DOCSLIB.ORG

I. Development of Novel Silicon Precursors for Rapid and Efficient Radiofluorination Reactions

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
I. Development of Novel Silicon Precursors for Rapid and Efficient Radiofluorination Reactions I. DEVELOPMENT OF NOVEL SILICON PRECURSORS FOR RAPID AND EFFICIENT RADIOFLUORINATION REACTIONS: SYNTHESIS AND BIOLOGICAL EVALUATION OF A 18F-LABELLED ESTROGEN DENDRIMER CONJUGATE II. OTHER STUDIES ON 18F-LABELLED ESTROGENS BY VINCENT M. CARROLL DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Chemistry in the Graduate College of the University of Illinois at Urbana-Champaign, 2012 Urbana, Illinois Doctoral Committee: Professor John A. Katzenellenbogen, Chair Professor Paul J. Hergenrother Professor Benita S. Katzenellenbogen Professor Scott K. Silverman ABSTRACT Molecular imaging (MI) has revolutionized the visualization of complex biochemical processes in normal physiology and diseased states. Although still in its infancy, the data generated from MI studies aids in identifying sites of pathological involvement and provides key insight into the mechanisms that lead to the onset and progression of disease. Consequently, these techniques hold tremendous potential in the areas of diagnostics, therapy assessment, and drug development in the coming years. Amongst MI techniques, Positron Emission Tomography (PET) separates itself from the rest of the field with its exceptional sensitivity, near limitless depth of penetration and its ability to quantify metabolic processes in living patients. With the ability to visualize and quantify on an individualized basis, PET imaging has received considerable attention recently because of its potential for contributing to personalized medicine. Through better diagnosis, rational selection of targeted therapies, and individualization of therapy regimens for each patient, personalized medicine holds the promise of greatly improving patient outcomes as well as safeguarding against the use of unnecessary, harmful medical procedures. Given the current status of the PET field and the impact it has on many fields, significant effort is being made to expand the existing repertoire of imaging agents capable of further detailing pathophysiological processes beyond the most commonly used PET tracer, [18F]fluorodeoxyglucose, including the use of large, sensitive biomolecules such as peptides and antibodies, which may be of considerable clinical importance. However, the available methodology associated with PET isotope incorporation, specifically fluorine-18, involves rather harsh conditions that are incompatible with sensitive substrates, which restricts the availability of these agents and their subsequent clinical evaluation. Thus, there remains a tremendous need for rapid, mild and efficient methodology that can be used to label these previously inaccessible substrates in a direct, late-stage fashion. Chapter 1 presents a brief introduction into molecular imaging and the techniques available for use in the preclinical and clinical setting as well as in drug development. Additionally, the basics of PET principles and radiochemistry are introduced, with a significant focus on the synthetic difficulties involved in working with the most commonly used PET isotope, fluorine-18, and why there is a need for improved methodology for its incorporation into new radiopharmaceutical agents, especially sensitive ones. ii Chapter 2 details the development of methodology that targets the shortcomings of C- 18F strategies through Si-18F bond formation approaches. We have developed a simple and straightforward strategy in radiofluorinating complex substrates at a late stage, at room temperature, or in an aqueous environment in high radiochemical yields and specific activities through a reactive silyl acetate moiety. The utility and versatility of the approach is showcased in three main areas of research: small adaptor molecules, small molecules, and peptides. We have applied this Si-18F labeling strategy (Chapter 3) to prepare a fluorine-18 labeled version of 17α-ethynylestradiol conjugated PAMAM dendrimer that can be used for in vivo distribution studies of this novel hormone-polymer conjugate. Through biodistribution studies, we have found that the EDC, a dendrimer-bound estrogen that provides selective cardiovascular protection without classical stimulation of uterus and mammary tissues, also shows selective, ER-mediated