Progress in Inorganic Chemistry: Bioinorganic Chemistry, Volume 38

550 Pages·1990·13.975 MB·English

Progress in
Inorganic Chemistry
Volume 38
Advisory Board
JACQUELINE K. BARTON
CALIFORNIA INSTITUTE OF TECHNOLOGY, PASADENA,
CALIFORNIA
THEODORE L. BROWN
UNIVERSITY OF ILLINOIS, URBANA, ILLINOIS
JAMES P. COLLMAN
STANFORD UNIVERSITY, STANFORD, CALIFORNIA
F. ALBERT COTTON
TEXAS A&M UNIVERSITY, COLLEGE STATION, TEXAS
ALAN H. COWLEY
UNIVERITY OF TEXAS, AUSTIN, TEXAS
RONALD J. GILLESPIE
McMASTER UNIVERSITY, HAMILTON, ONTARIO, CANADA
RICHARD H. HOLM
HARVARD UNIVERSITY, CAMBRIDGE, MASSACHUSETTS
KENNETH D. KARLIN
THE JOHNS HOPKINS UNIVERSITY, BALTIMORE, MARYLAND
TOBIN J. MARKS
NORVIWESTERN UNIVERSITY, EVANSTON, ILLINOIS
KARL WIEGHARDT
RUHR-UNIVERSITAT, BOCHUM, FEDERAL REPUBLIC OF
GERMANY
GEOFFREY WILKINSON
IMPERIAL COLLEGE, LONDON, ENGLAND
Progress in Inorganic Chemistry:
BIOINORGANIC
CHEMISTRY
Edited by
STEPHEN J. LIPPARD
DEPARTMENOTF CHEMISTRY
MASSACHUSETTINSS TITUTE OF TECHNOLOGY
CAMBRIDGEM, ASSACHUSETTS
VOLUME 38
AN INTERSCIENCE@P UBLICATION
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Preface
Work in bioinorganic chemistry has accelerated substantially since 1973,
when Volume 18 of Progress in Inorganic Chemistry was published high-
lighting current research topics in the field. The Preface and Introduction
to that volume are reprinted here as an historical benchmark by which to
judge the enormous progress that has been made in the intervening 17
years. During this interval, the first International Conference on Bioinor-
ganic Chemistry (ICBIC) was convened, and the fourth such conference
was held last summer on the MIT campus. The present volume of Progress
in Inorganic Chemistry was conceived in conjunction with ICBIC-4 as an
opportunity to present authoritative reviews by many experts in bioinor-
ganic chemistry who were gathering in Cambridge for the meeting. Ac-
cordingly, ali of the plenary lecturers were invited to contribute a chapter,
and most graciously agreed to do so. In addition, a number of other speak-
ers at the conference were asked to review their areas of research expertise
in order to provide additional scope of coverage for this volume.
The topics reviewed here touch on many aspects of current research in
bioinorganic chemistry, exploring the amazing breadth of the field that
ranges from solid state physics to cell biology and medicine. There are of
course many subjects not covered, but from the eight chapters included
the reader should be able to assess the full span of activities in what has
become a forefront subject in both chemistry and biology. As witness to
the latter claim one need only recall that the journal CELL recently dis-
played a zinc finger peptide on its cover, a debut that was hailed by many
in the bioinorganic community as official recognition of the discipline by
“big biology.” Although zinc finger proteins are not specifically covered
in this volume, they were the subject of an article by Jeremy Berg in Volume
37 of our series.
In order to produce this volume in a timely fashion, the publisher has
agreed to a new, if somewhat risky, experiment. The chapters were set
directly into pages, bypassing the usual reading of galley proofs. In addi-
tion, in an attempt to make the book more accessible to individual readers,
as well as libraries, we are for the first time providing a paperback edition
at a substantial reduction in cost, Both of these innovations were greatly
facilitated with the assistance of our new in-house editor, Dr. Philip Manor,
to whom I am very much indebted. In addition, I should like to thank
Professor Kenneth D. Karlin, the organizer of ICBIC-4, for his help in
planning this volume. Finally, the time has come to acknowledge publicly
the talents of Jeannette Stiefel who, for many years, has served as the
freelance copy-editor of the Progress in Inorganic Chemistry volumes; the
uniform high quality of the chapters is in no small measure due to her
efforts. ,
STEPHENJ. LIPPARD
Cambridge, Massachusetts
May I WO
Introduction
In the Introduction to Volume 18 of Progress in Inorganic Chemistry,
subtitled “Current Research Topics in Bioinorganic Chemistry” and re-
printed herein, three major avenues of research in the field were delineated.
