Solid-Phase Synthesis of Tris-heteroleptic Ruthenium(II) Complexes and Application to Acetylcholinesterase Inhibition

Abstract

A synthetic route with two consecutive coordination chemistry steps on a solid support affords tris-heteroleptic ruthenium(II) polypyridyl complexes with high purity and in good yields. As an application we report the identification of a nanomolar acetylcholinesterase inhibitor from a small ruthenium complex library synthesized on Lanterns.

The phospha-Michael addition of dimethyl- and diphenylphosphites to the η1-N-maleimidato ligand: Inhibition of serine hydrolases by half-sandwich metallocarbonyl azaphosphonates

“…In this area, several polypyridyl Ru(II) complexes were shown to behave as potent inhibitors of AChE with IC 50 in the submicromolar range [32].…”

Polypyridyl Metal Complexes with Biological Activity

“…enzyme inhibition, antiproliferative properties) of different complexes and isomers obtained accordingly are investigated. [20] For instance, complex 8 (Scheme 2) is able to inhibit acetylcholinesterase (AChE) activity at a submicromolar level with 50-fold more efficiency than the reference complex [Ru(bpy) 3 ]Cl 2 . Such improvement in activity is achieved by functionalizing the periphery of the Ru polypyridyl complex.…”

Organometallics as Structural Scaffolds for Enzyme Inhibitor Design

“…Mulcahy and Meggers recently followed up on this work and identified with the help of solid phase combinatorial coordination chemistry the complex SPM1 to be a nanomolar inhibitor (IC 50 ¼ 200 nM) for AChE from E. electricus (Fig. 1a) [14]. Compared with the parent [Ru(phen) 3 ]Cl 2 (IC 50 ¼ 10 mM), this is an improvement by a factor of around 50-fold, just by modifying the periphery of this ruthenium polypyridine scaffold.…”