Bioorganometallic Chemistry E-Book

• Herausgeber: Wiley-VCH
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 750

Veröffentlichungsjahr: 2014

Beschreibung

An up-to-date reference reflecting the significant advances and important breakthroughs made in this emerging discipline over the last decade.
As such, the book provides an overview of the latest developments and future trends in the field, focusing on such applications as the development of potentially active organometallic drugs against incurable diseases, as well as in such areas as catalysis, energy, analytical chemistry, and imaging.
The renowned editor, who established the term "bioorganometallics", and his international team of experts have put together a valuable resource for researchers in organometallic, inorganic, medicinal, and biochemistry.

Leseprobe

CONTENTS

Cover

Related Titles

Title Page

Copyright

List of Contributors

Preface

Part One: Medicinal Chemistry

Chapter 1: Organometallic Complexes as Enzyme Inhibitors: A Conceptual Overview

1.1 Introduction

1.2 Organometallic Compounds as Inert Structural Scaffolds for Enzyme Inhibition

1.3 Organometallic Compounds Targeting Specific Protein Residues

1.4 The Bioisosteric Substitution

1.5 Novel Mechanisms of Enzyme Inhibition with Organometallic Compounds

1.6 Organometallic Compounds as Cargo Delivers of Enzyme Inhibitors

1.7 Organometallic Enzyme Inhibitors for Theranostic Purposes

1.8 Conclusion

Acknowledgments

Abbreviations

References

Chapter 2: The Biological Target Potential of Organometallic Steroids

2.1 Introductory Note on Nuclear Receptors

2.2 Steroids and Organometallics: An Overview of the Transitional Period from the Use of Organometallics in Synthesis to the Emergence of Bioorganometallics

2.3 Epilog

Acknowledgments

References

Chapter 3: Chirality in Organometallic Anticancer Complexes

3.1 Introduction

3.2 Chirality in Arene Complexes

3.3 CIP System for the Nomenclature of Chiral-at-Metal Arene Complexes

3.4 Chiral Organometallic Complexes as Anticancer Agents

3.5 Half-Sandwich Complexes with Chiral Metal Centers

3.6 Conclusions

Acknowledgments

References

Chapter 4: Gold Organometallics with Biological Properties

4.1 Introduction: The Use of Gold in Medicine

4.2 Anticancer Gold Organometallics and Proposed Biological Targets

4.3 Conclusions and Perspectives

List of Abbreviations

References

Chapter 5: On the Molecular Mechanisms of the Antimalarial Action of Ferroquine

5.1 History and Development

5.2 Mechanism(s) of Action of 4-Aminoquinoline Antimalarials

5.3 Mechanism(s) of Action of Ferroquine as an Antimalarial

5.4 Conclusion

Acknowledgments

List of Abbreviations

References

Chapter 6: Metal Carbonyl Prodrugs: CO Delivery and Beyond

6.1 Introducing CO in Biology

6.2 Therapeutic Delivery of CO

6.3 Biological and Therapeutic Results Obtained with the Early-Stage CORMs

6.4 Beyond the Early-Stage CORMs: Strategies for Finding New Candidates

6.5 Intracellular Detection of CORMs, Mechanistic Studies, and Other Unanswered Questions

6.6 Designing Pharmacologically Useful, Drug-like CORMs

6.7 Final Remarks and Perspectives

List of Abbreviations

References

Chapter 7: Dinitrosyl Iron Complexes with Natural Thiol-Containing Ligands: Physicochemistry, Biology, and Medicine

7.1 Introduction

7.2 The History of Detection and Identification of DNIC with Thiol-Containing Ligands in Microorganisms and Animal Tissues

7.3 Physicochemistry of DNIC with Natural Thiol-Containing Ligands

7.4 Biological Effects of DNIC with Thiol-Containing Ligands

7.5 DNIC with Thiol-Containing Ligands as a Basis in the Design of Drugs with a Broad Range of Therapeutic Activities

List of Abbreviations

Acknowledgments

References

Part Two: Metalloproteins, Catalysis, and Energy Production

Chapter 8: The Bioorganometallic Chemistry of Hydrogenase

8.1 Introduction

8.2 Structure and Function

8.3 Natural Biosynthesis and Synthetic Analogs of the Active Sites

8.4 Comments and Conclusion

References

Chapter 9: Bio-Organometallic Systems for the Hydrogen Economy: Engineering of Electrode Materials and Light-Driven Devices

