DOCSLIB.ORG

Metal Complexes and Medicine: a Successful Combination

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Metal Complexes and Medicine: a Successful Combination Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2015 Metal Complexes and Medicine: A Successful Combination Gasser, Gilles DOI: https://doi.org/10.2533/chimia.2015.442 Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-114192 Journal Article Originally published at: Gasser, Gilles (2015). Metal Complexes and Medicine: A Successful Combination. CHIMIA International Journal for Chemistry, 7:442-446. DOI: https://doi.org/10.2533/chimia.2015.442 442 CHIMIA 2015, 69, No. 7/8 SCS LAUREATES AND AWARDS & FALL MEETING 2015 doi:10.2533/chimia.2015.442 Chimia 69 (2015) 442–446 © Schweizerische Chemische Gesellschaft Metal Complexes and Medicine: A Successful Combination Gilles Gasser* Werner Prize 2015 Abstract: Since the start of our independent research at the Department of Chemistry of the University of Zurich in 2009, our group has been, among other topics, working on the use of metal complexes in medicinal chemistry. In this short review article, we highlight our recent achievements in the use of such compounds to fight the parasitic disease schistosomiasis. Keywords: Bioorganometallic chemistry · Medicinal inorganic chemistry · Medicinal organometallic chemistry · Schistosomiasis SNSF Assistant Professor (2010). Gilles plexes of Fe, Sn, Bi, Lu, Hg, Sb, Pt, Au or is a recipient of several awards including As, for example, have been or are approved the Jean Landry Award of the University for the treatment of a range of conditions of Neuchâtel for Excellence during his in medicine. The majority of the readers Diploma Thesis, the Jürg Engi Award of of this article have most probably used in the University of Neuchâtel for the student the not-so-distant past the orange mercury- with the best marks in organic chemistry containing compound Merbromin (notably (2000), the Syngenta Award for the best marketed as Mercurochrome) as a topical PhD thesis in Chemistry of the University antiseptic (Fig. 1) although mercury is only of Neuchâtel (2004), an Alexander von perceived by the general public as a toxic Gilles Gasser was born and raised in Humboldt fellowship (2007) and the heavy metal. Even more surprising is the Neuchâtel (Switzerland). After his gradu- Werner Prize (2015). case of As2O3, which was used, among ation in chemistry at the University of others, by the Borgia family as a homi- Neuchâtel in 2000, Gilles worked for one cidal agent in the 15th and 16th centuries, year for the chemical company Lonza in 1. Introduction but which is approved by the FDA for the Visp (Switzerland). He then joined the lab- treatment of relapsed acute promyelocytic oratories of Prof. Helen Stoeckli-Evans at Thanks notably to the pioneering work leukemia under the trade name Trisenox. the University of Neuchâtel to undertake of Alfred Werner at the University of Zurich Finally, the metal gold, which is mostly a PhD thesis in supramolecular chemistry. in the field of coordination chemistry, the associated with luxury, has also found He was awarded his PhD in 2004. After use of metal complexes as reaction cata- application in medicinal chemistry. Three post-doctoral stays at Monash University lysts could be significantly advanced dur- Au(i) complexes, namely Auranofin (Fig. (Australia) with Prof. Leone Spiccia in ing the 20th century.[1] Another less obvious 1), Aurothiomalate and Aurothiosulfate bioinorganic chemistry and at the Ruhr- field which has undoubtedly profited from are approved drugs for the treatment of University Bochum (Germany) with Prof. the research performed by Alfred Werner rheumatoid arthritis. Nonetheless, the Nils Metzler-Nolte in bioorganometallic is medicinal chemistry.[2] Although metal most relevant examples in the field of chemistry, Gilles was given the opportuni- ions/metal complexes have been employed medicinal chemistry are undoubtedly the ty to start his independent research career in medicine since ancient times, the use of platinum-based anticancer drugs Cisplatin, at the University of Zurich, first as Swiss structurally defined metal complexes in Oxaliplatin and Carboplatin (Fig. 1). National Science Foundation (SNSF) this field mostly appeared at the beginning These metal complexes are currently used Ambizione fellow (2009) and then as a of the 20th century with the discovery by in more than 50% of the chemotherapeu- Ehrlich, in collaboration with Sahachiro tic treatments, often in combination with Hata, of the arsenic-containing organome- other drugs. tallic complex Arsphenamine (also called Despite the impressive success of these Salvarsan or Compound 606, see Fig. 1) as metal-based drugs, and more generally of an agent against syphilis.