ScienceWeek

SCIENCEWEEK

ScienceWeek
June 13, 2003
Vol. 7 Number 24A

An Online Digest of Research in the Sciences

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The chemists are a strange class of mortals who seek their
pleasures among soot and flame, poisons and poverty... yet among
all these evils I seem to live so sweetly... may I die if I would
change places with the Persian King.
-- John Joachim Becher, alchemist, ca. 1650

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Section 1

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Symposium: Catalysis

1. Introduction
2. Homogeneous Catalysis
3. Heterogeneous Catalysis
4. Surface Catalysis
5. Enzyme Catalysis
6. Antibody Catalysis
7. Frontiers in Catalysis

Notices and Subscription Information

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Section 2

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1. INTRODUCTION

TERMINOLOGY

The term "catalysis" was invented in 1835 by the chemist J.J.
Berzelius (1779-1848) to describe chemical reactions in which the
progress of the reaction is affected by a substance that is not
consumed in the reaction and thus apparently not involved in the
reaction. But this definition, proposing no interaction by the
catalyst with reactants, is not useful, and it was later amended
by W. Ostwald (1853-1952), who proposed the more modern
definition: "A catalyst is a substance that accelerates the rate
of a chemical reaction without being part of its final products."
Essentially, as is now recognized, the catalyst acts by forming
intermediate compounds with the molecules involved in the
reaction, providing an alternate and more rapid path to the final
products. Catalysis is of vital importance: In biological
systems, enzymes are essential catalysts for various biosynthetic
pathways; in the chemical and petroleum industries, key processes
are based on catalysis; in environmental chemistry, catalysts are
essential to breaking down pollutants such as automobile and
industrial exhausts.

If the catalyst and the reacting species are in the same phase
(e.g., in a liquid), then the process is known as "homogeneous
catalysis".

More relevant in industrial processes is "heterogeneous
catalysis", where the catalyst is a solid and the reacting
molecules interact with the surface of the solid from the gaseous
or liquid phases.

An "antibody" is a protein molecule (immunoglobulin) produced by
vertebrates that binds with high specificity to a usually
"foreign" entity (antigen) that has entered the system by one
means or another (for example, via bacteria, tissue grafts, or
blood transfusions). Antibodies are therefore key elements in all
vertebrate immune systems. That is the first point. The second
point is that we now know that enzymes work the way they do
mostly because they bind transition state entities in chemical
reactions, this binding lowering the energy barrier to the
transition state, and thereby increasing the reaction rate many-
fold. Which provokes the notion that it might somehow be possible
to use the high specificity of antibodies in catalysis. And the
notion is correct. A catalytic antibody, sometimes called an
"abzyme", is an antibody capable of catalyzing specific chemical
reactions. The general strategy in producing catalytic antibodies
has been to 1) design and synthesize a molecule whose charge and
shape closely resemble those of the transition state of the
reaction to be catalyzed; 2) attach this molecule to a larger
molecule and provoke an immune response in a living system to
this complex; and 3) isolate the resultant antibodies for
catalytic activity of the type desired. These resultant
antibodies are highly specific for binding to the transition
state, and they will be potentially capable of catalyzing the
reaction. Antibody catalysis has become a multifaceted field of
research involving many bridges between the biological and
chemical sciences.

ON THE CHEMICAL INDUSTRY AND APPLIED CHEMISTRY

By and large the chemical industry in the developed countries has
been in the hands of private commercial firms and, however
altruistic some of their activities may be at times, the ultimate
reason for a process or product to be developed is that it will
make a profit. It is worth noting that this profit is the source
of funds for research by the state and the universities whether
by direct sponsorship or indirectly through taxes. Because of the
successful and systematic application of theoretical chemistry,
first in inorganic then in organic chemistry and physical
chemistry, especially the mechanism of reactions, the range of
substances which the chemical industry has produced for man's
use, with ever-improving quality, has been truly remarkable. The
comparison with several millennia of near stagnation makes the
progress of the last two centuries all the more striking.

In 1800 the chemical industry was important, but on a small
scale, its products limited to metals, acids, alkalis, pigments,
tan-stuffs, medicines and a few other chemicals, some made on a
scale not much greater than in the laboratory. Now the scale is
vast, yet the industrial chemist exercises a precise control over
the processes to yield an exactly predictable result. The source
of this progress has been research. Sometimes progress has come
by directing research to solving a particular problem, such as
making a substance with certain required properties. But the more
fruitful source has been to apply discoveries not made with a
particular practical end in view. An example of the first is
presented by Alfred Nobel (1833-1896) and his intention to make
nitroglycerine a safe explosive. In the course of this he
invented dynamite and blasting gelatin.

But the more remarkable discoveries have been those that were not
intended. Thus William Perkin (1860-1929), while trying to
synthesize quinine lighted on something quite unexpected, the
first aniline dye, mauve -- which led to a whole new industry. An
example of the deliberate application of the results of pure
research can be seen in the hydrogenation of oils to make fats
like margarine, stemming from the study of the catalytic
hydrogenation of unsaturated compounds in the presence of a
metallic catalyst by Paul Sabatier (1854-1941) and his colleagues
around 1900. Until then, the production of margarine, invented in
1869 by the French chemist Hippolyte Mege Mouries (1817-1880),
had been limited by the availability of raw materials, but the
hydrogenation process enabled almost unlimited quantities of oils
such as cottonseed oil to be converted into solid fats.

Adapted from Lance Day: Ian McNeil (Ed.): An Encyclopedia of the
History of Technology. Routledge 1990, p.189.

ON CATALYSIS AND WILHELM OSTWALD

In the final quarter of the nineteenth century, Germany was
leading the world in the study of the physical changes associated
with chemical reactions. The outstanding worker in this field of
physical chemistry was the Russian-German chemist Friedrich
Wilhelm Ostwald (1853-1932). It was thanks to him, more than to
any other individual, that physical chemistry came to be
recognized as a discipline in its own right. By 1887, he had
written the first textbook on the subject and founded the first
journal to be devoted exclusively to the field.

Fittingly enough, Ostwald was among the first Europeans to
discover and appreciate the work of Josiah Willard Gibbs (1839-
1903). Ostwald translated Gibbs's papers on chemical
thermodynamics into German in 1892. Ostwald proceeded to put
Gibbs's theories to use almost at once in connection with the
phenomenon of catalysis.

Catalysis (a word suggested in 1835 by J.J. Berzelius [1779-
1848]) is a process whereby the rate of a particular chemical
reaction is hastened, sometimes enormously so, by the presence of
small quantities of a substance which does not itself seem to
take part in the reaction. Thus, powdered platinum will catalyze
the addition of hydrogen to oxygen and to a variety of organic
compounds, as Humphry Davy (1778-1829) (the isolator of sodium
and potassium) discovered in 1816. Again, acid will catalyze the
breakdown to simpler units of a number of organic compounds, as
G.S. Kirchhoff (1824-1887) first showed in 1812. At the
conclusion of the reaction, the platinum or the acid is still
present in its original quantity.

Ostwald prepared, in 1894, a summary of someone else's paper on
the heat of combustion of foods, this summary to appear in his
own journal. He disagreed strongly with the conclusions of the
writer, and to buttress his disagreement discussed catalysis. He
pointed out that the theories of Gibbs made it necessary to
assume that catalysts hastened reactions without altering the
energy relationships of the substances involved. The catalyst, he
maintained, must combine with the reacting substance to form an
intermediate that breaks up to give the final products. The
breakup of the intermediate released the catalyst, which thus
resumed its original form.

Without the presence of this catalyst-combined intermediate, the
reaction would proceed much more slowly, sometimes so slowly as
to be imperceptible. Hence, the effect of the catalyst was to
hasten the reaction without itself being consumed. Furthermore,
since a molecule of catalyst was used over and over, a small
quantity of catalyst was sufficient to hasten a great deal of
reaction.

This view of catalysis is still held today. It has helped to
explain the activity of the protein catalysts ("enzymes") which
control the chemical reactions in living tissue.

Adapted from: Isaac Azimov: A Short History of Chemistry.
Doubleday 1965, p.155.

ON METAL-CATALYZED REACTIONS

Catalysts are substances that accelerate the rates of chemical
reactions, facilitate the establishment of equilibria and are
capable of greatly enhancing product selectivities; they allow
chemical transformations to be performed with increased
efficiency, minimal waste and reduced energy consumption. It is
not surprising therefore that the vast majority of products of
the chemical industry involve a catalyst at some stage in their
manufacture. This applies to bulk chemicals ("commodities")
produced on a large scale as the starting materials for
innumerable end-products, such as alcohols, ketones, carboxylic
acids, hydrocarbons such as olefins and dienes that can be
polymerized to polyolefins (e.g., polyethylene, polypropylene,
and rubbers), and also increasingly to fine chemicals, i.e., high
added-value compounds produced on a smaller scale, as well as
pharmaceuticals.

The term "catalyst" is often ambiguous and not clearly defined.
Most catalysts are heterogeneous, for example, finely divided
metal particles or a metal oxide. Here the term refers to
substances that contain some catalytically active centers, of
usually unknown structures and concentrations. On the other hand,
homogeneous catalysts that operate in solution are usually
derived from well-defined precursors. The simplest example of a
homogeneous catalyst is H+, for example, in the acid catalyzed
esterification of carboxylic acids.

Concerning the role of transition metal complexes as catalysts,
in these systems all of the metal species can be expected to be
active. The reaction usually starts with a stable precursor
complex which brings about a chemical reaction by entering a
catalytic cycle involving a series of metal complexes linked to
each other by consecutive reaction steps. In such a cycle no one
species can therefore be said to be "the" catalyst, and it is
sometimes possible to enter the cycle at several different
points.

