About

Jonathan Rittle is a Professor of Chemistry at the University of California, Berkeley, with a research focus on inorganic chemistry and chemical biology. His work applies structure and spectroscopy to understand and enhance the reactivity of metalloenzymes and transition metal clusters, which are crucial for processes such as oxygen activation, hydrocarbon transformation, and pollutant detoxification. His research aims to develop powerful and selective synthetic catalysts utilizing multiple transition metal ions and to inspire new therapeutic strategies. Rittle's lab employs synthetic chemistry, structural biology, and spectroscopic methods to elucidate the molecular and electronic structures of reactive polynuclear fragments, with particular interest in diiron enzymes that convert alkanes into alcohols or alkenes/alkynes, and in designing modular ligand frameworks for the development of cluster compounds supporting redox and protonation states. His long-term goal is to understand and manipulate these biological and chemical processes to advance society through innovative catalysis and biocatalysis.

Research topics

• Chemistry
• Stereochemistry
• Organic chemistry
• Biochemistry
• Crystallography
• Computational chemistry
• Aerospace engineering
• Photochemistry
• Inorganic chemistry

Selected publications

• The Factors Governing Metal Dependence of an Emergent Superfamily of Bimetallic Oxygenases

  Journal of the American Chemical Society · 2026-04-23

  articleOpen accessSenior author

  the metal preference for the majority of reported ARO sequences. These annotations were validated via the characterization of multiple new AROs, including ones implicated in key oxidative steps of natural product biosyntheses. This study establishes the key structure-function relationships governing metal preferences in AROs and highlights their vastly underappreciated role in myriad biological processes.

  PublisherOA PDFDOI

• Isocyanide Activation by Phosphinimide-Ligated Cr(II) Centers

  Organometallics · 2025-10-23

  articleSenior authorCorresponding

  This report describes the synthesis and reactivity of the heteroleptic phosphinimide/phosphinimine Cr(II) complex HL′CrAdHMDS, which was obtained by incomplete protonolysis of Cr(HMDS)2(THF)2 in the presence of the bisphosphinimine pro-ligand H2L′Ad. Addition of common ligands such as N-heterocyclic carbenes and isocyanides displaces the remaining HMDS ligand concomitant with complete deprotonation of the phosphinimine pro-ligand furnishing three- and four-coordinated complexes, respectively. The resulting tetrahedral chromium(II) bis(isocyanide) species was found to adopt an unusual S = 1 spin state at room temperature. Under certain reaction conditions, one coordinated isocyanide ligand was found to insert into a chromium-phosphinimide bond. The described compounds are characterized by single-crystal X-ray diffraction and solution-phase spectroscopy, and the mechanism for isocyanide insertion was investigated by DFT calculations.

  PublisherDOI

• O ₂ Activation and Enzymatic C–H Bond Activation Mediated by a Dimanganese Cofactor

  Journal of the American Chemical Society · 2025-01-01 · 6 citations

  articleOpen accessSenior authorCorresponding

  Dioxygen (O2) is a potent oxidant used by aerobic organisms for energy transduction and critical biosynthetic processes. Numerous metalloenzymes harness O2 to mediate C–H bond hydroxylation reactions, but most commonly feature iron or copper ions in their active site cofactors. In contrast, many manganese-activated enzymes─such as glutamine synthetase and isocitrate lyase─perform redox neutral chemical transformations and very few are known to activate O2 or C–H bonds. Here, we report that the dimanganese-metalated form of the cambialistic monooxygenase SfbO (Mn2–SfbO) can efficiently mediate enzymatic C–H bond hydroxylation. The activity of the dimanganese form of SfbO toward substrate hydroxylation is comparable to that of its heterobimetallic Mn/Fe form but exhibits distinct kinetic profiles. Kinetic, spectroscopic, and structural studies invoke a mixed-valent dimanganese cofactor (MnIIMnIII) in O2 activation and evidence a stoichiometric role for superoxide in maturing an O2-inert MnII2 cofactor. Computational studies support a hypothesis wherein superoxide addition to the MnII2 cofactor installs a critical bridging hydroxide ligand that stabilizes higher-valent manganese oxidation states. These findings establish the viability of proteinaceous dimanganese cofactors in mediating complex, multistep redox transformations.

