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Ligand Design inMedicinal Inorganic
Chemistry

Ligand Design in Medicinal
Inorganic Chemistry
Edited by Tim Storr. John
Wiley & Sons, Hoboken,
2014. 472 pp., hardcover,E 149.00.—ISBN 9781118488522

2324

Medicinal inorganic chemistry isa thriving field of research and theimpact of the ligands on the propertiesof metal complexes has been obvious since
the discovery of the anticancer properties of acompound as simple as cisplatin and the numberof analogues reported following its clinical approval. Even small modifications of the ligand structure often change the biological properties of thepharmacophore significantly. With the rise oftargeted therapy, the use of other metals andexpansion of their fields of application, the design
strategies of metal complexes and the ligands
bonded to them have become more sophisticatedand are summarized in the book Ligand Design inMedicinal Inorganic Chemistry edited by Tim Storr.
Chapter 1 gives a short introduction to medicinal inorganic chemistry, the roles of metal ions inbiological systems and the importance of homeostasis, the development of the field and some of themajor milestones achieved in recent years. The
second chapter focuses on platinum anticancer
agents and Hambley and Klein highlight some of
the new developments in this area. In particular,
the introduction of ligands to improve the selectivity of toxic platinum anticancer agents and also to
track them through fluorescence measurements inbiological systems is a hot topic. This chapter isfollowed by several chapters on the application of
metal complexes and the roles of the ligands mainly
in imaging. Radiopharmaceuticals and the highimportance of ligand choice to obtain stable complexes is highlighted in Chapter 3, followed by thediscussion of optical imaging agents, sensors andluminescent probes mainly used in cell systems andrecent advances in terms of metal distribution
studies in organelles and bioconjugation. Contrast
agents in magnetic resonance imaging (MRI) are
discussed in Chapter 12, together with the factors
influencing the MRI response. The detailed background given will be surely helpful to the newcomerin this research area.
Carbohydrate transporters have been of interest for some time and in particular in tumor andinflammatory tissue, carbohydrate-derived radiotracers have been used for imaging purposes but
similar strategies may also be applied for selective
delivery of drug compounds, as pointed out by
Mikata and Gottschaldt. The biological propertiesof the common class of Schiff base ligands appear
to be dependent on the presence of metal ions.
Several types of ligands are presented mainly forthe treatment of cancer, such as well-known
Triapine, with some discussion on their potential

in imaging and against Chagas disease. Antimalarial treatments involving metal-containing compounds are discussed by Navarro and Biot (Chapter8), highlighting the potential of compounds basedon Au, Pt, Ru, etc. and especially ferrocene-based
derivatives of chloroquine. Gold compounds havefound application in the treatment of rheumatoid
arthritis and more recently the design of newderivatives has led to potential cancer chemotherapeutics with DNA-independent modes of action
and also to antiparasitic compounds (Chapter 9).
A range of metal ions have important roles forproper function of the brain, although sometimes
present only in trace amounts. Ligand design tomodulate metal–protein interactions in neurodegenerative diseases such as Alzheimers and Parkinsons is discussed in Chapter 10, showing
potential in medicinal inorganic chemistry in formof chelators. Chelating ligands are also important in
the treatment of copper and iron overload, i.e.,
Wilsons disease and hemochromatosis, respectively, and this is what is discussed extensively inChapter 11, summarizing classical, well-establishedtherapeutics and the design of next-generation
coordination compounds. Martin et al. show inChapter 14 the potential of chelating ligands toinhibit metalloproteins, many of which haveattracted attention as potential targets in diseases
like cancer, hypertension and asthma.
Photoactivation of cancer chemotherapeutics
may improve their selectivity and reduce sideeffects. This may occur through changes in theoxidation state or by inducing ligand exchange
reactions, as discussed in Chapter 13 for Pt, Ru andother metal compounds, and potential applications
beyond cancer treatment are demonstrated. Ru incancer treatment and the use of biologicallyderived ligands is the focus of the last chapter ofthis book which includes besides the well-established ruthenium(III) complexes also more recentcompounds, designed with targeting principles inmind.
In summary, the book is well written and gives abroad overview on ligand design in medicinal
inorganic chemistry. One minor criticism would
be that the chapters focusing on imaging could havebeen co-located and while some chapters arefocused on the ligands, as implied by the booktitle, others take the metal as the shining star.
Overall, this book fulfills its aim as an introduction
to graduate students and newcomers in thisresearch area and is a valuable source of information for established medicinal inorganic chemists.
Christian Hartinger
University of Auckland (New Zealand)
DOI: 10.1002/anie.201412260

 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Angew. Chem. Int. Ed. 2015, 54, 2324