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Book Review Handbook of Downstream Processing. Edited by E. Goldberg

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(on page 13) the conclusions that can be
drawn from the three-dimensional energy
diagram, the authors would have cited
this as evidence for a dissociative mechanism in the hydrolysis of phosphoric acid
monoesters (S. J. Admiral, D. Herschlag,
Chemistry and Biology 1995,2,729-739).
In this chapter the possible reaction paths
are described only in a general way, which
is regrettable. Again, in Chapter 8, the important role of metal ions in the hydrolysis of acyl derivatives is not covered adequately, being limited to the Lewis acid
activity and the increase in the acidity of
coordinated water. Some important aspects, such as the suppression of pseudorotation in the hydrolysis of phosphates, are not mentioned.
Chapter 9 describes enzyme models,
mainly involving a host -guest interaction
followed by a reaction. Here the authors
mention the important studies by Breslow
using cyclodextrin as the guest molecule,
as well as reactions involving micelles or
macromolecules. Lastly, in Chapter 10,
enzyme mechanisms are classified under
five basic types--acyl group transfers,
proton transfers, C -C bond-forming reactions, hydride transfers, and alkyl
group transfers-and are discussed with
the help of examples. The description of
the mechanisms in this chapter gives a
useful insight into enzymatic reactions, although the depth of treatment is scarcely
more than one finds in a good organic
chemistry textbook. Also the chapter fails
to cover some important mechanisms,
such as that of ribonucleotide reductase,
or to discuss important techniques used to
study enzymatic mechanisms, such as
ESR spectroscopy.
The authors place special emphasis on
the quantitative treatment of the reaction
kinetics, and to this end they provide a
useful appendix containing tables of various kinetic parameters, such as Hammett
The book‘s main strength is in the descriptions of organic reactions. Although
the authors cover the theoretical fundamentals for describing complex enzymatic
reactions very thoroughly, the treatment
of the mechanisms of such reactions in the
second part of the book does not match
up to the first part as regards depth and
detail. As a further criticism of the book,
some important methods that give only a
semiquantitative or purely qualitative description of enzymatic processes are not
mentioned, even though there exist many
important and highly topical processes for
which kinetic data alone are insufficent to
determine the mechanism. The book can
be recommended for readers who wish to
brush up their knowledge about solvent
Angew. Chem In1 Ed Engl 1997,36, No. 22
effects and isotope effects, and about kinetic measurements for studying reaction
mechanisms. However, for anyone seeking a comprehensive treatment of the details of biological reaction mechanisms,
this is not a suitable book.
Murkus Kulesse
Institut fur Organische Chemie
der Universitat Hannover (Germany)
Fundamental Toxicology for Chemists.
Edited by .
H. Duffus and H. G . J.
Worth. Royal Society, Cambridge,
1996. 329 pp., paperback S 29.50.-
ISBN 0-85404-529-5
Modern toxicology is an interdisciplinary subject involving chemistry, biology, medicine, and pharmacology, with the
aim of understanding the dangers caused
by chemicals and identifying areas of risk.
These arise in the field of university teaching just as elsewhere, and lectures on the
subject are provided for science students
in German universities. Attendance at
these is compulsory for chemistry students. The German Chemical Society
(GDCh) recently set up a new working
group on “Umweltchemie und Okotoxikologie” (Environmental Chemistry and
Ecotoxicology), a choice of name which
underlines the importance attached to this
subject. The main purpose of ecotoxicology is to investigate the risks of environmental damage from chemicals, and to
suggest preventive measures.
This book has been sponsored by the
International Union of Pure and Applied
Chemistry (IUPAC), and is intended to
serve mainly as an introductory textbook
for chemistry undergraduates in British
and American universities. The 21 chapters are the work of 16 authors. An introduction to the principles and methods of
toxicology is followed by chapters dealing
with the following aspects in the order
given: toxicological kinetics and dynamics; the interpretation of data; risk assessment; risk management; exposure and
monitoring; mutagenicity; carcinogenicity; reproductive toxicology; immunotoxicology ; skin toxicity; inhalation toxicity;
liver toxicology; renal toxicology; neurotoxicology ; behavioral toxicology and cotoxicology; a chapter on radionuclides,
biocides, and pesticides; safe handling of
chemicals. Finally there are two appendices containing a curriculum on toxicology for chemists, and a glossary of commonly used terms. The topics covered
correspond essentially to those that make
up a typical lecture series on toxicology
for students of natural sciences. The book
could serve both as a useful accompani-
8 WILEY-VCH Verlag GmbH, D-69451 Wemhelm, 1997
ment to such a lecture course for chemists,
and as an introduction to toxicology for
individual study.
