molecular frontier final
Beyond
challenges
the Molecular Frontier
For cheMistry and cheMical engineering
Chemistry is central to providing the products, materials, and
processes that support human needs and to understanding life itself. In
the past century, chemical discoveries have raised the standard of living
throughout the world and deined modern life. Metals, concrete, glass,
paper, plastics, electronic materials, agrochemicals, drinking water,
fuels, refrigerants, and pharmaceuticals are among the many products
that have been created or advanced through chemistry.
The astonishing developments of the 20th century have made
it possible to dream of new goals that were previously unthinkable.
Chemistry is moving rapidly from a reductionist science concerned
with atoms, molecules and pure substances to an integrationist science
concerned with organized molecular systems. Chemists and chemical
engineers, working in concert with biologists, physicists, electrical engineers, and other professionals,
are on the road to fantastic achievements: commercially viable replacement organs; computer chips
that are not carved in silicon, but rather self-assembled from chemical components; therapeutics
tailor-made for individual genetic make-up; and materials that interact with living tissue.
What else could we dare to dream in the 21st century? Is it possible that we could conquer
disease, deter terrorism, solve our energy problems, clean the environment, and reduce poverty and
inequality? Beyond the sociopolitical and economic dimensions of these problems lie scientiic
questions that chemists and chemical engineers will help solve.
The National Academies’ report Beyond the Molecular Frontier: Challenges for Chemistry
and Chemical Engineering outlines numerous challenges for chemists and chemical engineers in the
21st century –a daunting but tremendously important list of goals that, if accomplished, could lead
to many new discoveries. The report breaks new ground by summarizing, for the irst time, the full
spectrum of chemical science activities from fundamental, molecular-level chemistry to large-scale
chemical processing technology. The authors of the report fully expect that the challenges they
outline can and will be realized.
Chemists as Creators: Challenges in Synthesis
Chemistry, more than any other science, seeks not only to discover but also to create. Chemists
create new compounds, consisting of new molecules, at the rate of more than one million per year
with the aim that their properties will have a tangible beneit for society or will create new scientiic
knowledge. Beyond the millions of molecules that occur in nature, there is a nearly ininite number
of molecules that could exist within the limits of natural law.
One of the most important continuing challenges for chemists is to devise new ways to
manipulate molecules in order to create and manufacture useful new substances. Polymers, along with
pharmaceuticals, are arguably the most important and beneicial substances that synthetic chemistry
has brought to the human race. For more than a half-century, polymers (chains of repeating subunits)
have transformed our world through the development of novel materials--from nylon to synthetic
tires to new copolymers that combine, for example, rubbery polymers with glassy polymers for better
windshields. Signiicant progress continues to be made in polymer synthesis, including a current
focus on how the architecture of macromolecules affects function.
Developments in electronic, optoelectronic, photonic, and magnetic devices provide another
great story of science and have enabled television, computers, and iber optic telecommunications
among other applications. Chemists continue to develop materials that are superconductors, which
conduct electricity free of any resistance and thus free of power loss. Superconductors that operate
at room temperature are being actively pursued, which, if made, could transfer electric power very
eficiently over long distances, or even pave the way to futuristic visions of using magnetic levitation
for transportation systems.
A good example of the integrationist trend in chemistry is advancing work with composites,
which combine different materials to gain beneicial properties. For example, ceramics are of
interest for use in automobile engines because they are poor conductors of heat and electricity and
perform well at high temperatures. However, they are fragile. A challenge for the future is to invent
improved structural materials, such as composites based on resins or ceramics, that are stable at high
temperatures and easily machined.
The study of surfaces is another important area of focus. The chemistry of gene chips used
in genomic research, for example, depends on properties of system surfaces. New techniques and
tools that enable researchers to penetrate and manipulate nanometer-thick surfaces are fundamentally
changing the ability to characterize and prepare surface materials.
One of the grandest challenges in synthesis for chemists is to learn how to design and produce
new substances and materials with properties that can be predicted, tailored, and tuned before
production. Unlike architects, who know enough about buildings that they can design them in great
detail before breaking ground, chemists seeking to produce a substance with certain properties must
now conduct time-consuming trial-and-error procedures in the laboratory.
Inspired by Nature
Nature is an inventive chemist. Explaining the processes of life in
chemical terms is one of the greatest challenges continuing into the future.
Such complex events as the cleavage of RNA by the enzyme ribonuclease, the
multistep synthesis of ATP in vivo (Paul Boyer and John E. Walker received
Nobel prizes in 1997 for working this out), and the activity of molecular motors
that power bacterial lagellae are now understood in molecular detail, but these
represent only a tiny fraction of the universe of natural processes.
Imitating some aspects of life, biomimetic chemistry, is not the only way
to invent new things, but it is an important way. Today, the chemical industry
produces ammonia for fertilizers and other products by causing nitrogen to
react with hydrogen at high temperature and pressure. Yet microorganisms in the roots of some
legumes are capable of carrying out the same conversion at ordinary temperatures and pressures.
We need to understand their chemistry, even if it is not as practical as our current methods.