[3] This compound, drugs in all fields of medicine, there is un- whose exact structure was only unveiled doubtedly still an important need for the *Correspondence: Prof. Dr. G. Gasser in 2005,[4] was used against this infection development of new drugs to either treat University of Zurich [5,6] Department of Chemistry disease until the discovery of penicillin. incurable conditions or to improve the Winterthurerstrasse 190 Since then, many other metal complexes current available treatments which, for ex- CH-8057 Zurich have been found to be useful in medicinal ample, can lead to severe side-effects (i.e. Tel.: +41 44 635 46 30 [7–10] E-mail: [email protected] chemistry. As surprisingly as it can be treatment with Cisplatin). When we started www.gassergroup.com seen for the non-expert in the field, com- our independent research at the University SCS LAUREATES AND AWARDS & FALL MEETING 2015 CHIMIA 2015, 69, No. 7/8 443 this field of research is based on the pio- OH neering work of the groups of the French OH NH2 scientists Jaouen, Brocard and Biot. Those NH2 H2N researchers demonstrated that the addition H N 2 HO OH of a ferrocenyl moiety into the structure of As two known organic drugs, namely the anti- HO As As OH As As As As As As As NH2 cancer compound Tamoxifen and the anti- NH2 H N 2 H N malarial Chloroquine, to give the so-called 2 organometallic complexes Ferrocifens and HO OH HO OH Initial Envisaged Structure H2N H2N Ferroquine, respectively, allowed for nov- el, additional mode of actions compared to the parent organic drugs (Fig. 3). More specifically, the Ferrocifens were Official Structures shown to bind to the estrogen receptor Arsphenamine similarly to Tamoxifen.[23,24] This compet- OH itive binding represses estradiol-mediated Hg DNA transcription in the tumor tissue and NaO O O is therefore responsible for the anticancer OAc [25] H3N Cl activity of Tamoxifen. However, very O Br Br AcO S Au P Pt interestingly, the Ferrocifen with n = 4 AcO H N Cl COONa OAc 3 (Fig. 3) was also found to be active against breast cancer cell lines lacking this estro- gen receptor (i.e. ER(–) cell line), contrary Merchurochrome Auranofin Cisplatin to Tamoxifen, which is inactive on this cell line. This discovery was extremely exciting for two reasons: 1) one third of the breast O H2 O N O H3N O cancer patients do not express this recep- Pt Pt tor, rendering hormone therapy inefficient; O N O H3N H O O 2 2) the expression of the estrogen receptor sometimes becomes down-regulated under Tamoxifen treatment, turning the drug in- Carboplatin Oxaliplatin effective. This interesting observation was explained by the specific presence of the Fig. 1. Structures of metal complexes used in medicinal chemistry. organometallic moiety. Indeed, a redox activation was found to be responsible for the observed cytotoxicity in ER(–) cancer cells.[26] As shown in Scheme 1, the ac- of Zurich, our group decided to primarily of schistosomes (i.e. S. haematobium, S. tive metabolite hydroxyferrocifen can be focus its attention on two diseases, namely intercalatum, S. japonicum, S. mansoni, readily oxidized to give a quinone methide cancer and schistosomiasis. While the for- and S. mekongi), which are accountable for intermediate.[26] This quinine methide can mer disease does not need to be presented, human infections leading either to intesti- be then attacked by nucleophiles such as the latter is, very surprisingly, unknown nal or urogenital schistosomiasis.[16] This glutathione and nucleobases. This leads to to the general public. Schistosomiasis, disease is often associated with liver dam- the general toxicity and mutagenic poten- also known as bilharziasis, is a parasitic age resulting in swelling of the abdomen of tial of this compound. This mode of action disease which is responsible for 207 mil- the person affected. While this disease can was further confirmed when the research- lion infections each year in tropical and be treated at present, with the organic drug ers could prepare and biologically evalu- subtropical regions of sub-Saharan Africa, Praziquantel (PZQ, Fig. 2), the therapeutic ate the ruthenocene analogue of the active Asia and America.