uptake and retention by the vascular target tissues, heart and aorta, but not the classical target, the uterus. These findings suggest that the selective cardiovascular protective effect of EDC is the result of two factors, one mechanistic (selective stimulation of the extra-nuclear pathway of ER action) and one pharmacokinetic (selective accumulation of EDC in vascular targets). This points to a new dimension for extending the selective, potentially beneficial actions of estrogens. Chapter 4 details the synthetic approaches towards the radiosynthesis a promising ER imaging agent, 2-[18F]fluoroestradiol, and illustrates the most well-known difficulty encountered in fluorine-18 chemistry, specifically the radiofluorination of electron-rich aromatic rings. Efforts have focused on the use of diaryliodonium salts which has afforded synthetically useful radiochemical yields of the desired compound and is currently being scaled up, in terms of radioactivity, for evaluation in animal studies. iii ACKNOWLEDGMENTS First and foremost, I am forever indebted to Dr. K for giving me the chance to work in his laboratory. It seems like only yesterday I was still trying to convince him to accept me as one of his last graduate students. When I first joined the lab, I was, and still am today, in awe of his brilliant scientific mind and how quickly he can grasp any chemistry or biology-related topic. He has been an amazing role model, showing me the proper way of approaching problems, analyzing data, and most of all, asking the right questions, and as our relationship grew, I thought of Dr. K not only as my boss, but as a good friend. I am truly appreciative of everything he has done for me as a chemist and as a person and I will always cherish our time together. I have also been fortunate to work with Dr. Michael Welch of Washington University, who has recently passed on. It was always interesting working in St. Louis, especially since I was going from the calm, soft-spoken personality of Dr. K to a rather unique personality of Dr. Welch. It is an understatement that Dr. Welch liked to speak his mind and I could never stop laughing being in his presence because of it. I will always remember the one day I was complaining about the possibility of getting a high hand dose the one month and in his typical quick wit, responded in saying that he has been injected with over 20 radiopharmaceuticals and look how he turned out. But there was so much more to his humor, he was a great scientist, a great person and the world has lost a great man. He may be gone from us but his memories will live on forever. Great things happen because of great people and I am truly grateful for the group of colleagues that I have had a chance to work with. First and foremost, I will never forget the times with my good friend, Dr. Sung Hoon Kim. He is a remarkably driven and smart chemist and his strong work ethic has always been something for me to model off of. He has been there through the good times and the bad times, but his support for me and our projects never strayed and anything that was needed, I always knew I could rely on him. I thank him for everything that he has done for me. Norio Yasui has been a great lab mate for many years now and has always been there to help out whenever I needed him. I am grateful for Dr. Dong Zhou at Wash U for teaching the ins and outs of being a radiochemist and the proper way of not contaminating myself with radioactivity. And although it’s only been a short time, I appreciate Dr. Julie Pollock for being a good friend and trivia buddy. A great deal of thanks goes to other previous members that had an influence on my graduate career including Dr. Terry Moore, Dr. John Comninos, Dr. Davis Oldham, Dr. Chris Mayne, and Dr. Alex Parent. A special thanks also goes to Kathy iv Carlson and Kathleen Myerscough for everything they have done for me and always having an open ear to talk to. I appreciate the efforts of my thesis committee, Dr. Paul Hergenrother, Dr. Benita Katzenellenbogen, Dr. Scott Silverman, and formerly, Dr. Anne Baranger. I am thankful for all their advice and suggestions during the process. Finally, I would not be here today if it wasn’t for the constant and unyielding support of my family and friends. My parents have always been there for me and gave me everything I needed to succeed in the world and words can’t describe how thankful I am to have them in my life. Mark and Jill Knafl have been the best friends I could ever ask for and I will miss them dearly when I move away. I owe my biggest debt of gratitude to my wife, Mary, who has supported me through all these years. She is the most sincere and compassionate person I have ever met and although I may not have always expressed it during my time here, I wouldn’t have wanted anyone but her by my side. v TABLE OF CONTENTS LIST OF ABBREVIATIONS…………………………………………………………………………….vii CHAPTER 1: INTRODUCTION..