Modeling metallo-oxidoreductase active site dynamics with bis(μ-hydroxo)dicobalt complexes

DeLucia, Alyssa A.

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https://hdl.handle.net/2142/122132 Copy

Description

Title

Modeling metallo-oxidoreductase active site dynamics with bis(μ-hydroxo)dicobalt complexes

Author(s)

DeLucia, Alyssa A.

Issue Date

2023-11-26

Director of Research (if dissertation) or Advisor (if thesis)

Olshansky, Lisa

Doctoral Committee Chair(s)

Olshansky, Lisa

Committee Member(s)

• Gewirth, Andrew
• Fout, Alison
• Vura-Weis, Josh

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Inorganic synthesis
• kinetics
• spectroscopy

Abstract

Nonheme dinuclear metalloenzyme active sites play critical roles in O2 transport, O2 activation, and essential cellular activities. These dinuclear metalloenzymes generally feature bridging oxo/hydroxo ligands within a histidine and carboxylate-rich active site. The carboxylate residues are extremely versatile; they can accommodate a variety of metal ions and oxidation states by changing coordination modes in a low-energy process known as “carboxylate shift”. They take part in hydrogen bonding (H-bonding) interactions that are critical to catalysis and proton-coupled electron transfer processes (PCET). Insights from synthetic model systems can provide opportunities to explore the consequences of intramolecular H-bonds and carboxylate shift reactivity and define the specific ways in which the dynamicity of these ligands can be used in catalysis, as these mechanisms are challenging to observe spectroscopically within enzyme active sites. Herein, [Co2(µ-OH)2(μ-1,3-OAc)(κ-OAc)2(py)4]PF6 ([1H]PF6), (where OAc– = acetate, and py = pyridine) is employed as a tunable structural mimic for nonheme diiron systems to study the structure-function relationship of PCET and carboxylate shift dynamics in those active sites. [1H]PF6 is isolated as the kinetic product in the synthesis of the cobalt tetramer, [Co4(µ3-O)4(μ-1,3-OAc)4(py)4], the thermodynamic sink, from the self-assembly of a cobalt(II) salt, para-R-pyridine, sodium acetate, and an oxidant, in an aqueous solution. To tune the electronic structure of [1H]PF6, the homologous series [1R]PF6 were prepared in which R is the para-substituent of py and R = NMe2, OMe, tBu, Me, H, C(O)Me, CF3, or CN. [1R]PF6 exhibits minimal structural variation by X-ray diffraction (XRD) and FTIR spectroscopy, but their 1H-NMR spectra reveal a linear free energy relationship (LFER) between the chemical shift of the bridging μ-OH and electron-donating capabilities of R. When R = electron-withdrawing, the μ-OH resonance is shifted downfield compared to R = H, versus when R = electron-donating an upfield shift of the μ-OH resonance is observed. Therefore, it was hypothesized that as R is more electron-withdrawing, the O–H bond weakens, and its subsequent pKa decreases. The hypothesis was tested by reacting [1R]PF6 with bases but found that deprotonation caused [1R]PF6 to be unstable and quantitatively converted to the cobalt tetramer [Co4(µ3-O)4(μ-1,3-OAc)4(pyR)4]. Stopped-flow UV-vis kinetics experiments were performed to correlate the rate of reaction of [1R]PF6 (R = CN, H, and OMe) deprotonation to its pKa, revealing a 6,000-fold rate acceleration on going from R = OMe to R = CN. These results demonstrate the drastic effect R has on modulating the μ-OH pKa and how the presence of intramolecular H-bond interactions can maintain stability as the octahedral Co d6 centers become increasingly acidic. [1R]PF6 (R = CN, H, and OMe) cannot be oxidized chemically or electrochemically. Instead, chemical oxidants reacted as Lewis acids due to the high oxidation potential of the complexes. This Lewis acid reactivity leads to decarboxylation assisted by a carboxylate shift mechanism in which a κ-OAc switches to a µ-1,3 bridging mode to form [Co2(µ-OH)2(μ-1,3-OAc)2(pyR)4]2+ ([2R]2+). [2R]2+ is susceptible to solvent binding, affording [Co2(µ-OH)2(μ-1,3-OAc)(κ-OAc)(MeCN)(pyR)4]2+ ([3R]2+) in MeCN. The kinetics of the formation and decay of [1R]PF6, [2R]2+, and [3R]2+ were examined in situ by 1H-NMR spectroscopy to provide a kinetic model that found increasing the electron density at Co increases rate of oxidation of [1R]PF6 but decreases stability of [2R]2+ as it is more susceptible to the degradation pathways. Leveraging robust diamagnetic CoIII complexes, these studies provide mechanistic details of carboxylate shift reactivity and H-bond tuneability which may inform both a deeper understanding of enzyme mechanism, and the potential impact of incorporating ligand dynamicity into synthetic catalyst systems.

Graduation Semester

2023-12

Type of Resource

Thesis

Copyright and License Information

Copyright 2023 Alyssa DeLucia

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