Reagan Hooper

All Publications

• Mixed Valence {Ni2+Ni1+} Clusters as Models of Acetyl Coenzyme A Synthase Intermediates. Journal of the American Chemical Society Wilson, D. W., Thompson, B. C., Collauto, A., Hooper, R. X., Knapp, C. E., Roessler, M. M., Musgrave, R. A. 2024

  Abstract

  Acetyl coenzyme A synthase (ACS) catalyzes the formation and deconstruction of the key biological metabolite, acetyl coenzyme A (acetyl-CoA). The active site of ACS features a {NiNi} cluster bridged to a [Fe4S4]n+ cubane known as the A-cluster. The mechanism by which the A-cluster functions is debated, with few model complexes able to replicate the oxidation states, coordination features, or reactivity proposed in the catalytic cycle. In this work, we isolate the first bimetallic models of two hypothesized intermediates on the paramagnetic pathway of the ACS function. The heteroligated {Ni2+Ni1+} cluster, [K(12-crown-4)2][1], effectively replicates the coordination number and oxidation state of the proposed "Ared" state of the A-cluster. Addition of carbon monoxide to [1]- allows for isolation of a dinuclear {Ni2+Ni1+(CO)} complex, [K(12-crown-2)n][2] (n = 1-2), which bears similarity to the "ANiFeC" enzyme intermediate. Structural and electronic properties of each cluster are elucidated by X-ray diffraction, nuclear magnetic resonance, cyclic voltammetry, and UV/vis and electron paramagnetic resonance spectroscopies, which are supplemented by density functional theory (DFT) calculations. Calculations indicate that the pseudo-T-shaped geometry of the three-coordinate nickel in [1]- is more stable than the Y-conformation by 22 kcal mol-1, and that binding of CO to Ni1+ is barrierless and exergonic by 6 kcal mol-1. UV/vis absorption spectroscopy on [2]- in conjunction with time-dependent DFT calculations indicates that the square-planar nickel site is involved in electron transfer to the CO pi*-orbital. Further, we demonstrate that [2]- promotes thioester synthesis in a reaction analogous to the production of acetyl coenzyme A by ACS.

  View details for DOI 10.1021/jacs.4c06241

  View details for PubMedID 39023163

• Iron(iv) alkyl complexes: electronic structure contributions to Fe-C bond homolysis and migration reactions that form N-C bonds from N2. Chemical science Bhutto, S. M., Hooper, R. X., McWilliams, S. F., Mercado, B. Q., Holland, P. L. 2024; 15 (10): 3485-3494

  Abstract

  High-valent iron alkyl complexes are rare, as they are prone to Fe-C bond homolysis. Here, we describe an unusual way to access formally iron(iv) alkyl complexes through double silylation of iron(i) alkyl dinitrogen complexes to form an NNSi2 group. Spectroscopically validated computations show that the disilylehydrazido(2-) ligand stabilizes the formal iron(iv) oxidation state through a strongly covalent Fe-N π-interaction, in which one π-bond fits an "inverted field" description. This means that the two bonding electrons are localized more on the metal than the ligand, and thus an iron(ii) resonance structure is a significant contributor, similar to the previously-reported phenyl analogue. However, in contrast to the phenyl complex which has an S = 1 ground state, the ground state of the alkyl complex is S = 2, which places one electron in the π* orbital, leading to longer and weaker Fe-N bonds. The reactivity of these hydrazido(2-) complexes is dependent on the steric and electronic properties of the specific alkyl group. When the alkyl group is the bulky trimethylsilylmethyl, the formally iron(iv) species is stable at room temperature and no migration of the alkyl ligand is observed. However, the analogous complex with the smaller methyl ligand does indeed undergo migration of the carbon-based ligand to the NNSi2 group to form a new N-C bond. This migration is followed by isomerization of the hydrazido ligand, and the product exists as two isomers that have distinct η1 and η2 binding of the hydrazido group. Lastly, when the alkyl group is benzyl, the Fe-C bond homolyzes to give a three-coordinate hydrazido(2-) complex which is likely due to the greater stability of a benzyl radical compared to that for methyl or trimethylsilylmethyl. These studies demonstrate the availability of a hydrocarbyl migration pathway at formally iron(iv) centers to form new N-C bonds directly to N2, though product selectivity is highly dependent on the identity of the migrating group.

