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Open Access Publications from the University of California

Scholarly Works (7 results)

  • Article
  • Peer Reviewed
Lawrence Berkeley National Laboratory (2012)
    Cover page: Selective Monoterpene-like Cyclization Reactions Achieved by Water Exclusion from Reactive Intermediates in a Supramolecular Catalyst
    • Thesis
    • Peer Reviewed
    UC Berkeley Electronic Theses and Dissertations (2015)

    Abstract

    Mechanistic Studies of Biomimetic Reactions by Synthetic Enzyme Mimics

    By

    William Michael Hart-Cooper

    Doctor of Philosophy in Chemistry

    University of California, Berkeley

    Professor Kenneth N. Raymond, Co-chair

    Professor Robert G. Bergman, Co-chair

    Chapter 1. A brief introduction to common synthetic host structures and justification for the work described herein is provided.

    Chapter 2. The development of 1 and related hosts as a new class terpene synthase mimics that catalyze intramolecular Prins cyclizations. The property of water exclusion is observed. Host 1 is also shown to compensate for the gem-disubstituent effect.

    Chapter 3. The development of new terephthalamide hosts enabled an investigation of the effect of host structure on the enantio- and diastereoselectivity of these reactions, as well as a simple kinetic analysis. Rate accelerations and turnover numbers are notably high.

    Chapter 4. The mechanism of proton transfer in an archetypal enzyme mimic is studied using amide hydrogen deuterium exchange (HDX) kinetics. Collectively, these data shed light on the role of acid, base and water-mediated proton transfer in a synthetic active site with relevance to proton-mediated catalysis. Moreover, the emergent mechanism of solvent-occupied proton transfer raises the prospect of designable hosts with properties that are unique to the integration of their parts

    Chapter 5. A short overview is provided, which places the results of chapters 2-4 in context with some broader goals of biomimetic supramolecular chemistry.

      Cover page: Mechanistic Studies of Biomimetic Reactions by Synthetic Enzyme Mimics
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2023)
      The discovery that the commercial rubber antidegradant 6PPD reacts with ozone (O3) to produce a highly toxic quinone (6PPDQ) spurred a significant research effort into nontoxic alternatives. This work has been hampered by lack of a detailed understanding of the mechanism of protection that 6PPD affords rubber compounds against ozone. Herein, we report high-level density functional theory studies into early steps of rubber and PPD (p-phenylenediamine) ozonation, identifying key steps that contribute to the antiozonant activity of PPDs. In this, we establish that our density functional theory approach can achieve chemical accuracy for many ozonation reactions, which are notoriously difficult to model. Using adiabatic energy decomposition analysis, we examine and dispel the notion that one-electron charge transfer initiates ozonation in these systems, as is sometimes argued. Instead, we find direct interaction between O3 and the PPD aromatic ring is kinetically accessible and that this motif is more significant than interactions with PPD nitrogens. The former pathway results in a hydroxylated PPD intermediate, which reacts further with O3 to afford 6PPD hydroquinone and, ultimately, 6PPDQ. This mechanism directly links the toxicity of 6PPDQ to the antiozonant function of 6PPD. These results have significant implications for development of alternative antiozonants, which are discussed.
        Cover page: Computational Studies of Rubber Ozonation Explain the Effectiveness of 6PPD as an Antidegradant and the Mechanism of Its Quinone FormationCreative Commons 'BY' version 4.0 license
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2015)
        The mechanism of proton exchange in a metal-ligand enzyme active site mimic (compound 1) is described through amide hydrogen-deuterium exchange kinetics. The type and ratio of cationic guest to host in solution affect the rate of isotope exchange, suggesting that the rate of exchange is driven by a host whose cavity is occupied by water. Rate constants for acid-, base-, and water-mediated proton exchange vary by orders of magnitude depending on the guest, and differ by up to 200 million-fold relative to an alanine polypeptide. These results suggest that the unusual microenvironment of the cavity of 1 can dramatically alter the reactivity of associated water by magnitudes comparable to that of enzymes.
          Cover page: Protein-like proton exchange in a synthetic host cavity
          • Article
          LBL Publications (2013)
            Cover page: Chiral Amide Directed Assembly of a Diastereo- and Enantiopure Su-pramolecular Host and its Application to Enantioselective Catalysis of Neutral Substrates
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2015)
            The effect of host structure on the selectivity and mechanism of intramolecular Prins reactions is evaluated using K12Ga4L6 tetrahedral catalysts. The host structure was varied by modifying the structure of the chelating moieties and the size of the aromatic spacers. While variation in chelator substituents was generally observed to affect changes in rate but not selectivity, changing the host spacer afforded differences in efficiency and product diastereoselectivity. An extremely high number of turnovers (up to 840) was observed. Maximum rate accelerations were measured to be on the order of 105, which numbers among the largest magnitudes of transition state stabilization measured with a synthetic host-catalyst. Host/guest size effects were observed to play an important role in host-mediated enantioselectivity.
              Cover page: The effect of host structure on the selectivity and mechanism of supramolecular catalysis of Prins cyclizationsCreative Commons 'BY' version 4.0 license
              • Article
              • Peer Reviewed
              UC Berkeley Previously Published Works (2017)
              Preservatives deter microbial growth, providing crucial functions of safety and durability in composite materials, formulated products, and food packaging. Concern for human health and the environmental impact of some preservatives has led to regulatory restrictions and public pressure to remove individual classes of compounds, such as parabens and chromated copper arsenate, from consumer products. Bans do not address the need for safe, effective alternative preservatives, which are critical for both product performance (including lifespan and therefore life cycle metrics) and consumer safety. In this work, we studied both the safety and efficacy of a series of phenolic preservatives and compared them to common preservatives found in personal care products and building materials. We quantified antimicrobial activity against Aspergillus brasiliensis (mold) and Pseudomonas aeruginosa (Gram negative bacteria), and we conducted a hazard assessment, complemented by computational modeling, to evaluate the human and environmental health impacts of these chemicals. We found that octyl gallate demonstrates better antimicrobial activity and comparable or lower hazards, compared to current-use preservatives. Therefore, octyl gallate may serve as a viable small-molecule preservative, particularly in conjunction with low concentrations of other preservatives that act through complementary mechanisms.
                Cover page: Design and Testing of Safer, More Effective Preservatives for Consumer Products
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