DOI: 10.1002/chem.201002042 Structure and Reactivity of the Cysteine Methyl Ester Radical Cation Sandra Osburn, [a] Jeffrey D. Steill, [b] Jos Oomens, [b] Richard A. J. OHair,* [c] Michael van Stipdonk, [d] and Victor Ryzhov* [a] Introduction Protein radicals exhibit dual “personalities”. As “Dr. Jeckyl”, they are well behaved and play key roles in enzyme sites where they are utilized to transform substrates by taking advantage of radical chemistry. [1] Some key classes of radicals found in enzyme sites are shown in Scheme 1 and include the following: a) the glycyl radical found in class III ribonucleotide reductase ; [2a] b) the tyrosyl radical involved in class I ribonucleotide reductase; [2b] c) the tryptophyl radi- cal cation found in cytochrome oxidase; [2c] and d) the cys- teinyl radical involved in pyruvate formate lyase . [2d] As “Mr. Hyde”, protein radicals wreak havoc in oxidative damage, [3] which can lead to oxidation of side chains; forma- tion of reactive groups (e.g., HOOR); fragmentation; cross- Abstract: The structure and reactivity of the cysteine methyl ester radical cation, CysOMe . + , have been exam- ined in the gas phase using a combina- tion of experiment and density func- tional theory (DFT) calculations. CysOMe . + undergoes rapid ion–mole- cule reactions with dimethyl disulfide, allyl bromide, and allyl iodide, but is unreactive towards allyl chloride. These reactions proceed by radical atom or group transfer and are consis- tent with CysOMe . + possessing struc- ture 1, in which the radical site is locat- ed on the sulfur atom and the amino group is protonated. This contrasts with DFT calculations that predict a captodative structure 2, in which the radical site is positioned on the a carbon and the carbonyl group is pro- tonated, and that is more stable than 1 by 13.0 kJ mol 1 . To resolve this appar- ent discrepancy the gas-phase IR spec- trum of CysOMe . + was experimentally determined and compared with the theoretically predicted IR spectra of a range of isomers. An excellent match was obtained for 1. DFT calculations highlight that although 1 is thermody- namically less stable than 2, it is kineti- cally stable with respect to rearrange- ment. Keywords: cysteine · density func- tional calculations · gas-phase chemistry · IR spectroscopy · radical ions [a] S. Osburn, Prof. V. Ryzhov Department of Chemistry and Biochemistry Northern Illinois University, Dekalb, Illinois (USA) and Center for Biochemical and Biophysical Studies Northern Illinois University, Dekalb, Illinois (USA) Fax: (+ 01) 815-753-4802 E-mail : ryzhov@niu.edu [b] Dr. J.D. Steill, Prof. J. Oomens FOM Institute for Plasma Physics Nieuwegein (The Netherlands) and University of Amsterdam Amsterdam (The Netherlands) [c] Prof. R. A. J. O)Hair School of Chemistry, The University of Melbourne Mebourne, Victoria 3010 (Australia) and Bio21 Institute of Molecular Science and Biotechnology The University of Melbourne, Melbourne, Victoria 3010, (Australia) and ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, Melbourne, Victoria 3010 (Australia) Fax: (+ 61) 393-475-180 E-mail: rohair@unimelb.edu.au [d] Prof. M. van Stipdonk Department of Chemistry, Wichita State University Wichita, Kansas (USA) Scheme 1. Some key radicals involved in enzymes: a) a-glycyl radical found in class III ribonucleotide reductase; [2a] b) tyrosyl radical involved in class I ribonucleotide reductase; [2b] c) tryptophyl radical cation found in cytochrome oxidase; [2c] d) cysteinyl radical involved in pyruvate for- mate lyase. [2d] Chem. Eur. J. 2011, 17, 873 – 879 # 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 873 FULL PAPER