…………...………………………………………………………..…1 CHAPTER 2: DEVELOPMENT OF NOVEL SILICON PRECURSORS FOR RAPID AND EFFICIENT RADIOFLUORINATION REACTIONS……………………..…………………….……22 CHAPTER 3: A NEW DIMENSION IN SELECTIVE ESTROGEN ACTION: A VASCULAR- PROTECTING ESTROGEN DENDRIMER CONJUGATE SHOWS SELECTIVE RECEPTOR- MEDIATED UPTAKE IN THE HEART AND VASCULATURE………………..……………………77 CHAPTER 4: SYNTHETIC APPROACHES
Load more

Recommended publications
  • BI(III) Initiated Cyclization Reactions and Iodonium Fragmentation Kinetics
    W&M ScholarWorks Dissertations, Theses, and Masters Projects Theses, Dissertations, & Master Projects 2005 BI(III) Initiated Cyclization Reactions and Iodonium Fragmentation Kinetics Yajing Lian College of William & Mary - Arts & Sciences Follow this and additional works at: https://scholarworks.wm.edu/etd Part of the Inorganic Chemistry Commons Recommended Citation Lian, Yajing, "BI(III) Initiated Cyclization Reactions and Iodonium Fragmentation Kinetics" (2005). Dissertations, Theses, and Masters Projects. Paper 1539626842. https://dx.doi.org/doi:10.21220/s2-zj7g-fp23 This Thesis is brought to you for free and open access by the Theses, Dissertations, & Master Projects at W&M ScholarWorks. It has been accepted for inclusion in Dissertations, Theses, and Masters Projects by an authorized administrator of W&M ScholarWorks. For more information, please contact [email protected]. BI(III) INITIATED CYCLIZATION REACTIONS AND IODONIUM FRAGMENTATION KINETICS A Thesis Presented to The Faculty of the Department of Chemistry The College of William and Mary in Virginia In Partial Fulfillment Of the Requirements for the Degree of Master of Science by Yajing Lian 2005 APPROVAL SHEET This thesis is submitted in partial fulfillment of The requirements for the degree of Master of Science A Yajing Lian Approved by the Committee, December 20, 2005 Robert J. Hinkle, Chair Christopher Jl A] Robert D. Pike TABLE OF CONTENTS Page Acknowledgements VI List of Tables Vll List of Schemes V lll List of Figures IX Abstract XI Introduction Chapter I Secondary
    [Show full text]
  • Design, Synthesis and Applications of Novel Hypervalent Iodine Reagents
    Design, Synthesis and Applications of Novel Hypervalent Iodine Reagents A Thesis Submitted to Cardiff University in Fulfilment of the Requirements for the Degree of Doctor of Philosophy by Jihan Qurban PhD Thesis July 2019 Cardiff University Jihan Qurban PhD Thesis 2019 __________________________________________________________________________________ DECLARATION This work has not been submitted in substance for any other degree or award at this or any other university or place of learning, nor is being submitted concurrently in candidature for any degree or other award. Signed …………………………… (Jihan Qurban) Date ………………….… STATEMENT 1 This thesis is being submitted in partial fulfillment of the requirements for the degree of ……………………… (insert MCh, MD, MPhil, PhD etc, as appropriate) Signed …………………………… (Jihan Qurban) Date ………………….… STATEMENT 2 This thesis is the result of my own independent work/investigation, except where otherwise stated, and the thesis has not been edited by a third party beyond what is permitted by Cardiff University’s Policy on the Use of Third-Party Editors by Research Degree Students. Other sources are acknowledged by explicit references. The views expressed are my own. Signed …………………………… (Jihan Qurban) Date ………………….… STATEMENT 3 I hereby give consent for my thesis, if accepted, to be available online in the University’s Open Access repository and for inter-library loan, and for the title and summary to be made available to outside organisations. Signed …………………………… (Jihan Qurban) Date ………………….… STATEMENT 4: PREVIOUSLY APPROVED BAR ON ACCESS I hereby give consent for my thesis, if accepted, to be available online in the University’s Open Access repository and for inter-library loans after expiry of a bar on access previously approved by the Academic Standards & Quality Committee.
