Abstract:
The development of organic molecules to
target nucleic acid is an active area of research at the interface
of chemistry and biochemistry, which involves DNA binding,
nuclear imaging, and antitumor studies. These molecules bind
with DNA through covalent interactions, electrostatic
interactions, or intercalation. However, they are less
permeable to membrane, and they have a significant
cytotoxicity, which limits their application under in vivo
conditions. In the present work, various mono- and
disubstituted 1,8-naphthalimides-based derivatives (S-12, S13, S-15, and S-21) have been synthesized and characterized
through various spectroscopic techniques. Among these, 3-
amino-4-bromo-1,8-naphthalimide (S-15) was found to have
an attractive water solubility and act as a nuclear imaging agent. The spectroscopic absorption and emission data showed that S15 has a strong affinity for salmon sperm DNA with a binding constant of 6.61 × 104 M−1
, and the ratiometric fluorescence
intensity (I489/I552) of S-15 has a linear relationship in the 0−50 μM range of DNA concentrations. It intercalates with DNA
through the hydrophobic planar naphthalimide core as confirmed through cyclic voltammetry, circular dichroism, 1
H NMR
titration, and thermal denaturation studies. Positively charged amine groups also participate in H-bonding with the bases and
backbone of DNA. The S-15 intercalator showed a large Stokes shift and photostability, which made it attractive for direct
imaging of Legionella pneumophila, without the need for a prior membrane permeabilization