[11] In fact, it is the sec- situation is far from ideal. Reduced sus- Ferrocifen (see Fig. 3 – this compound will ond most prevalent parasitic disease in the ceptibility to PZQ has been reported, sug- be called Ruthenocifen in this review arti- world after malaria. The number of deaths gesting that this drug could become (much cle). These two complexes are isostructural associated with this disease significantly less) effective in the future.[17–19] This fact but, compared to Ferrocifen, Ruthenocifen varies depending on the studies (between is extremely worrying since there is no cur- is not redox active. Hence, as
Load more

Recommended publications
  • Zinc Complexes with Nitrogen Donor Ligands As Anticancer Agents
    molecules Review Zinc Complexes with Nitrogen Donor Ligands as Anticancer Agents Marina Porchia 1,* , Maura Pellei 2,* , Fabio Del Bello 3 and Carlo Santini 2 1 ICMATE-C.N.R., Corso Stati Uniti 4, 35127 Padova, Italy 2 Chemistry Division, School of Science and Technology, University of Camerino, via S. Agostino 1, 62032 Camerino, Italy; [email protected] 3 Medicinal Chemistry Unit, School of Pharmacy, University of Camerino, Via S. Agostino 1, 62032 Camerino, Italy; [email protected] * Correspondence: [email protected] (M.P.); [email protected] (M.P.) Academic Editor: Kogularamanan Suntharalingam Received: 7 November 2020; Accepted: 7 December 2020; Published: 9 December 2020 Abstract: The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. Zinc, the second most abundant trace element in the human body, is one of the most important micro-elements essential for human physiology. Its ubiquity in thousands of proteins and enzymes is related to its chemical features, in particular its lack of redox activity and its ability to support different coordination geometries and to promote fast ligands exchange. Analogously to other trace elements, the impairment of its homeostasis can lead to various diseases and in some cases can be also related to cancer development. However, in addition to its physiological role, zinc can have beneficial therapeutic and preventive effects on infectious diseases and, compared to other metal-based drugs, Zn(II) complexes generally exert lower toxicity and offer few side effects.
    [Show full text]
  • An Overview on Ligands of Therapeutically Interest
    Pharmacy & Pharmacology International Journal Review Article Open Access An overview on ligands of therapeutically interest Abstract Volume 6 Issue 3 - 2018 The principles governing metal-ligand complex stability and specificity depend on the 1 2 properties of both the metal and the chelating agent. The exploration of coordination Julia Martín, Miguel Ropero Alés, Agustin G 2 chemistry offers the real prospects of providing new understanding of intractable diseases Asuero and of devising novel therapeutics and diagnosis agents. Refinement in the approach to 1Department of Analytical Chemistry, Escuela Politécnica chelator design has come with a more subtle understanding of binding kinetics, catalytic Superior, University of Seville, Spain mechanisms and donor interactions. Ligands that effectively bind metal ions and also include 2Department of Analytical Chemistry, Faculty of Pharmacy, specific features to enhance targeting, reporting, and overall efficacy are driving innovation University of Seville, Spain in areas of disease, diagnosis and therapy. In this contribution the topics of bioinorganic medicinal chemistry, chelating agents in the treatment of metallic ion overload in the body, Correspondence: Julia Martín, Department of Analytical and expanding the notion of chelating agent in medicine are successively dealt with, paying Chemistry, Escuela Politécnica Superior, University of Seville. C/ then attention to platinum, gold, iron, copper and aluminium ion metal complexes having Virgen de África, 7, E–41011 Seville, Spain, Tel +34-9-5455-6250, medicinal interest. A tabular summary containing selected applications of ligands and Email [email protected] complexes of therapeutic interest is also shown to including the most relevant and current Received: March 26, 2018 | Published: May 30 2018 bibliography.
