Spectroscopic Studies on Photoinduced Reactions of the Anticancer Prodrug, trans,trans,trans-[Pt(N3)2(OH)2(py)2]

Robbin R. Vernooij, Tanmaya Joshi, Michael D. Horbury, Bim Graham, Ekaterina I. Izgorodina, Vasilios G. Stavros, Peter J. Sadler, Leone Spiccia, Bayden R. Wood

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The photodecomposition mechanism of trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1, py=pyridine), an anticancer prodrug candidate, was probed using complementary Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR), transient electronic absorption, and UV/Vis spectroscopy. Data fitting using Principal Component Analysis (PCA) and Multi-Curve Resolution Alternating Least Squares, suggests the formation of a trans-[Pt(N3)(py)2(OH/H2O)] intermediate and trans-[Pt(py)2(OH/H2O)2] as the final product upon 420 nm irradiation of 1 in water. Rapid disappearance of the hydroxido ligand stretching vibration upon irradiation is correlated with a −10 cm−1 shift to the antisymmetric azido vibration, suggesting a possible second intermediate. Experimental proof of subsequent dissociation of azido ligands from platinum is presented, in which at least one hydroxyl radical is formed in the reduction of PtIV to PtII. Additionally, the photoinduced reaction of 1 with the nucleotide 5′-guanosine monophosphate (5′-GMP) was comprehensively studied, and the identity of key photoproducts was assigned with the help of ATR-FTIR spectroscopy, mass spectrometry, and density functional theory calculations. The identification of marker bands for some of these photoproducts (e.g., trans-[Pt(N3)(py)2(5′-GMP)] and trans-[Pt(py)2(5′-GMP)2]) will aid elucidation of the chemical and biological mechanism of anticancer action of 1. In general, these studies demonstrate the potential of vibrational spectroscopic techniques as promising tools for studying such metal complexes.

Original languageEnglish
Pages (from-to)5790-5803
Number of pages14
JournalChemistry - A European Journal
Volume24
Issue number22
DOIs
Publication statusPublished - 17 Apr 2018

Keywords

  • anticancer agents
  • attenuated total reflection
  • mechanism of action
  • Pt prodrugs
  • vibrational spectroscopy

Cite this

Vernooij, Robbin R. ; Joshi, Tanmaya ; Horbury, Michael D. ; Graham, Bim ; Izgorodina, Ekaterina I. ; Stavros, Vasilios G. ; Sadler, Peter J. ; Spiccia, Leone ; Wood, Bayden R. / Spectroscopic Studies on Photoinduced Reactions of the Anticancer Prodrug, trans,trans,trans-[Pt(N3)2(OH)2(py)2]. In: Chemistry - A European Journal. 2018 ; Vol. 24, No. 22. pp. 5790-5803.
@article{ee34339b55e04055abddfb38c2a53453,
title = "Spectroscopic Studies on Photoinduced Reactions of the Anticancer Prodrug, trans,trans,trans-[Pt(N3)2(OH)2(py)2]",
abstract = "The photodecomposition mechanism of trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1, py=pyridine), an anticancer prodrug candidate, was probed using complementary Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR), transient electronic absorption, and UV/Vis spectroscopy. Data fitting using Principal Component Analysis (PCA) and Multi-Curve Resolution Alternating Least Squares, suggests the formation of a trans-[Pt(N3)(py)2(OH/H2O)] intermediate and trans-[Pt(py)2(OH/H2O)2] as the final product upon 420 nm irradiation of 1 in water. Rapid disappearance of the hydroxido ligand stretching vibration upon irradiation is correlated with a −10 cm−1 shift to the antisymmetric azido vibration, suggesting a possible second intermediate. Experimental proof of subsequent dissociation of azido ligands from platinum is presented, in which at least one hydroxyl radical is formed in the reduction of PtIV to PtII. Additionally, the photoinduced reaction of 1 with the nucleotide 5′-guanosine monophosphate (5′-GMP) was comprehensively studied, and the identity of key photoproducts was assigned with the help of ATR-FTIR spectroscopy, mass spectrometry, and density functional theory calculations. The identification of marker bands for some of these photoproducts (e.g., trans-[Pt(N3)(py)2(5′-GMP)] and trans-[Pt(py)2(5′-GMP)2]) will aid elucidation of the chemical and biological mechanism of anticancer action of 1. In general, these studies demonstrate the potential of vibrational spectroscopic techniques as promising tools for studying such metal complexes.",
keywords = "anticancer agents, attenuated total reflection, mechanism of action, Pt prodrugs, vibrational spectroscopy",
author = "Vernooij, {Robbin R.} and Tanmaya Joshi and Horbury, {Michael D.} and Bim Graham and Izgorodina, {Ekaterina I.} and Stavros, {Vasilios G.} and Sadler, {Peter J.} and Leone Spiccia and Wood, {Bayden R.}",
year = "2018",
month = "4",
day = "17",
doi = "10.1002/chem.201705349",
language = "English",
volume = "24",
pages = "5790--5803",
journal = "Chemistry - A European Journal",
issn = "1521-3765",
publisher = "Wiley-VCH Verlag GmbH & Co. KGaA",
number = "22",