In the early part of this century, coal and coal tar products
were the main source of bulk chemicals. Acetylene was the major
feedstock, obtained by converting coal to calcium carbide
followed by hydrolysis. As the petroleum and natural gas
industries developed, ethylene and other products obtained by
"cracking" hydrocarbons became increasingly important. The
present-day chemical industry is almost exclusively olefin-based.
The interaction of olefins or acetylenes with transition metals
is therefore of key importance in catalytic reactions and forms
the basis for many processes.

The majority of catalyzed processes employ heterogeneous
catalysts which have the obvious advantage of ease of separation
from the product. However, where high selectivity and mild
reaction conditions are required, homogeneous catalysts with
their well-defined ligand systems and high chemical uniformity
have the advantage. It is also possible to "heterogenize" a
homogeneous catalyst, either by attachment to a solid support or
by using two immiscible media, without altering the underlying
chemistry of these catalysts.

The rise of homogeneous catalysis, as well as the understanding
of the mechanistic principles of many heterogeneously catalyzed
reactions, is inextricably linked to the development of
organometallic chemistry. Catalytic reactions can be understood
on the basis of a limited number of basic reaction types.

Catalytic reaction cycles are based on a number of reaction
principles, such as coordinative unsaturation/ligand substitution
for substrate or reagent binding to the metal center, oxidative
addition, migration (insertion) reactions to achieve suitable
functionalization of the substrate, and reductive elimination.
They provide the mechanistic framework for the understanding of
catalytic processes that involve the making and breaking of M C
bonds. There are numerous model reactions which indicate the
wide-ranging synthetic potential of metal-mediated reactions;
many of these offer promise but have not yet become the basis of
effective catalysts.

Adapted from F.A. Cotton et al: Advanced Inorganic Chemistry, 6th
Edition. John Wiley & sons 1999, p.1167.

ON CATALYSIS, SUPRAMOLECULES, AND LIVING SYSTEMS

The chemistry of life needs a helping hand. There is scarcely a
biochemical reaction that does not require a catalyst for it to
proceed efficiently towards the desired product. Nature's
catalysts are enzymes and the way in which they act has the
characteristics of a supramolecular process: as Emil Fischer
(1852-1919) realized, it involves the highly specific binding of
a substrate to a receptor site in the enzyme molecule. In his
Nobel award lecture of 1902, Fischer said "I can foresee a time
in which physiological chemistry will not only make greater use
of natural enzymes but will actually resort to creating synthetic
ones.". The tremendous prescience of this remark is attenuated
only by the emphasis on physiological chemistry, because today
natural enzymes are used not only in medical chemistry but also
in industrial processes that synthesize products ranging from
foodstuffs to biodegradable plastics. One of the major goals of
supramolecular chemistry is to devise new catalysts -- artificial
enzymes, if you will -- that will expand and augment this range.

Just about every catalytic process involves three steps: binding
of the substrate, followed by its chemical transformation into
the product and finally the release of the product to regenerate
the active catalyst. Supramolecular catalysts may be
distinguished from traditional industrial catalysts like metal
surfaces by their use of molecular recognition both to
accommodate the substrate at a reactive site and to carry out
"molecular surgery" to transform it into a particular product.

The trick that all catalysts perform is to reduce the amount of
energy needed to transform the substrate to the specified
product. At the crest of the energetic hurdle separating reactant
from product sits an ephemeral, energetic species called the
transition state. The function of a catalyst is to lower the
energy of this transition state relative to that of the initial
substrate. For supramolecular catalysts, what this means is that
the transition state must be more strongly bound (more
stabilized) than the substrate -- if this condition is not
satisfied, the reaction is not assisted no matter how efficiently
the catalyst recognizes the substrate.

Adapted from J-M. Lehn and P. Ball: in: Nina Hall (Ed.): The New
Chemistry. Cambridge University Press 2000, p.323

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2. HOMOGENEOUS CATALYSIS

HOMOGENEOUS CATALYSIS: NEW APPROACHES TO CATALYST SEPARATION,
RECOVERY, AND RECYCLING

Science 2003 299:1702

The following points are made by David J. Cole-Hamilton:

1) Homogeneous catalysts offer a number of important advantages
over their heterogeneous counterparts. For example, all catalytic
sites are accessible because the catalyst is usually a dissolved
metal complex. Furthermore, it is often possible to tune the
chemoselectivity, regioselectivity, and/or enantioselectivity of
the catalyst.

2) Despite these advantages, many homogeneous catalytic systems
have not been commercialized because of one major disadvantage
compared with heterogeneous catalysts: the difficulty encountered
when trying to separate the reaction product from the catalyst
and from any reaction solvent. This problem arises because the
most commonly used separation method, distillation, requires
elevated temperatures unless the product is very volatile. Most
homogeneous catalysts are thermally sensitive, usually
decomposing below 150øC. The thermal stress caused by product
distillation even at reduced pressure will therefore decompose
the often expensive catalyst. Other conventional processes such
as chromatography or extraction also lead to catalyst loss. The
homogeneous reactions that have been commercialized either
involve volatile substrates and products or do not contain
thermally sensitive organic ligands.

3) The hydroformylation of propene to butanal (1) is carried out
in a continuous process (2) on a scale of 4 ž 10^(12) to 5 ž
10^(12) g/year with volatile Rh/PPh3 catalysts (Ph, phenyl); the
volatile product is distilled directly from the reaction pot. A
more thermally robust catalyst, [RhI2(CO)2]-, is used in the
manufacture of acetic acid from the carbonylation of methanol.
This catalyst can withstand relatively high temperatures,
although in this case the distillation is carried out in a flash
evaporator at low pressure, outside the reaction chamber, making
it a batch continuous process (3). The use of low pressure during
distillation often causes other problems. Because the catalysts
have been optimized for stability, activity, and selectivity
under the high-pressure reaction conditions, they may undergo
undesirable side reactions under the reduced pressure conditions
of the separator. In some specialized applications, alternative
separation strategies have been commercially applied, but these -
-such as the removal of 1,4-butanediol, the product of the
hydroformylation of allyl alcohol, from the toluene solvent by
washing with water (4) -- are often suitable only for a narrow
range of reactions.

4) Many catalysts with highly desirable properties in terms of
activity and selectivity have therefore not been commercialized
for anything but the most valuable products. To overcome the
separation problems, chemists and engineers are investigating a
wide range of strategies other than distillation for recycling
the catalyst (5).

References (abridged):

1. C. D. Frohling, C. W. Kohlpaintner, in Applied Homogeneous
Catalysis with Organometallic Compounds, B. Cornils, W. A.
Herrmann, Eds. (VCH, Weinheim, Germany, 1996), vol. 1, pp. 27-104

2. In continuous processes, the substrates are continuously fed
into the reactor and the products are removed, usually by
distillation. In batch continuous processes, the substrates are
fed continuously, but some of the reaction solution is removed
for product separation and the recovered catalyst is returned to
the reactor. In batch processes, the reaction is carried out in a
sealed vessel and the work-up involves cooling, depressurizing,
and product separation.

3. M. J. Howard, M. D. Jones, M. S. Roberts, S. A. Taylor, Catal.
Today 18, 325 (1993)

4. A. M. Brownstein, Chemtech. 21, 506 (1991)

5. C. C. Tzschucke, et al., Angew. Chem. Int. Ed. 41, 3964 (2002)

Related Material:

LANTHANIDE COMPLEXES AND ASYMMETRIC CATALYSIS

Chem. Rev. 2002 102:2187

The term "asymmetric catalysis" refers to the use of of
homogeneous catalysts for the synthesis of chiral compounds. In
general, the major goal of this field in synthetic organic
chemistry is the development of highly stereoselective and
efficient catalysts for the synthesis of enantiomerically pure
compounds.

The following points are made by M. Shibasaki and N. Yoshikawa:

1) Asymmetric catalysis has received considerable attention over
the past few decades, and its contribution toward organic
synthesis has become increasingly significant.(1) A wide variety
of enantioselective chemical transformations are now performed
with only catalytic amounts of chiral promoters, providing highly
economic access to optically active compounds. Some of these
enantioselective transformations can be applied to industrial
production. Nonetheless, the performance of most artificial
catalysts is still far from satisfactory in terms of generality
and reactivity. On the other hand, enzymes catalyze a broad range
of organic transformations under rather mild conditions, even
though they are often specific for certain substrates. An
advantage of enzymes over most artificial catalysts is that they
often contain two or more active sites for catalysis. The
synergistic functions of the active sites make substrates more
reactive in the transition state and control their positions so
that the functional groups are proximal to each other. This
concept of multifunctional catalysis is key to increasing the
scope of natural and artificial catalysts.(2)

2) The development of asymmetric catalysis to date has been
accomplished by employing various metal elements on the basis of
the type of reaction targeted. While asymmetric catalysts
containing p-block metal elements or d-block elements have been
studied extensively,(1) the use of f-block elements (lanthanides
and actinides) as metal components for asymmetric catalysts has
not been studied until recently.(3) The utility of lanthanides
for asymmetric catalysis was first demonstrated by Danishefsky et
al.(4) These authors reported promotion of hetero Diels-Alder
reactions by Eu(hfc)3 with moderate enantiomeric excess (up to
58%). Several groups reported other examples of enantioselective
catalytic cycloaddition.(5) Other lanthanide complexes were
reported as catalysts in other enantioselective reactions such as
Meerwein-Ponndorf-Verley reductions, hydrogenations,
hydrosilylations, hydroaminations, polymerizations, and Mukaiyama
aldol reactions. These studies demonstrate the exceptional
capability of lanthanides as Lewis acids.

