IMCN thesis defence - MU Xiao


December 09, 2020


Histidine Brace Containing Ligand Scaffolds for Developing Biomimetics of Lytic Polysaccharide Monooxygenases

Promotors : Professeur Olivier Riant (UCLouvain) & Professeur Michael Singleton (UCLouvain)

Defense only organized by teleconference and publicly accessible by the link 

Abstract :

Lytic polysaccharide monooxygenases (LPMOs) have attracted considerable attention due to their ability to enhance enzymatic degradation of recalcitrant polysaccharide biomass via an oxidative cleavage mechanism. The active site of LPMOs contains a copper ion in a T-shaped N3 coordination environment known as the histidine brace motif. Beyond this, the role of certain first and second coordination sphere features is unclear from the biological studies. Understanding the factors that contribute to the high oxidative capabilities of the enzyme can facilitate the design of future catalysts for biomass conversion. The aim of this research is the design and synthesis of new model complexes of the LPMO active site, specifically the histidine brace.

First, four small molecule ligands containing two imidazole groups connected by an aliphatic amide linker were designed and synthesized successfully. The amide ligands were used to coordinate with CuCl2 to form the Cu(II) complexes in the presence of Et3N as base. The UV-Vis spectrophotometric titration, Job’s plot analysis and MS data suggest that the stoichiometries between CuCl2 and the ligands in MeOH and H2O were 1:1. The FTIR data indicate the participation of the amide for Cu(II) coordination, and the ligand could provide the N3 coordination environment to copper.

In the second part, the use of conformationally stable and predictable folded aromatic oligoamides as ligand scaffolds can represent a powerful tool to design first and second coordination spheres. Based on this idea, two scaffold ligands, containing imidazole/histamine functionalized quinoline units and diazaanthracene were designed and synthesized successfully. The UV-vis spectra of the reaction of Cu(II) salts with scaffold ligands suggest that the scaffolds do coordinate a Cu(II) center. However, additional structural studies are needed to validate the exact coordination environment of Cu and see if it matches with the active site of LPMO.