Enzyme Design from the Bottom Up: An Active Nickel Electrocatalyst with a Structured Peptide Outer Coordination Sphere

Abstract

Catalytic, peptide-containing metal complexes with a well-defined peptide structure have the potential to enhance molecular catalysts through an enzyme-like outer coordination sphere. Here, we report the synthesis and characterization of an active, peptide-based metal complex built upon the well-characterized hydrogen production catalyst [Ni(P(Ph)2N(Ph))2](2+) (P(Ph)2N(Ph)=1,3,6-triphenyl-1-aza-3,6-diphosphacycloheptane). The incorporated peptide maintains its β-hairpin structure when appended to the metal core, and the electrocatalytic activity of the peptide-based metal complex (≈100,000 s(-1)) is enhanced compared to the parent complex ([Ni(P(Ph)2N(APPA))2](2+); ≈50,500 s(-1)). The combination of an active molecular catalyst with a structured peptide provides a scaffold that permits the incorporation of features of an enzyme-like outer-coordination sphere necessary to create molecular electrocatalysts with enhanced functionality.

Artificial hydrogenase: biomimetic approaches controlling active molecular catalysts

“…The dipeptide-based outer sphere was found to significantly improve the rate constant of H 2 production relative to that of the parent Ni complex without the dipeptides [43,44]. The Ni complex containing the larger peptide with a stable structure was also studied to investigate the effect of limited motion of the outer sphere peptides [45]. The Ni core of [Ni(P 2 Ph N R 0 ) 2 ] 2+ was linked to four peptides that fold as a rigid b-hairpin structure (Figure 3d, 19).…”

Investigating the role of chain and linker length on the catalytic activity of an H2 production catalyst containing a β-hairpin peptide

“…link the phenyl ring to the peptide (figure 1). Both ligands and Ni II -parent complexes were prepared following previously reported procedures [27,31,32]. The ligands were isolated as white powders containing the meso-and rac-isomers and the Ni II -parent complexes were isolated as red to orange crystalline products containing the nickel bound only to the meso isomer [31].…”

“…In the seminal work reported for this complex, R10 largely maintained its structure within the Prop-R10 complex and improved the catalytic current relative to the parent complex (Prop) demonstrating the impact of the outer coordination sphere on electrochemical hydrogen production [27]. However, the propionic acid linker allows a great deal of structural flexibility of the peptide relative to the catalyst core, limiting the R10 peptide from creating a precisely positioned outer coordination sphere around the active site.…”

“…Due to the enhanced performance of the enzymes compared to synthetic catalysts, several research groups have focused on incorporating features of the enzyme scaffold into molecular mimics to achieve the enhanced activity, specificity, selectivity, and stability observed in enzymes [5][6][7][8][9][10][11][12][13]. For hydrogenase mimics, several approaches have been undertaken to introduce features found in the outer coordination spheres of enzymes, from using viscous media and binding to resin beads [14][15][16], to attaching solubilized polymers [17][18][19] and amino acids/peptides [20][21][22][23][24][25][26][27][28]. A peptide-based outer coordination sphere allows for the emulation of a minimal biomimetic scaffold around the active site that has the potential to offer all of the advantages of the enzyme framework; an essential step is to synthetically incorporate structured peptides around the active molecular catalysts.…”

“…These complexes have a well-understood first coordination sphere, making them ideal platforms on which to test the influence of a peptide-based outer coordination sphere on catalytic reactivity. We recently reported the incorporation of a β-hairpin peptide (R10) onto [Ni(P Ph 2 N Prop ) 2 ] 2+ (Prop) to produce [Ni(P Ph 2 N Prop-R10 ) 2 ] 2+ (Prop-R10), where Prop = para-phenylpropionic acid and R10 = WIpPRWTGPR-NH 2 (p = D-proline) [27]. This β-hairpin peptide is an ideal peptide motif because it has a very stable secondary structure and the primary sequence can be readily modified to examine different features of the outer coordination sphere [29,30].…”