A Beginner’s Guide to Thermodynamic Modelling of [FeFe] Hydrogenase

James A Birrell,Adrian Hery-Barranco,Patricia Rodríguez-Maciá

doi:10.3390/catal11020238

Abstract

[FeFe] hydrogenases, which are considered the most active naturally occurring catalysts for hydrogen oxidation and proton reduction, are extensively studied as models to learn the important features for efficient H2 conversion catalysis. Using infrared spectroscopy as a selective probe, the redox behaviour of the active site H-cluster is routinely modelled with thermodynamic schemes based on the Nernst equation for determining thermodynamic parameters, such as redox midpoint potentials and pKa values. Here, the thermodynamic models usually applied to [FeFe] hydrogenases are introduced and discussed in a pedagogic fashion and their applicability to additional metalloenzymes and molecular catalysts is also addressed.

Highlights

Hydrogen is considered as a possible fuel for the future due to its high energy density and efficient combustion that produces only water as a waste product [1]
While it may not be possible to apply the same exact models described here for studying [FeFe] hydrogenases, we are certain that building a thermodynamic picture of events in nitrogenases and other complex metalloenzymes will contribute to our understanding of their mechanism
We have tried to provide a foundation in building thermodynamic models and we have reviewed how this model has been applied to experimental data to extract important thermodynamic parameters, hopefully dispelling the notion that these are somehow overly complex and inaccessible

Summary

Introduction

Hydrogen is considered as a possible fuel for the future due to its high energy density and efficient combustion that produces only water as a waste product [1]. [FeFe] hydrogenases have an intriguing active site named the H-cluster (for H2 converting cluster, Figure 1A,B), which is composed of a canonical [4Fe-4S] cluster, tightly ligated to the protein through the thiolate groups of four cysteine amino acids [17,18] One of these thiolates bridges to a unique diiron subcluster, which is decorated with a terminal cyanide (CN− ) and carbon monoxide (CO) ligand on each iron as well as a CO and a 2-azapropane-1,3-dithiolate (ADT) ligand bridging the two iron ions [19]. The protein environment forces an open coordination site on the iron furthest from the [4Fe-4S] cluster This low valent Fe site behaves as a Lewis acid, while the nitrogen bridgehead atom of the dithiolate ligand behaves as a base, which protonates around neutral pH. For those who are interested, all the models presented in this review are available as a supplementary spreadsheet Models.xlsx from the MDPI website

The Basics

Proton Coupled Electron Transfer

Redox Anticooperativity Model

Discussion

Conclusions