In this Viewpoint, we address limitations within our current understanding of the complex chemistry of the enzymes in the Nitrogen Cycle. Understanding of these chemical processes plays a key role in limiting anthropogenic effects on our environment.
Nickel-containing
enzymes such as methyl coenzyme M reductase (MCR) and carbon monoxide
dehydrogenase/acetyl coenzyme A synthase (CODH/ACS) play a critical
role in global energy conversion reactions, with significant contributions
to carbon-centered processes. These enzymes are implied to cycle through
a series of nickel-based organometallic intermediates during catalysis,
though identification of these intermediates remains challenging.
In this work, we have developed and characterized a nickel-containing
metalloprotein that models the methyl-bound organometallic intermediates
proposed in the native enzymes. Using a nickel(I)-substituted azurin
mutant, we demonstrate that alkyl binding occurs via nucleophilic
addition of methyl iodide as a methyl donor. The paramagnetic NiIII-CH3 species initially generated can be rapidly
reduced to a high-spin NiII-CH3 species in the
presence of exogenous reducing agent, following a reaction sequence
analogous to that proposed for ACS. These two distinct bioorganometallic
species have been characterized by optical, EPR, XAS, and MCD spectroscopy,
and the overall mechanism describing methyl reactivity with nickel
azurin has been quantitatively modeled using global kinetic simulations.
A comparison between the nickel azurin protein system and existing
ACS model compounds is presented. NiIII-CH3 Az
is only the second example of two-electron addition of methyl iodide
to a NiI center to give an isolable species and the first
to be formed in a biologically relevant system. These results highlight
the divergent reactivity of nickel across the two intermediates, with
implications for likely reaction mechanisms and catalytically relevant
states in the native ACS enzyme.
Coupled dinuclear copper oxygen cores (Cu 2 O 2 ) featured in type III copper proteins (hemocyanin, tyrosinase, catechol oxidase) are vital for O 2 transport and substrate oxidation in many organisms. m-1,2-cis peroxidod icopper cores ( C P)h ave been proposed as key structures in the early stages of O 2 binding in these proteins;their reversible isomerization to other Cu 2 O 2 cores are directly relevant to enzyme function. Despite the relevance of such species to type III copper proteins and the broader interest in the properties and reactivity of bimetallic C P cores in biological and synthetic systems,t he properties and reactivity of C P Cu 2 O 2 species remain largely unexplored. Herein, we report the reversible interconversion of m-1,2-trans peroxido ( T P)a nd C P dicopper cores.C a II mediates this process by reversible binding at the Cu 2 O 2 core,h ighlighting the unique capability for metal-ion binding events to stabilizenovel reactive fragments and control O 2 activation in biomimetic systems.
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