    [Show full text]
  • Here's Your E-Book
    Detox Outside the Box 1 Chronic degenerative diseases flood the American healthcare system with sufferers. ln spite of modern medicine's ability to reduce symptoms of many illnesses, their fundamental causes- and cures- still elude traditional practitioners. Because toxic heavy metals are associated with our two biggest challenges, cancer and heart disease (as well as many other severe disease states), the etiology of heavy metal toxicity must be recognized and addressed. Chelation is the answer. A therapy whose time has come, chelation should now be defined and understood as a 21st century modality of choice for removing toxic metals from the body. Some of the world's best known therapies and treatments were not accepted in their early days. For example, acceptance of vitamin C's benefits as a powerful antioxidant took a long time to influence traditional viewpoints. While chelation therapy with EDTA is in its infancy, it will prove as a powerful agent for the removal of toxic heavy metals. I also encourage all clinicians to get on board with this amazing modality. Intravenous chelation has been recognized for decades by the United States Food and Drug Administration as the treatment of choice for lead poisoning. Since intravenous chelation is time consuming and expensive, l've been administering chelation in the form of a suppository, and believe it is a revolutionary advancement. l've seen excellent results for over ten years with thousands of my patients and within the last three years I decided to study calcium disodium EDTA suppositories. I have now published proven results of its safety and efficacy in approved clinical trials.
    [Show full text]
  • Noble Metals in Medicine
    Noble Metals in Medicine Transition Metal Complexes as Drugs and Chemotherapeutic Agents BY NICHOLASFARRELL, Kluwer Academic Publishers, Dordrecht, 1989, 291 pages, ISBN 90-277-2828-3, Dfl. 180.00, €59.00 A number of books dealing with the generally having mechanisms of action different biological activity, particularly the therapeutic from that of cisplatin. In some cases metal ions activity, of metal complexes have been publish- are acting by enhancing cellular uptake of ac- ed in recent years. Interest in the field has been tive ligands, a principle which is exemplified promoted by the clinical use of a number of several more times in subsequent chapters deal- precious metal complexes, including platinum ing with anti-bacterial, anti-viral and anti- anti-cancer, gold anti-arthritis and silver anti- arthritic activity. bacterial agents. Now a useful new addition to The utilisation of the redox properties of the literature has been published, somewhat metal compounds is illustrated by a chapter oddly, as Volume I I in the series “Catalysis by devoted to metal ions as mediators of the anti- Metal Complexes”. tumour action of antibiotics such as the In addition to an introduction and appendices bleomycins. Binding of a metal ion, for exam- the book contains 12 chapters, the first six of ple iron(II), to the antibiotic is believed to be which are devoted primarily to the anti-tumour involved in generating activated oxygen species activity of metal complexes, an area to which leading to oxidative cleavage of DNA. the author has made a number of interesting Another chapter discusses the interaction of contributions through his publications on metal complexes with radiation in biological platinum complexes.