  View details for DOI 10.1039/d3sc05939a

  View details for PubMedID 38455018

  View details for PubMedCentralID PMC10915813

• Evaluating Diazene to N2 Interconversion at Iron-Sulfur Complexes. Chemistry (Weinheim an der Bergstrasse, Germany) Hooper, R. X., Wertz, A. E., Shafaat, H. S., Holland, P. L. 2024: e202304072

  Abstract

  Biological N2 reduction occurs at sulfur-rich multiiron sites, and an interesting potential pathway is concerted double reduction/protonation of bridging N2 through PCET. Here, we test the feasibility of using synthetic sulfur-supported diiron complexes to mimic this pathway. Oxidative proton transfer from μ-η1:η1-diazene (HN=NH) is the microscopic reverse of the proposed N2 fixation pathway, revealing the energetics of the process. Previously, Sellmann assigned the purple metastable product from two-electron oxidation of [{Fe2+(PPr3)L1}2(μ-η1:η1-N2H2)] (L1 = tetradentate SSSS ligand) at -78 °C as [{Fe2+(PPr3)L1}2(μ-η1:η1-N2)]2+, which would come from double PCET from diazene to sulfur atoms of the supporting ligands. Using resonance Raman, Mössbauer, NMR, and EPR spectroscopies in conjunction with DFT calculations, we show that the product is not an N2 complex. Instead, the data are most consistent with the spectroscopically observed species being the mononuclear iron(III) diazene complex [{Fe(PPr3)L1}(η2-N2H2)]+. Calculations indicate that the proposed double PCET has a barrier that is too high for proton transfer at the reaction temperature, and is so exergonic that it would be irreversible as a result of the high Fe3+/2+ redox potential. This system establishes the "ground rules" for designing reversible N2/N2H2 interconversion through PCET, such as tuning the redox potentials of the metal sites.

  View details for DOI 10.1002/chem.202304072

  View details for PubMedID 38376370

• Desulfurization and N2 Binding at an Iron Complex Derived from the C-S Activation of Benzothiophene. Organometallics Hooper, R. X., Mercado, B. Q., Holland, P. L. 2023; 42 (15): 2019-2027

  Abstract

  Metal insertion into the C-S bonds of thiophenes is a facile route to interesting polydentate ligand scaffolds with C and S donors. Here, we describe iron-mediated C-S activation of a diphenylphosphine-functionalized benzothiophene proligand. Metalation of the proligand with "tetrakis(trimethylphosphine)iron" gives an initial five-coordinate, diamagnetic iron(II) species with two PMe3 ligands and a dianionic PCS pincer ligand. Upon one-electron reduction, a reactive anionic iron(I) complex is formed. This species then undergoes deep-seated changes, notably cleavage of C-S and C-P bonds in the supporting ligand. Substantial coordination sphere alterations accompany the ligand C-S bond activation, including loss of a sulfur anion from the S-Fe-C metallacycle and reorganization of the two PMe3 ligands. The resulting desulfurized six-coordinate PCC iron complex also has an N2 ligand trans to the vinyl C. Reducing this complex then cleaves a C-P bond in the appended diphenylphosphine, giving a phosphido arm. These ligand transformations demonstrate novel approaches to pincers with thiolates and phosphides, which would be difficult to synthesize using typical methods through free ligand salts.

  View details for DOI 10.1021/acs.organomet.3c00220

  View details for PubMedID 38282963

  View details for PubMedCentralID PMC10810089

• Engineering Band Gap and Photoconduction in Semiconducting Metal Organic Frameworks: Metal Node Effect JOURNAL OF PHYSICAL CHEMISTRY LETTERS Nyakuchena, J., Ostresh, S., Neu, J., Streater, D., Cody, C., Hooper, R., Zhang, X., Reinhart, B., Brudvig, G. W., Huang, J. 2023; 14 (26): 5960-5965

  Abstract

  We report a systematic study on the correlation of the metal nodes in M-THQ conducting MOFs (M = Fe, Ni, Cu, and Zn; THQ = tetra-hydroxybenzoquinone) with their structure, photophysical property, and photoconductivity. We found that the structural preference in these MOFs is controlled by metal node identity where Cu prefers a square planar coordination which leads to a 2D Kagome-type structure. Fe, Ni, and Zn prefer an octahedral sphere which leads to a 3D structure. Fe-THQ has the smallest band gap and highest photoconduction as well as a long-lived ligand-to-metal charge transfer state due to the mixed valence state revealed by time-resolved optical and X-ray absorption and terahertz spectroscopy. These results demonstrate the importance of the metal node in tuning the photophysical and photocatalytic properties of MOFs.