As always with multiauthor textbooks,
there is a danger that the chapters may
show large differences in the quality of the
writing. It is part of the editors’ role to
prevent this, but in this case they have not
been very successful. In fact, a few of the
chapters are of a poor standard. For example, the author of the chapter on mutagenicity gives a detailed description of the
structure and function of DNA and of the
genetic code, but fails to devote similar
attention to commonly used toxicological
procedures such as the Ames test or the
HPRT/TK mutagenicity test using mammalian cell cultures (V79 etc.). Also the
book does not include enough discussion
of the relationship between chemical
structures or compound classes and their
toxicological properties, an aspect that is
of particular interest to the chemist.
The value of this monograph must also
be measured against the several German
language textbooks on toxicology that
have appeared in the last few years. If we
compare it, for example, with the recently
published book by Greim and Deml
(Toxikologie), it fails to reach a similar
standard. Also the new book by Dekant
and Vamvakis (Toxikologie) is considerably better as an introduction for
chemists, and is more soundly planned
than this English-language textbook.
Thus we can, at best, only recommend this
book as supplementary reading to accompany a lecture course on toxicology.
Johunnes Dohmer and Dierer Lenoir
GSF-Forschungszentrum fur Umwelt
und Gesundheit
Neuherberg (Germany)
Handbook of Downstream Processing.
Edited by E. Goldberg. Chapman &
Hall, London, 1997.720 pp., hardcover
E 149.00.-ISBN
One of the more complex, and at the
same time fascinating, tasks of pharmaceutical biotechnology is that of isolating
products from downstream processing,
starting from biological sources, to
provide new lead structures. There are no
standard and universally applicable
methodologies or strategies for isolating
secondary metabolites or recombinant
proteins produced by fermentation. The
route from the culture solution to the pure
isolated substance still depends to a large
extent on the experimentalist’s store of
past experience and imaginative resources. Moreover, the procedure of finding new biologically active lead structures
0570-083319713622-2529 $17 SO+ 5010
from natural sources is made much more
complicated when, in addition to the
problems of isolating pure substances
from fermentation products, one is constrained by the regulations and guidelines
of “good manufacturing practice”. One of
the main aims of this book edited by E.
Goldberg is to provide help with that task
and to apply some systematic concepts to
the complex subject of downstream processing.
The 720-page book contains 26 chapters by 33 different practitioners and experts, of whom all but two are from the
USA and other parts of the Englishspeaking world. Many of these have a
background in process technology. Thus
the book is intended mainly for chemical
and pharmaceutical process engineers
who are involved in the design and construction of plant and buildings for biotechnology, and/or with the production
and isolation of biologically active natural
products, including the development and
optimization of the relevant processes.
Accordingly, therefore, most of the chapters deal with routine process stages such
as cell disruption, filtration, solvent extraction, solid-phase extraction, membrane techniques, crystallization, and
freeze-drying. However, it is unfortunate
that chromatographic methods, which often serve as the key steps in work-up procedures, are not given enough space here,
with no more than just a short chapter
on affinity chromatography and one on
the scale-up of column chromatography
methods. In contrast, for example, the
chapter on distillation processes is quite
long. Thus the treatment of chromatographic processes is inadequate for a book
with the above title.
