Michelle Livings LOG!!!!!

23 September 2010
For the first assignment I'm going to look at properties of emeraldine polyaniline, which I will be synthesizing in the lab within the next few weeks.
[You probably can't do 5 properties from 5 sources for a polymer because it will have varying MW - maybe do a monomer? JCB]
For the research project my topic will involve the chemistry and biology aspects of cancer treatments. After some reading I will try to narrow down the topic significantly.

30 September 2010 - week 2
For the first assignment I'm going to look at properties of aniline:
Melting point:
1: http://en.wikipedia.org/wiki/Aniline Wikipedia gives the melting point of aniline to be -6.3 C
2: http://msds.chem.ox.ac.uk/AN/aniline.html this MSDS (found on chemspider) gives the melting point of aniline to be -6 C
3: http://www.chemicalland21.com/petrochemical/ANILINE.htm Chemical Land 21 page gives the melting point of aniline to be -6 C
4: http://www.chemguide.co.uk/organicprops/aniline/background.html ChemGuide page gives the melting point of aniline to be -6.2 C
5: http://www.daviddarling.info/encyclopedia/A/aniline.html Internet Encyclopedia of Science gives the melting point of aniline to be -6.2 C

Boiling point:
1: http://en.wikipedia.org/wiki/Aniline Wikipedia gives the boiling point of aniline to be +184.13 C
2: http://www.alfa.com/content/msds/USA/A14443.pdf Alfa Aesar MSDS gives the boiling point of aniline to be +184 C
3: http://www.cdc.gov/niosh/npg/npgd0033.html the CDC gives the boiling point of aniline to be +363 F = +183.89 C
4: http://www.chemicalland21.com/petrochemical/ANILINE.htm Chemical Land 21 page gives the boiling point of aniline to be +184 C
5: http://www.chemguide.co.uk/organicprops/aniline/background.html ChemGuide page gives the boiling point of aniline to be +184 C

Viscosity:
1: http://en.wikipedia.org/wiki/Aniline Wikipedia gives the viscosity of aniline to be 3.71 cP (centipoise) at 25 C
2: http://www.engineersedge.com/fluid_flow/fluid_data.htm Engineers Edge page gives the viscosity of aniline to be 4.37 centistokes = 4.37 cP at 20 C at specific gravity of 1

Density:
1: http://en.wikipedia.org/wiki/Aniline Wikipedia gives the density of aniline to be 1.0217 g/mL (no temperature listed)
2: http://www.alfa.com/content/msds/USA/A14443.pdf Alfa Aesar MSDS gives the density of aniline to be 1.02 g/cm3 at 20 C
3: http://physics.nist.gov/cgi-bin/Star/compos.pl?matno=109 NIST physics gives the density of aniline to be 1.02350 E+00 g/cm3 (no temperature listed)
4: http://www.engineersedge.com/fluid_flow/fluid_data.htm Engineers Edge page gives the density of aniline to be 1.021 kg/L = 1.021 g/mL at 20 C
5:

Solubility in water:
1: http://en.wikipedia.org/wiki/Aniline Wikipedia gives the solubility of aniline in water to be 3.6 g / 100 mL = 0.036 g/mL at 20 C
2: http://www.alfa.com/content/msds/USA/A14443.pdf Alfa Aesar MSDS gives the solubility of aniline in water to be 34 g/L = 0.034 g/mL at 20 C
3: http://www.cdc.gov/niosh/npg/npgd0033.html the CDC gives the solubility of aniline to be 4% = 4 g / 100 mL = 0.04 g/mL (no temperature listed)
4: http://www.chemicalland21.com/petrochemical/ANILINE.htm Chemical Land 21 page gives the solubility of aniline to be 0.3 g/L = 0.0003 g/mL at 20 C
5: http://www.chemguide.co.uk/organicprops/aniline/background.html ChemGuide gives the solubility of aniline in water to be 3.6 g / 100 mL = 0.036 g/mL at 20 C