9.1 Introduction

9.2 Electrode Materials for Hydrogen Evolution and Uptake

9.3 Light-Driven Systems for Hydrogen Evolution

9.4 Artificial Photosynthetic Systems

9.5 Summary and Conclusions

List of Abbreviations

References

Chapter 10: Artificial Metalloenzymes Containing an Organometallic Active Site

10.1 Introduction

10.2 Dative Anchoring

10.3 Supramolecular Anchoring

10.4 Covalent Anchoring

10.5 Mixed Anchoring Modes

10.6 Peptide Scaffolds

10.7 Summary and Outlook

List of Abbreviations

References

Part Three: Bioanalysis

Chapter 11: Organometallic Bioprobes for Cellular Imaging

11.1 Introduction

11.2 Luminescence

11.3 Vibrational Spectroscopy

11.4 Miscellaneous

11.5 Conclusions

Acknowledgments

Abbreviations

References

Index

End User License Agreement

List of Tables

Table 2.1

Table 2.2

Table 2.3

Table 2.4

Table 2.5

Table 2.6

Table 2.7

Table 3.1

Table 7.1

Table 7.2

Table 11.1

List of Illustrations

Figure 1.1

Figure 1.2

Figure 1.3

Figure 1.4

Figure 1.5

Figure 1.6

Figure 1.7

Figure 1.8

Figure 1.9

Scheme 1.1

Scheme 1.2

Figure 1.10

Figure 1.11

Scheme 1.3

Scheme 1.4

Figure 1.12

Figure 1.13

Figure 1.14

Figure 1.15

Figure 1.16

Scheme 1.5

Figure 1.17

Figure 1.18

Figure 1.19

Figure 1.20

Figure 1.21

Figure 1.22

Figure 1.23

Figure 1.24

Figure 1.25

Figure 1.26

Figure 1.27

Scheme 1.6

Figure 2.1

Figure 2.2

Figure 2.3

Scheme 2.1

Scheme 2.2

Scheme 2.3

Scheme 2.4

Figure 2.4

Figure 2.5

Scheme 2.5

Scheme 2.6

Scheme 2.7

Scheme 2.8

Figure 3.1

Figure 3.2

Figure 3.3

Scheme 3.1

Figure 3.4

Figure 3.5

Figure 3.6

Figure 3.7

Figure 3.8

Figure 3.9

Figure 3.10

Figure 3.11

Figure 3.12

Figure 3.13

Figure 3.14

Figure 3.15

Figure 3.16

Figure 3.17

Figure 3.18

Figure 3.19

Figure 3.20

Figure 4.1

Figure 4.2

Scheme 4.1

Figure 4.3

Figure 4.4

Figure 4.5

Scheme 4.2

Figure 4.6

Figure 4.7

Figure 4.8

Figure 4.9

Figure 4.10

Figure 5.1

Figure 5.2

Figure 5.3

Figure 5.4

Figure 5.5

Figure 5.6

Figure 5.7

Figure 5.8

Figure 5.9

Figure 6.1

Scheme 6.1

Figure 6.2

Figure 6.3

Figure 6.4

Figure 6.5

Figure 6.6

Figure 6.7

Figure 6.8

Figure 6.9

Figure 6.10

