Metallopeptide Based Mimics with Substituted Histidines Approximate a Key Hydrogen Bonding Network in the Metalloenzyme Nickel Superoxide Dismutase
Nickel superoxide dismutase (NiSOD) is a recently discovered superoxide dismutase that utilizes the Ni{sup III}/Ni{sup II} couple to facilitate the disproportionation of O{sub 2}{sup {sm_bullet}-} into H{sub 2}O{sub 2} and O{sub 2}. A key structural component of NiSOD is an elongated axial His-imidazole Ni{sup III} bond (2.3-2.6 {angstrom}) that is the result of a H-bonding network between His(1), Glu(17), and Arg(47). Herein we utilize metallopeptide based mimics of NiSOD with His(1) {var_epsilon}-nitrogen substituted imidazoles to approximate the electronic influence of this H-bonding network ({l_brace}Ni{sup III/II}(SOD{sup M1}-Im-X){r_brace} X = Me, H, DNP, and Tos; SOD{sup M1}-Im-X = H{prime}CDLPCGVYDPA where H{prime} is an N-substituted His). All reduced {l_brace}Ni{sup II}(SOD{sup M1}-Im-X){r_brace} are similar to one another as assessed by electronic absorption spectroscopy, circular dichroism (CD) spectroscopy, and Ni K-edge x-ray absorption (XAS). This indicates that the change in His(1) is having little influence on the square-planar Ni{sup II}N{sub 2}S{sub 2} center. In contrast, changes to the axial His(1) ligand impart differential spectroscopic properties on the oxidized {l_brace}Ni{sup III}(SOD{sup M1}-Im-X){r_brace} metallopeptides. Resonance Raman spectroscopy (405 nm excitation) in conjunction with a normal coordinate analysis indicates that as the axial His imidazole is made less Lewis basic there is an increase in Ni{sup III}-S bond strength in the equatorial plane, with force constants for the Ni-S bond trans to the amine ranging from 1.54 to 1.70 mdyn {angstrom}{sup -1}. The rhombic electron paramagnetic resonance (EPR) spectra of the four oxidized metallopeptides are all consistent with low-spin Ni{sup III} contained in a square pyramidal coordination environment, but show changes in the hyperfine coupling to {sup 14}N along g{sub z}. This is attributable to a reorientation of the g{sub z} vector in the more (along the Ni{sup III}-N{sup imidazole} bond) versus less (along the S-Ni{sup III}-N{sup amine} bond) Lewis basic imidazole bases. This reorientation of g{sub z} along the xy plane translates into a decrease in A{sub zz} by {approx}20 MHz. A decrease in Lewis-basicity of the axial imidazole also translates into a 2 orders of magnitude increase in SOD catalysis across the metallopeptide series, with k{sub cat} ranging from 6(1) x 10{sup 6} M{sup -1} s{sup -1} for the metallopeptide with the most Lewis basic imidazole to 6(2) x 10{sup 8} M{sup -1} s{sup -1} for the metallopeptide with the least basic imidazole. This likely results from a fine-tuning of the electron transfer properties of the Ni-center, which optimize it for SOD catalysis.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- DOE - OFFICE OF SCIENCE
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 1019912
- Report Number(s):
- BNL-95758-2011-JA; INOCAJ; TRN: US201115%%548
- Journal Information:
- Inorganic Chemistry, Vol. 48, Issue 22; ISSN 0020-1669
- Country of Publication:
- United States
- Language:
- English
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