7 October 2010 - week 3
This week I am trying to finish the first assignment, also input all of my properties to the validation spreadsheet.
Here is the completed assignment:
Melting point:
1: http://en.wikipedia.org/wiki/Aniline Wikipedia gives the melting point of aniline to be -6.3 C
2: http://msds.chem.ox.ac.uk/AN/aniline.html this MSDS (found on chemspider) gives the melting point of aniline to be -6 C
3: http://www.chemicalland21.com/petrochemical/ANILINE.htm Chemical Land 21 page gives the melting point of aniline to be -6 C
4: http://www.chemguide.co.uk/organicprops/aniline/background.html ChemGuide page gives the melting point of aniline to be -6.2 C
5: http://www.daviddarling.info/encyclopedia/A/aniline.html Internet Encyclopedia of Science gives the melting point of aniline to be -6.2 C

Boiling point:
1: http://en.wikipedia.org/wiki/Aniline Wikipedia gives the boiling point of aniline to be +184.13 C
2: http://www.alfa.com/content/msds/USA/A14443.pdf Alfa Aesar MSDS gives the boiling point of aniline to be +184 C
3: http://www.cdc.gov/niosh/npg/npgd0033.html the CDC gives the boiling point of aniline to be +363 F = +183.89 C
4: http://www.chemicalland21.com/petrochemical/ANILINE.htm Chemical Land 21 page gives the boiling point of aniline to be +184 C
5: http://www.chemguide.co.uk/organicprops/aniline/background.html ChemGuide page gives the boiling point of aniline to be +184 C

Viscosity:
1: http://en.wikipedia.org/wiki/Aniline Wikipedia gives the viscosity of aniline to be 3.71 cP (centipoise) at 25 C
2: http://www.wolframalpha.com/input/?i=aniline Wolfram Alpha gives the viscosity of aniline to be 0.003847 Pa*s = 3.847 cP at STP
3: http://www.hbcpnetbase.com/ CRC Handbook of Chemistry and Physics gives the viscosity of aniline to be 3.85 mPa*s = 3.85 cP at 25 C
anilineviscostyCRChandbook.JPG
4: http://pubs.acs.org/doi/pdf/10.1021/ac50126a004 L.A. Steiner gives the viscosity of aniline to be 3.770 cP at 25 C
5: http://pubs.acs.org/doi/pdf/10.1021/j150199a001 E.C. Bingham gives the viscosity of aniline to be 3.781 cP at 25 C (average of 3 values given in paper)

Density:
1: http://en.wikipedia.org/wiki/Aniline Wikipedia gives the density of aniline to be 1.0217 g/mL (no temperature listed)
2: http://www.alfa.com/content/msds/USA/A14443.pdf Alfa Aesar MSDS gives the density of aniline to be 1.02 g/cm3 at 20 C
3: http://physics.nist.gov/cgi-bin/Star/compos.pl?matno=109 NIST physics gives the density of aniline to be 1.02350 E+00 g/cm3 (no temperature listed)
4: http://www.engineersedge.com/fluid_flow/fluid_data.htm Engineers Edge page gives the density of aniline to be 1.021 kg/L = 1.021 g/mL at 20 C
5: http://www.wolframalpha.com/input/?i=aniline Wolfram Alpha gives the density of aniline to be 1.019 g/cm3 at STP

Solubility in water:
1: http://en.wikipedia.org/wiki/Aniline Wikipedia gives the solubility of aniline in water to be 3.6 g / 100 mL = 0.036 g/mL at 20 C
2: http://www.alfa.com/content/msds/USA/A14443.pdf Alfa Aesar MSDS gives the solubility of aniline in water to be 34 g/L = 0.034 g/mL at 20 C
3: http://www.cdc.gov/niosh/npg/npgd0033.html the CDC gives the solubility of aniline to be 4% = 4 g / 100 mL = 0.04 g/mL (no temperature listed)
4: http://www.chemicalland21.com/petrochemical/ANILINE.htm Chemical Land 21 page gives the solubility of aniline to be 0.3 g/L = 0.0003 g/mL at 20 C
5: http://www.chemguide.co.uk/organicprops/aniline/background.html ChemGuide gives the solubility of aniline in water to be 3.6 g / 100 mL = 0.036 g/mL at 20 C

Also I have updated everything in the validation spreadsheet. This weekend and next week I will begin working on the 2nd assignment. Does everything for the 1st assignment look okay?
[See comments in status column of validation sheet JCB]

14 October 2010 - week 4
Today I answered my FAQ, #13, about Markush structures and their uses. Not sure if I have to put my answer on my log as well as on the FAQ page?