3) Since the first report of a catalytic asymmetric nitroaldol
reaction in 1992, Shibasaki et al. continued to develop the
concept of multifunctional catalysis, wherein the catalysts
exhibit both Lewis acidity and Bronsted basicity using lanthanide
complexes. The synergistic effects of the two functions enable
transformations that have never been possible using conventional
catalysts employing only Lewis acidity. Furthermore, a variety of
enantioselective transformations has been realized by carefully
choosing the metal elements according to the type of the
reaction, consistent with the above-mentioned concept. In
particular, the development of heterobimetallic complexes that
contain a lanthanide and alkali metal offer a versatile framework
for asymmetric catalysts, because the property of the catalyst
can be tuned dramatically according to the choice of alkali metal
and further refined by choosing the proper lanthanide.

References (abridged):

1. For recent reviews, see: (a) Comprehensive Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer: New York, 1999. (b) Catalytic Asymmetric Synthesis, 2nd
ed.; Ojima, I., Ed.; Wiley: New York, 2000.

2. For recent reviews of artificial enzymes, see: (a) Kirby, A.
J. Angew. Chem., Int. Ed. Engl. 1996, 35, 707. (b) Breslow, R.;
Dong, S. D. Chem. Rev. 1998, 98, 1997. (c) Williams, N. H.;
Takasaki, B.; Wall, M.; Chin, J. Acc. Chem. Res. 1999, 32, 485.
(d) Molenveld, P.; Engbersen, J. F. J.; Reinhoudt, D. N. Chem.
Soc. Rev. 2000, 29, 75.

3. For a review of asymmetric catalysis by lanthanide Lewis
acids, see: Shibasaki, M.; Yamada, K.-i.; Yoshikawa, N. In Lewis
Acids in Organic Synthesis; Yamamoto, H., Ed.; Wiley-VCH:
Weinheim, Germany, 2000; Vol. 2, Chapter 20.

4. Bednarski, M.; Maring, C.; Danishefsky, S. Tetrahedron Lett.
1983, 24, 3451.

5. (a) Kobayashi, S.; Hachiya, I.; Ishitani, H.; Araki, M.
Tetrahedron Lett. 1993, 34, 4535. (b) Kobayashi, S.; Ishitani,
H.; Hachiya, I.; Araki, M. Tetrahedron 1994, 50, 11623. (c)
Kobayashi, S.; Ishitani, H. J. Am. Chem. Soc. 1994, 116, 4083.
(d) Kobayashi, S.; Ishitani, H.; Araki, M.; Hachiya, I.
Tetrahedron Lett. 1994, 35, 6325. (e) Ishitani, H.; Kobayashi, S.
Tetrahedron Lett. 1996, 37, 7357. (f) Kobayashi, S.; Kawamura, M.
J. Am. Chem. Soc. 1998, 120, 5840. (g) Kawamura, M.; Kobayashi,
S. Tetrahedron Lett. 1999, 40, 3213.

Related Material:

ON CATALYTIC OXIDATION OF HYDROCARBONS

J. Am. Chem. Soc. 2001 123:8531

The following points are made by A.M. Khenkin et al:

1) In classic terms, homogeneous catalysis may be defined as a
reaction in a liquid phase whereby a dissolved compound of well-
defined molecular structure and properties is used as a catalyst.
Heterogeneous catalysis, on the other hand, usually occurs at a
solid-gas or solid-liquid interface, with the solid catalyst
often or usually ill-defined from the point of view of molecular
structure.

2) In the area of catalytic oxidation of hydrocarbons using
molecular oxygen as oxidant, homogeneous and heterogeneous
catalysis also often differ entirely as to the mechanism of
oxidation and the mode of activation of molecular oxygen.
Typically, in classic homogeneous liquid-phase aerobic oxidation,
molecular oxygen reacts via the well-established metal-catalyzed
free radical autoxidation pathways. Additional possibilities
include activation of molecular oxygen through formation of
singlet oxygen, use of oxygen to reoxidize redox active metals,
as in Wacker-type reactions, or activation in the presence of
reducing agents, as is typical for monooxygenase enzymes and
their mimetic counterparts. There are also a few examples of
activation of molecular oxygen by splitting of the oxygen-oxygen
bond in the absence of a reducing agent.

3) The authors report a mechanistic scheme for the oxidation of
anthracene, the reaction beginning with an electron transfer from
anthracene to a polyoxometalate.

Related Material:

SILICA-SUPPORTED HOMOGENEOUS CATALYSTS

J. Am. Chem. Soc. 2001 123:8468

The following points are made by A.J. Sandee et al:

1) The development of well-defined catalyst systems that allow
rapid and selective chemical transformations and at the same time
can be completely recovered from the product is still a paramount
challenge in basic and applied chemistry. Although highly active
and selective reusable catalyst systems have been reported, key
problems for many systems involve catalyst stability and leaching
of catalytic material in the product phase.

2) An intensively studied and promising approach to facilitate
catalyst-product separation is the attachment of homogeneous
catalysts to polymeric organic, inorganic, or hybrid supports,
and more recently to dendrimeric supports. Inorganic materials
such as silica are particularly suited as heterogeneous catalyst
supports because of their high physical strength and chemical
inertness. In the past three decades, much research has been
devoted to the development of recyclable catalyst systems for the
hydroformylation of higher alkenes.

3) The authors report the development of a polysilicate
immobilized homogeneous catalyst system that can act both as a
hydrogenation and a regioselective hydroformylation catalyst. The
system affords a quantitative and straightforward separation of
the catalyst from the products, it is reusable in numerous
catalytic cycles without any deterioration of catalytic activity,
and it enables clean and selective reactions for different
important catalytic processes using only one catalyst system.

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3. HETEROGENEOUS CATALYSIS

THE IMPACT OF NANOSCIENCE ON HETEROGENEOUS CATALYSIS

Science 2003 299:1688

The following points are made by Alexis T. Bell:

1) Inexpensive transportation fuels, high-temperature lubricants,
chlorine-free refrigerants, high-strength polymers, stain-
resistant fibers, cancer treatment drugs, and many thousands of
other products required by modern societies would not be possible
without the existence of catalysts. These critical materials
mediate the pathways by which chemical reactions occur, enabling
the highly selective formation of desired products at rates that
are commercially viable.

2) Catalysts are also essential for the reduction of air and
water pollution and contribute thereby to reducing the emissions
of products that are harmful to human health and the environment.
A recent article discussing the economic contributions of
catalysis noted that "one-third of material gross national
product in the U.S. involves a catalytic process somewhere in the
production chain" (1).

3) The majority of the industrial catalysts are high-surface-area
solids onto which an active component is dispersed in the form of
very small particles. These moieties have dimensions of 1 to 20
nm and are often referred to as nanoparticles. To illustrate the
importance of dispersed nanoparticles, one need only look inside
the automotive converter found under the floor of every new car
manufactured in the US since the early 1970s. The converter
consists of a honeycomb whose walls are covered with a thin
coating of porous aluminum oxide (alumina). The alumina washcoat
is impregnated with nanoparticles of Pt, Rh, Ce, zirconia, and
lanthana, and occasionally baria. The Pt serves to oxidize
hydrocarbons and carbon monoxide, and the Rh serves to reduce
NOx. The ceria, particularly in combination with zirconia, works
as an oxygen storage component, enabling the oxidation of
hydrocarbons and carbon monoxide to occur during moments when the
engine exhaust is fuel-rich. The lanthana serves to stabilize the
alumina against a loss of surface area, and the baria acts as a
trap for sulfur trioxide: a catalyst deactivator, or "poison."

4) The importance of small particles to the performance of
catalysts has stimulated extensive efforts to develop tools for
their characterization (2,3). Originating from the fields of
physics, chemistry, materials science, and chemical engineering,
this area of study is now often referred to as "nanoscience".
Local size and composition of catalyst particles affect their
performance (their activity and selectivity) and advances in
nanoscience have contributed to a detailed understanding of the
effects of particle composition, size, and structure on catalyst
performance. Advances in synthetic methods are leading to
increasingly precise control of the variables affecting catalyst
activity and selectivity.(4,5)

References (abridged):

1. Chem. Ind., 21 January 2002, p. 22

2. C. B. Duke, E. W. Plummer, Eds., Frontiers in Surface and
Interface Science (North-Holland, Amsterdam, 2002)

3. R. Maisel, Principles of Adsorption and Reaction on Solid
Surfaces (Wiley, New York, 1996)

4. G. C. Bond and D. T. Thompson, Catal. Rev. Sci. Eng. 41, 319
(1999)

5. M. Valden, X. Lai, D. W. Goodman, Science 281, 1647 (1998)

Related Material:

ON CATALYST PROMOTERS

Science 2001 294:1508

The following points are made by T.W. Hansen et al:

1) In many industrial catalyst systems, the presence of so-called
"catalyst promoters" is essential to achieve the required
activity or selectivity. Usually, a promoter is defined as a
substance that causes a more than proportional increase in
activity or selectivity when added to the catalyst. In many
cases, the promoter alone is completely inactive in the catalytic
process, where it is used to boost productivity.

2) It is common practice to distinguish between structural
promoters that cause an increase in the number of active sites
and electronic promoters that produce active sites with a higher
intrinsic activity, i.e., higher turnover frequencies. In early
work, Mittasch (1950) performed systematic studies of the
influence of various catalyst promoters with ammonia synthesis
catalysts. Previously, the influence of such "impurities" had
only been observed more or less inadvertently.

3) Although the effect of the promoter on the catalytic activity
and reaction kinetics is easily measured, structural information
is rarely available. Very often, electronic promoters are present
in relatively small amounts and are not found as crystalline
structures, which complicates the structural characterization.
More importantly, the promoter is often distributed between
various phases of the catalyst, making the establishment of
structure-activity relations very difficult.