  PublisherOA PDFDOI

• <i>In Crystallo</i> O ₂ Cleavage at a Preorganized Triiron Cluster

  Journal of the American Chemical Society · 2024-12-24 · 5 citations

  articleOpen accessSenior authorCorresponding

  In Nature, the four-electron reduction of O2 is catalyzed at preorganized multimetallic active sites. These complex active sites often feature low-coordinate, redox-active metal centers precisely positioned to facilitate rapid O2 activation processes that obviate the generation of toxic, partially reduced oxygen species. Very few biomimetic constructs simultaneously recapitulate the complexity and reactivity of these biological cofactors. Herein, we report solid-state O2 activation at a triiron(II) active site templated by phosphinimide ligands. Insight into the structure of the O2 reduction intermediates was obtained via in crystallo O2 dosing experiments in conjunction with spectroscopic, structural, magnetic, and computational studies. These data support the in situ formation of an Fe2IIIFeIV-dioxo intermediate upon exposure to O2 that participates in oxygen atom and hydrogen atom transfer reactivity with exogenous substrates to furnish a stable FeIIFe2III-oxo species. Combined, these studies provide an extraordinary level of detail into the dynamics of bond-forming and -breaking processes operative at complex multimetallic active sites.

  PublisherOA PDFDOI

• In Crystallo O2 Cleavage at a Preorganized Triiron Cluster

  ChemRxiv · 2024-09-27

  preprintSenior author

  In Nature, the four-electron reduction of O2 is catalyzed at preorganized multimetallic active sites. These complex active sites often feature low-coordinate, redox-active metal centers precisely positioned to facilitate rapid O2 activation processes that obviate the generation of toxic, partially-reduced oxygen species. Very few biomimetic constructs simultaneously recapitu-late the complexity and reactivity of these biological cofactors. Herein, we report solid-state O2 activation at a triiron(II) active site templated by phosphinimide ligands. Insight into the structure of the O2 reduction intermediates was obtained via in crystallo O2 dosing experiments in conjunction with spectroscopic, structural, magnetic, and computational studies. These data support the in situ formation of an Fe2IIIFeIV-dioxo intermediate upon O2 exposure that participates in oxygen atom and hydrogen atom transfer reactivity with exogenous substrates to furnish a stable FeIIFe2III-oxo species. Combined, these stud-ies provide an extraordinary level of detail into the dynamics of bond forming and breaking processes operative at complex multimetallic active sites.

  PublisherDOI

• Bioinformatic Discovery of a Cambialistic Monooxygenase

  Journal of the American Chemical Society · 2024-01-10 · 14 citations

  articleOpen accessSenior authorCorresponding

  Dinuclear monooxygenases mediate challenging C–H bond oxidation reactions throughout nature. Many of these enzymes are presumed to exclusively utilize diiron cofactors. Herein we report the bioinformatic discovery of an orphan dinuclear monooxygenase that preferentially utilizes a heterobimetallic manganese–iron (Mn/Fe) cofactor to mediate an O2-dependent C–H bond hydroxylation reaction. Unlike the structurally similar Mn/Fe-dependent monooxygenase AibH2, the diiron form of this enzyme (SfbO) exhibits a nascent enzymatic activity. This behavior raises the possibility that many other dinuclear monooxygenases may be endowed with the capacity to harness cofactors with a variable metal content.

  PublisherOA PDFDOI

• O2 Activation and Enzymatic C-H Bond Activation Mediated by a Dimanganese Cofactor

  ChemRxiv · 2024-07-08

  preprintOpen accessSenior author

  Dioxygen (O2) is a potent oxidant used by aerobic organisms for energy transduction and critical biosynthetic processes. Numerous metallocofactors, which most commonly feature iron or copper ions, harness O2 to mediate C-H bond hydroxylation reactions. In contrast, most manganese-dependent enzymes are redox-inert and infrequently activate O2 or C-H bonds. Here we report that the dimanganese-metalated form of the cambialistic monooxygenase SfbO (Mn2-SfbO) can efficiently mediate enzymatic C-H bond hydroxylation. Kinetic, spectroscopic and structural studies invoke a mixed-valent dimanganese cofactor (Mn2II/III) in catalytic O2 activation. Access to this redox form requires stoichiometric superoxide to mature a Mn2II cofactor to higher-valent forms that participate in catalysis. These findings establish the viability of proteinaceous dimanganese cofactors in mediating complex, multistep redox transformations.

