Academic Commons

Theses Doctoral

Zinc Supported by Nitrogen-Rich Ligands: Applications Towards Catalytic Hydrosilylation And Modeling Zinc Enzymes

Ruccolo, Serge Michel

In chapter 1, I discuss how ligand architecture in tripodal nitrogen-rich ligands can drastically affect the structure of zinc complexes featuring these ligands. The synthesis and characterization of zinc tris(1-methylimidazol-2-ylthio)methyl ([Titm^Me]) and tris(1-Pribenzimidazol-2-ylthio)methyl ([Titm^iPr,benzo]) complexes is presented. The ligand in [Titm^Me]Zn complexes binds the metal to form carbatrane structures that exhibit unusually long and flexible Zn–C bonds. The bonding between the zinc and the carbon in these complexes can therefore be more accurately described as a zwitterionic interaction between a carbanion and a zinc cation. Density functional theory calculations demonstrate that the energy profile for the Zn–C bond is shallow, such that large variations of the Zn–C distance result in very little change in the energy of the complex. The benzannulated ligand [Titm^iPr,benzo] allows access to a rare monomeric zinc hydride species [κ³-Titm^iPr,benzo]ZnH that can react with either CO₂ to produce a zinc formate, or B(C₆F₅)₃ to form the ion pair [κ⁴-Titm^iPr,benzo]ZnHB(C₆F₅)₃. The coordination chemistry of the [Titm^iPr,benzo] ligand also extends to the other metals of group 12.
In chapter 2, I report the use of the [Titm^Me] and [Titm^iPr,benzo] zinc complexes presented in chapter 1 as biomimetic models for zinc enzymes. First, [Titm^Me] zinc complexes present structural similarities with the active site of carbonic anhydrase, and can be used to study the binding of carbonic anhydrase inhibitors to the enzyme active site. Then, [κ⁴-Titm^iPr,benzo]ZnX (X = MeB(C₆F₅)₃, BPh₄) complexes and their interactions with ligands of relevance towards antibiotic resistance is reported. The non coordinating nature of the anions in [κ⁴-Titm^iPr,benzo]ZnX (X = MeB(C₆F₅)₃, BPh₄) lead to the formation of a Lewis acidic zinc cationic center, which can be coordinated by an additional ligand of biological interest. The binding of simple β-lactams to the [κ⁴-Titm^iPr,benzo]ZnX complexes can be probed using X-ray diffraction and Nuclear Magnetic Resonance (NMR) spectroscopy, thereby providing a way to model the binding of antibiotics to the active site of the metallo-β-lactamases enzymes responsible for broad antibiotic resistance. The binding of β-lactams can be compared to larger ring size lactams and linear amides. [κ⁴-Titm^iPr,benzo]ZnX (X = MeB(C₆F₅)₃, BPh₄) also allows for the study of the binding of potential metallo-β-lactamases inhibitors, such as, for example, glycinamide, picolinamide, and piperazine-2,3-dione. Binding studies between [κ⁴-Titm^iPr,benzo]ZnX and substrates bearing structural similarities to antibiotics reveal secondary interactions involving peripheral functional groups the cationic zinc center in [κ⁴-Titm^iPr,benzo]ZnX. These studies provide guidelines to modify existing antibiotics, in order to decrease their sensitivity to metallo-β-lactamases.
In chapter 3, I explore the reactivity of previously characterized tris(2-pyridylthio)methyl [Tptm] zinc complexes. First, an improved synthesis of [κ⁴-Tptm]ZnF using Me₃SnF as the fluorinating agent is reported. The fluorine atom in [κ⁴-Tptm]ZnF acts as a Lewis base, as illustrated by its reaction with B(C₆F₅)₃ to form [κ⁴-Tptm]ZnFB(C₆F₅)₃, in which the fluorine is transferred to the borane group. The fluoride ligand in [κ⁴-Tptm]ZnF also acts as a hydrogen bond and halogen bond acceptor and is capable of forming adducts with H₂O, indole, and iodopentafluorobenzene. [κ⁴-Tptm]ZnF undergoes metathesis with Ph₃CCl to form Ph₃CF, thereby providing a rare example of C–F bond formation promoted by a zinc complex. Then, [κ³-Tptm]ZnH is used as a catalyst for the hydrosilylation of aldehydes and ketones using phenylsilane to produce tris alkoxysilane products. The catalyst is very active with aldehydes, and shows slower reactivity towards dialkyl ketones. The reaction proceeds via insertion of the carbonyl group in the Zn–H bond to form a zinc alkoxide, which then undergoes metathesis with the silane to generate the desired product and regenerate the zinc hydride species. The complicated NMR spectroscopic features of the products resulting from the hydrosilylation of prochiral ketones are explained by the presence of different diastereomers. Finally, we report that [κ³-Tptm]ZnH is a catalyst for the hydrosilylation of silylformates to methoxy silanes with (EtO)₃SiH, (MeO)₃SiH and κ⁴-N(CH₂CH₂O)₃SiOMe. We show that CO₂ can be reduced to methoxy silane species in a one pot reaction using (MeO)₃SiH and catalytic amounts of [κ³-Tptm]ZnH.
In chapter 4, I report the synthesis and characterization of a silicon based analogue of [Titm^iPr,benzo], namely the tris(1-Pribenzimidazol-2-yldimethylsilyl)methyl [Tism^iPr,benzo] ligand. The ligand possesses unique structural features, due to the proximity between the dimethylsilyl groups and the methyl carbanion. The formation of [κ⁴-Tism^iPr,benzo]Li proceeds via the doubly base stabilized silene intermediate [κ³-C(SiMe₂benzimid^iPr)₂]SiMe₂. [κ⁴-Tism^iPr,benzo]Li can be used as a precursor for copper and nickel [Tism^iPr,benzo] and [C₃-Tism^iPr,benzo] complexes, where [C3-Tism^iPr,benzo] represents the isomerized tris carbene version of [Tism^iPr,benzo]. [κ³-C(SiMe₂benzimid^iPr)₂]SiMe₂ reacts with ZnMe₂ to produce [κ³-C(SiMe₃)(SiMe₂benzimid^iPr)₂]ZnMe, which can be transformed to the phenoxide compound. This compound acts as a catalyst for the hydrosilylation of CO₂ to silyl formates and methoxy silanes. [κ³-C(SiMe₂benzimid^iPr)₂]SiMe₂ itself reacts with CO₂ to produce an unusual β-lactone.

Files

  • thumnail for Ruccolo_columbia_0054D_13573.pdf Ruccolo_columbia_0054D_13573.pdf binary/octet-stream 30.7 MB Download File

More About This Work

Academic Units
Chemistry
Thesis Advisors
Parkin, Gerard F.
Degree
Ph.D., Columbia University
Published Here
September 22, 2016
Academic Commons provides global access to research and scholarship produced at Columbia University, Barnard College, Teachers College, Union Theological Seminary and Jewish Theological Seminary. Academic Commons is managed by the Columbia University Libraries.