Bipyridines as Mediating Artificial Cofactors to replace NAD(P)H

In the quest for a sustainable and eco-friendly future, enzymatic catalysis has emerged as a pivotal platform, steering chemical synthesis towards environmentally benign pathways.

The use of natural cofactors such as NADH (nicotinamide adenine dinucleotide, reduced) and NADPH (nicotinamide adenine dinucleotide phosphate, reduced) has been instrumental in these processes, providing essential reducing equivalents for numerous enzymatic transformations.

In the production of valuable chemicals and pharmaceuticals via biocatalysis, NAD(P)H is utilized by various enzymes.NAD(P)H-dependent processes play a key role in pharmaceutical industry and the environment (reducing CO2 emissions), in the production of valuable fuels and chiral active pharmaceutical ingredients (APIs).While NAD(P)H is effective as a cofactor, it presents several issues that limit its practicality and sustainability mainly due to high cost of cofactor, high process costs due to lack of recyclability and complex downstream processing.

The central idea of BPYMAC is to leverage the advantages of bipyridines as ideal mediating artificial cofactors (MACs) to replace NAD(P)H due to their synthetic versatility, recyclability, tunability and stability.

Synthetic strategies enable their conversion to redox polymer enabling their application as polymer films on electrodes, allowing their use in reactors with facile product separation. This will be the end goal of BPYMAC, meeting significant gaps in the state of the art.

BPYMAC's research outcomes will help revolutionise bioelectrocatalyis by targeting synthesis of valuable products from CO2 reduction and production of chiral APIs in a reactor consisting of polymeric MAC and enzyme, optimised to produce products in high yield and with high stereoselectivity.

These reactions will provide proof-of-concept for the potential of BPYMAC's tailored MACs as NAD(P)H replacements for reactions of interest for industry, society and the scientific community.