Inorganic compounds have been used in medi-cine for thousands of years, often without aknown molecular basis for their mechanism ofaction, and with little attempt to design them. Thedesign of coordination (metal) complexes is not aneasy task. The organic chemist often deals withdiamagnetic compounds which are both kinetic-ally and thermodynamically stable, and benefitsfrom the use of well developed speciation tech-niques, especially 1H and 13C nuclear magneticresonance (NMR) spectroscopy. For metal com-pounds the situation is more complicated. Ligandsubstitution and redox reactions can be facile, canoccur over very wide timescales, and are not soeasily followed by conventional techniques, es-pecially under physiologically relevant conditions(for instance, at micromolar concentrations). Butthe challenge is real and worth exploring. We neednew drugs with novel mechanisms of action.Inorganic chemistry offers that possibility.

Platinum Anticancer DrugsTwo areas of work have highlighted the poten-

tial of inorganic chemistry in recent years: theplatinum anticancer field and gadolinium com-pounds, used as contrast agents in magneticresonance imaging (MRI). Both of these are wellcovered in this new book. Platinum commandsabout forty pages. This is warranted. Platinumcompounds are now the worlds best-selling anti-cancer drugs they have billion-dollar sales eachyear. If you are not familiar with atomic structure,types of chemical bonds, oxidation states, coordi-nation geometries, isomerism, electronicstructure and magnetism, then there are some onehundred pages (just over a quarter of the book) of

introduction to help you, including thebackground on square-planar platinum com-plexes needed to understand the mechanismof action of the first platinum complex to be approved for clinical use: cisplatin (cis-diamminedichloroplatinum(II)).

The section on platinum, like the others, is ingeneral well illustrated with line diagrams of chem-ical structures, and gives a good coverage of newdevelopments, such as active trans complexes andpotent di- and tri-Pt anticancer complexes, such asBBR3464. Not quite so good are some of the(grayscale) views of structures of DNA, proteinsand their adducts, e.g. Figures 10 and 11 inChapter 4. There is an omission concerning anintriguing feature of the structure of the adductbetween guanine-guanine platinated DNA and theprotein HMG1A, which is the intercalation of aprotein phenylalanine side chain between the plati-nated guanine bases on DNA. Such an adductprobably plays a crucial role in the mechanism ofaction of cisplatin. But this feature is not shown inthe picture on page 254; Figure 1 of this reviewshows an alternative view (1).

Diagnostic ImagingIt is a tribute to clever coordination chemistry

that gram quantities of potentially toxic gado-linium ions can be safely injected into a patientundergoing an MRI scan, in fact into millions ofpatients each year. The Gd3+ ion binds strongly tomultidentate chelated ligands, while still havingsufficient room in its coordination sphere to bindand relax water. Much elegant research is beingundertaken to optimise this effect: investigatingthe choice of the ligand donors, the size of the

21Platinum Metals Rev., 2008, 52, (1), 2122

Medicinal Applications of CoordinationChemistryBY CHRIS J. JONES (University of Birmingham and The University of Manchester, U.K.) AND JOHN R. THORNBACK (MassTag

Technologies Ltd., U.K.), Royal Society of Chemistry, Cambridge, U.K., 2007, xii + 354 pages, ISBN 978-0-85404-596-9, 89.95,

U.S.$169.00

Reviewed by Peter J. SadlerDepartment of Chemistry, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, U.K.; E-mail: p.j.sadler@warwick.ac.uk

DOI: 10.1595/147106708X259497

complex, control of rotation, water exchangerates, targeting and so on. These features are welldescribed in thirty pages of Chapter 3, which alsodeals with radiopharmaceuticals, another area ofmuch commercial interest. Much attention isdeservedly focused on 99mTc, the short-lived (6 hhalf-life) technetium isotope-of-choice for manydiagnostic imaging procedures, with its wide rangeof oxidation states and potential for being targetedwith the right choice of ligands.

Other MetalsCoverage of other precious metals includes

gold, ruthenium (currently two complexes in clinical anticancer trials), palladium (much morekinetically labile than platinum, currently the subject of research) and rhodium (anticancerpotential). Surprisingly, silver is not dealt with,even though it is a very effective antibacterialagent. Washing machines containing slow-releasesilver are even being sold these days, to steriliseclothes as you wash them (see SamsungsSilverCare Washing Machine!). Gold drugs have

been used for the treatment of difficult cases ofrheumatoid arthritis for over seventy years: gold istransported by albumin in the blood by binding tothe thiol at cysteine-34. This is depicted in Figure18 on page 288, but in fact the thiol group is par-tially buried in a crevice and not totally exposed onthe surface of the protein as the figure suggests.

Other topics covered include chelation therapy(for iron in thalassaemia, copper in Wilsonsdisease), vanadium as an insulin mimetic andsuperoxide dismutase mimics. A final chapter ondesign emphasises the need to control both thethermodynamics and kinetics of the reactions ofmetal complexes in biological (physiological)systems, in order to make real progress in thisfield. I missed bismuth (antiulcer drugs), antimony(antiparasitic) and arsenic (mentioned in passing,now a first-line treatment for certain typesof leukaemia). Three elements with poor NMRnuclei! Missing too, except as a passing men-tion, is lithium for treatment of bipolar disorder(taken by more than 1 in every 1000 of theU.K. population).

Concluding RemarksIt is fortunate that the authors included a dis-

claimer on page vii that their information must notbe relied upon to guide clinical decisions, since itsays on page 11 that Phase I clinical trials involvehealthy volunteers. This is not usually the casewith anticancer drugs, many of which are knownto be cytotoxic. For these, Phase I (which is main-ly concerned with establishing a safe dose foradministration) involves patients who have notresponded to other treatments.

This book will serve a useful role in teachinginorganic chemistry to both undergraduate andpostgraduate students. The topic helps to bringinorganic chemistry to life, and in my experiencedoes arouse their curiosity at all levels. It will be auseful addition to libraries, or if you shop aroundon the web, perhaps affordable for your ownpersonal bookshelves.

Reference1 U.-M. Ohndorf, M. A. Rould, Q. He, C. O. Pabo

and S. J. Lippard, Nature, 1999, 399, (6737), 708

Platinum Metals Rev., 2008, 52, (1) 22

Fig. 1 The insertion (intercalation) of phenylalanine-37side-chain (grey) from the HMG protein into thehydrophobic lesion on DNA created by a cisplatinintrastrand crosslink between two adjacent guanine bases(based on the Protein Data Bank (PDB) entry 1ckt (1)). Colour key: Yellow = platinum; Dark blue = N of NH3;Red helices = HMG protein; DNA bases: Green =guanine, G; Purple = cytosine, C; Red = adenine, A;Cyan = thymine, T