The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer Drugs

Abstract

Platinum(II) complexes have been found to be effective against cancer cells. Cisplatin curbs cell replication by interacting with the deoxyribonucleic acid (DNA), reducing cell proliferation and eventually leading to cell death. In order to investigate the ability of platinum complexes to affect cancer cells, two examples from the class of polyfluorophenylorganoamidoplatinum(II) complexes were synthesised and tested on isolated DNA. The two compounds trans-[N,N′-bis(2,3,5,6-tetrafluorophenyl)ethane-1,2-diaminato(1-)](2,3,4,5,6-pentafluorobenzoato)(pyridine)platinum(II) (PFB) and trans-[N,N′-bis(2,3,5,6-tetrafluorophenyl)ethane-1,2-diaminato(1-)](2,4,6-trimethylbenzoato)(pyridine)platinum(II) (TMB) were compared with cisplatin through their reaction with DNA. Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy was applied to analyse the interaction of the Pt(II) complexes with DNA in the hydrated, dehydrated and rehydrated states. These were compared with control DNA in acetone/water (PFB, TMB) and isotonic saline (cisplatin) under the same conditions. Principle Component Analysis (PCA) was applied to compare the ATR-FTIR spectra of the untreated control DNA with spectra of PFB and TMB treated DNA samples. Disruptions in the conformation of DNA treated with the Pt(II) complexes upon rehydration were mainly observed by monitoring the position of the IR-band around 1711 cm−1 assigned to the DNA base-stacking vibration. Furthermore, other intensity changes in the phosphodiester bands of DNA at ~1234 cm−1 and 1225 cm−1 and shifts in the dianionic phosphodiester vibration at 966 cm−1 were observed. The isolated double stranded DNA (dsDNA) or single stranded DNA (ssDNA) showed different structural changes when incubated with the studied compounds. PCA confirmed PFB had the most dramatic effect by denaturing both dsDNA and ssDNA. Both compounds, along with cisplatin, induced changes in DNA bands at 1711, 1088, 1051 and 966 cm−1 indicative of DNA conformation changes. The ability to monitor conformational change with infrared spectroscopy paves the way for a sensor to screen for new anticancer therapeutic agents.

An Analysis of Isolated and Intact RBC Membranes—A Comparison of a Semiquantitative Approach by Means of FTIR, Nano-FTIR, and Raman Spectroscopies

“…This clearly proved the usefulness of this technique in the tracking of alterations in the lipid profile strictly associated with the membrane’s composition. Nevertheless it remains challenging to draw detailed conclusions about the exact changes in the lipidic structure and composition, the general trends in lipid and protein changes can still be useful in detection of pathological alterations and even disease determination. − Moreover, because of the specific spectral markers for the intact RBC membranes, we can extract information such as the length of fatty acyl chains, ratios of esters to proteins and phospholipids to cholesterol, which are uniquely recognized by FTIR spectroscopy.…”

Molecular Spectroscopic Markers of DNA Damage

“…The control DNA also gets transformed from the B-to the A-DNA form during dehydration. However, this phenomenon is reversible [48]. Using quasi-elastic neutron scattering (QENS) techniques coupled with synchrotron-based extended X-ray absorption fine structure (SR-EXAFS), and Fourier-transform infrared spectroscopy-attenuated total reflectance (SR-FTIR-ATR), Batista de Carvalho et al studied the effect of Pt/Pd drugs on the structure of DNA.…”

Novel quercetin and apigenin-acetamide derivatives: design, synthesis, characterization, biological evaluation and molecular docking studies

“…Nucleic acids are powerful tools in the recognition and monitoring of vital compounds. [28][29][30][31] The monitoring of DNA-drug interactions using spectroscopic methods is based on the fact that the uorescence of free ligands interacts with DNA in the electronic absorption spectra. 32,33 The Ames test 34 is used to determine the mutations occurring by chemicals at the cell level.…”