Access Type

Open Access Dissertation

Date of Award

January 2023

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Chemistry

First Advisor

Stanislav Groysman

Abstract

Nature provides a useful guideline for the design of an efficient earth-abundant catalyst for CO oxidation that relies on bimodal heterobimetallic cooperativity. Molybdenum-copper carbon monoxide dehydrogenase (Mo-Cu CODH) is an enzyme of the xanthine oxidoreductase family that catalyzes reversible oxidation of CO; it is inhibited by cyanide CN- and inserts isocyanide CNR between Cu and O/S. The active site contains molybdenum(VI) in a square pyramidal configuration with apical oxo and basal dithiolene, oxo, and sulfide ligands. The two-coordinate Cu(I) is coordinated by cysteinate and Mo-sulfide to form Mo-S-Cu bridge.While several groups have reported structural models of the active site of Mo-Cu CODH, none of the models were able to demonstrate reactivity with CO or isocyanide. We believe that the lack of reactivity in the prior models can be attributed to model instability in the absence of the supporting protein environment. We hypothesize that the inherent instability of the active site model can be remedied by the application of the robust heterodinucleating ligand which would hold the metals together. My dissertation focuses on the development of structural and functional models of the Mo-Cu CODH active site on a xanthene-based heterodinucleating ligand platform to serve as structural and functional models of Mo-Cu CODH. Specific objectives of my research include: (1) design and synthesis of xanthene-based heterodinucleating ligands capable of selective coordination of an early and a late metal; (2) synthesis and characterization of the respective Mo(VI)/Cu(I) complexes with these ligands, and the study of their biomimetic reactivity with CO, CNR, and other relevant substrates; and (3) synthesis and investigation of CO oxidation by heterobimetallic compelxes containing with [M0(CO)3] (M = Mo, Cr) fixed in the proximity of [MoVIO3] . A significant part of my work focused on synthesis of two new heterodinucleating ligands. The synthesis of dipyridylamine ligand (L2H2) involved initial protection of one of the amine sites by tert-butyloxycarbonyl (BOC), followed by double alkylation of the unprotected site, deprotection, and imine formation. L2H2 was isolated in a 28% overall yield. This new heterodinucleating ligand (L2H2) features two different chelating sites, bis(pyridyl) amine for soft low-oxidation-state transition metals and catecholate for hard high-oxidation-state transition metals bridged by a xanthene linker. Similarly, pyridylamine ligand (L3H2) can be synthesized by the methylation of the unprotected amine, followed by imine formation; this ligand was isolated in 38% overall yield. The L3H2 retains the catecholate site for chelating hard high-oxidation-state early transition metals, but its soft site has been modified to a pyridylamine site. Next, we investigated the reactivity of dipyridylamine ligand with Cu(I) and Mo(VI) precursors, as well as conducting studies pertaining to the functional modeling of Mo-Cu CODH activity. The reaction of L2H2 with [Cu(NCMe)4]+ led to the tetradentate coordination of Cu(I) via all nitrogen donors of the ligand, including the imine. Cu(I) complex was characterized by multinuclear NMR spectroscopy, high-resolution mass spectrometry (HRMS), X-ray crystallography, and DFT calculations. The reaction of the Cu(I) complex with a variety of monodentate ligands X (Cl-, SCN-, CN-) released the metal from coordination to the imine. The release of the imine from metal coordination is facilitated by the formation of the hydrogen bond with nearby catechol proton. The second catechol proton engages in H-bonding with Cu-X (X = Cl, CN, SCN), which can be intermolecular (XRD) or intramolecular (DFT). The protonolysis reaction of LH2 with molybdate [MoO4]2- led to insertion of [MoVIO3] at the catecholate position, producing [MoO3(L)]2-. Similarly, the reaction of [Cu(LH2)]+ with [MoO4]2- formed the heterodinuclear [CuMoO3(L)]- complex. The desired heterobimetallic complex was characterized by multinuclear NMR, UV-vis, and HRMS. HRMS in both cases confirmed the constitution of the complexes, containing molecular ions with the expected isotopic distribution. However, this complex showed limited stability in solution and a more stable variant of the heterobimetallic complex was obtained by reacting the silylated Mo(VI) precursor (Et4N)(MoO3(OSiPh3)) with L2H2, followed by the addition of [Cu(NCMe)4]+. This complex showed increased stability and it was characterized by NMR spectroscopy, high-resolution mass spectrometry, and X-ray crystallography. The oxidation capability of Cu(I) phosphine and isocyanide complexes with molybdate was interrogated. IR (for isocyanide) and 31P NMR (for PPh3/PMe3) spectroscopy demonstrates the lack of oxidation reactivity. The lack of oxidation can be attributed to the presence of coordinately saturated Cu(I) and anti conformation of two metal centers. Finally, we described synthesis, characterization, and reactivity of a heterobimetallic complex combining Mo(VI) trioxo with Mo(0) tricarbonyl. The formation of the heterobimetallic complex is facilitated by the xanthene-bridged heterodinucleating ligand (L1H2) containing hard catecholate chelate and soft iminopyridine chelate. The iminopyridine-bound [Mo0(CO)3] fragment coordinated to catechol-bound square-pyramidal [MoVIO3] fragment with a single (oxo) bridge. The overall arrangement of this unit is related to the proposed first step in the CODH mechanism where square-pyramidal [MoVIO2S] interacts with the [Cu-CO] via a single sulfido bridge. Our attempt to obtain a sulfido-bridge analogue (using [MoO3S]2- precursor) led to a mixture of products possibly containing different (oxo and sulfido) bridges. No internal CO oxidation is observed even though a direct interaction between Mo(VI) and Mo(0) segments were observed. The low-lying unoccupied MOs being d-π orbitals at MoVIO3 and the high-lying occupied MOs being mostly d-π orbitals at Mo0(CO)3. This heterobimetallic complex was found to be stable in DMF-d7 up to 100 °C due to its overall rigid structure (based on 1H NMR). Above this temperature, the complex dissociates to form stable Mo(CO)3(DMF)3 (according to IR) without producing CO2 (according to GC). We have also synthesized and studied the reactivity of the Mo(VI)/Cr(0) analogue. While this complex demonstrated more facile decomposition, no CO2 production was observed as well. DFT calculations suggest that the formation of [CO2]2- and its subsequent reductive elimination is endergonic in the present system, likely due to the stability of fac-Mo0(CO)3 and nucleophilic character of the carbonyl carbon engendered by Mo(0). The calculations also indicate that the replacement of one oxo by sulfido (both terminal and bridging), replacement of catechol with dithiolene, and replacement of Mo(0) with Cr(0) does not affect significantly the energetics of the process, likely requiring the use a less stable and less π-basic CO anchor.

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