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Reaction Kinetics of Mixed Amine Platinum (II) Complexes Tony Rivera, Dr. Stephen U. Dunham, Dr. Shari U. Dunham

Department of Chemistry, Moravian College, 1200 Main Street, Bethlehem, PA 18018

In the 21st century, health care communities across the globe face the

challenges of competing against lethal cancer diseases, which continue to emerge and develop resistance to many therapies. However, cisplatin chemotherapy continues to be a useful drug treatment for carcinocoma types such as testicular, ovarian, and uterine (2007, Kelland). From Barnett Rosenburg’s bench discovery in 1978, to current clinical trials, cisplatin drugs continue to show promising results in cellular apoptosis; especially useful for cancer cells. Due to drug resistant strains and toxicity , scientist continue to pursue the design of new platinum complex analogs (2005, McKeage).

Our study focuses on the synthetic chemistries used in the development of many platinum (II) complexes. In our previous research, using 195Pt NMR characterization, we were able to identify key reagents and reaction conditions to successfully yield mixed amine platinum (II) analogs in a one pot reaction (Scheme 1).

Reaction kinetics were both followed by 195Pt NMR and Diode Array UV-VIS spectroscopy. Conclusions from the initial research suggests that reaction 2 to 3 is the rate determining step; therefore, we hypothesize that increasing the concentration of amine reagent will increase the rate.

The energy state of individual electrons of atomic orbitals in chemical compounds will influence the amount of absorbed light at specific frequencies, the light that is not absorbed is transmitted, which is the color that is visible (2015, Davidson). In our research we studied the changes in absorbance (0.0-1.0) at wavelengths near 350 nm. Over a period of 24 hours, as the reaction goes from compound 1 (amber color) to compound 2 (yellow), data is collected, and the change in concentration over time gives us the rate of the reaction.

Introduction

Figure 1. Kinetics Followed by 195Pt NMR Over 24hr

Experimental Method

One Pot Method: 12 mM Platinum reagent (Tetraphenylphosphonium trichloroamine platinate II) 1.8 equivalence Amine reagent (Ethanolamine, Cyclohexylamine, or Picoline) 5.9 x 10-2 mM Iodide reagent ( Sodiumiodide) Solvent (N,N-Dimethylformamide)

Followed reaction over a period of 24 hrs, ran multiple trials increasing the concentration of amine reagent while keeping the concentration of the other reagents constant. Determined the rate for each trial. Compared rates of 195Pt NMR and UV-VIS spectra.

The goal of this research is to characterize the mechanism of the One Pot

Method synthesis of different mixed amine platinum (II) products by 195Pt NMR and UV-VIS. NMR spectra shows how the substitution of individual amine vary among each amine ligands, which plays an important role in the rate. After four hours, synthesis of ethanolamine and cyclohexylamine ligand substitution yield higher product turnover rates compared to picoline substitution. This substitution rate order suggests that there is a dependency of the amine reagent during the reaction, which support the amine reagent as the rate determining step.

NMR is useful for characterizing the changes in platinum synthesis, which shows that there is amine substitution occurring. Figure 1, in all three synthesis, chemical shifts show the intensity of resonance for the platinum reagent decreasing as the platinum product increases over time. Integration of the spectra is not very reliable to determine exact change in platinum concentration over time. However, UV-VIS analysis reveals a more accurate way to follow the reaction. In this research, we identified that the platinum species at Abs350 is dependent upon increasing concentration. With further testing of UV-VIS, we expect to see that the kinetics work the same for all the mixed amine platinum (II) species in this study.

Discussion

Figure 2. Kinetics Followed by UV-VIS Figure 3. Kinetic Fit of UV-VIS

Results

-0.2

0.3

0.8

1.3

300 350 400 450 500

REAGENT PRODUCT

1.  Kelland, L. The resurgence of platinum-based cancer chemotherapy.Nature

Pub. 2007 Aug. Vol. 7. 573-84.

2.  Mckeage, M.J. Lobaplatin: a new antitumuor platinum drug. Ashley PubTaylor and Francis Group.Exp.Opin.Invest. Drugs.2001 10:1,119-128.24Feb2005. http://dx.doi.org/10.1517/13543784.10.1.119

3.  Davidson, M.W., Tchouriokanov, K.I., Electron Excitation and Emission.

FSU. 2015 ed. micro.magnet.fsu.edu/primer/java/scienceopticsu/exciteemit/

References

Scheme 1. Proposed Mechanism of Mixed Amine Platinum (II) Complex

•  195Pt NMR characterization shows that the One Pot Methods yields mixed amine platinum (II) complexes. Platinum reagents exhibits chemical shifts near (-1700,-1800) ppm, where the mixed amine platinum products shift near -2100 ppm.

•  After integration of each peak over time, reaction rates show the reactivity of cyclohexylamine > ethanolamine > picoline in the respective synthesis.

•  UV-VIS analysis identified changes in absorbance (Abs350). In Figure 2, there are two platinum species that exhibit absorbance in the UV range.

•  In Figure 3, the platinum reagent (blue) Abs350 decreases over time at a steady

rate as the platinum product (aqua green) Abs350 increases.

wavelength (nm)

Abs

orba

nce

0.00E+00

2.00E-01

4.00E-01

6.00E-01

8.00E-01

1.00E+00

1.20E+00

1.40E+00

0 2 4 6 8 10 12 14 16 18 20 22 24

REAGENT PRODUCT A

bsor

banc

e Time (hrs)

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1 2

2 3 1

DMF