Related Material:

ON STRUCTURE SENSITIVITY OF CATALYTIC REACTIONS

Phys. Rev. Lett. 89:016102

The following points are made by B. Hammer:

1) Structure sensitivity in heterogeneous catalytic reactions
provides a means of optimizing the reactivity and selectivity of
a catalyst. In general, the structure of a catalyst is subject to
the thermodynamic and chemical conditions during reaction. For
oxide supported metal particle catalysts, the support serves as a
structural promoter that, in combination with the metal
deposition conditions, determines the size and shape of the
catalyst particles and thereby the types of metal crystal faces
exposed [1-3]. Owing to improved particle preparation techniques,
the reaction of very small catalyst particles is currently
receiving much attention. Nano-scaled metal particles supported
on metal oxide surfaces are now routinely synthesized with a
narrow particle size dispersion [2] if not as size selected,
monodispersed particles [4]. Surface-science characterization of,
e.g., CO oxidation at 25-60-angstrom-wide gold particles on ti-
tania [5] and NO reduction at 28-156-angstrom-wide palladium
particles on magnesia have revealed intermediate sized particles
to be the most reactive. Likewise, studies of, e.g., Pd(subn) or
Au(subn) (1 =< n =< 20-30) particles on magnesia films have
revealed "magic" metal particle sizes (Pd(sub13), Au(sub8)) of
particular high reactivity for reactions such as acetylene
cyclotrimerization and CO oxidation.

2) The observed structure sensitivity of reactions on oxide
supported metal particles is generally believed to arise from
several different factors including strain, charge transfer,
special reaction sites, and electronic structure changes of the
metal systems due to their nano-sized dimensions. Goodman and
coworkers conclude in their CO oxidation studies [5] that the
metal particle thickness is an important parameter, with 2
monolayer (ML) thick Au clusters showing the highest reactivity.
In their combined experimental and theoretical work on CO
oxidation at atomic sized gold clusters on magnesia, Landman and
co-workers (1999) emphasize the significance of electronic
charging of the metal clusters and the presence of defects in the
oxide support. The suggestions for the atomistic reasons behind
structurally enhanced activity at certain metal clusters are thus
several.

3) In summary: The author reports a calculation of the potential
energy diagram for the NO + CO reaction on 1, 2, and 3 monolayer
(ML) Pd films supported by MgO(l00) using density functional
theory. Thin Pd films are generally found to be more reactive
than thick films, with a notable exception for nitrogen
adsorption on 2 ML Pd/MgO(100). For this system, an attractive
through-the-metal adsorbate-oxide interaction of 0.5 eV is
identified. Nitrogen adsorption is consequently estimated to
provide a thermodynamic driving force for the reconstruction of
MgO(l00) supported 3 ML (or thicker) Pd clusters into thinner Pd
clusters.

References (abridged):

1. C.T. Campbell, Surf. Sci. Rep. 27, 1 (1997).

2. C.R. Henry, Surf. Sci. Rep. 31, 235 (1998).

3. M. Baumer and H.J. Freund, Prog. Surf. Sci. 61, 127 (1999).

4. U. Heiz and W.-D. Schneider, J. Phys. D 33, R85 (2000).

5. M. Valden, X. Lai, and D. W. Goodman, Science 281, 1647
(1998).

Related Material:

ON HETEROGENEOUS CATALYSIS AND SURFACE SCIENCE

Physics Today 1999 January

The following points are made by G. Ertl and H-J. Freund:

1) The economic significance of heterogeneous catalysis is
reflected in the fact that the world market for solid catalysts
in the automotive, petroleum, and other industries is of the
order of US$100 billion per year and growing rapidly.

2) In heterogeneous catalysis, the chemical transformation
typically occurs in a flow reactor through which the reacting
species pass. Atoms in the surface of the catalyst may form
chemical bonds with atoms in impinging molecules, a phenomenon
known as "chemisorption". If existing bonds in the impinging
molecule break, the process is known as "dissociative
chemisorption". The chemisorbed species are mobile on the surface
and may bond to other particles, thus leading to new molecules,
which eventually leave the surface (desorb) as the desired
reaction products.

3) Detailed identification and characterization of these
elementary processes of heterogeneous catalysis are hampered by
several fundamental problems: a) The reacting systems exist
merely as 2-dimensional phases for which most of the usual
methods of investigation are not well suited. b) The surfaces of
real catalysts are typically inhomogeneous as a result of methods
to increase catalytic efficiency. For example, because in
heterogeneous catalysis efficiency, in general, increases with
total surface area of the solid catalyst, finely divided
particles are usually applied to a support material which is only
relatively inert. Also, catalytic activity is often further
enhanced by the addition of compounds called "promoters". At the
present time, analysis of the fundamentals of heterogeneous
catalysis is largely dependent on the use of surface science
models, real but simple systems such as single crystal surfaces
whose structure may be varied by choosing different surface
orientations.

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4. SURFACE CATALYSIS

CATALYSIS ON OXIDE SURFACES

Science 2000 287:1407

1) Free coordination sites play a major role in catalysis by
metal complexes, because reactants may bind to these sites and
become activated for catalytic conversion (1). Similar
considerations apply to the surfaces of solid catalysts in
general and of metal oxides in particular, because the surface
atoms are characterized by a "ligand" sphere that differs from
that in the bulk. The surface atoms generally have lower
coordination numbers than those characteristic for the bulk (2).
Their coordination sphere may be completed by adsorbed molecules,
and these may be activated for catalytic transformations, in
close analogy to processes occurring on metal complexes.

2) The coordination numbers of surface atoms in real catalysts
may vary over wide ranges because different crystallographic
faces, edges, steps, point defects, and dislocations may be
exposed, resulting in an often substantial energetic
heterogeneity (4). Oxide surfaces typically expose coordinatively
unsaturated site (CUS) cations and CUS oxygen anions, and
chemisorption --adsorption involving chemical bond formation --
frequently involves both simultaneously. For a specific catalytic
transformation, certain geometric and energetic requirements must
be fulfilled, so that frequently only a small percentage of all
surface atoms may act as active sites.

3) The CUS surface sites on real, high-surface area catalysts can
only be characterized indirectly, using probe molecules that can
fill the free coordination sites. For example, the carbonyl
infrared spectra of CO adsorbed on microcrystalline a-Cr2O3 (5)
and on epitaxially grown chromium oxide films show a complex
pattern of bands of carbonyl surface complexes characterizing the
heterogeneity of chromium sites.

References (abridged):

1. B. C. Gates, Catalytic Chemistry (Wiley, New York, 1992)

2. R. L. Burwell Jr., G. L. Haller, K. C. Taylor, J. F. Read,
Adv. Catal. 20, 1 (1969)

3. H. Over et al., Science 287, 1474 (2000)

4. H. S. Taylor, Proc. R. Soc. London Ser. A 108, 105 (1925)

5. D. Scarano, A. Zecchina, A. Reller, Surf. Sci. 198, 11 (1988)

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5. ENZYME CATALYSIS

ENZYME DYNAMICS DURING CATALYSIS

Science 2002 295:1520

The following points are made by E. Eisenmesser et al:

1) Although classical enzymology together with structural biology
have provided profound insights into the chemical mechanisms of
many enzymes (1), enzyme dynamics and their relation to catalytic
function remain poorly characterized. Because many enzymatic
reactions occur on time scales of micro- to milliseconds, it is
anticipated that the conformational dynamics of the enzyme on
these time scales might be linked to its catalytic action (2).
Classically, enzyme reactions are studied by detecting substrate
turnover.

2) Dynamics of enzymes during catalysis have been detected with
methods such as fluorescent resonance energy transfer, atomic
force microscopy, and stopped-flow fluorescence, which report on
global motions of the enzyme or dynamics of particular molecular
sites. In contrast, nuclear magnetic resonance (NMR) spectroscopy
enables investigations of motions at many atomic sites
simultaneously (3,4). NMR studies reporting on the time scales,
amplitudes, and energetics of motions in proteins have provided
information on the relation between protein mobility and function
(5).

3) The authors report an examination of enzyme catalysis in a
nonclassical way by characterizing motions in the enzyme during
substrate turnover. The authors have used NMR relaxation
experiments to advance these efforts by characterizing
conformational exchange in an enzyme, human cyclophilin A (CypA),
during catalysis. CypA is a member of the highly conserved family
of cyclophilins that are found in high concentrations in many
tissues. Cyclophilins are peptidyl-prolyl cis/trans isomerases
that catalyze the interconversion between cis and trans
conformations of X-Pro peptide bonds, where "X" denotes any amino
acid. CypA operates in numerous biological processes. It is the
receptor for the immunosuppressive drug cyclosporin A, is
essential for HIV infectivity, and accelerates protein folding in
vitro by catalyzing the rate-limiting cis/trans isomerization of
prolyl peptide bonds. However, its function in vivo and its
molecular mechanism are still in dispute.

4) In summary: Internal protein dynamics are intimately connected
to enzymatic catalysis. However, enzyme motions linked to
substrate turnover remain largely unknown. The authors have
studied dynamics of an enzyme during catalysis at atomic
resolution using nuclear magnetic resonance relaxation methods.
During catalytic action of the enzyme cyclophilin A, the authors
detect conformational fluctuations of the active site that occur
on a time scale of hundreds of microseconds. The rates of
conformational dynamics of the enzyme strongly correlate with the
microscopic rates of substrate turnover. The authors suggest that
the present results, together with available structural data,
allow a prediction of the reaction trajectory.