    [Show full text]
  • A Metal-Free Approach to Biaryl Compounds: Carbon-Carbon Bond Formation from Diaryliodonium Salts and Aryl Triolborates
    Portland State University PDXScholar Dissertations and Theses Dissertations and Theses Winter 4-3-2015 A Metal-Free Approach to Biaryl Compounds: Carbon-Carbon Bond Formation from Diaryliodonium Salts and Aryl Triolborates Kuruppu Lilanthi Jayatissa Portland State University Follow this and additional works at: https://pdxscholar.library.pdx.edu/open_access_etds Part of the Catalysis and Reaction Engineering Commons Let us know how access to this document benefits ou.y Recommended Citation Jayatissa, Kuruppu Lilanthi, "A Metal-Free Approach to Biaryl Compounds: Carbon-Carbon Bond Formation from Diaryliodonium Salts and Aryl Triolborates" (2015). Dissertations and Theses. Paper 2229. https://doi.org/10.15760/etd.2226 This Thesis is brought to you for free and open access. It has been accepted for inclusion in Dissertations and Theses by an authorized administrator of PDXScholar. Please contact us if we can make this document more accessible: [email protected]. A Metal-Free Approach to Biaryl Compounds: Carbon-Carbon Bond Formation from Diaryliodonium Salts and Aryl Triolborates. by Kuruppu Lilanthi Jayatissa A thesis submitted in partial fulfillment of the requirement for the degree of Master of Science in Chemistry Thesis Committee: David Stuart, Chair Robert Strongin Theresa McCormick Portland State University 2015 Abstract Biaryl moieties are important structural motifs in many industries, including pharmaceutical, agrochemical, energy and technology. The development of novel and efficient methods to synthesize these carbon-carbon bonds is at the forefront of synthetic methodology. Since Ullmann’s first report of stoichiometric Cu-mediated homo-coupling of aryl halides, there has been a dramatic evolution in transition metal catalyzed biaryl cross-coupling reactions.
    [Show full text]
  • Metathetical Redox Reaction of (Diacetoxyiodo)Arenes and Iodoarenes
    Article Metathetical Redox Reaction of (Diacetoxyiodo)arenes and Iodoarenes Antoine Jobin-Des Lauriers and Claude Y. Legault * Received: 25 November 2015 ; Accepted: 15 December 2015 ; Published: 17 December 2015 Academic Editors: Wesley Moran and Arantxa Rodríguez Centre in Green Chemistry and Catalysis, Department of Chemistry, University of Sherbrooke, 2500 boul. de l’Université, Sherbrooke, QC J1K 2R1, Canada; [email protected] * Correspondence: [email protected]; Tel./Fax: +1-819-821-8017 Abstract: The oxidation of iodoarenes is central to the field of hypervalent iodine chemistry. It was found that the metathetical redox reaction between (diacetoxyiodo)arenes and iodoarenes is possible in the presence of a catalytic amount of Lewis acid. This discovery opens a new strategy to access (diacetoxyiodo)arenes. A computational study is provided to rationalize the results observed. Keywords: hypervalent iodine; (diacetoxyiodo)arenes; metathesis 1. Introduction In the recent years, the development of hypervalent iodine-mediated synthetic transformations has been receiving growing attention [1–5]. This is not surprising considering the importance of improving oxidative reactions and reducing their environmental impact. Hypervalent iodine reagents are a great alternative to toxic heavy metals often used to effect similar transformations [6–10]. Among the plethora of iodine(III) compounds [11], it is undeniable that the (diacetoxyiodo)arenes remain the most common and used ones [12]. They are usually stable solids and can serve as precursors to numerous other iodanes, such as other (diacyloxyiodo)arenes and [hydroxy(tosyloxy) iodo]arenes [13,14]. Access to (diacetoxyiodo)arenes is, of course, usually accomplished by the oxidation of the corresponding iodoarene substrate.