Although the book’s main emphasis is
on practical aspects, some chapters also
discuss the physical-chemical fundamentals of the methods concerned, and include the most important mathematical
formulas that are essential for understanding the principles. Each chapter ends
with a comprehensive and fairly up-todate bibliography, covering publications
up to 1992. Some chapters also include
information about commercial manufacturers of equipment. However, it is regrettable that these are limited to suppliers in
the USA, even in cases where the market
leader in a particular field is based in Europe or Japan. Moreover, it is not very
helpful that numerical data are often
given in feet, inches, or gallons, so that
one has to convert these to SI units. Admittedly there is a conversion table in the
book, but American authors in engineering disciplines should by now be gradually
becoming accustomed to internationally
accepted units. Also, the usual practice internationally is to give temperatures in degrees Celsius or Kelvin rather than
Fahrenheit. Also, not surprisingly, the biological safety levels used in the USA do
not have quite the same meaning as those
in European countries. Nevertheless, the
importance of these criticisms should not
be exaggerated.
Some notes and comments on a few of
the chapters now follow. First there is an
excellent description of the most important methods of mechanical cell disruption. The advantages and disadvantages
of grinding and high-pressure homogenization are discussed. In a future revised
edition it would be useful to also treat
nonmechanical methods in more detail
than here; such methods are becoming increasingly important, e.g. for isolating
This is followed by chapters on filtration, extraction, and crystallization.
These describe the current state of the art
in these processes, although I found them
too theoretically orientated. On the other
hand, the chapters on drying and freezedrying are highly informative, even for the
specialist; the latter chapter is especially
good. The contribution on membrane
processes is also excellent, but that on
electrodialysis is too long, especially since
this method has only limited use in scaledup versions.
The comprehensive treatment of methods for cleaning and sterilizing machinery, plants, and work areas is especially
welcome. “Clean-in-place” and “sterilization-in-place” methods are described in
detail, with examples showing how to set
out protocols for these procedures. Water
purification methods are also given due
attention, and there is even a chapter
devoted to waste treatment, an important
aspect of any biotechnological process.
I was especially impressed by the chapters
on the planning and validation of biotechnological processes, which contain a
wealth of useful information, even for the
specialist. The manufacturing processes
for bulk materials and for biologically active agents are compared in a chapter
which makes interesting reading, even
though this topic was not strictly necessary in a book on downstream processing.
The book is very attractively produced,
with a clear typeface. The text is relieved
by many figures and tables which contribute to the reader’s understanding.
These include flow charts showing biotechnological processes and plants in accurate detail.
To summarize, the book offers a great
deal of useful information for readers
from all disciplines concerned with the
0 WILEY-VCH Verlag GmbH, D-69451 Weinheim,
work-up of feedstocks produced by biological processes under cGMP conditions,
even though the relative emphasis given to
the individual topics does not always seem
appropriate. For a handbook of this kind
the treatment of chromatography is less
than adequate. Apart from this criticism,
the book will certainly be a valuable resource, especially for technologists involved in the design and setting up of
biotechnological processes and plant. It
also contains many useful ideas for
everyone seeking mild techniques for the
work-up of culture solutions, and it is a
valuable addition to the literature on biotechnology.
Eberhard Ehlers
Hoechst Marion Roussel
Process Development, Frankfurt a. M.
Molecular Chemistry of the Transition
Elements. An Introductory Course. By
R Mathey and A . Sevin. John Wiley
& Sons, Chichester, 1996. 232 pp.,
0-471paperback C 18.99.-ISBN
A growing demand for modern textbooks in transition metal chemistry recently has led to the publication of several
new textbooks covering various aspects of this vast
field. Whereas some
emphasize classical
coordination chemistry and its concepts based on the
paradigm set by Alfred Werner and his
successors (e.g., M.
Gerloch and E. C. Constable, Transition
Metal Chemistry, VCH Verlagsgesellschaft), others are primarily devoted to
the area of organometallic complex chemistry (and explicitly say so in their title,
e.g., C. Elschenbroich and A. Salzer,
Organometallics, 2nd edition, VCH Verlagsgesellschaft). The book by Mathey
and Sevin belongs to the latter category
and the choice of the title may be traced to
the “unconventional approach” that the
authors announce in the preface. This
textbook, which is based on lecture notes
and the teaching experience of both authors, is intended as a guide to the different aspects of structure and reactivity in
organometallics, emphasizing a conceptual approach, in particular the molecular
orbital picture.
In a very short (possibly too short!) introductory chapter the authors give an
overview of the history of organometallic
0570-083319713622-2530 $17.50+.50/0
Angew. Chem. Int. Ed. Engl. 1997,36, No. 22
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