What is a Markush structure and how is it used? Provide a specific example.
A Markush structure is a general description of a related set of chemical compounds. Markush structures are used specifically in patents.
Dr. Eugene Markush was a dye manufacturer who founded the Pharma Chemical Corporation in 1917. In 1924, Markush was received a patent for pyrazolone dyes, USP # 1,506,316. This patent was groundbreaking because Markush not only claimed several chemical structures which had been synthesized in the lab, he also claimed in the patent a general chemical structure for pyrazolone dyes. Markush was the first person to claim general chemical structures in a patent, thus structures of this type became known as "Markush structures" after the US Patent Office ruled to permit such structures in 1925.
A specific example of a Markush structure, represented by a chemical drawing, is a bond drawn to the center of a ring, indicating that the ring can be substituted at any position. Several other specific examples can be seen in the image below, from an article Comparison of Markush Structure Databases from the Journal of Chemical Information and Modeling:
markush.JPG

http://www.colorantshistory.org/MarkushBiography.html
http://en.wikipedia.org/wiki/Markush_structures#Markush
Image reference: http://pubs.acs.org/doi/pdf/10.1021/ci00016a001 J. Chem. Inf. Comput. Sci. 1993, 33, 799-804.


20 October 2010 Wednesday week 5
For my final project, I would like to look at the history, development, and synthesis of Cysplatin.[A good starting point would be using SciFinder and Beilstein to search for published syntheses - note that the correct spelling is cisplatin JCB]
So for assignment #2 I'll be doing an article summary directly related to this. I'll finalize my "5 properties" lists and find the article for my summary in class tomorrow evening.


25 October 2010 Monday week 6
Today I corrected everything that was wrong with my section of the validation spreadsheet - I converted the solubility values into M; fixed the three bad links; and also added the following images:

This is a snapshot from the ChemicalLand21 website with melting point, boiling point, and solubility in water (in case the link stops working again):
anilineproperties_chemland.JPG

This is the viscosity chart from the primary publication I found from ACS; there are three measured experimental viscosities at 25 C so for the "source value" column I listed all three values in the same box, and for the "common value" column I took the average of the three viscosities: (the three values at 25 C are highlighted in yellow, and the viscosities are in the far right column):
anilineviscosities.JPG


27 October 2010 Wednesday week 6
Today I started looking for articles about the cisplatin project. The first article I am reading is a review article published in the Journal of Chemical Education, Vol 83 No 5 May 2006; the article is called "The Discovery and Development of Cisplatin" by Rebecca A. Alderden, Matthew D. Hall, and Trevor W. Hambley, from the University of Sydney. Hopefully this thorough review will help me to find more sources and to get started on the article summary for assignment 2. I also found a useful website at http://www.ch.ic.ac.uk/local/projects/s_liu/Html/Frames.html [link broken JCB], a project from 1998 about anti-cancer agents, specifically cisplatin and its analogues.
[Substance search on SciFinder would also be a good place to start figuring out what you want to cover about it JCB]

28 October 2010 Thursday week 6
I (hopefully finally) fixed the last 3 errors in my part of the validation spreadsheet. Also in reading the review article that I mentioned yesterday, I have found several other sources for the research project, including several different reaction schemes and some information about transplatin (the trans isomer of the square planar molecule). Research continues!


8 November 2010 Monday week 8
Assignment 2: Article summary
J Am Chem Soc 1988, 110, 5018
Bis(platinum) complexes containing two platinum cis-diammine units. Synthesis and initial DNA-binding studies.
Nicholas P. Farrell, Sergio D. Almeida, Kirsten A. Skov.
J. Am. Chem. Soc., 1988, 110 (15), 5018-5019.
DOI: 10.1021/ja00223a019
[Full Marks JCB]