Scheme 6.2

Figure 6.11

Figure 6.12

Figure 6.13

Figure 7.1

Figure 7.2

Scheme 7.1

Scheme 7.2

Scheme 7.3

Scheme 7.4

Figure 7.3

Figure 7.4

Figure 7.5

Figure 7.6

Figure 7.7

Figure 7.8

Figure 7.9

Figure 7.10

Figure 7.11

Figure 7.12

Figure 7.13

Figure 7.14

Figure 8.1

Figure 8.2

Figure 8.3

Figure 8.4

Figure 8.5

Figure 8.6

Figure 8.7

Figure 8.8

Scheme 8.1

Scheme 8.2

Scheme 8.3

Figure 8.9

Figure 8.10

Figure 8.11

Figure 8.12

Scheme 8.4

Figure 8.13

Figure 8.14

Figure 8.15

Figure 8.16

Figure 8.17

Figure 8.18

Figure 9.1

Figure 9.2

Figure 9.3

Figure 9.4

Figure 9.5

Figure 9.6

Figure 9.7

Figure 9.8

Figure 9.9

Figure 9.10

Figure 9.11

Figure 9.12

Figure 9.13

Figure 9.14

Figure 9.15

Figure 9.16

Scheme 10.1

Scheme 10.2

Scheme 10.3

Figure 10.1

Scheme 10.4

Figure 10.2

Scheme 10.5

Scheme 10.6

Figure 10.3

Figure 10.4

Figure 10.5

Figure 10.6

Scheme 10.7

Scheme 10.8

Figure 10.7

Figure 10.8

Scheme 10.9

Scheme 10.10

Scheme 10.11

Figure 10.9

Scheme 10.12

Figure 10.10

Scheme 10.13

Scheme 10.14

Figure 10.11

Figure 10.12

Figure 10.13

Scheme 10.15

Figure 10.14

Scheme 10.16

Figure 10.15

Figure 10.16

Scheme 10.17

Figure 10.17

Figure 10.18

Figure 10.19

Figure 10.20

Scheme 10.18

Scheme 11.1

Scheme 11.2

Figure 11.1

Figure 11.2

Scheme 11.3

Scheme 11.4

Figure 11.3

Figure 11.4

Scheme 11.5

Figure 11.5

Figure 11.6

Figure 11.7

Figure 11.8

Scheme 11.6

Figure 11.9

Scheme 11.7

Figure 11.10

Figure 11.11

Figure 11.12

Figure 11.13

Figure 11.14

Scheme 11.8

Figure 11.15

Scheme 11.9

Figure 11.16

Scheme 11.10

Figure 11.17

Figure 11.18

Figure 11.19

Figure 11.20

Scheme 11.11

Figure 11.21

Scheme 11.12

Figure 11.22

Guide

Cover

Table of Contents

Begin Reading

Part 1

Chapter 1

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Bioorganometallic Chemistry

Applications in Drug Discovery, Biocatalysis, and Imaging

Edited by

Gérard Jaouen

Michèle Salmain

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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany

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Print ISBN: 978-3-527-33527-5