References (abridged):

1. T.C. Bruice and S.J. Benkovic, Biochemistry 39, 6267 (2000)

2. A. Fersht, Structure and Mechanism in Protein Science. A Guide
to Enzyme Catalysis and Protein Folding (Freeman, New York, ed.
1, 1999) pp. 44-51

3. M.W. Fischer, A. Majumdar, E. R. P. Zuiderweg, Progr. Nucl.
Magn. Reson. Spectrosc. 33, 207 (1998)

4. A.G. Palmer, 3rd, Curr. Opin. Struct. Biol. 7, 732 (1997)

5. R. Ishima and D.A. Torchia, Nature Struct. Biol. 7, 740 (2000)

Related Material:

CRYSTAL STRUCTURE OF A HAIRPIN RIBOZYME INHIBITOR COMPLEX WITH
IMPLICATIONS FOR CATALYSIS

Nature 2001 410:780

The following points are made by P.B. Rupert and A.R. Ferr‚-
D'amare:

1) The hairpin ribozyme is a catalytic RNA derived from the self-
cleaving and ligating domain of the negative polarity strand of
the satellite RNA of tobacco ringspot virus. In vivo, this domain
is responsible for generating unit-length circular satellite RNA
during the course of its rolling-circle replication (1). The
cleavage reaction generates products with 5'-hydroxyl and 2',3'-
cyclic phosphate termini, which are analogous to those produced
by three other natural ribozymes that are part of circular
satellite RNAs: the hammerhead, the hepatitis delta virus (HDV)
and the Varkud satellite (VS) ribozymes. These four ribozymes,
however, are structurally unrelated, and therefore represent
independent evolutionary solutions to the same biochemical
problem (2). None of these ribozymes require proteins for
activity. They are also quite small, for example the hairpin
ribozyme requires about 50 nucleotides for activity. The hairpin
ribozyme is an ideal experimental system to help understand how a
small catalytic RNA self-assembles and forms an active site.

2) Biochemical experiments demonstrated that the active site of
the hairpin ribozyme results from the association of two largely
helical segments of the satellite RNA, stems A (one strand of
which contains the scissile phosphate) and B. Both contain
nucleotides necessary for catalysis(1). The stems can be
synthesized as two separate RNAs and mixed in vitro to
reconstitute an active ribozyme(3,4). Most biochemical
experiments have been carried out using constructs where the two
stems are connected by a single-stranded linker. In the satellite
RNA, stems A and B are part of a four-helix junction(5).
Fluorescence resonance energy transfer (FRET) measurements
demonstrated that the docking of stems A and B is greatly
favoured in constructs that contain the four-helix junction,
compared with systems where the two stems are connected by an
extended linker(5).

3) In summary: The hairpin ribozyme catalyses sequence-specific
cleavage of RNA. The active site of this natural RNA results from
the docking of two irregular helices: stems A and B. One strand
of stem A harbors the scissile bond. The 2.4 angstrom resolution
structure of a hairpin ribozyme inhibitor complex reveals that
the ribozyme aligns the 2'-OH nucleophile and the 5'-oxo leaving
group by twisting apart the nucleotides that flank the scissile
phosphate. The base of the nucleotide preceding the cleavage site
is stacked within stem A; the next nucleotide, a conserved
guanine, is extruded from stem A and accommodated by a highly
complementary pocket in the minor groove of stem B. Metal ions
are absent from the active site. The bases of four conserved
purines are positioned potentially to serve as acid-base
catalysts. This is the first structure determination of a fully
assembled ribozyme active site that catalyses a phosphodiester
cleavage without recourse to metal ions.

References (abridged):

1. Fedor, M. J. Structure and function of the hairpin ribozyme.
J. Mol. Biol. 297, 269-291 (2000)

2. McKay, D. B. & Wedekind, J. E. in The RNA World (eds
Gesteland, R. F., Cech, T. R. & Atkins, J. F.) 265-286 (Cold
Spring Harbor Press, Cold Spring Harbor, 1999).

3. Butcher, S. E., Heckman, J. E. & Burke, J. M. Reconstitution
of hairpin ribozyme activity following separation of functional
domains. J. Biol. Chem. 270, 29648-29651 (1995)

4. Shin, C. et al. The loop B domain is physically separable from
the loop A domain in the hairpin ribozyme. Nucleic Acids Res. 24,
2685-2689 (1996)

5. Murchie, A. I. H., Thomson, J. B., Walter, F. & Lilley, D. M.
J. Folding of the hairpin ribozyme in its natural conformation
achieves close physical proximity of the loops. Mol. Cell 1, 873-
881 (1998)

Related Material:

ON BIOCATALYSIS IN INDUSTRIAL SYNTHESIS

Science 2003 299:1683

The following points are made by H.E. Schoemaker et al:

1) Microbial cells and the enzymes therein have been used for
millennia in the production of valuable food products. Several
decades ago, the first applications of biocatalysis in the
chemical industry were implemented. Examples include the use of
acylases, hydantoinases, and aminopeptidases in the production of
optically pure amino acids, and the use of nitrile hydratase in
the enzymatic production of the bulk chemical acrylamide from
acrylonitrile (1-3). The recognition that lipase and other
enzymes can be used in organic media (4,5) and even in the solid
phase has further increased the potential of enzymes as catalysts
in organic synthesis.

2) Today, both the academic and the industrial community see
biocatalysis as a highly promising area of research, especially
for the development of sustainable technologies for the
production of chemicals (green chemistry) and more selective and
complex active ingredients in pharmaceuticals and agrochemicals.
High stereoselectivities and hence enantiomerically pure products
are a particularly attractive feature of biocatalysis. Large-
scale industrial applications of enzyme catalysis include the
thermolysin-catalyzed synthesis of the low-calorie sweetener
aspartame and the synthesis of semi-synthetic beta-lactam
antibiotics with the use of acylases. Further, acrylamide and
nicotinamide are produced with the help of a nitrile hydratase,
and the organic solvent 1,5-dimethyl-2-piperidone (1,5-DMPD) is
manufactured using a nitrilase. There is also a multitude of
smaller scale applications, particularly for manufacturing
pharmaceutical ingredients(1-3).

3) Yet, despite widespread research efforts in academia and
industry, the number and diversity of biocatalyst applications
remain rather modest. This situation may be attributed to several
perceived limitations of biocatalysis, including the availability
of the biocatalysts, their substrate scope, and their operational
stability. It may in part also be due to the reluctance of the
chemical community to explore the potential of biocatalysts in
more depth.

4) In summary: Biocatalysis has emerged as an important tool in
the industrial synthesis of bulk chemicals, pharmaceutical and
agrochemical intermediates, active pharmaceuticals, and food
ingredients. However, the number and diversity of the
applications are modest, perhaps in part because of perceived or
real limitations of biocatalysts, such as limited enzyme
availability, substrate scope, and operational stability. Recent
scientific breakthroughs in genomics, directed enzyme evolution,
and the exploitation of biodiversity should help to overcome
these limitations. As a result, one expects many new industrial
applications of biocatalysis to be realized, from single-step
enzymatic conversions to customized multistep microbial synthesis
by means of metabolic pathway engineering.

References (abridged):

1. K. Drauz, H. Waldmann, Enzyme Catalysis in Organic Synthesis:
A Comprehensive Handbook (Wiley-VCH, Weinheim, Germany, ed. 2,
2002)

2. A. Liese, K. Seelbach, C. Wandrey, Industrial
Biotransformations (Wiley-VCH, Weinheim, Germany, 2000)

3. A. Schmid, et al., Nature 409, 258 (2001)

4. P. J. Halling, Curr. Opin. Chem. Biol. 4, 74 (2000)

5. A. Zaks and A. M. Klibanov, Proc. Natl. Acad. Sci. U.S.A. 82,
3192 (1985)

Related Material:

IMPROVING SUBSTRATE SPECIFICITY OF SMALL CATALYTIC PEPTIDES

J. Am. Chem. Soc. 2002 124:3510

The following points are made by F. Tanaka and C.F. Barbas III:

1) Substrate specificity is one of the hallmarks of enzymes.
Substrate specificity allows an enzyme to catalyze a reaction
involving substrate molecules found within a complex mixture of
compounds possessing the same functional groups. Generation of
designer protein catalysts that possess substrate specificity has
been demonstrated by modification of nature's enzymes(1) and by
the preparation of catalytic antibodies.(2) In contrast to large
proteins, small peptide catalysts have demonstrated limited
specificity for small-molecule substrates.(3) This is presumably
a result of the limited opportunities small peptides have to fold
in a manner that provides for the formation of an isolated
reaction vessel that effectively binds and sequesters substrates
from bulk solvent while at the same time catalyzing their
transformation.

2) The authors report that to explore routes for the preparation
of small peptide enzymes that possess improved substrate
specificity, they have examined a modular assembly strategy. The
authors report a demonstration of the potential of this strategy
with the construction of a small 35-amino acid residue aldolase
peptide with improved substrate specificity. The design strategy
attempts to recruit a substrate-specific module for providing
substrate specificity to an otherwise promiscuous catalyst.
Covalent combination of binding- and catalytic-domain modules
might improve the substrate specificity of the catalyst. When the
binding site is in close proximity to the catalytic site, the
catalytic site would receive the benefit of a higher local
substrate concentration provided by sequestering the substrate in
close proximity to the catalytic site. The potential advantages
of this approach are that it reduces the demand on the
functionalization of the catalytic site, which is limited in
small peptides, and it is modular, therefore making its
adaptation to a variety of specificities rapid.

References (abridged):

1. Petrounia, I. P.; Arnold, F. H. Curr. Opin. Biotechnol. 2000,
11, 325. Cedrone, F.; Menez, A.; Quemeneur, E. Curr. Opin.
Struct. Biol. 2000, 10, 405.

2. Reymond, J.-L. Top. Curr. Chem. 1999, 200, 59. Barbas, C. F.,
III; Rader, C.; Segal, D. J.; List, B.; Turner, J. M. Adv.
Protein Chem. 2000, 55, 317. Schultz, P. G.; Lerner, R. A.
Science 1995, 269, 1835. Tanaka, F.; Lerner, R. A.; Barbas, C.
F., III. J. Am. Chem. Soc. 2000, 122, 4835.