Much research in recent times has centered on trying to understand the chemical mechanisms
by which various biological processes occur. Enzymes are of particular interest because of their
unique selectivity. They can react at a particular site on a molecule even though it’s not the most
chemically reactive site. Enzymes can selectively bind a particular molecule out of the mixture of
substances in the cell, then hold it in such a way that the geometry of the enzyme-substrate complex
determines what happens next in a sequence.
The catalytic mechanisms of enzymes are understood well enough to have already produced
drugs, such as cholesterol-reducing agents, that block the active sites of enzymes. However, the
factors that contribute to enzymes high selectivity are not completely understood, and we do no yet
have good synthetic analogs. A full understanding of enzymes will be of great value in manufacturing
and also the development of new classes of medicines.
The sequencing of the human genome has provided a molecular foundation from which other
complex biological processes might be tackled at a molecular level. A critical challenge in the
postgenomic era will be to make the connections between protein sequence and architecture, and
between protein architecture and functions. The 3D shape of a protein is a key factor in determining
its function. If chemists could predict how a protein folds and how that folded structure is related
to function, they could then seek to design new functions for proteins that would have a profound
impact on medicine.
One of the most intriguing aspects of nature is the process of evolution, which illustrates the
ability of living systems to self-optimize. If the chemical sciences could build on this approach,
a system would produce the optimal new substance as a single product, rather than as a mixture
from which the desired component must be isolated and identiied. Self-optimizing systems would
allow visionary chemical scientists to use this approach to make new medicines, catalysts, and
other important chemical products, in part by combining new approaches to informatics with rapid
experimental screening methods.
Self-Assembly and Nanotechnology
Sidebar 1
Chemists have been moving atoms with subnanometer
Soft Lithography
precision for most of the last century. However, the new
Building ever smaller devices has been a
areas of nanoscience and nanotechnology—work with
dominant trend in microelectronics technology
particles that range in size from about 1 to 100 nm (about
for 50 years. Photolithography, a kind of
1/100,000 the width of a hair)—are exploding as tools used
photography used to fabricate small devices,
to explore these dimensions have become available. One
changed the world by enabling the computing
vision of this revolution includes the possibility of making
revolution.
tiny machines that can imitate many of the processes in
A less expensive, more versatile technique
called “soft lithography” has been developed to
single-cell organisms that possess much of the information
make micro- and nano-structures. It is a “back
content of biological systems. Several techniques are now
to the future” strategy that uses stamping,
available to fabricate nanostructures, including electron
printing, and molding. Patterns of small
beam writing, scanning probe devices, and soft lithography
features are embossed on a stamp or mold that
(see Sidebar 1).
can print lines that are
challenges
the Molecular Frontier
For cheMistry and cheMical engineering
Chemistry is central to providing the products, materials, and
processes that support human needs and to understanding life itself. In
the past century, chemical discoveries have raised the standard of living
throughout the world and deined modern life. Metals, concrete, glass,
paper, plastics, electronic materials, agrochemicals, drinking water,
fuels, refrigerants, and pharmaceuticals are among the many products
that have been created or advanced through chemistry.
The astonishing developments of the 20th century have made
it possible to dream of new goals that were previously unthinkable.
Chemistry is moving rapidly from a reductionist science concerned
with atoms, molecules and pure substances to an integrationist science
concerned with organized molecular systems. Chemists and chemical
engineers, working in concert with biologists, physicists, electrical engineers, and other professionals,
are on the road to fantastic achievements: commercially viable replacement organs; computer chips
that are not carved in silicon, but rather self-assembled from chemical components; therapeutics
tailor-made for individual genetic make-up; and materials that interact with living tissue.
What else could we dare to dream in the 21st century? Is it possible that we could conquer
disease, deter terrorism, solve our energy problems, clean the environment, and reduce poverty and
inequality? Beyond the sociopolitical and economic dimensions of these problems lie scientiic
questions that chemists and chemical engineers will help solve.
The National Academies’ report Beyond the Molecular Frontier: Challenges for Chemistry
and Chemical Engineering outlines numerous challenges for chemists and chemical engineers in the
21st century –a daunting but tremendously important list of goals that, if accomplished, could lead
to many new discoveries. The report breaks new ground by summarizing, for the irst time, the full
spectrum of chemical science activities from fundamental, molecular-level chemistry to large-scale
chemical processing technology. The authors of the report fully expect that the challenges they
outline can and will be realized.
Chemists as Creators: Challenges in Synthesis
Chemistry, more than any other science, seeks not only to discover but also to create. Chemists
create new compounds, consisting of new molecules, at the rate of more than one million per year
with the aim that their properties will have a tangible beneit for society or will create new scientiic
knowledge. Beyond the millions of molecules that occur in nature, there is a nearly ininite number
of molecules that could exist within the limits of natural law.
One of the most important continuing challenges for chemists is to devise new ways to
manipulate molecules in order to create and manufacture useful new substances. Polymers, along with
pharmaceuticals, are arguably the most important and beneicial substances that synthetic chemistry
has brought to the human race. For more than a half-century, polymers (chains of repeating subunits)
have transformed our world through the development of novel materials--from nylon to synthetic
tires to new copolymers that combine, for example, rubbery polymers with glassy polymers for better
windshields. Signiicant progress continues to be made in polymer synthesis, including a current
focus on how the architecture of macromolecules affects function.