  View details for DOI 10.1021/acs.jpclett.3c00499

  View details for Web of Science ID 001013708100001

  View details for PubMedID 37345878

• Mechanism of Nitrogen-Carbon Bond Formation from Iron(IV) Disilylhydrazido Intermediates during N2 Reduction JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Bhutto, S. M., Hooper, R. X., Mercado, B. Q., Holland, P. L. 2023: 4626-4637

  Abstract

  We recently reported a reaction sequence that activates C-H bonds in simple arenes as well as the N-N triple bond in N2, delivering the aryl group to N2 to form a new N-C bond (Nature 2020, 584, 221). This enables the transformation of abundant feedstocks (arenes and N2) into N-containing organic compounds. The key N-C bond forming step occurs upon partial silylation of N2. However, the pathway through which reduction, silylation, and migration occurred was unknown. Here, we describe synthetic, structural, magnetic, spectroscopic, kinetic, and computational studies that elucidate the steps of this transformation. N2 must be silylated twice at the distal N atom before aryl migration can occur, and sequential silyl radical and silyl cation addition is a kinetically competent pathway to a formally iron(IV)-NN(SiMe3)2 intermediate that can be isolated at low temperature. Kinetic studies show its first-order conversion to the migrated product, and DFT calculations indicate a concerted transition state for migration. The electronic structure of the formally iron(IV) intermediate is examined using DFT and CASSCF calculations, which reveal contributions from iron(II) and iron(III) resonance forms with oxidized NNSi2 ligands. The depletion of electron density from the Fe-coordinated N atom makes it electrophilic enough to accept the incoming aryl group. This new pathway for the N-C bond formation offers a method for functionalizing N2 using organometallic chemistry.

  View details for DOI 10.1021/jacs.2c12382

  View details for Web of Science ID 000937489900001

  View details for PubMedID 36794981

• Cobalt-Carbon Bonding in a Salen-Supported Cobalt(IV) Alkyl Complex Postulated in Oxidative MHAT Catalysis JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Wilson, C., Kim, D., Sharma, A., Hooper, R. X., Poli, R., Hoffman, B. M., Holland, P. L. 2022; 144 (23): 10361-10367

  Abstract

  The catalytic hydrofunctionalization of alkenes through radical-polar crossover metal hydrogen atom transfer (MHAT) offers a mild pathway for the introduction of functional groups in sterically congested environments. For M = Co, this reaction is often proposed to proceed through secondary alkylcobalt(IV) intermediates, which have not been characterized unambiguously. Here, we characterize a metastable (salen)Co(isopropyl) cation, which is capable of forming C-O bonds with alcohols as proposed in the catalytic reaction. Electron nuclear double resonance (ENDOR) spectroscopy of this formally cobalt(IV) species establishes the presence of the cobalt-carbon bond, and accompanying DFT calculations indicate that the unpaired electron is localized on the cobalt center. Both experimental and computational studies show that the cobalt(IV)-carbon bond is stronger than the analogous bond in its cobalt(III) analogue, which is opposite of the usual oxidation state trend of bond energies. This phenomenon is attributable to an inverted ligand field that gives the bond Coδ--Cδ+ character and explains its electrophilic reactivity at the alkyl group. The inverted Co-C bond polarity also stabilizes the formally cobalt(IV) alkyl complex so that it is accessible at unusually low potentials. Even another cobalt(III) complex, [(salen)CoIII]+, is capable of oxidizing (salen)CoIII(iPr) to the formally cobalt(IV) state. These results give insight into the electronic structure, energetics, and reactivity of a key reactive intermediate in oxidative MHAT catalysis.