3. Broo, K. S.; Nilsson, H.; Nilsson, J.; Baltzer, L. J. Am.
Chem. Soc. 1998, 120, 10287. Broo, K. S.; Brive, L.; Ahlberg, P.;
Baltzer, L. J. Am. Chem. Soc. 1997, 119, 11362. Johnsson, K.;
Allemann, R. K.; Widmer, H.; Benner, S. A. Nature 1993, 365, 530.
Peptide ligases operate via template-assisted catalysis and
demonstrate good substrate specificity: Kennan, A. K.; Haridas,
V.; Severin, K.; Lee, D. H.; Ghadiri, M. R. J. Am. Chem. Soc.
2001, 123, 1797. Yao, S.; Ghosh, I.; Zutshi, R.; Chmielewski, J.
Nature 1998, 396, 447.

Related Material:

RNA WORLD: RNA-CATALYZED RNA POLYMERIZATION

Science 2001 292:1319

The following points are made by W.K. Johnston et al:

1) The "RNA world hypothesis" states that early life forms lacked
protein enzymes and depended instead on enzymes composed of RNA.
Much of the appeal of this hypothesis arises from the realization
that RNA-enzymes (ribozymes) would have been far easier to
duplicate than proteinaceous enzymes. Whereas coded protein
replication requires numerous macromolecular components
(including messenger RNAs, transfer RNAs, the ribosome, etc.),
replication of a ribozyme requires only a single macromolecular
activity: an RNA-dependent RNA polymerase that synthesizes first
a complement, and then a copy of the ribozyme. If this RNA
polymerase were itself a ribozyme, then a simple ensemble of
molecules might be capable of self-replication and eventually, in
the course of evolution, give rise to the protein-nucleic acid
world of contemporary biology.

2) Finding a ribozyme that can efficiently catalyze general RNA
polymerization would support the idea of the RNA world and would
provide a key component for the laboratory synthesis of minimal
life forms based on RNA. The authors report the generation of an
RNA molecule that catalyzes the type of polymerization needed for
RNA replication. The ribozyme uses nucleotide triphosphates and
the coding information of an RNA template to extend RNA primer by
the successive addition of up to 14 nucleotides -- more than a
complete turn of an RNA helix.

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6. ANTIBODY CATALYSIS

ANTIBODY DESIGN BY MAN AND NATURE

Science 2002 296:2247

The following points are made by Paul Wentworth Jr:

1) Throughout evolutionary history, nature has in effect screened
large libraries of proteins to solve key problems of molecular
recognition and catalysis, resulting in the present-day
functional proteome. Sixteen years ago, Lerner (1) and Schultz
(2) independently reported that probing the natural repertoire of
antibodies with transition state analogs enables new catalysts to
be identified on the evolutionary time scale of the immune
response (2 to 3 weeks), and they demonstrated that the antibody
molecule can mediate chemistry more complex than simple binding.

2) The original reports of catalytic antibodies focused on well-
characterized transformations, such as acyl transfer. Scientists
have since shown, however, that antibodies can be programmed to
catalyze many different classes of chemical reactions with
typical rate enhancements ranging between 10^(3) and 10^(6) (3).
These processes have included "disfavored" reactions that are
difficult to carry out with existing chemical methods, such as an
anti-Baldwin cyclization (4) and BAC2 carbamate ester hydrolysis
(5). In addition, catalytic antibodies can perform reactions that
are not catalyzed by endogenous enzymes. These have been used,
for example, to activate anticancer prodrugs. Antibodies can also
catalyze processes with highly reactive chemical intermediates,
such as carbocations, 1,3-dipoles, and triplet biradicals. They
generally perform well in experiments that require the control of
chirality, typically giving high enantio- and
diastereoselectivities. In fact, antibodies are peerless designer
catalysts because of their programmability and ability to
catalyze an amazing diversity of reactions (3).

3) The increasingly sophisticated strategies for generating
catalytic antibodies parallel the complex chemical reactions that
antibodies can catalyze. In the primary method for eliciting
antibody catalysts, an animal (typically, a mouse) is immunized
with a stable analog of the transition state for a given
reaction. The researcher then harvests and immortalizes the
antibody-generating cells (B cells) with Koehler and Milstein's
hybridoma technology. Thus, in principle, each monoclonal
antibody in the immune repertoire library that was elicited to
the hapten is isolated, expressed in milligram to gram levels in
high purity, and screened for catalytic activity. On the basis of
the principles of transition state theory, antibodies that bind
tightly and stabilize the transition state for a reaction should
catalyze that reaction. This successful approach (called
transition state stabilization) has been expanded to incorporate
more sophisticated catalytic mechanisms, such as general acid or
general base and covalent catalysis, into antibody catalysts.

References (abridged):

1. A. Tramontano, K. D. Janda, R. A. Lerner, Science 234, 1566
(1986)

2. S. J. Pollack, J. W. Jacobs, P. G. Schultz, Science 234, 1570
(1986)

3. P. Wentworth Jr., K. D. Janda, Curr. Opin. Chem. Biol. 2, 138
(1998); G. M. Blackburn, A. Datta, H. Denham, P. Wentworth Jr.,
Adv. Phys. Org. Chem. 31, 249 (1998)

4. K. D. Janda, C. G. Shevlin, R. A. Lerner, Science 259, 490
(1993)

5. P. Wentworth Jr. et al., J. Am. Chem. Soc. 119, 2315 (1997)

Related Material:

ANTIBODY CATALYSIS: COMPLETING THE CIRCLE

Nature 2002 418:485

The following points are made by P.G. Schultz and R.A. Lerner:

1) Historically, immunochemistry has focused on understanding and
exploiting the remarkable binding affinity and specificity of
antibody molecules. With the advent of antibody catalysis,
chemists could ask for the first time whether this sophisticated
system of molecular diversity can be used to create new chemical
tools -- efficient and selective catalysts. From these
experiments have arisen a host of antibody catalysts, in some
cases with specificities and activities that rival those of
enzymes.

2) Moreover, characterization of the mechanisms and immunological
evolution of catalytic antibodies has provided fundamental
insights into the evolution of binding and catalytic functions in
nature. The field has also had a broader influence on chemistry -
- chemists are increasingly incorporating the biological idea of
molecular diversity into their efforts to synthesize molecules
with new functions. Finally, the study of antibody catalysis has
led to the realization that all antibodies are oxidative
catalysts, suggesting a previously unrecognized role for the
antibody molecule in the immune response.

3) The classic early theories of enzyme catalysis by Linus
Pauling (1901-1994)and J.B.S. Haldane (1892-1964) focused on the
ability of proteins to use selective binding energy to stabilize
rate-limiting transition states or to destabilize substrates in
order to lower the free energy of activation of a reaction. The
realization that one can similarly direct the binding energy of
an antibody molecule provided an experimental approach to test
these theories, much as chemists have synthesized small molecules
to test mechanistic hypotheses.

4) Consider, for example, the generation of an antibody that
catalyses the metallation of porphyrins. It is thought that the
enzyme ferrochelatase, which catalyses this reaction in haem
biosynthesis, does so by straining or distorting the planar
porphyrin substrate. By generating antibodies against a synthetic
mimic of a bent porphyrin, an antibody was evolved with catalytic
properties similar to those of the natural enzyme. The X-ray
crystal structure of the Michaelis complex provided the first
direct structural support for the strain hypothesis. Similar
studies have made it possible to analyze the energetic
contributions of transition-state stabilization, covalent and
general base catalysis, and proximity effects to biological
catalysis. In some cases, such as antibodies that catalyse
efficient acyl-transfer reactions, the immune system converges on
the same mechanisms that are used by enzymes for a reaction,
underscoring the remarkable similarity between these two
evolutionary systems.(1,2)

References (abridged):

1. Haldane, J. B. S. Enzymes (Longmans Green, London, 1930).

2. Schultz, P., Yin, J. & Lerner, R. Angew. Chem. Int. Engl. Edn
(in the press).

Related Material:

EVIDENCE FOR ANTIBODY-CATALYZED OZONE FORMATION IN BACTERIAL
KILLING AND INFLAMMATION

Science 2002 298:2195

The following points are made by P. Wentworth Jr et al:

1) A central concept of immunology is that antibodies perform the
sole function of marking antigens for destruction by effector
systems such as complement and phagocytic cells (1). Work on
antibody catalysis has demonstrated that the antibody molecule is
capable of carrying out highly sophisticated chemistry, although
there has been no direct evidence that this catalytic potential
is used in nature (2). This view is consistent with the known
organization of the humoral immune system, in that simple antigen
binding is sufficient to activate more sophisticated effector
systems and, thus, killing of pathogens can be achieved without
the need to invoke any chemistry within the antibody molecule
itself.

2) Recently however, the authors found that all antibodies,
regardless of source or antigenic specificity, can catalyze redox
chemistry that is independent of antibody binding (3) and appears
to be highly analogous to that carried out by the effector
mechanism of phagocytic cells (4). When exposed to singlet
molecular oxygen, antibodies oxidize water to produce H2O2 via
the postulated intermediacy of H2O3 (5).

3) In summary: Antibodies catalyze the generation of hydrogen
peroxide (H2O2) from singlet molecular oxygen and water. The
authors demonstrate that this process can lead to efficient
killing of bacteria, regardless of the antigen specificity of the
antibody. H2O2 production by antibodies alone was found to be not
sufficient for bacterial killing. The authors suggest their
studies indicate that the antibody-catalyzed water-oxidation
pathway produces an additional molecular species with a chemical
signature similar to that of ozone. This species is also
generated during the oxidative burst of activated human
neutrophils and during inflammation. The authors suggest these
observations indicate that alternative pathways may exist for
biological killing of bacteria that are mediated by potent
oxidants previously unknown to biology.

