Theses and Dissertations at Montana State University (MSU)
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Item Ni-catalyzed cross-coupling reactions of phenol-derived electrophiles(Montana State University - Bozeman, College of Letters & Science, 2022) Russell, John Emmet Alam; Chairperson, Graduate Committee: Sharon Neufeldt; This is a manuscript style paper that includes co-authored chapters.Herein we present in three parts our work on a variety of Ni-catalyzed cross-coupling reactions using phenol-derived electrophiles. The first part details an efficient Ni-catalyzed Stille cross-coupling of C-O electrophiles through a combination of computational and experimental methods. These allowed for the investigation of the mechanism and showed the formation of a novel 8-centered transition state involving KF. Chloride inhibits the reaction through forming a low-energy Ni(II)-chloride species during oxidative addition that has a high activation barrier towards transmetalation. This methodology was shown effective for a wide variety of C-O electrophiles and organostannanes including several difficult bond constructions. The second part explores the development of a chemoselective Ni-catalyzed Suzuki cross-coupling that is selective for C-O bonds in the presence of C-Cl bonds. This selectivity is unusual since organohalides typically undergo oxidative addition with Ni(0) and Pd(0) at similar or faster rates to phenol- derived electrophiles. We were able to pair computational and experimental investigations to develop a reliable strategy and understand the likely origin of this unique selectivity. Stoichiometric experiments showed that small phosphines, like PMe 3 and PPhMe 2 , are unique in their ability to facilitate the selective reaction at C-O bonds in the presence of C-Cl bonds. Computational investigations show the electronic and steric properties of these small ligands are crucial for a close interaction between nickel and a sulfonyl oxygen during oxidative addition, the step where selectivity is determined. The third part looked at the use of aryl methyl ethers as an electrophile under Ni-catalyzed Suzuki-Miyaura and Kumada cross-coupling conditions. Three ligands bearing chelating arms were synthesized, two known and one new, to explore the respective scopes and how these ligands compare to more commonly used ligands such as PCy 3 or ICy. We saw no success under Suzuki-Miyaura conditions but found the hydroxyphosphine ligands facilitated the Ni-catalyzed Kumada cross-coupling of Ar-OMe, which had not been reported. Further investigations proved the hydroxyphosphines had no apparent benefit over commercial ligand as far as yield, scope, or mild reaction conditions.Item Design, synthesis, and evaluation of novel antimicrobials for the eradication of biofilms(Montana State University - Bozeman, College of Letters & Science, 2020) Walsh, Danica Jade; Chairperson, Graduate Committee: Thomas S. Livinghouse; Thomas Livinghouse was a co-author and corresponding author and Darla M. Goeres, Madelyn Mettler, and Philip S. Stewart were co-authors of the article, 'Antimicrobial activity of naturally occurring phenols and derivatives against biofilm and planktonic bacteria' in the journal 'Frontiers in chemistry' which is contained within this dissertation.; Thomas Livinghouse was a co-author and corresponding author and Greg M. Durling, Yenny Chase-Bayless, Adrienne D. Arnold and Philip S. Stewart were co-authors of the article, 'Sulfenate esters of simple phenols exhibit enhanced activity against biofilms' submitted to the journal 'ACS Omega' which is contained within this dissertation.; Thomas Livinghouse was a co-author and corresponding author and Greg Durling, Adrienne Arnold, Whitney Braiser, Luke Berry, Darla M. Goeres and Philip S. Stewart were co-authors of the article, 'Enhanced antimicrobial activity of prodrug phenols against biofilms and planktonic bacteria' which is contained within this dissertation.The majority of microorganisms live in association with surfaces as biofilms. Biofilm communities are encased in a robust, extracellular matrix that reduces their susceptibility to antimicrobial agents. This poses a health concern due to the potential for pathogenic bacteria to cause serious infections. For example, hospital-acquired infections are among the top ten leading causes of death in the U.S. and are responsible for nearly 23,000 deaths per year. The goal of my research is to develop efficient antimicrobial agents capable of eradicating biofilms. In this project, I have focused on three different derivatizations of small, phenolic compounds in effort to increase efficacy towards biofilms. An initial study compared the potency of small, naturally occurring phenols and their corresponding allyl, propyl, and methallyl derivatives against bacteria. This study showed that in parent and derivative pairs potency increased towards free floating cells but decreased towards biofilms. This illustrated the importance of evaluating antimicrobial efficacy toward biofilms when the bacteria they intend to treat has the propensity to form biofilms. This was in contrast to a second studyishowing that trichloromethylsulfenate ester derivatives generally increased potency towards both biofilms and planktonic cells. In a third study, we found that iminodiacetoxy-methylester (AM) appendages increase potency towards planktonic cells and biofilms. AM appendages are ester groups that are employed as part of a prodrug design. Prodrugs are biologically inactive compounds until metabolized. Ester groups are commonly used in prodrug intracellular dyes, where, once inside the cell, ester groups are cleaved enzymatically, resulting in a negatively charged dye that is retained in the cell. Similarly, after the cleavage event, the AM antimicrobial compound will concentrate within the cell. This design serves two functions to increase potency: increasing permeability towards the biofilm matrix and achieving cellular retention. We have shown that the efficacy of antimicrobial agents towards biofilms can be increased through this strategic design. This class of prodrugs presents a wide array of potential applications, from controlling hospital-acquired infections to incorporation into household cleaning products and addresses the need for novel treatments of pathogenic bacteria.Item Removal of phenols from a refinery waste stream utilizing porous biomass supports in an aerated reactor(Montana State University - Bozeman, 1988) Center, Ray; Chairperson, Graduate Committee: Howard S. PeavyItem Improving the removal of phenols in the biological portion of the Conoco Oil refinery wastewater treatment plant, Billings, MT(Montana State University - Bozeman, 1987) Gilman, Greta; Chairperson, Graduate Committee: Howard S. PeavyItem Solubilities of phenol in supercritical carbon dioxide from aqueous phenol solutions(Montana State University - Bozeman, College of Engineering, 1986) Leland, Eric RaymondItem Expression and characterization of copper-containing proteins: galactose oxidase and tyrosinase(Montana State University - Bozeman, College of Letters & Science, 2002) Kamlin, Ejan Marie