    [Show full text]
  • Bioinorganic Chemistry Module No and Title 1: Introduction
    Subject Chemistry Paper No and Title 15: Bioinorganic Chemistry Module No and 1: Introduction: Bioinorganic Chemistry Title Module Tag CHE_P15_M1 CHEMISTRY Paper No. 15: Bioinorganic Chemistry Module No. 1: Introduction: Bioinorganic Chemistry TABLE OF CONTENTS 1. Learning Outcomes 2. Introduction 3. Metal function in Metalloproteins 4. Functions of metalloenzymes 5. Communication roles for metals in Biology 6. Interactions of metal ions and nucleic acids 7. Metal-Ion Transport and Storage 7.1 General aspects of storage and transport of metal-ions 7.2 Iron: Function, Storage and Transport 7.2.1. Function 7.2.2. Iron storage 7.2.2.1. Ferritin 7.2.2.2. Hemosiderin 7.2.3. Transport of Iron: Transferrin 7.3 Calcium: Function, Storage and Transport 7.3.1. Function 7.3.2. Calcium Storage 7.3.3. Calcium Pump 7.4 Copper: Function, Storage and Transport 7.4.1. Function 7.4.2. Storage of Copper 7.4.3. Copper transport 8. Summary CHEMISTRY Paper No. 15: Bioinorganic Chemistry Module No. 1: Introduction: Bioinorganic Chemistry 1. Learning Outcomes After studying this module, you shall be able to Know the importance of inorganic elements. Categorize the inorganic elements according to their roles in the biological system. Learn the function of important elements such as Iron, Calcium and Copper. Identify the general aspects of storage and transport of metal-ions. Know the role of metals in medicine. 2. Introduction Bioinorganic chemistry constitutes the discipline at the interface of the more classical areas of inorganic chemistry and biology. Although biology is generally related to organic chemistry, inorganic elements are also important to life processes.
    [Show full text]
  • The First-Row Transition Metals in the Periodic Table of Medicine
    Review The First-Row Transition Metals in the Periodic Table of Medicine Cameron Van Cleave 1 and Debbie C. Crans 1,2,* 1 Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA 2 Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA * Correspondence: [email protected] Received: 21 June 2019; Accepted: 27 August 2019; Published: 6 September 2019 Abstract: In this manuscript, we describe medical applications of each first-row transition metal including nutritional, pharmaceutical, and diagnostic applications. The 10 first-row transition metals in particular are found to have many applications since there five essential elements among them. We summarize the aqueous chemistry of each element to illustrate that these fundamental properties are linked to medical applications and will dictate some of nature’s solutions to the needs of cells. The five essential trace elements—iron, copper, zinc, manganese, and cobalt—represent four redox active elements and one redox inactive element. Since electron transfer is a critical process that must happen for life, it is therefore not surprising that four of the essential trace elements are involved in such processes, whereas the one non-redox active element is found to have important roles as a secondary messenger.. Perhaps surprising is the fact that scandium, titanium, vanadium, chromium, and nickel have many applications, covering the entire range of benefits including controlling pathogen growth, pharmaceutical and diagnostic applications, including benefits such as nutritional additives and hardware production of key medical devices. Some patterns emerge in the summary of biological function andmedical roles that can be attributed to small differences in the first-row transition metals.
    [Show full text]
  • Targeting Schistosome Cholinesterases for Vaccine and Drug Development
    ResearchOnline@JCU This file is part of the following work: Tedla, Bemnet A. (2019) Targeting schistosome cholinesterases for vaccine and drug development. PhD Thesis, James Cook University. Access to this file is available from: https://doi.org/10.25903/5da91b6efb955 Copyright © 2019 Bemnet A. Tedla. The author has certified to JCU that they have made a reasonable effort to gain permission and acknowledge the owners of any third party copyright material included in this document. If you believe that this is not the case, please email [email protected] Targeting Schistosome Cholinesterases for Vaccine & Drug Development Thesis submitted by: Bemnet A Tedla College of Public Health, Medical & Veterinary Sciences Centre for Molecular Therapeutics Australian Institute of Tropical Health and Medicine James Cook University This dissertation is submitted for the degree of Doctor of Philosophy March 2019 Supervisors: Doctor Mark Pearson Professor Alex Loukas Statement of contribution Statement on the contributions of others Nature of assistance Contributions Name Affiliation Intellectual support Project plan and Dr Mark Pearson James Cook University development Prof Alex Loukas James Cook University Editorial support Dr Mark Pearson James Cook University Prof Alex Loukas James Cook University Lab facility support Prof Alex Loukas James Cook University Ruthenium metal Prof Grant Collins UNSW (ADFA) complex Dr Madhu Sundaraneedi UNSW (ADFA) Prof Richard Keens James Cook University, University of Adelaide Financial support Research Prof Alex