References (abridged):

1. R. B. Sim and K. B. Reid, Immunol. Today 12, 307 (1991)

2. P. Wentworth Jr., Science 296, 2247 (2002)

3. A. D. Wentworth, L. H. Jones, P. Wentworth Jr., K. D. Janda,
R. A. Lerner, Proc. Natl. Acad. Sci. U.S.A. 97, 10930 (2000)

4. S. J. Klebanoff, in Encyclopedia of Immunology, P. J. Delves,
I. M. Roitt, Eds. (Academic Press, San Diego, 1998), pp. 1713-
1718

5. P. Wentworth Jr., et al., Science 293, 1806 (2001)

Related Material:

ON THE USE OF ANTIBODY CATALYSIS IN ORGANIC CHEMISTRY

Proc. Nat. Acad. Sci. 1998 95:14590

The following points are made by Peter G. Schultz:

1) The use of catalytic antibodies in organic chemistry began
with the idea that chemists should be able to use the complex
machinery of the immune system, which is capable of generating
enormous chemical diversity through the processes of
*recombination and *somatic mutation, to create new molecular
functions, specifically highly selective catalysts.

2) The earliest examples involved the use of transition state
analogues to select antibodies with maximal binding affinity
toward the rate-limiting transition state for a given reaction.
Other strategies then emerged, strategies in which many of the
basic concepts of biological catalysis (e.g., strain, proximity,
general acid/base catalysis) were used in the design of molecules
that could guide the generation of catalytic antibodies for a
wide variety of reactions.

3) More recently, efforts have focused on detailed studies of
catalytic antibodies to gain new insights into the molecular
mechanisms of biological catalysis and of the immune response
itself. For example, structural studies of catalytic antibodies
have resulted in important new perspectives concerning the
*combinatorial processes involved in the immune response.

4) Another direction the field has taken involves efforts to
recapitulate the combinatorial processes of the immune system in
vitro. For example, strategies are now being developed to
directly select *bacteriophage mutants with enhanced catalytic
activities from large libraries of such mutants. Such strategies
are designed to provide a direct linkage between catalysis and
biological amplification in order to produce protein catalysts
for a broad range of chemical reactions.

5) A new strategy for generating antibody catalysis involves
"reactive immunization" --a designed covalent interaction between
immunogen and antibody, and this technique has now been used to
carry out the synthesis of key intermediates that in turn
simplify the synthesis of the natural product epothilone, a
powerful cytotoxic agent of considerable biomedical interest
[*Note #1].

Notes:

*antigen: In general, an antigen is any substance or moiety that
produces an immune response.

*transition state: (activated state) In general, in any chemical
reaction, the "transition state" is the high energy configuration
through which the reactants must pass before becoming products.

*recombination: In general, integration of DNA fragments into a
particular site in a genome.

*somatic mutation: In general, a mutation occurring in non-germ
cells, which means the mutation is not transmitted to the next
generation.

*combinatorial processes: Certain aspects of the immune response
and its production of antibodies apparently mimic a
"combinatorial process" in the sense that many factors are
involved in various combinations, rather than one factor involved
as a predominant determinant. (Combinatorial analysis is a branch
of mathematics involving analysis by means of combinations,
permutations, etc.) Combinatorial chemistry is a recent
technology involving the automated rapid production and screening
of thousands of compounds for specific properties, the population
of compounds consisting of a large number of possible
permutations of chemical constituents. One method, for example,
produces thin-film "libraries" of up to 25,000 different
substances on a 3-inch diameter substrate. The methods are
increasingly used in molecular biology for the production and
screening of large libraries of antibodies, peptides, DNA
ligands, and so on. A random peptide library synthesis may
involve as many as 100 million different peptides, with
subsequent screening of the library for the purposes of drug
discovery.

*bacteriophage: Bacteriophage is a virus that infects bacteria,
the virus essentially consisting of a naked strand of DNA
surrounded by a complex polyhedral shell ("capsid") composed
mainly of glycoproteins.

*Note #1: The Schultz review is a commentary on a research report
appearing in the same issue of the journal: S.C. Sinha et al: The
antibody catalysis route to the total synthesis of epothilones.
((Proc. Natl. Acad. Sci. US 1998 95:14603) Epothilones are
powerful cytotoxic agents isolated from *myxobacteria (Sorangium
cellulosum), the substances exhibiting a *taxol-like effect on
cellular *microtubules.

*myxobacteria: An order of bacteria bearing extracellular slime.

*taxol: An anti-tumor and anti-leukemic agent isolated from the
bark of the yew tree.

*microtubules: Microtubules are part of the cytoskeleton of
biological cells, the quasi-rigid matrix that among other things
determines cell shape. The microtubules are 25 nanometers in
diameter, and composed of the protein tubulin. They occur in
regular arrays in cilia, flagella, the mitotic spindle, and in
the cytoplasm in general, and they contribute not only to cell
shape, but also to cell motility.

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7. FRONTIERS IN CATALYSIS

ON CHIRAL CATALYSTS

Science 2003 299:1691

The following points are made by T.P. Yoon and E.N. Jacobsen:

1) Although the principles underlying asymmetric catalysis with
enzymes and small molecules are fundamentally the same (1), some
striking and rather surprising differences have been noted.
William S. Knowles, a pioneer in small molecule asymmetric
catalysis, made the following key observation in his Nobel
address: "When we started this work we expected these man-made
systems to have a highly specific match between substrate and
ligand, just like enzymes. Generally, in our hands and in the
hands of those that followed us, a good candidate has been useful
for quite a range of applications" (2). Indeed, the best
synthetic catalysts demonstrate useful levels of
enantioselectivity for a wide range of substrates. This is very
important to synthetic chemists, who must rely on the predictable
behavior of reagents and catalysts when planning new syntheses.

2) With a few important exceptions (such as certain lipases),
such generality of scope is not observed in enzymatic catalysis.
It is even more surprising that certain classes of synthetic
catalysts are enantioselective over a wide range of different
reactions. Such catalysts may be called "privileged structures,"
in much the same manner that the term has been applied in
pharmaceutical research to compound classes that are active
against a number of different biological targets (3). Privileged
chiral catalysts offer much more than one might have imagined,
creating effective asymmetric environments for mechanistically
unrelated reactions.

3) In summary: One of the most active current areas of chemical
research is centered on how to synthesize handed (chiral)
compounds in a selective manner, rather than as mixtures of
mirror-image forms (enantiomers) with different three-dimensional
structures (stereochemistries). Nature points the way in this
endeavor: different enantiomers of a given biomolecule can
exhibit dramatically different biological activities, and enzymes
have therefore evolved to catalyze reactions with exquisite
selectivity for the formation of one enantiomeric form over the
other. Drawing inspiration from these natural catalysts, chemists
have developed a variety of synthetic small-molecule catalysts
that can achieve levels of selectivity approaching, and in some
cases matching, those observed in enzymatic reactions.(4,5)

References (abridged):

1. E. N. Jacobsen, A. Pfaltz, H. Yamamoto, Eds., Comprehensive
Asymmetric Catalysis, Volumes I to III (Springer, New York, 1999)

2. W. S. Knowles, Angew. Chem. Int. Ed. 41, 1999 (2002)

3. B. E. Evans, et al., J. Med. Chem. 31, 2235 (1988)

4. T. Katsuki, Synlett 281 (2003)

5. E. N. Jacobsen, W. Zhang, A. R. Muci, J. R. Ecker, L. Deng, J.
Am. Chem. Soc. 113, 7063 (1991)

Related Material:

ON CATALYTIC NANOARCHITECTURES

Science 2003 299:1698

The following points are made by Debra R. Rolison:

1) Nothing (i.e., porosity) is an important part of any
nanostructured system that does chemistry. Whether the final
chemistry is labeled as catalysis, sensing, energy storage,
synthesis, or fabrication, the reactions are most effective when
the transport paths through which molecules move into or out of
the nanostructured material are included as an integral part of
the architectural design. The arrangement of matter in space is
even more critical when multiple mechanistic processes must occur
in concert to achieve the desired performance. Catalytic
bifunctionality, for instance, requires that each of the two
components provide a necessary but different reactive
contribution to achieve the end product. Metal nanoparticles
highly dispersed on an active oxide are a classic example of a
bifunctional catalyst in which chemisorptive activation of
substrate by the metal is coupled to oxygen atom transfer
mediated by the active oxide.

2) When multifunction and molecular transport paths are critical,
the challenge is to move beyond the fabrication of a functional
nanoscale object or feature. High performance requires
architectural design -- the integration of nanoscale building
blocks into a multifunctional edifice. Architectures contain a
lot of nothing, and the size of the "nothing" -- that is, the
physical dimensions of the porous path -- matters, especially to
the molecules that move into the interior of a catalytic
nanostructure. Although frequently misused in the era of
nanoscience, the terms that define variously sized pores have
been in use for decades and are internationally standardized by
IUPAC (1,2). The terminological yardstick of the past was based
on small molecules and their transport through pores, so
diffusion of molecules within microporous channels (<2 nm), such
as those found in zeolites, can exhibit hindered transport (3).
The transport of small molecules in media featuring large
mesopores (>10 nm) and macropores (>50 nm) can approach rates of
diffusion comparable to those in open medium.

3) Advanced mesoporous architectures are being created in which
the pore and solid structural components are controlled at the
nanoscale level. Surfactant-templated syntheses (4), which create
periodic porosity in the solid, are often thought of as the
primary way to create mesoporous materials. Means to mesoporous
materials that predate this protocol include the use of membrane-
templated syntheses (5) and sol-gel syntheses, with more recent
variants including block copolymer-templated syntheses and the
use of silica sol to "nanoglue" appropriate guests (added just
before the sol-to-gel transition) into the solid network of the
mesoporous architecture.