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List of Contributors

Maria Agostina Cinellu

Università degli Studi di Sassari

Dipartimento di Chimica e Farmacia

Via Vienna 2

Sassari 07100

Italy

Philipp Anstaett

University of Zurich

Department of Chemistry

Winterthurerstrasse 190

8057 Zurich

Switzerland

Vincent Artero

Univ Grenoble Alpes CNRS CEA-Grenoble

Laboratoire de Chimie et Biologie des Métaux

17 rue des Martyrs

38054 Grenoble Cedex 9

France

Ryan D. Bethel

Texas A&M University

Department of Chemistry

College Station, TX 77843

USA

Christophe Biot

Université Lille 1

Unité de Glycobiologie Structurale et Fonctionnelle

CNRS UMR 8576, IFR 147

CitéScientifique

59650 Villeneuve d'Ascq Cedex

France

Angela Casini

University of Groningen

Department Pharmacokinetics, Toxicology and Targeting

Research Institute of Pharmacy

Antonius Deusinglaan 1

Groningen 9713 AV

The Netherlands

Murielle Chavarot-Kerlidou

Univ Grenoble Alpes CNRS CEA-Grenoble

Laboratoire de Chimie et Biologie des Métaux

17 rue des Martyrs

38054 Grenoble Cedex 9

France

Pascale Chenevier

University Grenoble Alpes, INAC-SPRAM

CEA, INAC-SPRAM

CNRS UMR 5819

17 rue des Martyrs

38000 Grenoble

France

Marcetta Y. Darensbourg

Texas A&M University

Department of Chemistry

College Station, TX 77843

USA

Faustine Dubar

Université Lille 1

Unité de Glycobiologie Structurale et Fonctionnelle

CNRS UMR 8576, IFR 147

CitéScientifique

59650 Villeneuve d'Ascq Cedex

France

Gilles Gasser

University of Zurich

Department of Chemistry

Winterthurerstrasse 190

8057 Zurich

Switzerland

Takashi Hayashi

Osaka University

Department of Applied Chemistry

Graduate School of Engineering

2-1 Yamada-oka, Suita

Osaka 565-0871

Japan

Gérard Jaouen

PSL, Chimie ParisTech

11, rue Pierre et Marie Curie

F-75005 Paris

France

Emanuela Licandro

Università degli studi di Milano

Dipartimento di Chimica

Via C. Golgi, 19

I-20133 Milano

Italy

Michael J. McGlinchey

University College Dublin

UCD School of Chemistry and Chemical Biology

Belfield

Dublin 4

Ireland

Akira Onoda

Osaka University

Department of Applied Chemistry

Graduate School of Engineering

2-1 Yamada-oka, Suita

Osaka 565-0871

Japan

Ingo Ott

Technische Universität Braunschweig

Institute of Medicinal and Pharmaceutical Chemistry

Beethovenstr. 55

Braunschweig 38106

Germany

Monica Panigati

Università degli studi di Milano

Dipartimento di Chimica

Via C. Golgi, 19

I-20133 Milano

Italy

Carlos C. Romão

Universidade Nova de Lisboa

Instituto de Tecnologia Química e Biológica António Xavier

Av. da República

Oeiras 2780-157

Portugal

and

Alfama Lda

Instituto de Biologia Experimental e Tecnológica (IBET)

Av. da República

Oeiras 2780-157

Portugal

María J. Romero

University of Warwick

Department of Chemistry

Gibbet Hill Road

Coventry CV4 7AL

UK

Peter J. Sadler

University of Warwick

Department of Chemistry

Gibbet Hill Road

Coventry CV4 7AL

UK

Michèle Salmain

Sorbonne Universités, UPMC Univ Paris 06

UMR 8232, IPCM

F-75005 Paris

France

Siden Top

Sorbonne Universités, UPMC Univ Paris 06

UMR 8232, IPCM

F-75005 Paris

France

Anatoly F. Vanin

N.N. Semenov Institute of Chemical Physics

Russian Academy of Sciences

Kosygin Str. 4

119991 Moscow

Russia

Anne Vessières

Sorbonne Universités, UPMC Univ Paris 06

UMR 8232, IPCM

F-75005 Paris

France

Helena L.A. Vieira

Universidade Nova de Lisboa

CEDOC, Faculdade de Ciências Médicas

Campo dos Mártires da Pátria 130

Lisboa 1169-056

Portugal

and

Instituto de Biologia Experimental e Tecnológica (IBET)

Av. da República

Oeiras 2780-157

Portugal

Preface

Our first volume on bioorganometallic chemistry, published in 2006, laid down some markers to underline the emergence of this multidisciplinary research field, and provided a few significant points to illustrate its early successes. It also offered a glimpse of future developments foreseeable at that time. The success of this introductory volume, whether or not it actually inspired it, certainly coincided with an explosion of organometallic synthetic biology that has exceeded our expectations. In fact, this research field is now taught in many universities and features in the most recent textbooks on general organometallic chemistry. Bioorganometallic chemistry has also taken its place among the essential topics discussed by major international organometallic chemistry conferences alongside other key areas such as catalysis.

The rapid evolution of the field, and its ability to open up new areas while continuing to delve deeper into others that are still in their early stages, has led us to believe that it would be useful to attempt an examination of current developments in the form of a second volume. For this purpose we have called upon authors whose reputations are well established, as well as some who are just setting out in new directions. This balance seems to us a faithful reflection of the current situation, where we see a strongly growing cohort of talented young researchers. The selection is based on our subjectivity, our knowledge of the field, and our reflections on its future. We have tried to focus on the new and rare, on concepts newly emerging or re-emerging, on important achievements and realistic possibilities, in order to give the reader a sense of the fundamental trends in the field. To keep the volume to a manageable size, this decision has led us to skim over or omit other aspects that have been broadly covered elsewhere in recent reviews.

