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.
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.
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.
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).
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?
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?