A spectroscopic investigation into the binding of novel platinum(IV) and platium(II) anticancer drugs with DNA

Rukshani Haputhanthri; Ruchika Ojha; Ekaterina I. Izgorodina; Si Xuan Guo; Glen B. Deacon; Don McNaughton; Bayden R. Wood

doi:10.1016/j.vibspec.2017.02.006

A spectroscopic investigation into the binding of novel platinum(IV) and platium(II) anticancer drugs with DNA

Rukshani Haputhanthri, Ruchika Ojha, Ekaterina I. Izgorodina, Si Xuan Guo, Glen B. Deacon, Don McNaughton, Bayden R. Wood

School of Chemistry

Research output: Contribution to journal › Article › Research › peer-review

11 Citations (Scopus)

Abstract

Platinum(II) complexes have had enormous success in cancer chemotherapy and novel Pt^IV complexes show potential for reduced toxic side effects and different mechanisms of action. While the action of Pt^II anticancer drugs with DNA has been well characterized with X-ray and many spectroscopic modalities, the mechanisms of binding Pt^IV complexes to DNA require further fundamental studies. In the present work using ATR-FTIR spectroscopy, we have extensively analyzed conformational changes in both single-stranded (ss) and double-stranded (ds) calf-thymus DNA, after binding to the Pt^IV anticancer complex, [Pt{((p-HC₆F₄)NCH₂)₂}(py)₂(OH)₂] (py = pyridine) (Pt103(OH)₂), and its Pt^II analogue, [Pt{((p-HC₆F₄)NCH₂)₂}(py)₂] (Pt103) in buffered aqueous acetone (55% water), under which conditions no hydrolysis of drugs occurs. To aid in band assignments of the Pt derivatives, DFT calculations using the M062X/cc-pVDZ level of theory were performed. The ssDNA is distorted and its conformation changes more towards the A-like DNA of dsDNA upon binding to both Pt103 and Pt103(OH)₂. This conclusion is derived from the changes in the PO₂ ⁻ symmetric stretching vibrations (1086 to 1093 cm⁻¹) and C–O (1055 to 1062 cm⁻¹) and C–C (968 to 965 cm⁻¹) stretching vibrations of the phosphodiester backbone. Unlike ssDNA, only Pt103 binding to dsDNA induces distortions along with a conformational change in dsDNA from a more B-DNA like form to the more compact and distorted A-DNA form. The results show that there is no apparent reduction of Pt103(OH)₂. Moreover, we demonstrate that Pt103(OH)₂ can directly bind to ssDNA without any prior reduction. This study provides new insights into how these novel Pt^II and Pt^IV complexes interact with DNA. These results may have implications relevant to the development of new anti-cancer agents.

Original language	English
Pages (from-to)	82-95
Number of pages	14
Journal	Vibrational Spectroscopy
Volume	92
DOIs	https://doi.org/10.1016/j.vibspec.2017.02.006
Publication status	Published - 1 Sept 2017

Keywords

Anti-cancer drugs
Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR)
DNA
Platinum (II and IV)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.vibspec.2017.02.006

Cite this

@article{2f35b15b619040dbb98b312ac5bf6cf4,

title = "A spectroscopic investigation into the binding of novel platinum(IV) and platium(II) anticancer drugs with DNA",

abstract = "Platinum(II) complexes have had enormous success in cancer chemotherapy and novel PtIV complexes show potential for reduced toxic side effects and different mechanisms of action. While the action of PtII anticancer drugs with DNA has been well characterized with X-ray and many spectroscopic modalities, the mechanisms of binding PtIV complexes to DNA require further fundamental studies. In the present work using ATR-FTIR spectroscopy, we have extensively analyzed conformational changes in both single-stranded (ss) and double-stranded (ds) calf-thymus DNA, after binding to the PtIV anticancer complex, [Pt{((p-HC6F4)NCH2)2}(py)2(OH)2] (py = pyridine) (Pt103(OH)2), and its PtII analogue, [Pt{((p-HC6F4)NCH2)2}(py)2] (Pt103) in buffered aqueous acetone (55% water), under which conditions no hydrolysis of drugs occurs. To aid in band assignments of the Pt derivatives, DFT calculations using the M062X/cc-pVDZ level of theory were performed. The ssDNA is distorted and its conformation changes more towards the A-like DNA of dsDNA upon binding to both Pt103 and Pt103(OH)2. This conclusion is derived from the changes in the PO2 − symmetric stretching vibrations (1086 to 1093 cm−1) and C–O (1055 to 1062 cm−1) and C–C (968 to 965 cm−1) stretching vibrations of the phosphodiester backbone. Unlike ssDNA, only Pt103 binding to dsDNA induces distortions along with a conformational change in dsDNA from a more B-DNA like form to the more compact and distorted A-DNA form. The results show that there is no apparent reduction of Pt103(OH)2. Moreover, we demonstrate that Pt103(OH)2 can directly bind to ssDNA without any prior reduction. This study provides new insights into how these novel PtII and PtIV complexes interact with DNA. These results may have implications relevant to the development of new anti-cancer agents.",

keywords = "Anti-cancer drugs, Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), DNA, Platinum (II and IV)",

author = "Rukshani Haputhanthri and Ruchika Ojha and Izgorodina, {Ekaterina I.} and Guo, {Si Xuan} and Deacon, {Glen B.} and Don McNaughton and Wood, {Bayden R.}",

year = "2017",

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doi = "10.1016/j.vibspec.2017.02.006",

language = "English",

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journal = "Vibrational Spectroscopy",

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T1 - A spectroscopic investigation into the binding of novel platinum(IV) and platium(II) anticancer drugs with DNA

AU - Haputhanthri, Rukshani

AU - Ojha, Ruchika

AU - Izgorodina, Ekaterina I.