Within the discipline of Chemical Biology, which is advancing on a number of fronts, the bioorganometallic subdiscipline has a unique part to play. Its medicinal aspect is particularly well represented in the literature. It is now clear that the contribution of organometallics depends on types of activity that are different from, but complementary to, those of the coordination metallodrugs whose chief target is DNA. Organometallic compounds, because of their novel three-dimensional space-filling properties, can behave as enzyme inhibitors, as Meggers has shown with kinases. The redox properties of other organometallic complexes also permit targeting of proteins, some of which have now been identified. These key points are examined from various angles.

Chapter 1, by P. Anstaett and G. Gasser, shows the importance of organometallic enzyme inhibitors from an industrial perspective. By elucidating the unique geometric and electronic properties of organometallics, the authors reveal a new set of possibilities uncovered by the quest to develop new drugs in chemical biology.

Chapter 2, by G. Jaouen et al., underlines the renewed interest in research on organometallic steroids and their ability to bind with specific receptors, where they can also act as inhibitors as, for example, in the case of the estrogen receptor. But this is a vast area, whether in terms of radiopharmaceuticals or the topic of SERMs (selective estrogen receptor modulators), for example, as demonstrated by the ferrocifens. This research may prove to be of social benefit in addressing the problems caused by endocrine disruptors, where the organometallic component is still evolving.

Chapter 3 takes up, from the novel angle of metallodrug resolution, the essential question of chirality in inorganic chemistry as instigated by Werner, which in organometallics has demonstrated its power in asymmetric synthesis. Here Romero and Sadler, aware of the importance of gaining FDA approval for “chiral switch” drugs, tackle the as yet fairly undeveloped topic of the resolution of organometallic metallodrugs and their structural stability. This seminal article is likely to be highly influential for the future.

Chapter 4, by Casini et al., focuses on the rapid development over the last few years of gold organometallics as potential metallodrugs. The unusual character of the mechanism of action is revealed, whether for complexes of Au(I) or Au(III) bound to carbenes. In particular, their antiproliferative activity is often linked to their interference in the redox homeostasis of cancer cells. These compounds also have antiparasite potential. Finally, a possible approach to their use as theranostic agents is described. These species merit the wide interest they generate.

Chapters 5–7 illustrate the potential for commercial development of a number of promising organometallics. Dubar and Biot describe in detail the mechanism of action of ferroquine, an antimalarial agent in phase II clinical trials at Sanofi Aventis. He shows that this drug can be linked to an oxidizing stress effect and plays a key role in the inhibition of the reinvasion stage of merozoites. This is an important mechanistic discovery that may provide a source of inspiration.

Romão and Vieira meanwhile take on the different aspects of the metal-carbonyl prodrugs. It is in fact known that CO is a significant biological mediator requiring controlled release to make it suitable for therapeutic use. Using a temporary complexation in the form of CORMs shows considerable promise, if we can learn to use these tools at the cellular level. A multidisciplinary team has been working toward this, and a therapeutic approach via CO may well enter the clinical sphere quite quickly.

Chapter 7, authored by Vanin, underlines the importance of dinitrosyl iron complexes with thiolate ligands in designing new therapies. Clinical trials of some of these species have begun in human subjects, and show a stable hypotensive effect without secondary effects on the human cardiovascular system. Chemists are working on stabilized forms of these species for wound repair. This is another innovative area of therapeutic research.

In addition to this therapeutics-oriented research, an awareness of the current high stakes in energy provides Chapters 8 and 9 with their focus on the progress of research on hydrogenases and their derivatives. These ancient enzymes possess an organometallic active site and are the subject of multifaceted research. The contribution of Bethel and Darensbourg focuses on the three hydrogenase families presently identified, their structure, their mechanism of action, the biosynthetic routes of their active site, and finally the most recent advances in the development of useful models of active sites. This work is a useful primer for Chapter 9 of Artero et al. that deals with the key technological aspects of the future.

