Radical Reactions in Biological Systems Created by Rowan Arave and Alexandra Butler Edited by Margaret Hilton Honors Organic Chemistry CHEM 2321 (Sigman), 2013

Radical Organic Chemistry Overview: Free Radicals are atoms without a full set of valence electrons. This causes the outer electron shell to be ‘open’, and thus, more reactive. Radical reactions take place in a series of three steps: initiation, propagation, and termination. Mechanism Initiation Propagation Termination Wiki Page: http://en.wikipedia.org/wiki/Radical_(chemistry)

Radical Organic Chemistry Overview: Free Radicals are atoms without a full set of valence electrons. This causes the outer electron shell to be ‘open’, and thus, more reactive. Radical reactions take place in a series of three steps: initiation, propagation, and termination. Early Examples Moses Gomberg discovered the first free radical, a Triphenyl Methyl Radical, in 1900. Friedrich Paneth pioneered free radical decomposition in organic compounds. In 1929 he discovered the free methyl radical. Wiki Page: http://en.wikipedia.org/wiki/Radical_(chemistry)

Synthesis and Repair of DNA The reduction of ribonucleotides to deoxyribonucleotides (RNA  DNA) is the result of a radical reaction. Ribonucleotide reductase (RNR) is an enzyme that helps to catalyze this transformation. The reduction of RNA to DNA is the rate limiting step in synthesis of DNA. Therefore, this reaction plays a large part in cell growth and maintenance. M. Kolbergr et al. / Biochimica et Biophysica Acta 1699 (2004) 1–34

Problems 1. Lipid peroxidation occurs due to oxidative stress. Polyunsaturated fatty acids and sterols undergo radical chain oxidation to complete this process. Draw an arrow-pushing mechanism for the following reaction of triphenylmethyl radical with molecular oxygen. 2. The trityl radical is in equilibrium with an unsymmetrical dimer (note: not Ph3C-CPh3). Propose a mechanism for the formation of this unsymmetrical dimer. 3. BHT (butylated hydroxy toluene) is a synthetic anti-oxidant that interrupts radical chain reactions. Propose a mechanism for how this could occur and predict the resulting products. (Hint: think resonance) BHT 1.The Journal of Organic Chemistry DOI: 10.1021/jo4001433 2. Modern physical organic chemistry 3. Smith pg. 557

Contributed by: Created by Rowan Arave and Alexandra Butler (Undergraduates) Edited by Margaret Hilton Honors Organic Chemistry CHEM 2321 (Sigman), University of Utah 2013