Al-Jorani, K.; Rüther, A.; Martin, M.; Haputhanthri, R.; Deacon, G.B.; Li, H.L.; Wood, B.R. The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer Drugs. Sensors2018, 18, 4297.
Al-Jorani, K.; Rüther, A.; Martin, M.; Haputhanthri, R.; Deacon, G.B.; Li, H.L.; Wood, B.R. The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer Drugs. Sensors 2018, 18, 4297.
Al-Jorani, K.; Rüther, A.; Martin, M.; Haputhanthri, R.; Deacon, G.B.; Li, H.L.; Wood, B.R. The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer Drugs. Sensors2018, 18, 4297.
Al-Jorani, K.; Rüther, A.; Martin, M.; Haputhanthri, R.; Deacon, G.B.; Li, H.L.; Wood, B.R. The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer Drugs. Sensors 2018, 18, 4297.
Abstract
Platinum(II) complexes have been found to be effective against cancer cells. Cisplatin curbs cell replication by interacting with the deoxyribonucleic acid (DNA), eventually leading to cell death and reducing cell proliferation. In order to investigate the ability of platinum complexes to affect cancer cells, two examplesfrom the class of polyflurophenylorganoamidoplatinum(II) complexes were synthesised and tested on isolated DNA. The two compounds trans-[N,N’-bis(1,2,3,5,6-pentafluorophenyl)ethane-1,2-diaminato(1-)](2,3,4,5,6-pentafluorobenzoato)(pyridine)platinum(II) (PFB), and trans-[N,N’-bis(1,2,3,5,6-pentafluorophenyl)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 state. 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-bandaround 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.
Keywords
platinum; DNA; IR
Subject
Chemistry and Materials Science, Analytical Chemistry
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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