    [Show full text]
  • SELECTIVE C–H and ALKENE FUNCTIONALIZATION VIA ORGANIC PHOTOREDOX CATALYSIS Nicholas Paul Ralph Onuska a Dissertation Submitte
    SELECTIVE C–H AND ALKENE FUNCTIONALIZATION VIA ORGANIC PHOTOREDOX CATALYSIS Nicholas Paul Ralph Onuska A dissertation submitted to the faculty at the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry Chapel Hill 2021 Approved by: David Nicewicz Erik Alexanian Jeffrey Aubé Alexander Miller Andrew Moran © 2021 Nicholas Paul Ralph Onuska ALL RIGHTS RESERVED ii ABSTRACT Nicholas Paul Ralph Onuska: Selective C–H and Alkene Functionalization Via Organic Photoredox Catalysis (Under the direction of David A. Nicewicz) Photoinduced electron transfer (PET) can be defined as the promotion of an electron transfer reaction through absorption of a photon by a reactive species in solution. Photoredox catalysis has leveraged previous knowledge of PET processes to enable a wide variety of high value chemical transformations. Most early work in the field of photoredox catalysis centered around the use of visible-light absorbing transition metal catalyst systems based on ruthenium or iridium polypyridyl scaffolds, organic redox chromophores offer a more sustainable, accessible, and versatile alternative to these complexes. Organic photoredox catalysts are often less expensive, easier to prepare, and have expanded redox windows relative to many known transition-metal photoredox catalysts, enabling the generation of a wider variety of single electron reduced/oxidized species. This ultimately translates into the development of previously undiscovered modes of reactivity. Herein is described the development and mechanistic study of a several C–H and alkene functionalization reactions facilitated by visible light-absorbing acridinium salts, as well as the discovery and characterization of a neutral organic radical which possess one of the most negative excited state oxidation potentials observed to date.
    [Show full text]
  • Chapter 9 Hydrogen
    Chapter 9 Hydrogen Diborane, B2 H6• is the simplest member of a large class of compounds, the electron-deficient boron hydrid Like all boron hydrides, it has a positive standard free energy of formation, and so cannot be prepared direct from boron and hydrogen. The bridge B-H bonds are longer and weaker than the tenninal B-H bonds (13: vs. 1.19 A). 89.1 Reactions of hydrogen compounds? (a) Ca(s) + H2Cg) ~ CaH2Cs). This is the reaction of an active s-me: with hydrogen, which is the way that saline metal hydrides are prepared. (b) NH3(g) + BF)(g) ~ H)N-BF)(g). This is the reaction of a Lewis base and a Lewis acid. The product I Lewis acid-base complex. (c) LiOH(s) + H2(g) ~ NR. Although dihydrogen can behave as an oxidant (e.g., with Li to form LiH) or reductant (e.g., with O2 to form H20), it does not behave as a Br0nsted or Lewis acid or base. It does not r with strong bases, like LiOH, or with strong acids. 89.2 A procedure for making Et3MeSn? A possible procedure is as follows: ~ 2Et)SnH + 2Na 2Na+Et3Sn- + H2 Ja'Et3Sn- + CH3Br ~ Et3MeSn + NaBr 9.1 Where does Hydrogen fit in the periodic chart? (a) Hydrogen in group 1? Hydrogen has one vale electron like the group 1 metals and is stable as W, especially in aqueous media. The other group 1 m have one valence electron and are quite stable as ~ cations in solution and in the solid state as simple 1 salts.
    [Show full text]
  • Enantioselective Iodine(I/III) Catalysis in Organic Synthesis, Which Has Been Published in Final Form At
    "This is the peer reviewed version of the following article: Enantioselective Iodine(I/III) Catalysis in Organic Synthesis, which has been published in final form at https://doi.org/10.1002/adsc.201800521 . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving http://olabout.wiley.com/WileyCDA/Section/id-820227.html “ Enantioselective Iodine(I/III) Catalysis in Organic Synthesis Andrea Flores,a Eric Cots,a Julien Bergès,a and Kilian Muñiza,b* a Institute for Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science, Av. Països Catalans 16, 43007 Tarragona, Spain Fax: +34 977 920 224. E-mail: [email protected] b ICEA Passeig Lluís Companys, 23, 08010 Barcelona, Spain Abstract. Chiral aryliodine(III) reagents have provided an advanced concept for enantioselective synthesis and catalysis. Keywords: Chirality; Enantioselective Synthesis; With the advent of chiral iodine(I/III) catalysis, a large Homogeneous Catalysis; Iodine; Oxidation number of different structures have been explored in the area. The currently most prominent catalyst design is based on a resorcinol core and the attachment of two lactic side chains bearing ester or amide groups. It enables a privileged modular catalyst synthesis, in which fine-tuning with respect to the specific reaction requirement is straightforward. The present overview summarizes the structural variation and optimization of such chiral aryliodine catalysts and discusses structural properties of the active iodine(III) catalyst states. The status quo of enantioselective iodine(I/III) oxidation catalysis with respect to intramolecular and intermolecular reaction control is reviewed, and specific aspects of the individual catalytic cycles are discussed.
