The substituent group effect: investigation of naphthalimide-spermidine conjugates binding to DNA by spectroscopy, molecular docking and dynamics

Abstract

• The interaction of Naphthalimide-polyamine conjugates binding to DNA was studied by spectroscopy, molecular docking and dynamics. • Naphthalimide-polyamine conjugates binding to DNA by intercalation and groove into herring sperm DNA. • There was a substituted group effect in the course of DNA interaction with substituted naphthalide-polyamine conjugates. • Naphthalide-polyamine conjugates could cause the little conformation change of DNA. The investigation of mononaphthalimide spermidine conjugates ( 1∼4 ) binding to herring sperm DNA was performed by UV/vis absorption and fluorescent spectra under physiological conditions (pH=7.4). The molecular docking and dynamics were also applied to analyze the interactive mode and molecular dynamic property of their binding to DNA. The observed different spectral change of compounds 1∼4 binding to DNA and the replacement of EB from DNA-EB complexes by compounds showed that these compounds could bind to DNA in patterns of intercalation and groove binding. The further fluorescent variable temperature tests revealed that the quenching mechanism of compounds 1∼4 binding to DNA was belonged to a static one. The quenching constants, binding constants and thermodynamic parameters indicated that the binding force of the compounds-DNA was closely related to the substituent on the aromatic rings of the compounds. Besides, the forces between DNA and compounds were mainly hydrogen bond and hydrophobic force. The results of circular dichroism showed that the compounds caused insignificant conformational change of B-A type DNA, indicating these compounds were not classical DNA intercalating agents. Molecular docking and potassium iodide experiments on the fluorescence of the compound-DNA complex also supported their interactive modes and the substituent effects. The substituent effects in the compound-DNA complexes were further appraised by molecular dynamics, which resulted in the different values of root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF). The values of RMSD and RMSF of different compound-DNA complexes indicated that compounds 1∼4 could induce the slightly conformational change of DNA, which were similar to that of compound 5 .