Developments in electronic, optoelectronic, photonic, and magnetic devices provide another
great story of science and have enabled television, computers, and iber optic telecommunications
among other applications. Chemists continue to develop materials that are superconductors, which
conduct electricity free of any resistance and thus free of power loss. Superconductors that operate
at room temperature are being actively pursued, which, if made, could transfer electric power very
eficiently over long distances, or even pave the way to futuristic visions of using magnetic levitation
for transportation systems.
A good example of the integrationist trend in chemistry is advancing work with composites,
which combine different materials to gain beneicial properties. For example, ceramics are of
interest for use in automobile engines because they are poor conductors of heat and electricity and
perform well at high temperatures. However, they are fragile. A challenge for the future is to invent
improved structural materials, such as composites based on resins or ceramics, that are stable at high
temperatures and easily machined.
The study of surfaces is another important area of focus. The chemistry of gene chips used
in genomic research, for example, depends on properties of system surfaces. New techniques and
tools that enable researchers to penetrate and manipulate nanometer-thick surfaces are fundamentally
changing the ability to characterize and prepare surface materials.
One of the grandest challenges in synthesis for chemists is to learn how to design and produce
new substances and materials with properties that can be predicted, tailored, and tuned before
production. Unlike architects, who know enough about buildings that they can design them in great
detail before breaking ground, chemists seeking to produce a substance with certain properties must
now conduct time-consuming trial-and-error procedures in the laboratory.
Inspired by Nature
Nature is an inventive chemist. Explaining the processes of life in
chemical terms is one of the greatest challenges continuing into the future.
Such complex events as the cleavage of RNA by the enzyme ribonuclease, the
multistep synthesis of ATP in vivo (Paul Boyer and John E. Walker received
Nobel prizes in 1997 for working this out), and the activity of molecular motors
that power bacterial lagellae are now understood in molecular detail, but these
represent only a tiny fraction of the universe of natural processes.
Imitating some aspects of life, biomimetic chemistry, is not the only way
to invent new things, but it is an important way. Today, the chemical industry
produces ammonia for fertilizers and other products by causing nitrogen to
react with hydrogen at high temperature and pressure. Yet microorganisms in the roots of some
legumes are capable of carrying out the same conversion at ordinary temperatures and pressures.
We need to understand their chemistry, even if it is not as practical as our current methods.
Much research in recent times has centered on trying to understand the chemical mechanisms
by which various biological processes occur. Enzymes are of particular interest because of their
unique selectivity. They can react at a particular site on a molecule even though it’s not the most
chemically reactive site. Enzymes can selectively bind a particular molecule out of the mixture of
substances in the cell, then hold it in such a way that the geometry of the enzyme-substrate complex
determines what happens next in a sequence.
The catalytic mechanisms of enzymes are understood well enough to have already produced
drugs, such as cholesterol-reducing agents, that block the active sites of enzymes. However, the
factors that contribute to enzymes high selectivity are not completely understood, and we do no yet
have good synthetic analogs. A full understanding of enzymes will be of great value in manufacturing
and also the development of new classes of medicines.
The sequencing of the human genome has provided a molecular foundation from which other
complex biological processes might be tackled at a molecular level. A critical challenge in the
postgenomic era will be to make the connections between protein sequence and architecture, and
between protein architecture and functions. The 3D shape of a protein is a key factor in determining
its function. If chemists could predict how a protein folds and how that folded structure is related
to function, they could then seek to design new functions for proteins that would have a profound
impact on medicine.
One of the most intriguing aspects of nature is the process of evolution, which illustrates the
ability of living systems to self-optimize. If the chemical sciences could build on this approach,
a system would produce the optimal new substance as a single product, rather than as a mixture
from which the desired component must be isolated and identiied. Self-optimizing systems would
allow visionary chemical scientists to use this approach to make new medicines, catalysts, and
other important chemical products, in part by combining new approaches to informatics with rapid
experimental screening methods.
Self-Assembly and Nanotechnology
Sidebar 1
Chemists have been moving atoms with subnanometer
Soft Lithography
precision for most of the last century. However, the new
Building ever smaller devices has been a
areas of nanoscience and nanotechnology—work with
dominant trend in microelectronics technology
particles that range in size from about 1 to 100 nm (about
for 50 years. Photolithography, a kind of
1/100,000 the width of a hair)—are exploding as tools used
photography used to fabricate small devices,
to explore these dimensions have become available. One
changed the world by enabling the computing
vision of this revolution includes the possibility of making
revolution.
tiny machines that can imitate many of the processes in
A less expensive, more versatile technique
called “soft lithography” has been developed to
single-cell organisms that possess much of the information
make micro- and nano-structures. It is a “back
content of biological systems. Several techniques are now
to the future” strategy that uses stamping,
available to fabricate nanostructures, including electron
printing, and molding. Patterns of small
beam writing, scanning probe devices, and soft lithography
features are embossed on a stamp or mold that
(see Sidebar 1).
can print lines that are