Supramolecular Anchoring of NCN‐Pincer Palladium Complexes into a β‐Barrel Protein Host: Molecular‐Docking and Reactivity Insights

Abstract

Several prochiral NCN pincer complexes of palladium(II) including hemilabile ligands and a long aliphatic chain were synthesized and characterized spectroscopically. In some of the complexes, the presence of two different substituents on the N donor atoms made them stereogenic so that they were isolated as a mixture of diastereoisomers, which could be differentiated by 1 H NMR. Binding of some of these complexes to bovine b-lactoglobin by insertion within its inner cavity was theoretically investigated by molecular docking simulations and experimentally confirmed by CD spectroscopy.Adjunction of H-bond donor substituents on the ligand framework gave more stable supramolecular protein -complex assemblies. These constructs were shown to catalyze aldol condensation reactions in aqueous medium affording in some cases the less favorable cis-product. Since the corresponding complexes gave exclusively the trans product in the absence of b-lactoglobulin, this unusual diastereoselectivity was ensued by the second sphere of coordination brought by the protein host.2

Artificial Metalloenzymes: From Selective Chemical Transformations to Biochemical Applications

“…Two decades after the reports of metal-free artificial aldolases based on antibodies [ 84 , 85 ], Thorimbert et al introduced the prochiral Pd(II)·NCN-pincer complexes 57a – c into bovine β-lactoglobulin (βLG) by utilizing supramolecular recognition between βLG and a fatty acid ( Figure 11 ) [ 86 ]. A molecular docking simulation predicted that a hydroxy group installed on a substituent of the nitrogen atom of the NCN ligand would be beneficial for a stable supramolecular assembly because of the H -bond interaction between the OH group and the carboxylate of Asp85 in βLG.…”

“… Aldol condensation of tert -butyl isocyanoacetate and pivalaldehyde catalyzed by ArMs containing a palladium center. Adapted from [ 86 ]. …”

Pd-Oxazolone complexes conjugated to an engineered enzyme: improving fluorescence and catalytic properties

“…The conjugation of Pd complexes with proteins and enzymes, generating new types of artificial metalloenzymes, has shown to be an interesting and efficient tool to obtain materials with improved properties such as, among others, better stability, luminescence, catalytic activity and selectivity. [2][3][4][5][6][7][8][9] Additional advantages are based on the applicability of chemical processes in aqueous media, which represents more sustainable conditions for Pd-chemistry.…”

Protein-Pd Complexes Conjugates as Artificial Enzymes

“…This combined with tailor-made Pd organometallics have been successfully applied for the development of a new kind of synthetic artificial enzymes ( Figure 1). [9][10][11][12] In addition, the combination with the protein makes possible to take advantage of the mild enzymatic reaction conditions for performing more sustainable palladium chemistry. Within the methods for the preparation of these artificial Pd enzymes, there are not many examples of such conjugates so far.…”

“…In the preparation of these bioconjugates, the use of a core protein (human serum albumin (HSA), ferritin), the avidin-biotin strategy or, directly, the use of an enzyme with hydrolytic activity transformed into synthetic activity have been employed as synthetic strategies. [9][10][11][12] In addition to the type of anchoring either in a protein without catalytic activity or the use of a cavity with catalytic capability, the metal insertion method has also an important influence.…”