About

Dr. David Goldberg's research focuses on employing synthetic inorganic chemistry to answer fundamental questions regarding structure, spectroscopy, and reactivity pertinent to bioinorganic chemistry. His work involves understanding how transition metal ions in enzymes catalyze critical reactions related to energy utilization, biosynthetic pathways, natural defense systems, and cell signaling. The Goldberg laboratory aims to determine the fundamental principles that control this chemistry, including the key bond-making and bond-breaking steps at the metal center that enable these reactions. His research includes the synthesis of novel mononuclear Fe and Mn complexes that mimic features of both heme- and non-heme metal centers in biology, such as high-valent metal-oxo and metal-peroxo complexes relevant to oxygenases and other metalloenzymes. The lab employs ligand design and organic chemistry tools to tune the coordination sphere around the metal center, controlling reactivity and establishing structure-function relationships. Techniques such as inorganic spectroscopic methods—including EPR, Mössbauer, resonance Raman, and X-ray absorption spectroscopies—are integral to his work, often in collaboration with experts. Computational studies, including DFT, are routinely used to guide and inform the research.

Research topics

• Photochemistry
• Medicinal chemistry
• Chemistry
• Organic chemistry
• Stereochemistry
• Computational chemistry

Selected publications

• Highly Stable Mn(V)-Nitrido and Nitrogen-Atom Transfer Reactivity within a <i>De Novo</i> Protein

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-25

  articleOpen access

  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)≡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≡N unit upon modulation of the axial histidine ligand, while catalytic activity and stereochemical outcome are sensitive to its presence. Mechanistic studies identify monochloramine (NH 2 Cl) 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 ≈ 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.

  PublisherOA PDFDOI

• A Dinuclear Iron(II) Persulfide Complex Reacts with O ₂ to Give Sulfite: Relevance to Persulfide Dioxygenases

  Journal of the American Chemical Society · 2026-03-12

  articleSenior authorCorresponding

  Persulfides (RSSH) have been proposed as key players in biochemical transformations that often involve iron, including iron–sulfur cluster assembly, H2S regulation, post translational modifications, and mitochondrial sulfur oxidation. An example of the latter is found in the O2-mediated oxidation of glutathione persulfide to sulfite dianion (SO32–) catalyzed by ETHE1, a nonheme iron persulfide dioxygenase (PDO). The iron-mediated mechanism of persulfide oxidation by PDOs remains poorly understood, and there are no synthetic analogues to date. Herein, we report the synthesis, characterization, and O2 reactivity of a rare iron(II)-alkylpersulfide complex. The adamantyl persulfide anion (AdSS-) was isolated and characterized by X-ray diffraction as a complex with potassium 18-crown-6 [K(18-crown-6)][AdSS], and employed in the synthesis of a new dinuclear iron(II) complex, [(FeII(Me3TACN))2(μ2-SSAd)3][OTf] (1). Complex 1 was characterized by single crystal X-ray diffraction (XRD), UV–vis, 1H/19F NMR, and 57Fe Mössbauer spectroscopy. Reaction of 1 with O2 in CH3CN affords a diiron(III) oxo-bridged complex [(FeIII(Me3TACN))2(μ-O)(μ2-SO4)(μ2-SO3Ad)][OTf] (2) identified by XRD, and SO32– (∼0.5 equiv per Fe2). Isotopic labeling studies using 18O2 and H218O, supported by control experiments and ESI-MS analysis, indicate that SO32– production proceeds via an iron-centered S-oxygenation mechanism similar to that proposed for persulfide dioxygenases.

