Sign in
BiochemistryJournal of the American Chemical Society
Peer-reviewed journal article

Highly Stable Mn(V)-Nitrido and Nitrogen-Atom Transfer Reactivity within a De Novo Protein

Jithin Thomas, Sudha YadaviD, Paul H. OyalaiD, Veronica CartaiD, Alec H. FollmeriD, David Philip GoldbergiD, Samuel I. ManniD

Abstract

High-valent metal-nitrido species are powerful nitrogen-atom transfer intermediates but remain difficult to access and control due to intrinsic instability and bimolecular N-N coupling pathways. Herein, we report the first formation of a high-valent Mn(V)-nitrido complex within a de novo designed protein scaffold and demonstrate that a reactive precursor to this species can be catalytically intercepted for enantioselective aziridination. A Mn(V){equiv}N unit derived from an abiological diphenyl porphyrin is confined within a designed helical bundle protein, where the protein environment suppresses bimolecular decay and enables detailed spectroscopic characterization. Electron paramagnetic resonance, resonance Raman, and circular dichroism spectroscopies confirm formation of a low-spin Mn(V)-nitrido species that is stable for weeks at room temperature and exhibits minimal perturbation of the Mn{equiv}N unit upon modulation of the axial histidine ligand, while catalytic activity and stereochemical outcome are sensitive to its presence. Mechanistic studies identify monochloramine (NH2Cl) as the operative nitrogen-atom donor and support the involvement of a transient Mn-bound N-transfer intermediate en route to nitrido formation. Under catalytic conditions, this intermediate is inter-cepted to perform aziridination with TON {approx} 180 and an enantiomeric ratio of 65:35. Together, these results establish de novo protein design as a platform for stabilizing high-valent metal-nitrido species and harnessing their reactivity for nitrogen-atom transfer chemistry beyond the limits of natural metalloenzymes and small-molecule catalysts.

PDFDOI

02 /Specification & Classification

Click any tag to browse matching papers
Citations
1
FWCI
1.30
Field percentile
top 18%

Reproducibility ledger

Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.

Sign in to file a reproducibility report.

Similarity Map
SelectedSame fieldCross-field
THISMellor '26Kenney '25Higgins '25Mann '25Rutledge '22Shan '26
60% semantic matchBiochemistry
Cam Mellor, Christopher Williams, Ethan L. Bungay+9 more·bioRxiv·Jun 9, 2026