А.С. Носков Учиться, учиться и учиться ...катализу
Премии и награды по химии
Beyond the Molecular Frontier
Семинар
"Современное состояние и перспективы промышленной реализации результатов научных исследований"
Фомичев Ю.П.
"Государственная политика в области правовой
охраны, защиты, управления и коммерциализации интеллектуальной собственности"
За рубежом
"Чтобы ориентироваться в современных реалиях"
Advisers to the Nation on Science, Engineering, and Medicine
BEYOND THE MOLECULAR FRONTIER
Challenges 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 defined 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 scientific 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 first 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 benefit for society or will create new scientific knowledge. Beyond the millions of molecules that occur in nature, there is a nearly infinite 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 beneficial 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. Significant 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 fiber 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 efficiently 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 beneficial 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 flagellae 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 identified. 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
Chemists have been moving atoms with subnanometer precision for most of the last century. However, the new areas of nanoscience and nanotechnology-work with particles that range in size from about 1 to 100 nm (about 1/100,000 the width of a hair)-are exploding as tools used to explore these dimensions have become available. One vision of this revolution includes the possibility of making tiny machines that can imitate many of the processes in singlecell organisms that possess much of the information content of biological systems. Several techniques are now available to fabricate nanostructures, including electron beam writing, scanning probe devices, and soft lithography.
There is a growing focus on the use of "self-assembly" in constructing nanostructures. Self-assembly is the ability of properly designed mixtures of chemical components to organize themselves into complex, organized structures. It's as if the components of an automobile would automatically fall in the correct places, rather than being placed there by machines. In the computer industry, the etching of silicon chips could be replaced by self-assembly techniques. Such spontaneous self-assembly is possible on the molecular scale, but needs to be developed.
A vital aspect of chemical self-assembly is selection. In a mixture of compounds, the correct pairing of chemicals must occur, so the system must have a way to choose those pairings. An exciting new challenge is to develop ways to impose a process of selection on the mixture of components, so that unwanted interactions are suppressed. In biological systems, mutants convey an advantage to a cell, illustrating nature's ability to self-optimize. Chemists need similar tools, for example, a library of possible catalysts from which the system would self-select the most potent. This would remove the current need to screen the entire library for such activity.
New approaches in synthetic chemistry and biochemistry have paved the way for tremendous advances in self-assembly. The future will hold the opportunity for chemists to make molecules of size and complexity approaching protein structures-and to fold and assemble them. By creating the appropriate molecules, patterning them on surfaces, and providing them with the appropriate functions, chemists could mimic taste and smell, the most chemical of the senses.
Chemical engineers are now aiming to use these advances on larger scales. Taking selfassembly methodology from laboratory experimentation to the practical manufacturing arena could revolutionize chemical processing. The approach to the future should be a holistic one, with synthetic advances moving in concert with assembly and microstructural control.
Characterization and Measurement
The need for measurements of chemicals is ubiquitous-of mass and dimensions of chemical substances and their capacity to absorb heat, absorb or reflect light, and respond to pressure and temperature. The determination of quantity in complex mixtures is vital in developing pharmaceuticals and other products. There is a constant need for better methods of chemical analysis to answer, "What's in that, how much is present, and how long will it last?" The frontiers in this field lie in improving sensitivity to detect vanishingly small quantities, to separate extremely complex mixtures, and to assess the structures or compositions of components.
The number and types of customers who need analysis are growing and now encompass industrial enterprises and government functions that span manufacturing, shipping, communications, domestic power, water supplies, waste disposal, forensic analysis, environmental policies, and national security. These customers place urgent demands on chemical scientists for new, better, faster, cheaper, more sensitive and more selective measurements.
One of the grand challenges in chemistry is to understand how molecules react over all time scales and the full range of molecular size. An increase in this fundamental understanding will directly affect our ability to improve the practical applications in chemistry. However, there are still big gaps in our understanding of molecular details of chemical and biochemical reactions. Many intermediates along the path of a reaction cannot be directly observed with current instrumental technology, making this objective one of the long-standing goals of the chemical sciences.
An exciting advance was acknowledged in 1999 when Ahmed Zewail received the most recent of the several Nobel Prizes recognizing developments of methods to follow fast reactions. He was able to witness the bond-breaking and bond-making process on the time scale of
10-15 seconds, which some say is the limiting time scale for chemical reactions. Chemical science still seeks to develop ultrafast techniques, such as superfast electron diffraction, that will permit observation of the actual molecular structure of a transition state, not just its rate of passage.
Even mature instrumentation techniques continue to advance in small steps. Mass spectrometry requires that material being studied be converted into a vapor. Great strides have been made in recent years to entice large, thermally fragile molecules into the vapor states from solids and surfaces through new techniques. These strides have reinvigorated this field and provided a good example of how supposedly "dead" areas can find new life.
Detailed molecular structure determinations can be accomplished by diffraction techniques, electromagnetic radiation absorption, and emission techniques such as microwave spectroscopy and nuclear magnetic resonance (NMR). The major current limitation of NMR is its sensitivity. Stronger magnets, improved instrumentation, and software could help NMR move toward analyses of single molecules. A major limitation of diffraction techniques has been the need to obtain crystalline samples. Chemists are now devising techniques to crystallize proteins in two-or three-dimensional lattices but are still challenged to crystallize large molecules in a routine manner.
Chemical measurements will continue to advance toward the need for high-throughput, miniaturized instrumental analyses, preferably with "smart instruments" that are self-calibrating and highly automated. A related need exists for massive automation in data, reduction, storage, retrieval, and graphic presentation. Urgent expansion is needed in the following five broad categories.
1 High-performance instruments and measurements of unprecedented precision, sensitivity, spatial resolution, and specificity.