    [Show full text]
  • Chapter 3 Synthesis of HDAC Inhibitors
    A University of Sussex PhD thesis Available online via Sussex Research Online: http://sro.sussex.ac.uk/ This thesis is protected by copyright which belongs to the author. This thesis cannot be reproduced or quoted extensively from without first obtaining permission in writing from the Author The content must not be changed in any way or sold commercially in any format or medium without the formal permission of the Author When referring to this work, full bibliographic details including the author, title, awarding institution and date of the thesis must be given Please visit Sussex Research Online for more information and further details Biological Evaluation of Ferrocene Derivatives Supojjanee Sansook Supervisor Prof John Spencer Submitted to the University of Sussex in part fulfilment of the requirements of the degree of Doctor of Philosophy March 2017 i Declaration I hereby declare that this thesis is my own work and effort and that it has not been submitted anywhere for any award of another degree. I also undertake that any quotation or paraphrase from the published work of other people has been acknowledged. This work was supervised by Prof John Spencer. Supojjanee Sansook ii Acknowledgements Firstly, I would like to express my sincere thankfulness to my advisor Prof John Spencer for the continuous support of my Ph.D. study, for his encouragement, patience, motivation, guidance and enormous knowledge. His supervision helped me all the time of research and writing of my thesis. I am very grateful to my 2nd supervisor, Dr. Hazel Cox for useful discussions and her kindness in this research.
    [Show full text]
  • Medical Uses of Silver: History, Myths, and Scientific Evidence
    Perspective Cite This: J. Med. Chem. 2019, 62, 5923−5943 pubs.acs.org/jmc Medical Uses of Silver: History, Myths, and Scientific Evidence Serenella Medici,*,† Massimiliano Peana,*,† Valeria M. Nurchi,‡ and Maria Antonietta Zoroddu† † Department of Chemistry and Pharmacy, University of Sassari, 07100 Sassari, Italy ‡ Department of Life and Environmental Sciences, University of Cagliari, 09042 Cagliari, Italy ABSTRACT: Silver has no biological role, and it is particularly toxic to lower organisms. Although several silver formulations employed in medicine in the past century are prescribed and sold to treat certain medical conditions, most of the compounds, including those showing outstanding properties as antimicrobial or anticancer agents, are still in early stages of assessment, that is, in vitro studies, and may not make it to clinical trials. Unlike other heavy metals, there is no evidence that silver is a cumulative poison, but its levels can build up in the body tissues after prolonged exposure leading to undesired effects. In this review, we deal with the journey of silver in medicine going from the alternative or do-it-yourself drug to scientific evidence related to its uses. The many controversies push scientists to move toward a more comprehensive understanding of the mechanisms involved. 1. INTRODUCTION intestine) healthier than ever”, and “it acts as a second immune system”. Sometimes the impulse to write a review may arise from a casual fi fi conversation with a layperson under unusual circumstances. In The Chemist, nally, connected to the scienti c publication this case, the man in the street approached the Chemistry bench databases and began to work.
    [Show full text]
  • Therapeutic Use and Toxicity of Metal Ions in the Clinic
    Preface to Volume 19 Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic The metal ions discussed in this volume play significant roles in medicine. Most are deemed ‘essential’ for life: iron, manganese, cobalt, zinc, copper, molyb- denum, and the metalloid selenium. The essentiality of others, such as chromium, vanadium, and nickel, remains the subject of intense debate. As pointed out in Chapter 1, whether essential (or not), maintenance of metal ion homeostasis in humans is crucial, as perturbations often result in disease. In addition to the (possibly) essential metal ions, other metal ions play important roles in human health, often by causing harm (e.g., the metalloid arsenic) but also by their use in the diagnosis or treatment of human diseases (gadolinium, gallium, cobalt, molybdenum, lithium, gold, silver). After going through a brief history of drug development in Chapter 2, readers may appreciate the continuing challenges faced in human medicine. While the rise of biopharmaceuticals has proven beneficial for numerous diseases, they are costly, and unlikely to provide ‘cures’ for all diseases. Thus, small molecules continue to play an important role in the treatment of human diseases, as out- lined in the discussion of attempts to solve two therapeutic challenges: malaria and Alzheimer’s disease. Iron, while arguably the most intensely studied metal ion in human medicine, remains poorly understood. Iron is essential for life, yet toxic, as elegantly pre- sented in Chapters 3 to 7. The essentiality of iron for both humans and pathogens means that the administration of iron is a double-edged sword.
