1. The document reports on a study of the reaction kinetics of mixed amine platinum (II) complexes synthesized using a one-pot method. 2. 195Pt NMR spectroscopy and UV-Vis spectroscopy were used to monitor the reactions over 24 hours and determine that reaction 2 to 3 is the rate determining step. 3. Increasing the concentration of the amine reagent was found to increase the rate of the reaction, supporting the hypothesis that the amine reagent is involved in the rate determining step. Kinetic data showed the order of reactivity of different amine reagents.

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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)
Absorbance
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
Absorbance
Time (hrs)
+
1 2
2 3 1
DMF