This first comprehensive book to cover the expanding field of bioorganometallics represents the perfect starting point for beginners but also an excellent source of high quality information for experts in the field. Edited by a pioneer in the field with an excellent standing within the community, this book begins with the history of bioorganometallics, before going on to cover pharmaceuticals, bioorganometallic chemistry and radiopharmaceuticals. A must for bioinorganic chemists, the pharmaceutical industry, chemists working in organometallics and biochemists.
Metal-based anticancer drugs are among the most successful therapeutic agents, as evidenced by the frequent prescription of selected platinum and arsenic compounds to patients. Metal-based Anticancer Agents covers the interdisciplinary world of inorganic drug discovery and development by introducing the most prominent compound classes based on different transition metals, discussing emerging concepts and enabling methods, as well as presenting key pre-clinical and clinical aspects. Recent progress on the unique features of next-generation targeted metal-based anticancer agents, including supramolecular coordination complexes used for both therapy and drug delivery, promise a bright future beyond the benefits of pure cytotoxic activity. With contributions from global leaders in the field, this book will serve as a useful reference to established researchers as well as a practical guide to those new to metallodrugs, and postgraduate students of medicinal chemistry and metallobiology.
30 years after its discovery as an antitumor agent, cisplatin represents today one of the most successful drugs in chemotherapy. This book is intended to reminisce this event, to take inventory, and to point out new lines of development in this field. Divided in 6 sections and 22 chapters, the book provides an up-to-date account on topics such as - the chemistry and biochemistry of cisplatin, - the clinical status of Pt anticancer drugs, - the impact of cisplatin on inorganic and coordination chemistry, - new developments in drug design, testing and delivery. It also includes a chapter describing the historical development of the discovery of cisplatin. The ultimate question - How does cisplatin kill a cell? - is yet to be answered, but there are now new links suggesting how Pt binding to DNA may trigger a cascade of cellular reactions that eventually result in apoptosis. p53 and a series of damage recognition proteins of the HMG-domain family appear to be involved. The book addresses the problem of mutagenicity of Pt drugs and raises the question of the possible relevance of the minor DNA adducts, e.g. of interstrand cross-links, and the possible use of trans-(NH3)2Pt(II)-modified oligonucleotides in antisense and antigene strategies. Our present understanding of reactions of cisplatin with DNA is based upon numerous model studies (from isolated model nucleobases to short DNA fragments) and application of a large body of spectroscopic and other physico-chemical techniques. Thanks to these efforts there is presently no other metal ion whose reactions with nucleic acids are better understood than Pt. In a series of chapters, basic studies on the interactions of Pt electrophiles with nucleobases, oligonucleotides, DNA, amino acids, peptides and proteins are reported, which use, among others, sophisticated NMR techniques or X-ray crystallography, to get remarkable understanding of details on such reactions. Reactivity of cisplatin, once bound to DNA and formerly believed to be inert enough to stay, is an emerging phenomenon. It has (not yet) widely been studied but is potentially extremely important. Medicinal bioinorganic chemistry - the role of metal compounds in medicine - has received an enormous boost from cisplatin, and so has bioinorganic chemistry as a whole. There is hardly a better example than cisplatin to demonstrate what bioinorganic chemistry is all about: The marriage between classic inorganic (coordination) chemistry and the other life sciences - medicine, pharmacy, biology, biochemistry. Cisplatin has left its mark also on areas that are generally considered largely inorganic. The subject of mixed-valance Pt compounds is an example: From the sleeping beauty it made its way to the headlines of scientific journals, thanks to a class of novel Pt antitumor agents, the so-called "platinum pyrimidine blues". In the aftermath diplatinum (III) compounds were recognized and studies in large numbers, and now an organometalic chemistry of these diplatinum (III) species is beginning to emerge. The final section of the book is concerned with new developments such as novel di- and trinuclear Pt(II) drugs with DNA binding properties different from those of cisplatin, with orally active Pt(IV) drugs which are presently in clinical studies, and with attempts to modify combinatorial chemistry in such a way that it may become applicable to fast screening of Pt antitumor drugs. The potential of including computational methods in solving questions of Pt-DNA interactions is critically dealt with in the concluding chapter.
Due to a great chemical similarity with the biological calcified tissues, many calcium orthophosphates possess remarkable biocompatibility and bioactivity. Materials scientists use this property extensively to construct artificial bone grafts that are either entirely made of or only surface-coated with the biologically relevant calcium orthophospha
This book is organized into 12 important chapters that focus on the progress made by metal-based drugs as anticancer, antibacterial, antiviral, anti-inflammatory, and anti-neurodegenerative agents, as well as highlights the application areas of newly discovered metallodrugs. It can prove beneficial for researchers, investigators and scientists whose work involves inorganic and coordination chemistry, medical science, pharmacy, biotechnology and biomedical engineering.