    [Show full text]
  • Hypervalent Iodine Reagents in High Valent Transition Metal Chemistry
    molecules Review Hypervalent Iodine Reagents in High Valent Transition Metal Chemistry Felipe Cesar Sousa e Silva, Anthony F. Tierno and Sarah E. Wengryniuk * Department of Chemistry, Temple University, 1901 N. 13th St., Philadelphia, PA 19122, USA; [email protected] (F.C.S.S.); [email protected] (A.F.T.) * Correspondence: [email protected]; Tel.: +1-215-204-0360 Academic Editor: Margaret A. Brimble Received: 29 March 2017; Accepted: 8 May 2017; Published: 12 May 2017 Abstract: Over the last 20 years, high valent metal complexes have evolved from mere curiosities to being at the forefront of modern catalytic method development. This approach has enabled transformations complimentary to those possible via traditional manifolds, most prominently carbon-heteroatom bond formation. Key to the advancement of this chemistry has been the identification of oxidants that are capable of accessing these high oxidation state complexes. The oxidant has to be both powerful enough to achieve the desired oxidation as well as provide heteroatom ligands for transfer to the metal center; these heteroatoms are often subsequently transferred to the substrate via reductive elimination. Herein we will review the central role that hypervalent iodine reagents have played in this aspect, providing an ideal balance of versatile reactivity, heteroatom ligands, and mild reaction conditions. Furthermore, these reagents are environmentally benign, non-toxic, and relatively inexpensive compared to other inorganic oxidants. We will cover advancements in both catalysis and high valent complex isolation with a key focus on the subtle effects that oxidant choice can have on reaction outcome, as well as limitations of current reagents. Keywords: hypervalent iodine; oxidation; oxidant; redox; high valent; high oxidation state; catalysis 1.
    [Show full text]
  • Photoredox Catalysis with Metal Complexes Made from Earth-Abundant Elements
    Photoredox Catalysis with Metal Complexes Made from Earth-Abundant Elements Christopher B. Larsen,[a] and Oliver S. Wenger*[a] Abstract: Photoredox chemistry with metal complexes as here, and there have been 3 prior reviews of photoredox sensitizers and catalysts frequently relies on precious elements catalysis with this particular focus.[10] However, the present such as ruthenium or iridium. Over the past 5 years, important review is thematically broader with respect to the different CuI progress towards the use of complexes made from earth- and non-CuI photoredox studies considered. It focuses on abundant elements in photoredox catalysis has been made. This organic transformations that require excitation of (usually) well review summarizes the advances made with photoactive CrIII, defined transition metal complexes that act as light-absorbers FeII, CuI, ZnII, ZrIV, Mo0 and UVI complexes in the context of and photoredox catalysts. Polymerization initiation processes, synthetic organic photoredox chemistry using visible light as an UV-light induced click reactions, and reactions relying on the energy input. Mechanistic considerations are combined with photodriven formation of catalytically active partner complexes in discussions of reaction types and scopes. Perspectives for the their electronic ground states are usually not considered. future of the field are discussed against the background of recent significant developments of new photoactive metal complexes made from earth-abundant elements. 2. Principles Photoredox behavior arises due to excited-state redox 1. Introduction properties being drastically altered from the corresponding ground state redox properties.[1] This can be understood at the Many complexes with the d6 electron configuration made from most basic level by considering for example a metal-to-ligand RuII, ReI, OsII and IrIII exhibit comparatively long-lived charge-transfer excited state (Figure 1).
