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

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 can...

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Main Authors: Khansa Al-Jorani, Anja Rüther, Miguela Martin, Rukshani Haputhanthri, Glen B. Deacon, Hsiu Lin Li, Bayden R. Wood
Format: Article
Language:English
Published: MDPI AG 2018-12-01
Series:Sensors
Subjects:
Online Access:https://www.mdpi.com/1424-8220/18/12/4297
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author Khansa Al-Jorani
Anja Rüther
Miguela Martin
Rukshani Haputhanthri
Glen B. Deacon
Hsiu Lin Li
Bayden R. Wood
author_facet Khansa Al-Jorani
Anja Rüther
Miguela Martin
Rukshani Haputhanthri
Glen B. Deacon
Hsiu Lin Li
Bayden R. Wood
author_sort Khansa Al-Jorani
collection DOAJ
description 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 <i>trans</i>-[<i>N</i>,<i>N</i>&#8242;-bis(2,3,5,6-tetrafluorophenyl)ethane-1,2-diaminato(1-)](2,3,4,5,6-pentafluorobenzoato)(pyridine)platinum(II) (PFB) and <i>trans</i>-[<i>N</i>,<i>N</i>&#8242;-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<sup>(II)</sup> 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<sup>(II)</sup> complexes upon rehydration were mainly observed by monitoring the position of the IR-band around 1711 cm<sup>&#8722;1</sup> assigned to the DNA base-stacking vibration. Furthermore, other intensity changes in the phosphodiester bands of DNA at ~1234 cm<sup>&#8722;1</sup> and 1225 cm<sup>&#8722;1</sup> and shifts in the dianionic phosphodiester vibration at 966 cm<sup>&#8722;1</sup> 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<sup>&#8722;1</sup> 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.
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spelling doaj.art-8242f8c999bc45ed85bbc8dcd5f6d83c2022-12-22T03:10:03ZengMDPI AGSensors1424-82202018-12-011812429710.3390/s18124297s18124297The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer DrugsKhansa Al-Jorani0Anja Rüther1Miguela Martin2Rukshani Haputhanthri3Glen B. Deacon4Hsiu Lin Li5Bayden R. Wood6Centre for Biospectroscopy and School of Chemistry, Monash University, Clayton, VIC 3800, AustraliaCentre for Biospectroscopy and School of Chemistry, Monash University, Clayton, VIC 3800, AustraliaCentre for Biospectroscopy and School of Chemistry, Monash University, Clayton, VIC 3800, AustraliaCentre for Biospectroscopy and School of Chemistry, Monash University, Clayton, VIC 3800, AustraliaSchool of Chemistry, Monash University, Clayton, VIC 3800, AustraliaSchool of Chemistry, Monash University, Clayton, VIC 3800, AustraliaCentre for Biospectroscopy and School of Chemistry, Monash University, Clayton, VIC 3800, AustraliaPlatinum(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 <i>trans</i>-[<i>N</i>,<i>N</i>&#8242;-bis(2,3,5,6-tetrafluorophenyl)ethane-1,2-diaminato(1-)](2,3,4,5,6-pentafluorobenzoato)(pyridine)platinum(II) (PFB) and <i>trans</i>-[<i>N</i>,<i>N</i>&#8242;-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<sup>(II)</sup> 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<sup>(II)</sup> complexes upon rehydration were mainly observed by monitoring the position of the IR-band around 1711 cm<sup>&#8722;1</sup> assigned to the DNA base-stacking vibration. Furthermore, other intensity changes in the phosphodiester bands of DNA at ~1234 cm<sup>&#8722;1</sup> and 1225 cm<sup>&#8722;1</sup> and shifts in the dianionic phosphodiester vibration at 966 cm<sup>&#8722;1</sup> 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<sup>&#8722;1</sup> 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.https://www.mdpi.com/1424-8220/18/12/4297platinumDNAIR
spellingShingle Khansa Al-Jorani
Anja Rüther
Miguela Martin
Rukshani Haputhanthri
Glen B. Deacon
Hsiu Lin Li
Bayden R. Wood
The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer Drugs
Sensors
platinum
DNA
IR
title The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer Drugs
title_full The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer Drugs
title_fullStr The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer Drugs
title_full_unstemmed The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer Drugs
title_short The Application of ATR-FTIR Spectroscopy and the Reversible DNA Conformation as a Sensor to Test the Effectiveness of Platinum(II) Anticancer Drugs
title_sort application of atr ftir spectroscopy and the reversible dna conformation as a sensor to test the effectiveness of platinum ii anticancer drugs
topic platinum
DNA
IR
url https://www.mdpi.com/1424-8220/18/12/4297
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