AU - Guo, Si Xuan

AU - Deacon, Glen B.

AU - McNaughton, Don

AU - Wood, Bayden R.

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Platinum(II) complexes have had enormous success in cancer chemotherapy and novel PtIV complexes show potential for reduced toxic side effects and different mechanisms of action. While the action of PtII anticancer drugs with DNA has been well characterized with X-ray and many spectroscopic modalities, the mechanisms of binding PtIV complexes to DNA require further fundamental studies. In the present work using ATR-FTIR spectroscopy, we have extensively analyzed conformational changes in both single-stranded (ss) and double-stranded (ds) calf-thymus DNA, after binding to the PtIV anticancer complex, [Pt{((p-HC6F4)NCH2)2}(py)2(OH)2] (py = pyridine) (Pt103(OH)2), and its PtII analogue, [Pt{((p-HC6F4)NCH2)2}(py)2] (Pt103) in buffered aqueous acetone (55% water), under which conditions no hydrolysis of drugs occurs. To aid in band assignments of the Pt derivatives, DFT calculations using the M062X/cc-pVDZ level of theory were performed. The ssDNA is distorted and its conformation changes more towards the A-like DNA of dsDNA upon binding to both Pt103 and Pt103(OH)2. This conclusion is derived from the changes in the PO2 − symmetric stretching vibrations (1086 to 1093 cm−1) and C–O (1055 to 1062 cm−1) and C–C (968 to 965 cm−1) stretching vibrations of the phosphodiester backbone. Unlike ssDNA, only Pt103 binding to dsDNA induces distortions along with a conformational change in dsDNA from a more B-DNA like form to the more compact and distorted A-DNA form. The results show that there is no apparent reduction of Pt103(OH)2. Moreover, we demonstrate that Pt103(OH)2 can directly bind to ssDNA without any prior reduction. This study provides new insights into how these novel PtII and PtIV complexes interact with DNA. These results may have implications relevant to the development of new anti-cancer agents.

AB - Platinum(II) complexes have had enormous success in cancer chemotherapy and novel PtIV complexes show potential for reduced toxic side effects and different mechanisms of action. While the action of PtII anticancer drugs with DNA has been well characterized with X-ray and many spectroscopic modalities, the mechanisms of binding PtIV complexes to DNA require further fundamental studies. In the present work using ATR-FTIR spectroscopy, we have extensively analyzed conformational changes in both single-stranded (ss) and double-stranded (ds) calf-thymus DNA, after binding to the PtIV anticancer complex, [Pt{((p-HC6F4)NCH2)2}(py)2(OH)2] (py = pyridine) (Pt103(OH)2), and its PtII analogue, [Pt{((p-HC6F4)NCH2)2}(py)2] (Pt103) in buffered aqueous acetone (55% water), under which conditions no hydrolysis of drugs occurs. To aid in band assignments of the Pt derivatives, DFT calculations using the M062X/cc-pVDZ level of theory were performed. The ssDNA is distorted and its conformation changes more towards the A-like DNA of dsDNA upon binding to both Pt103 and Pt103(OH)2. This conclusion is derived from the changes in the PO2 − symmetric stretching vibrations (1086 to 1093 cm−1) and C–O (1055 to 1062 cm−1) and C–C (968 to 965 cm−1) stretching vibrations of the phosphodiester backbone. Unlike ssDNA, only Pt103 binding to dsDNA induces distortions along with a conformational change in dsDNA from a more B-DNA like form to the more compact and distorted A-DNA form. The results show that there is no apparent reduction of Pt103(OH)2. Moreover, we demonstrate that Pt103(OH)2 can directly bind to ssDNA without any prior reduction. This study provides new insights into how these novel PtII and PtIV complexes interact with DNA. These results may have implications relevant to the development of new anti-cancer agents.

KW - Anti-cancer drugs

KW - Attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR)

KW - DNA

KW - Platinum (II and IV)

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SN - 0924-2031

VL - 92

SP - 82

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JO - Vibrational Spectroscopy

JF - Vibrational Spectroscopy

ER -

A spectroscopic investigation into the binding of novel platinum(IV) and platium(II) anticancer drugs with DNA

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Spectroscopic investigations into nano-scale drug interactions and molecular processes in single living cells and isolated molecules

Coupling biophotonic modalities with machine based recognition systems for disease diagnosis

Cite this

A spectroscopic investigation into the binding of novel platinum(IV) and platium(II) anticancer drugs with DNA

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Projects

Spectroscopic investigations into nano-scale drug interactions and molecular processes in single living cells and isolated molecules

Coupling biophotonic modalities with machine based recognition systems for disease diagnosis

Cite this