  • The anticancer drug cisplatin, cis-[PtCl2-(NH3)2], is believed to target DNA, forming a link between two guanine "G" bases and causing a bend or "kink" in the DNA chain. This linkage formation can only be performed using the cis isomer of the compound, meaning the cis-isomer is an antitumor-active drug and the trans-isomer is not.
  • The authors believe that platinum targets a specific regulatory sequence, GGGCGG, in the tumor virus SV40; apparently platinum binds preferentially to guanine "G" bases (as implied in the previous bullet-point). However, binding to DNA may be sequence and conformation specific.
  • This paper discusses a brief synthesis, followed by details of DNA binding, of several bis(platinum) complexes consisting of two cis-diammine complex units linked by hydrocarbon chains of varying lengths, such as [{cis-PtCl2(NH3)}2NH2(CH2)nNH2].
  • Synthesis was completed via a reaction of K-[PtCl3(NH3)] with a diamine such as 1,4-diaminobutane in methanol; substitution occurs cis to the NH3 ligand on the platinum compound. Each final complex has two platinum cis-diammine units present in one molecule, separated by a hydrocarbon backbone.
  • Each complex is a white or off-white solid, poorly soluble in water or alcohols, and soluble in polar solvents.
  • The cis configuration of the chlorides on the platinum atoms was confirmed via IR; geometry and purity were further confirmed via 1H NMR and 195Pt NMR.
  • The authors used an assay to study the DNA-binding of bis-platinum complexes with the inhibition of restriction endonuclease activity in plasmid DNA, and they found that the binding of a molecule at or near the restriction site caused enzyme cleavage to be inhibited.
  • Figure 1 shows the amount of inhibition of bis(platinum) complexes compared to cisplatin, after one hour of incubation. Each complex was tested at various concentrations. To achieve 20% inhibition (which is preferred), n=4 bis(platinum) complex should be at concentration 4.5 micromoles; n=5 bis(platinum) complex should be at concentration 5.3 micromoles; n=6 bis(platinum) complex should be at concentration 7 micromolar; which are all significantly lower concentrations than 12 micromoles for cisplatin to achieve 20% inhibition.
  • Figure 2 shows a time study of inhibition by n=4, n=5, and n=6 bis(platinum) complexes, and cisplatin, each at a concentration of 10 micromoles; DNA binding is most rapid for the n=4 complex.
  • Cleavage caused by binding of cisplatin to DNA is enhanced by the presence of guanine bases close or adjacent to the cutting site.
  • bis(platinum) complexes are the first examples of platinum-chloride complexes with greater DNA affinity than cisplatin; sequences containing three or more subsequent guanine bases may be better targeted by bis(platinum) complexes than by cisplatin.
  • The authors promise detailed biological activity results to follow; followed by acknowledgements.


27November 2010 Saturday
Notes / outline on final project:
[Do you have a working title yet? JCB]
First paper - Slowing of Cisplatin Aquation in the Presence of DNA but Not in the Presence of Phosphate: Improved Understanding of Sequence Selectivity and the Roles of Monoaquated and Diaquated Species in the Binding of Cisplatin to DNA
Inorg. Chem. 2000, 39, 5603-5613
Second paper - Substitution Reactions of Trichloroammineplatinate(I1) Ion and the trans Effect
Inorg. Chem. 1964, 3, 1373-1383
#3 - Cisplatin as a Synthon: Synthesis and Characterization of Triplatinum Complexes Containing Three cis-Pt(amine)2 Linked in a Linear Fashion
Inorg. Chem. 1993, 32, 2591-2593
#4 - Studies on the Antitumor Activity of Group VIII Transition Metal Complexes: Part I: Platinum Complexes
Bioinorg. Chem. 1973, 2, 187-210
#5 - Reaction of Cis- and Trans-[PtCl2( NH3)2] with Reduced Glutathione Inside Human Red Blood Cells, Studied by 1H and 15N-{1H} DEPT NMR
J. Inorg. Biochem. 1990, 38, 327-345
#6 - Bis(platinum) Complexes Containing Two Platinum cis-Diammine Units: Synthesis and Initial DNA-Binding Studies
J. Am. Chem. Soc. 1988, 110, 5018-5019
#7 - Antitumor Platinum Compounds - Relationship Between Structure and Activity
Platinum Metals Rev. 1973, 17, 2-13
#8 - Alfred Werner's Research on the Platinum Metals: A Centennial Retrospect
Platinum Metals Rev. 1997, 41, 34-40


2 December 2010 Thursday week "11"
Final project completed!

MLivingsFinalProject