    [Show full text]
  • Hypervalent Iodine Chemistry Preparation, Structure and Synthetic Applications of Polyvalent Iodine Compounds
    Viktor V. Zhdankin Hypervalent Iodine Chemistry Preparation, Structure and Synthetic Applications of Polyvalent Iodine Compounds Hypervalent Iodine Chemistry Hypervalent Iodine Chemistry Preparation, Structure and Synthetic Applications of Polyvalent Iodine Compounds Viktor V. Zhdankin Department of Chemistry and Biochemistry University of Minnesota Duluth, Minnesota, USA This edition first published 2014 © 2014 John Wiley & Sons, Ltd Registered office John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, United Kingdom For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright materialin this book please see our website at www.wiley.com. The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose.
    [Show full text]
  • A Continuum from Halogen Bonds to Covalent Bonds: Where Do Λ3 Iodanes Fit?
    inorganics Article A Continuum from Halogen Bonds to Covalent Bonds: Where Do l3 Iodanes Fit? Seth Yannacone 1 , Vytor Oliveira 2 , Niraj Verma 1 and Elfi Kraka 1,* 1 Department of Chemistry, Southern Methodist University, 3215 Daniel Avenue, Dallas, TX 75275-0314, USA; [email protected] (S.Y.); [email protected] (N.V.) 2 Instituto Tecnológico de Aeronáutica (ITA), Departamento de Química, São José dos Campos, 12228-900 São Paulo, Brazil; [email protected] * Correspondence: [email protected]; Tel.: +1-214-768-2611 Received: 14 February 2019; Accepted: 15 March 2019; Published: 28 March 2019 Abstract: The intrinsic bonding nature of l3-iodanes was investigated to determine where its hypervalent bonds fit along the spectrum between halogen bonding and covalent bonding. Density functional theory with an augmented Dunning valence triple zeta basis set (wB97X-D/aug-cc-pVTZ) coupled with vibrational spectroscopy was utilized to study a diverse set of 34 hypervalent iodine compounds. This level of theory was rationalized by comparing computational and experimental data for a small set of closely-related and well-studied iodine molecules and by a comparison with CCSD(T)/aug-cc-pVTZ results for a subset of the investigated iodine compounds. Axial bonds in l3-iodanes fit between the three-center four-electron bond, as observed for the − 3 trihalide species IF2 and the covalent FI molecule. The equatorial bonds in l -iodanes are of a covalent nature. We explored how the equatorial ligand and axial substituents affect the chemical properties of l3-iodanes by analyzing natural bond orbital charges, local vibrational modes, the covalent/electrostatic character, and the three-center four-electron bonding character.
    [Show full text]
  • Post-Synthetic Functionalization of Bioactive Compounds for Rapid Anticancer
    Post-synthetic Functionalization of Bioactive Compounds for Rapid Anticancer Library Expansion and Mechanistic Probe Development for Antimicrobial Resistance DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Chido M. Hambira Graduate Program in Pharmaceutical Sciences The Ohio State University 2018 Dissertation Committee: Professor James Fuchs Advisor Professor David Nagib Co-Advisor Professor Karl Werbovetz Professor Mark Mitton-Fry Copyright by Chido M. Hambira 2018 Abstract Within the realm of medicinal chemistry, not only is it important to optimize for target potency and physicochemical properties of bioactive compounds, but development of enabling technologies that aid in elucidation of biochemical pathways is of equal importance. The body of work contained within this dissertation is a summary of my efforts toward the development of a new C-H functionalization method to facilitate late-stage derivatization of complex bioactive molecules, and post-synthetic modifications of known bioactive compounds of pharmaceutical agents for the development of mechanistic probes. By taking advantage of the versatile reactivity of hypervalent iodine, aided by the labile nature of the ligands, we have harnessed the mild yet enhanced reactivity of iodosobenzene chloroacetate for the chlorination of (hetero)arenes. My key contributions to this project were the discovery of methods amenable to the halogenation of challenging substrates of the (iso)quinoline class of compounds, and the cytotoxic natural product derivate 2”-acetyl phyllanthusmin D, in addition to conducting mechanistic investigations. A significant portion of my doctoral research has been spent developing tool compounds targeting two aspects contributing to the looming public health issue of antimicrobial resistance.
    [Show full text]