Artero et al. offer a cutting-edge contribution on the economy of hydrogen and gives examples of constructions of new electrodes and photoelectrodes for hydrogen evolution and water oxidation, the two components of water splitting. Access to effective immobilized molecular catalysts is now becoming a possibility. Given the worldwide importance of energy issues, an international collaboration should rapidly lead to photoelectrocatalytic systems free from noble metals and viable economically. Such is the expectation raised by this study.

Hayashi et al. deal in Chapter 10 with artificial organometallic metalloenzymes, putting the accent on major trends and current challenges such as hybrid biocatalysts with abiotic activity or catalysis of cascade reactions. Notable challenges include the optimized adaptation of the organometallic cofactor within the active site, good targeting, hybrid robustness and recycling, and the introduction of abiotic activity into the cellular medium. These are avenues that are only waiting to be fully mapped out.

In Chapter 11, Licandro et al. have chosen to focus on a few innovative aspects within the thicket of organometallic bioprobes, specifically applications in cellular imaging. These studies are founded on the unique spectroscopic properties of organometallics allied with advances in instrumentation. Examples would be the combination of AFM and IR spectroscopy using metal-carbonyl probes, or new fluorescence microscopy techniques that open the way to high-resolution imaging of tissue. This field is multidisciplinary by its very nature, but metals such as Re, Ir, and Pt have produced the most promising fluorescent organometallic probes to date. This leaves room for other synthetic approaches to provide access to other bioprobes with different specific properties.

These few examples of the present state of the field show that bioorganometallic chemistry is connected to questions at the cutting edge of current research. Exploration of new avenues makes it possible to envisage innovative solutions to pressing social needs. The medicinal organometallic aspect is already very advanced, with the promise of novel treatments for incurable or difficult-to-treat diseases. The mechanistic approach is providing insight into the reasons for this breakthrough into previously unexplored territory. This volume will open up new research paths in this area, where a number of start-up companies have already begun.

The metalloenzymes and modeling area is still very open, and it is now clear that certain complexes will play a role in the energy transition that is currently underway. In addition, organometallic bioprobes, connected or not with theragnosis, represent a vast area needing only to be developed. The lines of force, the promises, and directions of travel in the field are laid out before us here. It is hoped that the reader will envisage others, guided, inspired and stimulated by the work presented in this volume.

We offer our sincere thanks to the authors for contributions of such high quality.

Paris

October 2014

Gérard Jaouen

Michèle Salmain

Part OneMedicinal Chemistry

1Organometallic Complexes as Enzyme Inhibitors: A Conceptual Overview

Philipp Anstaett and Gilles Gasser

1.1 Introduction

Enzyme inhibitors are currently playing a crucial role in medicine. A high proportion of the drugs currently reaching the market are exerting their activity by inhibiting an enzyme. For example, the best-selling drug in pharmaceutical history, the lowering blood cholesterol drug Atorvastatin, sold under the trade name Lipitor, is inhibiting an enzyme present in liver tissue [1]. The anticancer drug Imatinib marketed under the trade names Gleevec and Glivec specifically targets a tyrosine kinase. From a medicinal inorganic chemistry perspective, the mechanism of action of several metal-based drugs having reached the market can be linked to enzyme inhibition. Examples of such compounds include the antiarthritic gold complexes, the antimony-based drugs against leishmaniasis, or the arsenic-based drugs against syphilis, trypanosomiasis, and cancer, although the exact mechanism(s) of action of these compounds have not been (yet) fully uncovered. Due to these successful examples, several research groups around the world are currently exploring the possibility of using organometallic compounds to inhibit enzymes involved in diseases. This field of research has been reviewed in detail over the last years [2–6]. In this chapter, we aim to take an alternative approach by presenting the different concepts employed to achieve enzyme inhibition using organometallic complexes rather than to list all organometallic compounds reported to date that can act as enzyme inhibitors. We will use a few concrete examples to exemplify each concept.