1. Studies on DMSOR. A Theoretical Approach Elizabeth Hernandez-Marin October 2, 2009

2. Introduction  Molybdoenzymes. Generalities  Molybdenum is the only 4d transition metal required for all forms of life.  Generally found as mononuclear active centers.  The metal ion is coordinated by a modified pyranopterin cofactor:  Functionally, they catalyze a net oxygen atom transfer: X + H 2 O = XO + 2H + + 2e - P. Basu, J. F. Stolz, M. T. Smith, Current Science, (2003) 84 1412.

3. Introduction  Molybdoenzymes. Generalities  Can be classified into 3 families represented by xanthine oxidase (XO), sulfite oxidase (SO) and DMSO reductase (DMSOR) P. Basu, J. F. Stolz, M. T. Smith, Current Science, (2003) 84 1412. XO : RCHO → RCOOH SO: SO 3 2- → SO 4 2 DMSOR: (H 3 C) 2 SO → (H 3 C) 2 S

4. Introduction  Reaction catalyzed by DMSOR N. Cobb, et. al, J. Biol. Chem. (2007), 282, 35519 ( CH 3 ) 2 SO + 2H + + 2e - → (CH 3 ) 2 S + H 2 O [Mo IV ] → [Mo VI ] + 2e -

5. Introduction S. Bailey, A. McAlpine, E.M.H. Duke, N. Benson, A. McEwan, Acta Cryst. 1996, D52, 194 A. McAlpine, A. McEwan, S. Bailey J. Mol. Biol 1998, 275, 613

6. -13.2 Mo VI + DMS -12.3 Results  Energy Profile. [Mo(OMe)(S2C2H2)2] - 0 10 20 -10 Kcal/mol  G 298  H 298 Mo IV + DMSO 26.4 9.0 30 28.7 16.6 8.1 23.9

7. Results  Comparison with actual enzyme Process Δ H ≠ kcal/mol Δ G ≠ Kcal/mol Experimental 1 [Mo IV ] + DMSO → M-5.0* M → ESnd13.0 ES → E’ + DMS15.615.0 Calculated[Mo IV ] + DMSO → I9.026.4 I → [Mo IV ] + DMS8.54.8 Kinetics studies 1 : E + DMSO → M → ES → E’ + DMS [Mo(OMe)(S 2 C 2 H 2 ) 2 ] - + DMSO → I → [Mo(OMe)(S 2 C 2 H 2 ) 2 ] - + DMSO * Free energy of formation 1 N. Cobb, T. Conrads, R. Hille J. Biol. Chem. (2005), 280, 3572

8. Results  Comparison with actual enzyme Enzyme: E + DMSO → M → ES → E’ + DMS Calculated: [Mo IV ] + DMSO → I → [Mo VI ] + DMSO Yellow: enzyme. Green: optimized structure.

9. Results  EPR Parameters

10. Results  EPR Parameters g= g e + Δg

11. MoH C ON 107.6° S 2.80 Results  MCD spectra for DMSOR and calculated 1 M. Seth, T. Ziegler and J. Autschbach J. Chem. Phys. (2008), 129, 104105

12. Contributions to C-terms

13. Final Remarks Based on complexes taken from the active site of the molybdoenzyme DMSOR it was possible to: Outline a plausible energy profile for the oxidation of DMSO to DMS by the enzyme. Explain the physical origin of the EPR parameters of the enzymatic Mo[V] species, due to the good agreement between the calculated and experimental parameters. Obtained a detailed account of the contributions that made up the MCD spectrum of the Mo[V]-DMSOR in terms of C- parameters.

14. Computational Details and models  Calculations performed with ADF.  Functional: BP86  Basis set: TZP. Small Core.  Default convergence criteria  Solvation model: COSMO (  =5)

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16. E. Hernandez-Marin, M. Seth, T. Ziegler; Inorg. Chem. (2009) 48, 2880. MCD. Calculation of the C-parameter  Magnetic Circular Dichroism