituted naphthalimide.  Optical melting experiments were used to measure the absorbance of the sample as the temperature was increased from 35�C to 80�C.  The Tm values of the DNA-intercalator complexes were compared to the Tm of the naked DNA duplex, resulting in ?Tm values.  The ?Tm values show that the substituents on the intercalator affect the stability of the DNA-intercalator complex.  Previous work by the Znosko lab investigated 3-substituted naphthalimides.  The stabilities of the DNA-intercalator complexes with substituents at the 3-position were compared to those complexes with substituents at the 4-position.  From the results of this study and the comparison to results from previous work, the effect of the substituent's identity and position on the naphthalimide ring was determined.

Substituents on a naphthalimide intercalator affect the stability of DNA-intercalator complexes

247th National Meeting (2014)

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