    [Show full text]
  • Dissertation (PDF)
    DISSERTATION APPROVED BY Na^ Ln,zÕrq är4.%*x% J / Date ,rá*.Martin, Jr., Ph.D., c¡ui, Lynn Gibson, Ph.D., Committee Member J Moss Breen, Ph.D., Director Gail M. Jensen, Ph.D., Dean ENVIRONMENTAL ISSUES ASSOCIATED WITH CREMATORIA: A REVIEW ___________________________________ By BRAD WILLIAM KUCHNICKI ___________________________________ A DISSERTATION Submitted to the faculty of the Graduate School of the Creighton University in Partial Fulfillment of the Requirements for the Degree of Doctor of Education in the Department of Interdisciplinary Studies _________________________________ Omaha, NE (May, 2019) Copyright 2019, Brad William Kuchnicki This document is copyrighted material. Under copyright law, no part of this document May be reproduced without the expressed permission of the author. iii Abstract This study aims to educate both funeral industry practitioners and the general public about toxic emissions from crematoria as well as introduce sustainable practices to offset toxic emissions. Using publicly available data from four crematoria around the world, this study examines various factors associated with emissions including mercury, polychlorinated dibenzofurans, and Sulphur dioxide. The data was then converted to correlate the emissions results from the crematoriums to that of hazardous waste incineration. Due to the United States limited to non-existent regulations towards the industrial process of cremation, it was necessary to infer the data into a more relatable output. Although the modern cremation has been in practice for over a century, it can be said that measures to improve and mitigate impacts to the environment have moved quite slow. The conclusion of this research points towards continued studies; to engage leaders to consider the ramifications of the trends, especially when documented dangers of the by-product exist.
    [Show full text]
  • Chemistry of Metals in Medicine
    COST ACTION D8 (1996-2001) Workshop Chemistry of Metals in Medicine- The Perspective In2d2ustrial-24 January 1997 Louvain-la-Neuve, Belgium Report Summary The Workshop was attended by 61 participants from 20 countries. Most of the speakers were industrialists and the Chairpersons and Discussion Leaders were academics. The area "Chemistry of Metals in Medicine" has the potential for producing innovative, high quality, and original research. This is a new and emerging area of biomedical chemistry. Small firms are already being established which are devoted to the new elemental medicine. Major pharmaceutical and healthcare industries too are becoming aware of the major impact which metal chemistry is likely to have on traditional organic pharmacology and of the new opportunities which it presents for advances including the development of metalloenzyme-specific inhibitors, targeted radionuclide complexes for diagnosis and therapy, contrast agents for magnetic resonance imaging, safer mineral and vitamin supplements, new agents for the treatment of neurological, gastrointestinal and cardiovascular disease, skin conditions, cancer, and microbial and viral infections. The European scientific and technological research base in this area is potentially attractive for business. Industrial collaboration and cooperation can be accommodated within the COST framework. The COST programme provides funds to allow concertation of research work in 25 European countries (and others if there is justified mutual benefit). The research work itself is funded by national bodies. COST is valuable because it promotes: working as a European team, development of synergy in research activities, establishment of an effective critical mass, avoidance of dupfication of work, rapid dissemination of results, the establishment of a strategy for fundamental research in Europe, coordination of scientific policies, optimisation of European mobility.
    [Show full text]