  PublisherDOI

• Multielectron Bond Cleavage Processes Enabled by Redox-Responsive Phosphinimide Ligands

  ChemRxiv · 2023-07-17 · 4 citations

  preprintOpen accessSenior author

  The activation of small molecules via multi-electron redox processes offers promise in mediating difficult transformations related to energy conversion processes. While molecular systems that engage in one- and two-electron redox processes are widespread, those that participate in the direct transfer of four or more electrons to small molecules are very rare. To that end, we report a mononuclear chromium(II) complex competent for the 4-electron reduction of dioxygen (O2) and nitrosoarenes. These systems additionally engage in facile two-electron group transfer reactivity including O-atom excision and nitrene transfer. Structural, spectroscopic and computational studies support bond activation processes that intimately occur at a mononuclear chromium(phosphinimide) center and highlight an unusual structural responsiveness of the phosphinimides in stabilizing a range of metal redox states.

  PublisherOA PDFDOI

• Four‐Electron Oxidative Addition of an N=N Double Bond at a Chromium Metallocyclopropene**

  Angewandte Chemie International Edition · 2023-09-01 · 5 citations

  articleOpen accessSenior authorCorresponding

  This report describes the synthesis of a pseudo-tetrahedral chromium alkyne complex supported by a bidentate phosphinimide ligand and its reactivity with an azobenzene derivative. Characterization of the former by structural and computational methods reveals an unprecedented extent of alkyne activation by a formal chromium(II) center, suggesting that this complex is best described as a chromium(IV)-metallocyclopropene. Exposure of this compound to 4,4'-difluoroazobenzene results in the formation of a chromium(VI) diimido complex, which constitutes a rare 4-electron oxidative addition of an N=N double bond. The isolation of a chromium(IV)-hydrazido intermediate enabled mechanistic investigations of this challenging bond cleavage process. This work substantiates the notion that terminal phosphinimide ligands can engender first-row transition metal ions with exceptional reactivity.

  PublisherOA PDFDOI

• Four‐Electron Oxidative Addition of an N=N Double Bond at a Chromium Metallocyclopropene**

  Angewandte Chemie · 2023-09-01 · 1 citations

  articleOpen accessSenior authorCorresponding

  Abstract This report describes the synthesis of a pseudo‐tetrahedral chromium alkyne complex supported by a bidentate phosphinimide ligand and its reactivity with an azobenzene derivative. Characterization of the former by structural and computational methods reveals an unprecedented extent of alkyne activation by a formal chromium(II) center, suggesting that this complex is best described as a chromium(IV)‐metallocyclopropene. Exposure of this compound to 4,4′‐difluoroazobenzene results in the formation of a chromium(VI) diimido complex, which constitutes a rare 4‐electron oxidative addition of an N=N double bond. The isolation of a chromium(IV)‐hydrazido intermediate enabled mechanistic investigations of this challenging bond cleavage process. This work substantiates the notion that terminal phosphinimide ligands can engender first‐row transition metal ions with exceptional reactivity.

  PublisherOA PDFDOI

Recent grants

• Preparation of Artificial Dicopper Enzymes for the Catalytic Reduction of CO2

  NIH · $102k · 2016–2019

Frequent coauthors

• Jonas C. Peters

  74 shared

• Theodor Agapie

  California Institute of Technology

  17 shared

• Heui Beom Lee

  University of California, Berkeley

  17 shared

• Charles Winslow

  University of California, Berkeley

  16 shared

• Gaël Ung

  University of Connecticut

  14 shared

• Guy Bertrand

  University of California, San Diego

  14 shared

• Paul Rathke

  13 shared

• R. David Britt

  University of California, Davis

  10 shared

Education

• Doctor of Philosophy, Chemistry

  California Institute of Technology

  2016

• Bachelor of Science, Chemistry

  Pennsylvania State University

  2010

Awards & honors

• Herbert Newby McCoy Award (2016)
• NSF Predoctoral Fellow (2011-2014)
• Caltech CEMI Predoctoral Fellow (2014-2015)
• NIH Postdoctoral Fellow, University of California San Diego…