  View details for DOI 10.1021/jacs.2c02128

  View details for Web of Science ID 000812451100001

  View details for PubMedID 35657101

  View details for PubMedCentralID PMC9206546

• Iron Complexes of a Proton-Responsive SCS Pincer Ligand with a Sensitive Electronic Structure INORGANIC CHEMISTRY Skubi, K. L., Hooper, R. X., Mercado, B. Q., Bollmeyer, M. M., MacMillan, S. N., Lancaster, K. M., Holland, P. L. 2022; 61 (3): 1644-1658

  Abstract

  Sulfur/carbon/sulfur pincer ligands have an interesting combination of strong-field and weak-field donors, a coordination environment that is also present in the nitrogenase active site. Here, we explore the electronic structures of iron(II) and iron(III) complexes with such a pincer ligand, bearing a monodentate phosphine, thiolate S donor, amide N donor, ammonia, or CO. The ligand scaffold features a proton-responsive thioamide site, and the protonation state of the ligand greatly influences the reduction potential of iron in the phosphine complex. The N-H bond dissociation free energy, derived from the Bordwell equation, is 56 ± 2 kcal/mol. Electron paramagnetic resonance (EPR) spectroscopy and superconducting quantum interference device (SQUID) magnetometry measurements show that the iron(III) complexes with S and N as the fourth donors have an intermediate spin (S = 3/2) ground state with a large zero field splitting, and X-ray absorption spectra show a high Fe-S covalency. The Mössbauer spectrum changes drastically with the position of a nearby alkali metal cation in the iron(III) amido complex, and density functional theory calculations explain this phenomenon through a change between having the doubly occupied orbital as dz2 or dyz, as the former is more influenced by the nearby positive charge.

  View details for DOI 10.1021/acs.inorgchem.1c03499

  View details for Web of Science ID 000742137200001

  View details for PubMedID 34986307

  View details for PubMedCentralID PMC8792349

• Assignment of Infrared-Active Combination Bands in the Vibrational Spectra of Protonated Molecular Clusters Using Driven Classical Trajectories: Application to N4H+ and N4D+ JOURNAL OF PHYSICAL CHEMISTRY A Hooper, R., Boutwell, D., Kaledin, M. 2019; 123 (26): 5613-5620

  Abstract

  We investigate the utility of the driven molecular dynamics (DMD) approach to complex molecular vibrations by applying it to linear clusters with several degenerate vibrational modes and infrared (IR) intense combination bands. Here, the prominent features in N4H+ and N4D+ IR spectra, reported and described by others previously, have been characterized for the first time by DMD using recently published high-level potential and dipole moment surfaces. Namely, the calculations closely correlate the parallel proton stretch vibration in N4H+, at 750 cm-1, with the one observed experimentally at 743 cm-1. Second, the intense IR-active combination bands found in experimental spectra within 900-1100 cm-1 have been properly recovered by DMD at 950 cm-1 as strongly IR-active and confirmed as consisting of H+ asymmetric stretch and N2···N2 intermolecular symmetric stretch modes. Furthermore, we show that certain combination bands involving overtone transitions may be recovered by DMD using a hard-driving regime, such as the 1409 cm-1 band measured in N4H+, revealed by DMD at 1375 cm-1, and assigned to a progressive combination of the parallel H+ stretch and two quanta of N2···N2 stretch, in agreement with quantum mechanical studies reported previously by others.

  View details for DOI 10.1021/acs.jpca.9b04480

  View details for Web of Science ID 000474796100020

  View details for PubMedID 31244119

• A stable Cerberus tris(maloNHC) and its coinage metal complexes CHEMICAL COMMUNICATIONS Hooper, R., Mason, A., Montgomery, M., Clinebell, B., Gaynor, R., McMillen, C., Tapu, D. 2019; 55 (42): 5942-5945

  Abstract

  The first trisanionic Cerberus-type maloNHC has been generated and coordinated to two different coinage metals (Au(i) and Ag(i)). The resulting triszwitterionic metal complexes have been characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. The molecular structures of the new metal complexes reveal an average AuAu and AgAg separation of 20.89 and 21.03 Å respectively, the longest distances reported to date for any related Cerberus-type NHCs.

  View details for DOI 10.1039/c9cc01892a

  View details for Web of Science ID 000468478100021

  View details for PubMedID 31049493