4) In summary: Heterogeneous catalysis has always been an
inherently nanoscopic phenomenon with important technological and
societal consequences for energy conversion and the production of
chemicals. New opportunities for improved performance arise when
the multifunctionality inherent in catalytic processes, including
molecular transport of reactants and products, is rethought in
light of architectures designed and fabricated from the
appropriate nanoscale building blocks, including the use of
"nothing" (void space) and deliberate disorder as design
components. Architectures with all of the appropriate
electrochemical and catalytic requirements, including large
surface areas readily accessible to molecules, may now be
assembled on the bench top. Designing catalytic nanoarchitectures
that depart from the hegemony of periodicity and order offers the
promise of even higher activity.

References (abridged):

1. K. S. W. Sing, et al., Pure Appl. Chem. 57, 603 (1985)

2. "Nanopore" and "nanoporous" have been used in the recent
literature to describe pores that range anywhere in size from one
to hundreds of nanometers; as descriptors of space through which
molecules transport, these terms are meaningless.

3. N. Y. Chen, T. F. Degnan Jr., C. M. Smith, Molecular Transport
and Reaction in Zeolites (VCH, New York, 1994)

4. J. Y. Ying, C. P. Mehnert, M. S. Wong, Angew. Chem. Int. Ed.
38, 56 (1999)

5. J. C. Hulteen and C. R. Martin, J. Mater. Chem. 7, 1075 (1997)

Related Material:

ON DENDRITIC CATALYSIS

Chem. Rev. 2001 101:2991

The following points are made by D. Astruc and F. Chardac:

1) The field of dendrimers was developed in the late 1970s and
early 1980s and has exploded during the past decade. The reason
for this, beyond the aesthetic interest in dendrimers, is their
great potential for applications in biology and materials
science. Among the main potential applications of dendrimers,
catalysis is one of the most promising, since dendrimers offer a
unique opportunity to combine the advantages of homogeneous and
heterogeneous catalysis yet maintain the well-defined molecular
features required for a full and detailed analysis of catalytic
events.

2) In general, it is possible to tune the structure, size, shape,
and solubility of dendrimers and metallodendrimers at will, and
to locate catalytic sites at the core or at the periphery of the
molecule. A large number and variety of metallodendrimers are now
known, and it is clear that structural design innovations of
dendrimers have not yet reached a limit. Researchers have
demonstrated that it is possible to remove the catalyst from the
reaction medium after a reaction carried out in the presence of a
metallodendrimer catalyst, with removal either by precipitation
or by ultrafiltration or ultracentrifugation, and membrane
reactors have been developed for this purpose.

3) Organometallic and inorganic catalysts supported on organic
polymers such as polystyrene or on inorganic polymers such as
silica have been used for some time, but dendrimers now offer a
much better control of the number, shape, and structure of the
catalytic sites and of their micro-environment.

Related Material:

GEL CATALYSTS THAT SWITCH ON AN OFF

Proc. Nat. Acad. Sci. 2000 97:9861

Our understanding of dynamic biochemical processes is greatly
improved when we can mimic these processes in detail in the
laboratory, and this is particularly true for understanding
enzymes -- the biological protein catalysts. Natural enzymes
catalyze chemical reactions and regulate such reactions by
reversibly and repeatedly switching their catalytic activities on
and off. What are the possible mechanisms for these reversible
switching actions?

The following points are made by G. Wang et al:

1) The authors report the development of a polymer gel with a
catalytic activity that can be switched on and off when the
solvent composition is changed. The gel consists of two species
of monomers. The major component, N-isopropylacrylamide, makes
the gel swell and shrink in response to a change in composition
of ethanol/water mixtures. The minor component, vinylimidazole,
which is capable of catalysis, is copolymerized into the gel
network. The reaction rate for catalytic hydrolysis of p-
nitrophenyl caprylate was small when the gel was swollen; in
contrast, when the gel was shrunken, the reaction rate increased
5 times. The authors report the activity changes discontinuously
as a function of solvent composition: thus, the catalysis can be
switched on and off by an infinitesimal change in solvent
composition.

2) The authors report the kinetics of catalysis by the gel in the
shrunken state is well described by the Michaelis-Menten formula,
indicating that the absorption of the substrate by the
hydrophobic environment created by the N-isopropylacrylamide
polymer in the shrunken gel is responsible for enhancement of
catalytic activity. In the swollen state, the rate vs. active
site concentration is linear, indicating that the substrate
absorption is not a primary factor determining the kinetics. The
authors report that catalytic activity of the gel was studied for
substrates with various alkyl chain lengths, and that of those
studied, the switching effect is most pronounced for the
substrate p-nitrophenyl caprylate.

3) The authors report the following interpretation of the
dynamics in this system: The major component (N-
isopropylacrylamide) allows the gel to reversibly swell and
shrink in response to changes in environmental parameters such as
temperature and solvent. On swelling and shrinking, the local
density of the hydrophobic moiety changes, and the affinity of
the substrate molecules is altered accordingly. The minor
component (vinylimidazole), capable of catalysis of substrate
decomposition, is copolymerized with the responsive monomers into
the gel network. The catalysis activity of the gel is thus
expected to be switched on and off as the substrate is reversibly
bound and released during the cycle of gel swelling and
shrinking.

4) The authors conclude: "The design idea shown in this paper can
be applied to development of gels that can be used for many other
purposes were enzymes have been used. The gel system, once its
catalytic rate is well improved, will have advantages over
enzymes in some important aspects -- e.g., it can be applied
where enzymatic action is needed but enzymes cannot be used."

Notes:

Michaelis-Menten formula: One form of the Michaelis- Menten
equation is as follows: v = V/(k + S) where (v) is the initial
velocity of the reaction, (V) is the maximum reaction rate (i.e.,
when the enzyme is saturated with substrate), (k) is the
Michaelis constant, which approximates to the enzyme-substrate
dissociation constant, and (S) is substrate concentration. In
biochemistry, a system described by such an equation is said to
obey "Michaelis kinetics".

Related Material:

ON BIMETALLIC ELECTROCATALYSTS

Science 2001 293:1811

The following points are made by F. Maroun et al:

1) Electrocatalytic reactions are of central importance in
electrochemistry and play a vital role in emerging technologies
related to environmental and energy-related applications such as
fuel cells. The efficiency and selectivity of electrocatalytic
processes can be substantially improved by replacing monometallic
catalysts with bimetallic catalysts. For example, the standard
platinum electrocatalysts in polymer electrolyte fuel cells are
now replaced by platinum-ruthenium and platinum-molybdenum
alloys. The development of these bimetallic catalysts has been
based primarily on empirical grounds, and a detailed knowledge of
the physical origins underlying the improvements in catalytic
performance has not been available.

2) Three explanations have been put forward for the higher
activity of bimetallic catalysts: a) Each metal component could
promote different elementary reaction steps, leading to a
"bifunctional mechanism". b) Electronic effects resulting from
interactions between the two metals could improve reactivity. c)
The concept of geometric ensemble effects (specific groupings of
surface atoms required to serve as active sites), developed in
heterogeneous gas-phase catalysis, has also been suggested for
electrocatalysis.

3) Direct experimental verification or quantitative assessment of
the relative contributions of these various effects has not been
possible up to now. The lack of data on the local atomic
arrangement at the surface, both for real supported
electrocatalysts and for model systems, has prevented an
unambiguous interpretation of electrochemical and spectroscopic
data.

Related Material:

NEW CATALYSTS IN OLEFIN POLYMERIZATION

Science 21 Jan 00 287:460

Although plastic materials (e.g., celluloid and bakelite) were
known in the 19th and early 20th centuries, it was not until the
second half of the 20th century that new plastics to replace wood
and metal became ubiquitous in daily life. One of the signal
events in this introduction of new plastics was the discovery in
1953 of the so-called Ziegler catalysts in olefin polymerization.
Olefins are hydrocarbons containing at least one double bond
between adjacent carbon atoms, and polyolefins are polymers
constructed of olefin monomers. Polyethylene is a typical
polyolefin and the foundation for a large variety of common
plastics. A Ziegler catalyst is derived from a transition-metal
halide and a metal hydride or metal alkyl, and such a catalyst
can be used to produce stereospecific (stereoregular) olefin
polymers, which are olefin polymers with a specific or definite
ordering of molecules in space (e.g., isotactic polypropylene),
with a consequent close packing of molecules that leads to a high
degree of crystallinity, strength, and durability. Karl Ziegler
(1898-1973) and Giulio Natta (1903-1979) shared the Nobel Prize
in Chemistry in 1963 for their work in discovering and developing
the class of Ziegler catalysts in the synthesis of stereospecific
polymers.

The following points are made by T.R. Younkin et al:

1) More than half of the 170 million metric tons of polymers
produced each year are polyolefins. Current technology uses
highly active cationic catalysts (Ziegler catalysts and
metallocene catalysts), which suffer from an inability to
tolerate *heteroatoms such as oxygen, nitrogen, and sulfur. These
systems require both scrupulously clean starting materials and
activating cocatalysts.

2) The authors report the development by rational design of a
family of nickel-complex organic catalysts whose members are
tolerant of both heteroatoms and less-pure starting materials.
These heteroatom-tolerant neutral late transition metal complexes
are highly active systems that produce high-molecular-weight
polyethylene, polymerize functionalized olefins, and require no
cocatalyst.

3) The authors suggest that the catalytic properties of the
family of neutral, single-component, late-transition metal olefin
polymerization catalysts which they have synthesized indicates
that a cationic metal center is not required to achieve high
polymerization activity. The authors conclude: "The promise of
these catalysts is realized in their ability to polymerize
ethylene in the presence of functional additives such as ethers,
ketones, esters, alcohols, amines, and water, and in their
incorporation of polar monomers into the polymer backbone in
variable quantities."

Notes:

In general, "heteroatoms" are any atoms other than carbon and
hydrogen in an organic compound.

The "early transition metals" are transitions metals on the left
side of the periodic table; the "late transition metals" are
transition metals on the right side of the periodic table.

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