Supporting Information for: Structure and Stability Studies of. Pharmacologically Relevant S-nitrosothiols: A Theoretical.

Transcription

1 Supporting Information for: Structure and Stability Studies of Pharmacologically Relevant S-nitrosothiols: A Theoretical Approach Benjamin Meyer (1,2), Alessandro Genoni (1,2) *, Ariane Boudier (3), Pierre Leroy (3)*, Manuel F. Ruiz-Lopez (1,2) * (1) CNRS, Laboratoire SRSMC, UMR 7565, Vandoeuvre-lès-Nancy, F-54506, France. (2) Université de Lorraine, Laboratoire SRSMC, UMR 7565, Vandoeuvre-lès-Nancy, F , France. (3) Université de Lorraine, Laboratoire CITHÉFOR, EA 3452, Nancy, F-54001, France. * Correspondence to: - Alessandro Genoni, CNRS and Université de Lorraine, Laboratoire SRSMC - UMR 7565, Boulevard des Aiguillettes, BP 70239, Vandoeuvre-lès-Nancy, France. Alessandro.Genoni@univ-lorraine.fr; Phone : +33 (0) ; Fax: +33 (0) Manuel F. Ruiz-Lopez, CNRS and Université de Lorraine, Laboratoire SRSMC - UMR 7565, Boulevard des Aiguillettes, BP 70239, Vandoeuvre-lès-Nancy, France. Manuel.Ruiz@univ-lorraine.fr; Phone : +33 (0) ; Fax: +33 (0) S1

2 Details of the NCI calculations. As already mentioned in the main text of the paper, in this study we have performed Non-Covalent Interactions (NCI) analyses 1,2 on the most stable syn and anti conformers about the S-NO bond, both for SNAP and NACNO. To accomplish this task we have carried out NCI calculations exploiting the software NCIPLOT-3.0 1,2 and using electron densities resulting from B3PW91/6-311+G(d,p) calculations. In particular, at first, we have preformed preliminary NCI computations with the following options: a) a default cubic grid with a minimum distance of ±2 Å from the outermost x, y, z coordinates, b) default increment of 0.1 atomic units (a.u.) along the x, y, z directions, c) cutoff interval for the electron density set to [-0.2 a.u., 0.2 a.u.] and d) cutoff for the reduced-gradient s(r) equal to 2.0 a.u.. These calculations allowed us to obtain two-dimensional graphs in which the reduced-gradient s(r) is plotted in function of the electron density ρ(r) previously multiplied by the sign of second eigenvalue (λ 2 ) of the electron density Hessian matrix (Figures S1 and S2). Since the resulting graphs have shown the presence of non-covalent interactions (namely, peaks in the [-0.05 a.u., 0.05 a.u.] electron density range) for all the conformers taken into account, we have afterwards carried further NCI computations that have enabled to better characterize the different interactions through the visualization of the corresponding reducedgradient isosurfaces (see Figures 3 and 4 of the paper). For these second-level NCI calculations, we have adopted the same default cubic grid and increment of the preliminary computations, but with a narrower electron density cutoff interval (i.e., [-0.05 a.u., 0.05 a.u.]) and a reduced-gradient cutoff set equal to 0.35 a.u. (values associated with the isosurfaces plotted in Figures 3 and 4 of the main text). S2

3 Figure S1. Reduced density gradient in function of the electron density multiplied by the sign of the second Hessian eigenvalue for (A) the most stable anti-syn (peptide bond-sno conformations) conformer of SNAP, (B) the most stable anti-anti conformer of SNAP, (C) the most stable anti-syn conformer of NACNO and (D) the most stable anti-anti conformer of NACNO. Both the reduced gradients and the electron densities are reported in a.u.. S3

4 Figure S2. Reduced density gradient in function of the electron density multiplied by the sign of the second Hessian eigenvalue for the most stable conformers of the denitrosated (A) SNAP and (B) NACNO radicals. Both the reduced gradients and the electron densities are reported in a.u.. S4

5 Table S1. Free energies of solvation (assuming the 1 atm 1 M solvation process, values in kcal mol -1 ) and solvation effects on the S-NO dissociation processes of SNAP and NACNO at K. The free energies in gas phase have been estimated with the geometries optimized in solution (ZPE and thermal contributions to solvation energies are neglected). The computed solvation free energy for the NO radical is +1.2 kcal mol -1 (1 atm 1 M solvation process) ΔG solv (RSNO) ΔG solv (RS ) ΔG solv (RS ) + ΔG solv (NO ) - ΔG solv (RSNO) - RT ln(24.46) NACNO SNAP References for the Supporting Information: 1. Johnson, E. R.; Keinan, S.; Mori-Sánchez, P.; Contreras-García, J.; Cohen, A. J.; Yang, W. Revealing Noncovalent Interactions. J. Am. Chem. Soc. 2010, 132, Contreras-García, J.; Johnson, E. R.; Keinan, S.; Chaudret, R.; Piquemal, J.-P.; Beratan, D. N.; Yang, W. NCIPLOT: A Program for Plotting Noncovalent Interaction Regions. J. Chem. Theory Comput. 2011, 7, S5