Part A.: Overviews of biological inorganic chemistry : 1. Bioinorganic chemistry and the biogeochemical cycles -- 2. Metal ions and proteins: binding, stability, and folding -- 3. Special cofactors and metal clusters -- 4. Transport and storage of metal ions in biology -- 5. Biominerals and biomineralization -- 6. Metals in medicine. -- Part B.: Metal ion containing biological systems : 1. Metal ion transport and storage -- 2. Hydrolytic chemistry -- 3. Electron transfer, respiration, and photosynthesis -- 4. Oxygen metabolism -- 5. Hydrogen, carbon, and sulfur metabolism -- 6. Metalloenzymes with radical intermediates -- 7. Metal ion receptors and signaling. -- Cell biology, biochemistry, and evolution: Tutorial I. -- Fundamentals of coordination chemistry: Tutorial II.
This book will describe Ruthenium complexes as chemotherapeutic agent specifically at tumor site. It has been the most challenging task in the area of cancer therapy. Nanoparticles are now emerging as the most effective alternative to traditional chemotherapeutic approach. Nanoparticles have been shown to be useful in this respect. However, in view of organ system complicacies, instead of using nanoparticles as a delivery tool, it will be more appropriate to synthesize a drug of nanoparticle size that can use blood transport mechanism to reach the tumor site and regress cancer. Due to less toxicity and effective bio-distribution, ruthenium (Ru) complexes are of much current interest. Additionally, lumiscent Ru-complexes can be synthesized in nanoparticle size and can be directly traced at tissue level. The book will contain the synthesis, characterization, and applications of various Ruthenium complexes as chemotherapeutic agents. The book will also cover the introduction to chemotherapy, classification of Ru- complexes with respect to their oxidation states and geometry, Ruthenium complexes of nano size: shape and binding- selectivity, binding of ruthenium complexes with DNA, DNA cleavage studies and cytotoxicity. The present book will be more beneficial to researchers, scientists and biomedical. Current book will empower specially to younger generation to create a new world of ruthenium chemistry in material science as well as in medicines. This book will be also beneficial to national/international research laboratories, and academia with interest in the area of coordination chemistry more especially to the Ruthenium compounds and its applications.
Contents: Gérard Jaouen, Nils Metzler-Nolte : Introduction ; Stéphane GIBAUD and Gérard JAOUEN: Arsenic - based drugs: from Fowler’s solution to modern anticancer chemotherapy; Ana M. Pizarro, Abraha Habtemariam and Peter J. Sadler : Activation Mechanisms for Organometallic Anticancer Complexes; Angela Casini, Christian G. Hartinger, Alexey A. Nazarov, Paul J. Dyson : Organometallic antitumour agents with alternative modes of action; Elizabeth A. Hillard, Anne Vessières, Gerard Jaouen : Ferrocene functionalized endocrine modulators for the treatment of cancer; Megan Hogan and Matthias Tacke : Titanocenes – Cytotoxic and Anti-Angiogenic Chemotherapy Against Advanced Renal-Cell Cancer; Seann P. Mulcahy and Eric Meggers : Organometallics as Structural Scaffolds for Enzyme Inhibitor Design; Christophe Biot and Daniel Dive : Bioorganometallic Chemistry and Malaria; Nils Metzler-Nolte : Biomedical applications of organometal-peptide conjugates; Roger Alberto : Organometallic Radiopharmaceuticals; Brian E. Mann : Carbon Monoxide – an essential signaling molecule.
Over the past 20 years aqueous organometallic catalysis has found applications in small- scale organic synthesis in the laboratory, as well as in the industrial production of chemicals with a combined output close to one million tons per year. Aqueous/organic two-phase reactions allow easy product-catalyst separation and full catalyst recovery which mean clear benefits not only in economic but also in environmental and green chemistry contexts. Instead of putting together a series of expert reviews of specialized fields, this book attempts to give a comprehensive yet comprehensible description of the various catalytic transformations in aqueous systems as seen by an author who has been working on aqueous organometallic catalysis since its origin. Emphasis is put on the discussion of differences between related non-aqueous and aqueous processes due to the presence of water. The book will be of interest to experts and students working in catalysis, inorganic chemistry or organic synthesis, and may serve as a basis for advanced courses.