  PublisherDOI

• US Supreme Court clarifies the scope of ‘defendant’s profits’ in trade mark matters in <i>Dewberry Grp, Inc v Dewberry Eng’rs Inc</i>, No. 23-900, 604 US 145 S Ct 681, slip op (26 February 2025)

  Journal of Intellectual Property Law & Practice · 2025-03-30

  article
  PublisherDOI

• Manipulation of Valence Trapping through Local Order of Fe₃O Units in an Intrinsically Mixed-Valence Coordination Polymer

  Inorganic Chemistry · 2025-05-16 · 3 citations

  articleOpen access

  Mixed-valence coordination polymers (CPs) can exhibit enhanced and tunable conductivity and stimulus-driven phase transitions, making them promising new electronic materials. However, the mechanisms of the electron transfer processes that underlie these properties in the solid state merit further study. Here, we report the synthesis of a new mixed-valence CP, FeIII2FeIIO(OAc)6(bpy)2 (OAc = acetate, bpy = 4,4’-bipyridine), which is obtained from the self-assembly of Fe3O(OAc)6 clusters and bpy linkers. Notably, the CP is charge-neutral in its mixed-valence form, making it one of the few established intrinsically mixed-valence CPs. Detailed characterization of the valence and spin states of the constituent Fe ions in the CP via variable-temperature Mössbauer spectroscopy, single-crystal X-ray diffraction, and magnetic susceptibility measurements reveals the occurrence of thermally activated electron transfer (i.e., valence detrapping) and antiferromagnetic exchange between FeII and FeIII ions. Intriguingly, valence-detrapping phenomena are confined to distinct regions of the CP and proceed to varying degrees of completion depending on the solid-state environment of the participating Fe ions. This study presents a convenient strategy for the direct synthesis of intrinsically mixed-valence coordination polymers and highlights the important role of solid-state structural order in manipulating electron transfer mechanisms in Class II Robin-Day mixed-valence materials.

  PublisherOA PDFDOI

• 61656 READY-4: Long-term safety with repeated injections using RelabotulinumtoxinA, a novel liquid formulation botulinum toxin, in the treatment of glabellar and lateral canthal lines

  Journal of the American Academy of Dermatology · 2025-09-01 · 2 citations

  article
  PublisherDOI

• Examining Pseudohalide (N3, NCS, NCO) Coordination in Nonheme Fe(II) and Fe(III) Complexes

  Journal of Inorganic Biochemistry · 2025-10-15 · 2 citations

  articleSenior authorCorresponding
  PublisherDOI

• Electronic Modification of a Reduced Mononuclear Nonheme Iron Nitrosyl Complex Leads to HNO Release

  Journal of the American Chemical Society · 2025-07-28 · 1 citations

  articleOpen accessSenior authorCorresponding

  A new pentadentate-fluorinated N4S(thiolate) ligand was synthesized. Reaction with Fe(BF4)2·6H2O gives a new thioether complex, [FeII(CH3CN)(N3PypFSEtCN)][BF4]2 (1), and on-metal deprotection gives the thiolate complex, [FeII(CH3CN)(N3PypFS)][BF4] (2). Reaction of 2 with NO forms a low-spin ground state (S = 1/2) {FeNO}7 complex (3). Chemical reduction of 3 with cobaltocene gives a metastable intermediate spin S = 1 {FeNO}8 complex (4). Protonation of 4 releases nitroxyl (HNO), as observed by ESI-MS and 31P NMR trapping experiments with PPh3. Complexes 1 and 2 were characterized by single-crystal X-ray crystallography, complexes 2–4 were characterized by EPR and FT-IR spectroscopies, and all iron complexes were characterized by 19F NMR, UV–vis, and 57Fe Mössbauer spectroscopies. These results show that a nonheme iron complex can generate and release HNO, suggesting that nonheme iron centers could be endogenous or exogenous sources of HNO in biological systems. Additionally, the fluorine-substituted N4S(thiolate) ligand provides a unique spectroscopic handle to monitor the reactivity of the iron center several bonds away from the fluorine substituent.

