Rich spectroscopic, molecular docking, and molecular dynamics studies of DNA interaction with a new oxaliplatin...

In this project, a new platinum complex with the formula [Pt(DACH)(tert-pentylgly)]NO₃, where DACH is 1R,2R-diaminocyclohexane and tert-pentylgly is 1,1-dimethylpropylglycine, was prepared and characterized using conductivity measurements, elemental analysis, LC mass, HPLC, and various spectroscopic methods. The CT-DNA binding with this compound was explored through absorption and emission spectroscopy. UV-Vis absorption studies revealed a hyperchromic effect in the spectra of DNA, indicating interaction. Furthermore, a competitive fluorescence spectroscopy using ethidium bromide showed that the complex binds to DNA via a groove binding mode. Circular dichroism (CD) spectroscopy demonstrated that the platinum complex can alter the secondary structure of DNA. Cytotoxicity studies were carried out on MCF7 and HCT116 cell lines, representing human breast and colorectal carcinoma, respectively. Molecular docking suggested that the Pt complex binds to DNA more strongly than oxaliplatin, predominantly through groove binding, which aligns with the experimental findings. In the molecular dynamics analysis, the fluctuations in RMSD for the DNA-complex and the RMSF assessment of DNA residues suggest that the DNA structure is unstable. The interaction of DNA with Pt compound leads to an increase in the radius of gyration and helical bending, which correlates with heightened flexibility and residual deviations.