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 language | English |
|---|---|
| Pages (from-to) | 5790-5803 |
| Number of pages | 14 |
| Journal | Chemistry - A European Journal |
| Volume | 24 |
| Issue number | 22 |
| DOIs | |
| Publication status | Published - 17 Apr 2018 |
Keywords
- anticancer agents
- attenuated total reflection
- mechanism of action
- Pt prodrugs
- vibrational spectroscopy
Cite this
}
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 journal › Article › Research › peer-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 -