}

Spectroscopic Studies on Photoinduced Reactions of the Anticancer Prodrug, trans,trans,trans-[Pt(N3)2(OH)2(py)2]. / Vernooij, Robbin R.; Joshi, Tanmaya; Horbury, Michael D.; Graham, Bim; Izgorodina, Ekaterina I.; Stavros, Vasilios G.; Sadler, Peter J.; Spiccia, Leone; Wood, Bayden R.

In: Chemistry - A European Journal, Vol. 24, No. 22, 17.04.2018, p. 5790-5803.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Spectroscopic Studies on Photoinduced Reactions of the Anticancer Prodrug, trans,trans,trans-[Pt(N3)2(OH)2(py)2]

AU - Vernooij, Robbin R.

AU - Joshi, Tanmaya

AU - Horbury, Michael D.

AU - Graham, Bim

AU - Izgorodina, Ekaterina I.

AU - Stavros, Vasilios G.

AU - Sadler, Peter J.

AU - Spiccia, Leone

AU - Wood, Bayden R.

PY - 2018/4/17

Y1 - 2018/4/17

N2 - The photodecomposition mechanism of trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1, py=pyridine), an anticancer prodrug candidate, was probed using complementary Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR), transient electronic absorption, and UV/Vis spectroscopy. Data fitting using Principal Component Analysis (PCA) and Multi-Curve Resolution Alternating Least Squares, suggests the formation of a trans-[Pt(N3)(py)2(OH/H2O)] intermediate and trans-[Pt(py)2(OH/H2O)2] as the final product upon 420 nm irradiation of 1 in water. Rapid disappearance of the hydroxido ligand stretching vibration upon irradiation is correlated with a −10 cm−1 shift to the antisymmetric azido vibration, suggesting a possible second intermediate. Experimental proof of subsequent dissociation of azido ligands from platinum is presented, in which at least one hydroxyl radical is formed in the reduction of PtIV to PtII. Additionally, the photoinduced reaction of 1 with the nucleotide 5′-guanosine monophosphate (5′-GMP) was comprehensively studied, and the identity of key photoproducts was assigned with the help of ATR-FTIR spectroscopy, mass spectrometry, and density functional theory calculations. The identification of marker bands for some of these photoproducts (e.g., trans-[Pt(N3)(py)2(5′-GMP)] and trans-[Pt(py)2(5′-GMP)2]) will aid elucidation of the chemical and biological mechanism of anticancer action of 1. In general, these studies demonstrate the potential of vibrational spectroscopic techniques as promising tools for studying such metal complexes.

AB - The photodecomposition mechanism of trans,trans,trans-[Pt(N3)2(OH)2(py)2] (1, py=pyridine), an anticancer prodrug candidate, was probed using complementary Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR), transient electronic absorption, and UV/Vis spectroscopy. Data fitting using Principal Component Analysis (PCA) and Multi-Curve Resolution Alternating Least Squares, suggests the formation of a trans-[Pt(N3)(py)2(OH/H2O)] intermediate and trans-[Pt(py)2(OH/H2O)2] as the final product upon 420 nm irradiation of 1 in water. Rapid disappearance of the hydroxido ligand stretching vibration upon irradiation is correlated with a −10 cm−1 shift to the antisymmetric azido vibration, suggesting a possible second intermediate. Experimental proof of subsequent dissociation of azido ligands from platinum is presented, in which at least one hydroxyl radical is formed in the reduction of PtIV to PtII. Additionally, the photoinduced reaction of 1 with the nucleotide 5′-guanosine monophosphate (5′-GMP) was comprehensively studied, and the identity of key photoproducts was assigned with the help of ATR-FTIR spectroscopy, mass spectrometry, and density functional theory calculations. The identification of marker bands for some of these photoproducts (e.g., trans-[Pt(N3)(py)2(5′-GMP)] and trans-[Pt(py)2(5′-GMP)2]) will aid elucidation of the chemical and biological mechanism of anticancer action of 1. In general, these studies demonstrate the potential of vibrational spectroscopic techniques as promising tools for studying such metal complexes.

KW - anticancer agents

KW - attenuated total reflection

KW - mechanism of action

KW - Pt prodrugs

KW - vibrational spectroscopy

UR - http://www.scopus.com/inward/record.url?scp=85041599511&partnerID=8YFLogxK

U2 - 10.1002/chem.201705349

DO - 10.1002/chem.201705349

M3 - Article

VL - 24

SP - 5790

EP - 5803

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

SN - 1521-3765

IS - 22

ER -