The synthesis of cisplatin is very well established and is one of the most classic examples of synthesis in inorganic chemistry (figure 1). Dhara reported in 1970 “A rapid method for the synthesis of cis-[PtCl2(NH3)2].”8 The starting material, K2[PtCl4], is treated with excess of KI to be converted into K2[PtI4]. The product is subsequently treated with NH3 to obtain yellow colored cis-[PtI2(NH3)2] that is collected and dried. cis-[PtI2(NH3)2] is then dissolved in AgNO3 to precipitate out AgI that is removed. The solution containing cis-[Pt(OH2)2(NH3)2]2+ is lastly treated with KCl to produce the final, yellow-colored product, cisplatin.
The synthesis scheme of cisplatin is deeply related to the trans effect. Chernyaev introduced the trans effect in platinum chemistry9. The theory is based on empirical observation that the rate of substitution of a ligand in a square planar complex is dependent on the group opposite (or trans) to it8. The trans effect can be explained by two factors: sigma-bonding effect and pi-bonding effect.
The sigma-bonding effect is the weakening of the bonding between platinum and X, or the leaving group, by the sigma bonding between platinum and the sigma-bonding ligand (T in figure 2) trans to X. The Pt-X bond is affected by Pt-T bond because both bondings make use of platinum Px and dx2-y2 orbitals. If the bonding between Pt-T becomes stronger, less of platinum dx2-y2 orbital is available for Pt-X bond, making the bond weaker as a result. Thus a strong sigma-bonding ligand “labilizes” the metal-ligand bond trans to it, which is sigma-bonding effect.
The pi-bonding effect is another factor that contributes to trans effect. When pi-bonding ligand (T in figure 2) that is trans to X result in strong pi-b...
... middle of paper ...
... c, which leads to APAF1 activation, followed by CASP9 activation that can also activate CASP3 and CASP711.
Studies have shown that the transduction of cisplatin-DNA adduct recognition signal occurs through pathways other than p53, including the following: AKT pathway, c-ABL, MAPK/JNK/ERK, and MKP1/CL10011. These other pathways are not covered in this paper due to page limits.
Reference
8. Alderden, Journal of Chemical Education, 2006, 83, 728-734.
9. Chernyaev, Ann, inst. Platine USSR., 1926, 4, 261.
10. Hromas, Cancer Letter, 1987, 36, 197-201.
11. Wang, Nature Reviews, 2005, 4, 307-320.
12. Takahara, Nature, 1995, 377, 649-652.
13. Imamura, The journal of Biological Chemistry, 2001, 276, 7534-7540.
14. Ohndorf, Nature, 1999, 399, 708-712.
15. Jayaraman, Genes & Development, 1998, 12, 462-472.
16. Vousden, Nature Reviews, 2002, 2, 594-604.
This week’s lab was the third and final step in a multi-step synthesis reaction. The starting material of this week was benzil and 1,3- diphenylacetone was added along with a strong base, KOH, to form the product tetraphenylcyclopentadienone. The product was confirmed to be tetraphenylcyclopentadienone based of the color of the product, the IR spectrum, and the mechanism of the reaction. The product of the reaction was a dark purple/black color, which corresponds to literature colors of tetraphenylcyclopentadienone. The tetraphenylcyclopentadienone product was a deep purple/black because of its absorption of all light wavelengths. The conjugated aromatic rings in the product create a delocalized pi electron system and the electrons are excited
David and John Free. (26 Nov 2006). MadSci Network: Chemistry. Retrieved on March 6, 2011, from http://www.madsci.org/posts/archives/2007-02/1171045656.Ch.r.html
Acknowledgements. Special thanks go to the Department of Chemistry and Chemical Biology at IUPUI, Dr. Ryan E. Denton, Professor and Dan Preston, TA.
... had a higher induction effect on HBD1 than their counterpart at the same concentration (Figure 3). While on LL-37, 5-phenyl valeric acid (C5), 6-phenyl hexanoic acid (C6) and 7-phenyl heptanic acid (C7) had a higher response than their fatty acids, the peak expression observed at 5-phenyl valeric acid (C5) (Figure 3).
