Modelling the Action of the Anti-Cancer Agent Bleomycin & Transition Metal Aspirinate Complexes

You may find the following useful for your coursework.
The first link is to the supplementary pages for Cheng et al (2014) Chem Commun 50 pp 7427-7430.
http://www.rsc.org/suppdata/cc/c4/c4cc00419a/c4cc00419a1.pdf
The next is a paper by Basu et al (2016) Dalton Trans. 45 pp 12992-13004.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987247/pdf/nihms808665.pdf
Instructions:
Complete all the questions by typing in your answer under each one. A single mark penalty of 10% reduction in the final mark will be made if any answers are given in hand writing, or if two files or pdf submission is used.
ASSESSED WORKSHEET 1
Modelling the action of bleomycin – an anti-cancer drug.
This worksheet is related to the lecture on anti-cancer drugs acting on DNA and to the practical information provided on Blackboard. Complete ALL the following questions (a)-(e) using the information provided, by accessing the references given below or in the practical booklet, or by searching the Internet. Give your references, cited in Harvard style, in each case.
Information provided:
In the experiment you used a complex, whose full name is (5-amino-5-methyl-3,7-diazanonanedioate)copper(II), to model the active site of a bleomycin. This complex was made by first reacting copper(II) ions, glycine and nitroethane (i), followed by reduction (ii) of the nitro group, -NO2, to amine, -NH2. Similar reactions can be carried out using other amino acids to produce a series of complexes with the generic structure shown below. In solution, during your experiment, the metal in this model of the active site of a bleomycin, shown right below (R=H), is coordinated to three nitrogen atoms, two oxygen atoms and a water molecule.
(a) How does this model complex damage tumour DNA, and does the type of amino acid used to make this model complex affect its ability to damage DNA? Give your reference.
(b) Crystal field theory describes the bonding between copper atom and the nitrogen and oxygen atoms as electrostatic, and magnetic properties of the complex are assumed to be only dependent upon the number of d electrons at the metal centre. By consultation of any Inorganic Chemistry book or the Internet, and assuming the measured magnetic moments of these model complexes are in the range 1.79-1.88 B.M, do these results support a diamagnetic or paramagnetic metal complex? Give your reference.
(c) What is the proposed role of the carbohydrate domain in bleomycins, and is the composition and position of the disaccharide thought to affect the uptake of bleomycin into cancer cells? (Schroeder et al, J. Am. Chem. Soc. (2014), 136, 13641-13656).
(d) Tallysomycins (TLMs), phleomycoins (PLMs) and zorbamycin (ZBM) are structurally related to the bleomycins (BLMs), and have been synthesised and compared for their DNA cleavage activity. (Huang et al, J. Am. Chem. Soc. (2012), 134, 13501-13509).
What are the structural similarities and differences between these four types of compound and were all the modified BLMs, TLMs, PLMs and ZBM investigated thought to have a common biological effect and level of oxidative DNA damage?
(e) A series of deglycoBLMs have been synthesised using solid phase synthesis, in which the area between the intercalating rings and redox active metal site is constrained (Rishel et al, J. Am. Chem. Soc. (2003), 125, 10194-10205).
What effect, if any, did this structural change have on the oxidative damage to DNA, and on RNA?
ASSESSED PRACTICAL WORKSHEET 2
Transition Metal Aspirinate Complexes
Complete ALL the following questions (a)-(e) by using the information provided, by accessing the references given below or in the practical booklet, or by searching the Internet. Give your references cited Harvard style, where appropriate.
Information provided:
A weight of 2.50 g of copper(II) sulfate pentahydrate and 3.6 g of aspirin were used to make copper aspirinate, [Cu2(asp)4], as given in the practical instruction sheet on Blackboard. A weight of 4.00g Cu2(asp)4 was obtained, and the infrared spectra of this complex and its pyridine (py) product, [Cu(asp)2(py)2], were recorded. The wavenumber positions for carbon to oxygen stretches of these two complexes are given below.
(CO2-) carboxylate:
Cu2(asp)4 = 1,620 and 1,420 cm-1
[Cu(asp)2(py)2] = 1,603 and 1,405 cm-1
(C=O) carbonyl:
Cu2(asp)4 = 1,756, 1724 and 1,614 cm-1
[Cu(asp)2(py)2] = 1,748 and 1,595 cm-1
(a) Give below your calculated theoretical weight expected, and the percentage yield obtained, of copper aspirinate. Show your calculations.
(b) By consideration of theIR stretching frequencies provided above, and those of aspirin, comment below on whether the aspirinate groups in [Cu(asp)2(py)2] are bonded to the metal in monodentate or bidentate form.
(c) Assuming the bonding between copper atom and nitrogen and oxygen atoms in the complexes [Cu2(asp)4] and [Cu(asp)2(py)2] is electrostatic, and magnetic properties of the complex are assumed to be only dependent upon the number of d electrons at the metal centre, if the measured magnetic moment of [Cu2(asp)4] was 1.79 B.M, and of [Cu(asp)2(py)2] was 1.88 B.M., do these results support a diamagnetic or paramagnetic complex in each case? Explain your answer.
(d) Aspirin has been usefully combined with platinum in the anti-cancer drug Asplatin (also known as Platin-A). What is the structure of Platin-A, and how has NMR spectroscopy been used to establish this structure?
(e) How does Platin-A enter human cells, what is thought to occur in the cytosol after Platin-A enters cancerous cells and what are the principal advantages of Platin-A over cis-platin in cancer treatment?

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