Synthesis and photophysical evaluation of a pyridinium 4-amino-1,8-naphthalimide derivative that upon intercalation displays preference for AT-rich double-stranded DNA

Abstract

The synthesis, characterisation and solid state crystal structure of a cationic 4-amino-1,8-naphthalimide derivative (1) are described. The photophysical properties of 1 are shown to vary with the solvent polarity and H-bonding ability. The fluorescence of 1 is enhanced and blue-shifted in its 1 : 1 complex with 5′-adenosine-monophosphate while it is partially quenched and red-shifted in its complex with 5′-guanosine-monophosphate. Linear and circular dichroism measurements show that 1 binds to double-stranded DNA by intercalation. Comparative UV-visible and fluorescence studies with double stranded synthetic polynucleotides poly(dA-dT) 2 and poly(dG-dC) 2 show that 1 binds much more strongly to the AT polymer; 1 also has a strong preference for A-T rich sequences in natural DNA. Thermal denaturation measurements also reveal a much greater stabilisation of the double-stranded poly (dA-dT) 2 than of natural DNA.

The effect of the 4-amino functionality on the photophysical and DNA binding properties of alkyl-pyridinium derived 1,8-naphthalimides

“…1) with 5′-AMP, 5′-GMP and DNA, which showed that the compound exhibits an enhanced fluorescence emission in the presence of 5′-AMP and DNA, while the fluorescence is quenched by 5′-GMP, indicating that the singlet excited state of the 4-amino-1,8-naphthalimide derivative can oxidise guanine but not adenine. 10 This study also showed that in contrast to what was reported for the unsubstituted compound, 11 the 4-amino-derivative 1 binds to DNA via intercalation and displays a strong preference for AT-rich sequences. 10 To further probe the binding of 4-amino-1,8-naphthalimides with DNA, we have synthesised two novel structurally related derivatives 2 and 3 ( Fig.…”

“…10 This study also showed that in contrast to what was reported for the unsubstituted compound, 11 the 4-amino-derivative 1 binds to DNA via intercalation and displays a strong preference for AT-rich sequences. 10 To further probe the binding of 4-amino-1,8-naphthalimides with DNA, we have synthesised two novel structurally related derivatives 2 and 3 ( Fig. 1).…”

“…The increase in relative quantum yield of emission of both compounds in the presence of 5′-AMP can be attributed primarily to a decrease of the rate of non-radiative decay processes in the complex, where the ligand is less accessible to solvent molecules and also is in a relatively more rigid orientation. Similar changes in non-radiative decay processes have been reported for the interaction of various 10 In contrast to what was observed with 5′-AMP, the addition of 5′-GMP (up to 50 mM) caused ca. 75% quenching of the emission intensity of 2 (λ ex = 460 nm), accompanied by a ca.…”

“…These observations suggest the formation of spectroscopically distinct free and 5′-XMP (X = A/G) bound naphthalimide species in solution, which has been previously observed for other 1,8-naphthalimide derivatives and has been attributed to naphthalimidenucleotide stacking interactions. 10,17 The changes in the UV/vis absorption spectra of 3 in the presence of 5′-AMP and 5′-GMP were significantly different from those observed for 2, since with increasing concentration of the mononucleotide, the band centred at 450 nm showed a ca. 8-9 nm red shift.…”

“…This can be attributed to photoinduced electron transfer (PET) occurring from guanine to the excited 4-amino naphthalimide derivative, as has been previously observed for other naphthalimide derivatives. 10,17 Quenching of the emission intensity of 2 at a lower concentration of 5′-GMP occurs in a 1 : 1 complex. The residual fluorescence observed at very high concentrations of 5′-GMP, where the ligand should be mostly bound, can be explained by considering fluorescence emission from the NI : 5′-GMP complexes.…”