These subtopics, the direct study of metal ions in biological macromole-
cules, the use of simpler, model systems to gain insight into the properties
of metalloprotein cores, and the application of inorganic reagents as probes
of biological structure and function, all continue to be important facets of
modern bioinorganic chemistry. They comprise a significant fraction of the
research described in the present volume. A very significant area of growth
in the discipline of bioinorganic chemistry, however, has been the appli-
cation of metals in medicine. Included are the use of cisplatin in the highly
successful treatment of genitourinary tumors, of technetium compounds
as radiodiagnostic agents, of orally administered gold phosphine complexes
for the management of rheumatoid arthritis, and of lithium to control
manic-depressive behavior. In addition, much attention is now beginning
to focus on the regulation of gene expression by metal ions, which bind to
proteins causing them to fold in specific conformations for interaction with
other macromolecules in the cell. Chapters illustrating these newer activ-
ities are also included in this volume.
Driving much of this research have been advances made in the fields of
molecular and cell biology, including technical developments such as gel
electrophoresis, DNA and RNA sequencing methodologies, site specific
mutagenesis, cloning, and the ability to obtain monoclonal antibodies.
Related instrumental developments from the physics and engineering com-
munities have similarly spurred progress in bioinorganic research. Syn-
chrotrons have afforded high intensity X-ray beams for absorption and
diffraction measurements; the scanning tunneling microscope promises to
yield high resolution images of single biomolecules; and new and more
powerful computers and software developments have brought molecular
mechanics, dynamics, and modelling calculations to the desktops of many
practicing graduate and postdoctoral students. These technical improve-
ments will be readily apparent to the reader in many of the review articles
collected here.
This volume begins with a discussion of iron sulfur clusters, a familiar
topic to bioinorganic chemists and one that has not lost its appeal. Although
long known for their role in biological electron transfer, they have recently
been shown also to possess catalytic activity through subsite specific chem-
istry, wherein one of the iron atoms in the cube catalyzes chemical trans-
formation at its particular corner. To reproduce such disymmetry in an
vii
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Vlll INTRODUCTION
otherwise symmetric cluster has presented a challenge to the synthetic
model builder that has been met by brilliant design and execution, which
the reader is sure to appreciate. In the following two chapters are intro-
duced the currently fashionable topic of nonheme iron and manganese
bioinorganic chemistry, much of which involves aspects of dioxygen me-
tabolism. The discovery of units such as the p-oxobis(p-carboxy-
lato)diiron(III) center in the marine invertebrate 0,-transport protein hem-
erythrin has spurred both the synthetic model builder and the protein
biochemist to enter this arena. Some of the most exciting goals are to
understand the diiron centers in methane monooxygenase, which uses CH4
as its sole carbon and energy sources, and in ribonucleotide reductase,
which activates dioxygen by a similar dinuclear iron center, and to elucidate
the nature of the tetramanganese unit in photosystem 11, which evolves
O2f rom water.
Many enzymes catalyze the transformation of organic substrates by de-
livering a functional group held in or near the coordination sphere of a
metal ion at their active sites. A thorough understanding of these reactions
has been greatly facilitated by careful studies of well-designed model sys-
tems. The next review addresses this topic, with specific emphasis on phos-
phate chemistry. The regulation of cellular events by phosphatases and
kinases, enzymes that remove or add phosphate groups to proteins, re-
spectively, is central to many forefront areas of modern biology, including
the study of oncogenes, development, and the cell cycle. Metal centers in
proteins that do not function as group transfer agents frequently serve to
facilitate electron transfer, the topic of the next chapter. It has now been
demonstrated that electrons can be transferred over long distances (>lo
A) in proteins. How they do so, and how the rates of these reactions
depend on their driving force, the distance between redox centers, and the
intervening medium, are addressed in this review. An exciting development
in this field has been the attachment of kinetically inert inorganic complexes
to amino acid side chains on the surface of redox metalloproteins to probe
the distance dependence of electron transfer to their naturally occurring
metal cores.
The final three chapters all deal largely with metal-nucleic acid chem-
istry. This topic, only in its infancy in 1973 when Volume 18 of Progress
in Inorganic Chemistry appeared, now accounts for a substantial fraction
of the work done in bioinorganic chemistry. Metal regulated gene expres-
sion, exemplified by the mercury resistance phenomenon, offers a won-
derful opportunity for the bioinorganic chemist to combine the power of
inorganic synthesis and structure determination with that of cloning and
protein structure determination. This relatively new subfield is replete with
fascinating unstudied problems and systems, the understanding of which
will undoubtedly benefit from a careful reading of this chapter. In the
penultimate chapter are reviewed the powerful ways that metal complexes
can be used as probes for DNA structure. By matching the shapes and
INI‘RODUCI‘ION ix
symmetries of metal complexes with their target sites on DNA emerges
the possibility to outdo nature in recognizing and cleaving the genome at
specific sequence-determined sites. This challenge has attracted many
members of the organic as well as the inorganic chemical communities
interested in the more general topic of molecular recognition. The practical
consequences of success are enormous, and include the localization of gene
defects responsible for diseases such as Huntington’s chorea, cleavage of
DNA into very long (-104 nucleotide) segments required for mapping the
human genome, and even chemotherapy by targeted destruction of viral
genomes in vivo. Finally, the last chapter reviews an aspect of the still
evolving platinum antitumor drug story that has not received attention
elsewhere, one that could lead ultimately to the complete unravelling of
the molecular mechanism of action of the drug. Although much is known
about the binding of cZS-[P~(NH~)~tCoI D~]N A and the resulting structural
changes in the target, we are still deficient in understanding how cells
process this damage such that cancer cells are selectively destroyed. Some
new discoveries that promise to elucidate these mechanisms are set forth
in the chapter.