If more than one complex is formed at different pH values, their existence can be decided by this type of study. The pH, at which the absorption due to a particular complex species is far greater than that of metal ion and or the ligand alone, is selected for the study of that species. As the complex formation is the function of pH; it should be kept constant for particular system. Similarly, ionic strength is maintained constant throughout by adding an appropriate volume of sodium perchlorate. pH can be remained constant by using suitable buffer, provided the buffer does not interfere with the complex formation at wavelength where complex species show maximum
This is a contribution of the conjugated structure of the molecule that permits the absorption of the electromagnetic radiation in the visible spectrum of 400-700nm wavelength. In addition, the TPCP compound adopts a propeller shape in its three dimensional conformation. This can be described by the four phenyl rings are rotated out of the plane from the central ring due to the steric repulsion between the compounds. Lastly, after undergoing the synthesis process approximately 0.2 g of purified TPCP product was yielded. In other words, the theoretical yield was found to be 1.067 g, while the percent yield was determined to be 18.750%. (The calculations done to receive these digits could be found in the Calculations section of the article at the end of the article) The absorbance of the compound at 330 nm and 480 nm was predicted to be 1.1 and 0.2 respectively. Furthermore, the concentration of the TPCP using the equation displayed in the Calculations section at the end of the article was found to be 3.729*10-4 (330 nm) and 3.290*10-4 (480 nm).
Our presentation from a chemist comes from Tim Storr, who completed a B.Sc at the University of Victoria before moving on to a Ph.D at UBC, and then became a postdoctoral fellow at Stanford. He is currently an associate professor at SFU, and teaches courses such as 1st year chemistry. His main area of research is medicinal inorganic chemistry, which has him researching and classifying drugs and treatment methods that target metal ions. Dr. Storr’s research includes areas such as: determining the connection between diseases and certain peptides/proteins, identifying metal ions that effectively suppress cancerous growths, and studying radiopharmaceuticals which are radioactive compounds that, once injected into the body, allow an MRI machine
Figure 1: Initial anti attack approach of bromine to the bottom side of the trans-cinnamic acid:
The American Cancer Society publishes current advances made in cancer research on their website. Many of the exciting discoveries about how best to treat the disease focus on the genetic aspects associated with certain types of cancer. In addition, treatments aimed at genetic solutions to cancer may be more effective and may cause fewer adverse side effects than traditional cancer treatments (American Can...
Mitogen-activated protein (MAP) kinase is a type of catalysis enzyme. Mitogen is a signal that causes cells to undergo mitosis. Since it is a catalysis it will amplify the transduction signal reaction rate across the membrane. MAP kinase cascade involves a series of accessory proteins which then transduces signal from the activated receptor on the cell surface to the regulatory genes in the nucleus. The activated receptor then undergoes phosphorylation. Activated MEK1/2 eventually will activate ERK1/2 which in turn will activate transcription factors of the AP-1 family. The transcription factors now move to the cell nucleus and bind to the AP-1 motif of DNA. The end results activation of transcription a resultant mRNA is transported from nucleus to the
The ligand field stabilization energy was also calculated for the high and low spin states using the equation LFSE = Δ_0 (-2/5 x+3/5 y), where x = number of unpaired electrons in the t2g orbital and y = the number of unpaired electrons in the eg orbital. The ligand field stabilization energy was calculated to be 2/5 Δ_0 for the high spin state and 0 for the low spin state.
In the reaction conducted in this experiment, three mechanisms were possible: Anti Addition, Syn Addition, and Anti and Syn Addition. Addition mechanisms involve removing a double bond between two adjacent carbons and adding one nucleophile (bromine in this case) to each of the carbons. Anti Addition results in a product in which the two bromines are anti-periplanar (or trans) to one another. Syn Addition results in a product in which the two bromines are syn-periplanar (or cis) to one another. Anti and
The synthesis of esomeprazole magnesium is divided into two sections; section I and II. Section I demonstrates the synthesis of omeprazole which is the S enantiomer of esomeprazole. It starts with 2,3,5 Trimethyl pyridine (1) which is oxidized by hydrogen peroxide in acetic acid to give the n-oxide (2). This is then nitrated with a mixture of sulfuric acid and nitric acid to give the 4-nitro derivative (3). The nitro group in compound (3) is then displaced by hydroxymethylation in a nucleophilic substitution reaction to yield compound (4). This is then treated with acetic acid anhydride in a redox reaction to yield the ester derivative (5). Compound 5 is then treated with a base to form the corresponding alcohol (6). The hydroxyl group of compound 6 is then displaced in a substitution reaction with a chloride using thionyl chloride to give 2-chloromethy...
Plontke, R. (2003, March 13). Chemnitz UT. TU Chemnitz: - Technische Universität Chemnitz. Retrieved April 1, 2014, from http://www.tu-chemnitz.de/en/
behaviour of the Fe-O-P bond angles and tilt angles in the beta-phase. During the transition from