  PublisherOA PDFDOI

• Axial Ligation Impedes Proton-Coupled Electron-Transfer Reactivity of a Synthetic Compound-I Analogue

  Journal of the American Chemical Society · 2024-04-26 · 17 citations

  articleOpen accessSenior authorCorresponding

  The nature of the axial ligand in high-valent iron-oxo heme enzyme intermediates and related synthetic catalysts is a critical structural element for controlling proton-coupled electron-transfer (PCET) reactivity of these species. Herein, we describe the generation and characterization of three new 6-coordinate, iron(IV)-oxo porphyrinoid-π-cation-radical complexes and report their PCET reactivity together with a previously published 5-coordinate analogue, FeIV(O)(TBP8Cz+•) (TBP8Cz = octakis(p-tert-butylphenyl)corrolazinato3–) (2) (Cho, K. A high-valent iron-oxo corrolazine activates C–H bonds via hydrogen-atom transfer. J. Am. Chem. Soc. 2012, 134, 7392–7399). The new complexes FeIV(O)(TBP8Cz+•)(L) (L = 1-methyl imidazole (1-MeIm) (4a), 4-dimethylaminopyridine (DMAP) (4b), cyanide (CN–)(4c)) can be generated from either oxidation of the ferric precursors or by addition of L to the Compound-I (Cpd-I) analogue at low temperatures. These complexes were characterized by UV–vis, electron paramagnetic resonance (EPR), and Mössbauer spectroscopies, and cryospray ionization mass spectrometry (CSI-MS). Kinetic studies using 4-OMe-TEMPOH as a test substrate indicate that coordination of a sixth axial ligand dramatically lowers the PCET reactivity of the Cpd-I analogue (rates up to 7000 times slower). Extensive density functional theory (DFT) calculations together with the experimental data show that the trend in reactivity with the axial ligands does not correlate with the thermodynamic driving force for these reactions or the calculated strengths of the O–H bonds being formed in the FeIV(O–H) products, pointing to non-Bell–Evans–Polanyi behavior. However, the PCET reactivity does follow a trend with the bracketed reduction potential of Cpd-I analogues and calculated electron affinities. The combined data suggest a concerted mechanism (a concerted proton electron transfer (CPET)) and an asynchronous movement of the electron/proton pair in the transition state.

  PublisherOA PDFDOI

• Influence of the second coordination sphere on O2 activation by a nonheme iron(II) thiolate complex

  Journal of Inorganic Biochemistry · 2024-11-17 · 5 citations

  articleOpen accessSenior authorCorresponding
  PublisherOA PDFDOI

• A Nonheme Iron(III) Superoxide Complex Leads to Sulfur Oxygenation

  Journal of the American Chemical Society · 2024-03-15 · 18 citations

  articleOpen accessSenior authorCorresponding

  A new alkylthiolate-ligated nonheme iron complex, FeII(BNPAMe2S)Br (1), is reported. Reaction of 1 with O2 at −40 °C, or reaction of the ferric form with O2•– at −80 °C, gives a rare iron(III)-superoxide intermediate, [FeIII(O2)(BNPAMe2S)]+ (2), characterized by UV–vis, 57Fe Mössbauer, ATR-FTIR, EPR, and CSIMS. Metastable 2 then converts to an S-oxygenated FeII(sulfinate) product via a sequential O atom transfer mechanism involving an iron-sulfenate intermediate. These results provide evidence for the feasibility of proposed intermediates in thiol dioxygenases.

  PublisherOA PDFDOI

Recent grants

• New Vistas in Porphyrinoid Chemistry: Corrolazine Synthesis and Reactivity

  NSF · $400k · 2006–2009

• New Vistas in Porphyrinoid Chemistry: Corrolazine Synthesis and Reactivity

  NSF · $170k · 2012–2013

• Synthetic Nonheme Iron O2 Activation and S-Oxygenation

  NIH · $3.2M · 2016–2025

• Heme and Nonheme Transition Metal Complexes, Reactivity, and Mechanism

  NIH · $1.6M · 2023–2028

• Reactivity of Manganese and Iron Metalloenzyme Models

  NIH · $3.4M · 2013–2025

Frequent coauthors

• Maxime A. Siegler

  163 shared

• Joshua Telser

  Roosevelt University

  97 shared

• Arnold L. Rheingold

  University of California, San Diego

  89 shared

• J. Krzystek

  National High Magnetic Field Laboratory

  80 shared

• Bobby Ramdhanie

  Johns Hopkins University

  78 shared

• Lev N. Zakharov

  Oregon State University

  63 shared

• Pierre Moënne‐Loccoz

  Oregon Health & Science University

  56 shared

• Brian M. Hoffman

  Northwestern University

  52 shared