As the reader of this volume will soon appreciate, the subject of bio-
inorganic chemistry has matured to the point where activities previously
labeled as “inorganic” or “biological” are now being carried out in the
same laboratory. Collaborations between experts in these separate areas
still occur, but increasingly entry level researchers want to do it all them-
selves. This development is most welcome and will continue to foster suc-
cess in meeting the difficult challenges posed by the great unsolved problems
of the field.
STEPHENJ. LIPPARD
Carnhridgt,, Massachusett.s
May IYYO
Preface to Progress in Inorganic Chemistry,
Volume 18
Work at the interface between the areas of inorganic and biological
chemistry has greatly intensified in recent years. Organization of the subject
material of this growing field of bioinorganic chemistry along topical lines
is fairly straightforward, if not completely satisfying. Thus whole literatures
have grown up around such problems as nitrogen fixation, heme proteins,
vitamin BI2c hemistry, carboxypeptidase structure and biochemistry, metal
ion transport through membranes, non-heme iron proteins, metal activa-
tion of ATP, and copper oxidases. In planning this special topics volume,
some attempt was made to achieve a broader scope. For example, instead
of a chapter on iron-sulfur redox proteins, it seemed desirable to have a
discussion of the entire family of metallo-redox proteins. To the extent
that the subject matter was amenable to such an approach, the chapters
reflect this philosophy.
The choice of topics for this particular volume was dictated by two
criteria. First, it was decided to sustain the long-standing policy of this
series to provide critical, comprehensive, in-depth coverage of material.
This decision necessitated a high selectivity since only a few such chapters
could be accommodated in a single volume. The second critrion was to
assure reasonably broad coverage by including subjects that represented
the various kinds of available biological ligands, namely proteins and nu-
cleic acids and their constituents, in addition to special-function ligands
such as the heme or corrin ring. To the extent that we have been successful,
this book should serve as a useful introduction and guide to scientists in
all fields who are interested in obtaining an overview of the emerging
discipline of bioinorganic chemistry. At the same time, the individual chap-
ters should provide current information and critical discussion of the more
specialized areas for both research workers and students. Parts of certain
chapters have already been adopted in manuscript form for instructional
purposes at the graduate student level.
I wish to thank the authors for their cooperation and efforts required
to produce this volume. If there is sufficient positive response, future bio-
inorganic volumes will be scheduled in this series. As usual, comments of
any kind are always welcome and will be given serious attention.
STEPHENJ . LIPPARD
New York, New York
February 1973
xi
Introduction to Progress in Inorganic Chemistry,
Volume 18
There are three major avenues of investigation in bioinorganic chem-
istry. The first involves direct study of the structure and function of “bio-
metallic” molecules, an area traditionally that of the biochemist. Here one
is interested in the role of metal ions in metalloenzymes, coenzymes, and
proteins, as well as their function as cofactors in DNA and RNA bio-
chemistry. In classic studies on carboxypeptidase, Vallee and co-workers
recognized the importance of the zinc atom as a functional group unique
among all others in the protein. By replacing the zinc with other metal
ions, chemical and spectroscopic probes of the active site were made avail-
able. More recently, X-ray diffraction studies have yielded detailed struc-
tural information about several metallomacromolecules. The three-
dimensional structure of a tRNA has just been made available through the
efforts of Rich, Kim, and their associates. The critical role of magnesium
ions in binding phosphate groups remote from each other in the sequence
(not a new concept, incidentally) has begun to emerge, and correlates well
with biochemical results from several laboratories. X-ray data serves not
only to bridle the occasional untamed structural speculations derived from
less direct approaches, but also provides the impetus and direction for
attempts to elucidate the structure-function relationships that form our
basic understanding of how biometallic molecules work. Delineation of the
function of the metal ion as a structural keystone (as in the example just
cited) , specific reaction organizer, electron transfer agent, or substrate
activator is the major objective of the direct approach, in which detailed
studies are performed on specimens usually obtained directly from natural
sources.
By contrast, the second major avenue involves an indirect approach,
commonly the domain of the inorganic or organic chemist. Through the
invention, synthesis, structure determination, physical study, and reactions
of so-called “model” compounds, some insight into the workings of the
natural system is sought. An additional objective might be to mimic in a
simple system the catalytic function of a metalloenzyme for industria1 or
biomedical synthetic purposes. Current attempts to fix molecular nitrogen
with homogeneous iron or molybenum catalysts exemplify this aspect. Al-
though few doubt that important chemistry might result from this approach,
serious reservation has been expressed about the relevance of such work
to the understanding of natural systems. Indeed, there are purists who
believe that even to study biometallic molecule in vitro is to oversimplify.
For instance, there are those who argue that to investigate solubilized
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