Synthesis and ct-DNA binding study of a donor-π-acceptor dihydropyrimidinone fluorophore

Abstract

We have described the synthesis of a Donor-π-Acceptor dihydropyrimidinone (DHP) fluorophore via functional group modification of dihydropyrimidinone, commonly known as Biginelli product, to probe ds-DNA. The intermediates including the target compounds was characterized by NMR, mass, and XRD. The inherent fluorescence of the synthesized DHP is very weak. However, in the presence of ds-DNA, the fluorescence emission intensity enhances up to 5 times. The type of interactions of the DHP with ds-DNA was investigated thoroughly by spectroscopic methods. The combined result of Gaussian calculation and the time-resolved fluorescence spectroscopy suggested the formation of an effective charge transfer of Donor-π-Acceptor system. The results of the iodide quenching effect and displacement assay with Hoechst and Ethidium bromide indicated a minor groove binding mechanism. A theoretical model has been constructed by using the AutoDoc Vina package to visualize different types of non-bonded interaction of the DHP with other heteroatomic units in the narrow and shallow cut of the minor groove of ds-DNA. We observed the incorporation of 3a within the cell and the targeting of the nucleus by using a confocal microscope.