2 Low-cost, robust instruments for analyzing exceptionally small volumes.
3 High-throughput measurements including informatics and mathematics for interpretation of large-volume data streams.
4 Separation and analysis of chemical and biological mixtures of extreme complexity.
5 Determining the structural arrangements of atoms within noncyrstalline chemical substances and resolving how they change as a function of time.
Advancing Chemical Theory and Modeling
The chemical sciences are built on a set of fundamental mathematical theories, such as quantum mechanics, that have increasing utility as computational hardware and software have become more powerful. Impressive recent progress has been made in determining molecular structures. A continuing important goal is to devise better and more accurate ways to predict molecular structures, bond energies, molecular properties, transition state structures, and energies for systems increasing in size. While quantum mechanics can be reliably applied to isolated molecules, another important goal is to develop methodologies for molecules in organized systems.
Chemistry covers an enormous span of time and space from atoms and molecules to industrial-scale processing. Chemical processes at the commercial scale ultimately involve spatial scales on the order of meters, and time scales ranging from seconds to hours and, in the case of many bioengineering processes involving fermentations, days or weeks. Advances in computing and modeling could help us connect phenomena at the electronic and molecular scale to the commercial processing.
The chemical industry can largely be viewed as being composed of two major segments. The "value preservation" industry is largely based on the large-scale production of commodity chemicals. The "value growth" industry is based on the small-scale production of specialty chemicals, biotechnology products, and pharmaceuticals. To stay competitive and economically strong, the "value preservation" industry must be able to reduce costs, operate efficiently, and continuously improve product quality. The value growth industry must be agile and quick to market new products, making supply chain management one of its key technologies. In both cases, major challenges over the next two decades will be to gain a better understanding of the structure and information flows underlying the chemical supply chain, and to develop novel mathematical models and methods for its simulation and optimization.
Greener by Design
An increasing concern with the environment is affecting all of chemistry from the laboratory to manufacturing. A half-century ago, people were only beginning to understand the extent to which human activity could affect the environment, often in very negative ways. Tough environmental problems of toxic waste dumps, smog acid rains, and polluted rivers and oceans require a full understanding of the complex chemical interactions of the earth and atmosphere. Almost all U.S. chemical manufacturers now subscribe to a program called Responsible Care, pledging to make only products that are harmless to the environment and its occupants through processes that are environmentally benign.
In addition, an important initiative called "green chemistry" seeks to design chemical products and processes that reduce or eliminate the use and generation of hazardous substances. New methods are still being sought for even the simplest transformations. For example, the oxidation of an alcohol to a ketone or aldehyde has long been performed in the laboratory by using chromium as the oxidant, which often further oxidize the end products and result in environmentally harmful waste products. If oxygen were used as an oxidant, water would be the resultant waste produce. Catalysts for air oxidation already exist; however, improved catalysts may be needed for manufacturing processes. Another example of the green revolution is the use of CO2 to replace organic solvents, reducing the use of both water and energy.
Reducing waste in chemical processes is another continuing challenge. In the pharmaceutical industry, for example, classical methods produce, on the average, about nine times as much disposable waste as desired product. This has led to the demand for procedures that have atom efficiency, in which all the atoms of the reacting compounds appear in the product. The use of multicomponent processes could contribute to this goal. Conventional process development has focused on optimizing single reactions. New processes that involve reaction cascades, where the product of one reaction feeds the next, will permit more efficient production of industrial or biomedical products. The future will also likely see greater use of more abundant or renewable raw materials and greater reuse of materials such as carbon dioxide, salts, tars,and sludges which are currently discarded as waste.
Chemistry and Medicine
Medicinal chemistry has greatly contributed to the fight against disease. Modern biochemical engineering began with the challenge of large-scale production of penicillin by fermentation during World War II, requiring the cooperation of microbiologists, biochemists, and chemical engineers. Other early contributions include the artificial kidney and "pharmacokinetic models" used to successfully deliver chemotherapeutic drugs and assess risk exposure from toxins. More recently, bioprocesses have been developed that produce high-purity proteins from genetically engineered cells that are used to treat stroke, heart attack and other diseases. Chemists, of course, are integrally tied to continuing advances in pharmaceuticals.
The explosive growth in our understanding of the chemical basis of life couldn't come at a better time. The aging generation of baby boomers will sorely challenge the nation's resources and intensify the need for more effective and cost-efficient therapies-therapies are on the horizon for problems of memory and cognition, vision and hearing, pain, addiction, sleep disorders, weight gain, or loss and even aging. Chemists and chemical engineers are working toward the production of human "spare parts": joints and valves, eyes and ears linked to the brain, and even implantable endocrine systems that act as mini chemical factories and delivery systems.
Progress in genomics and proteomics will become increasingly important in strategies for the prevention, diagnosis, and treatment of disease. We are entering a new era of molecular medicine where we will develop technologies to rapidly screen the effects of small molecules on large arrays of gene products. Capitalizing on self-assembly and nanoscience will enhance the ability to screen drugs for individual sensitivities. Advances in drug discovery, combinatorial synthesis, and screening with sensors that have the ability to detect multitudes of specific genetic matches- marrying microelectronics and self-assembly-are expected to be near-term breakthroughs enabling the possible creation of "in the field" or "in the office" tests for chemical risks, pharmaceutical compatibility, or environmental hazards. There are still many major challenges ahead: treating viral diseases from influenza to the AIDS and Ebola viruses; bacterial resistance to antibiotics, cures for cancer, heart disease, stroke, and Alzheimer's diseases; better treatments for diabetes, arthritis and psychological conditions such as schizophrenia or manic depression. Commercially viable organ replacements are more than a decade away, inhibited by a poor understanding of the signals tissues use to control the growth and differentiation of tissues.
Fueling New Energy Sources
The basic science of chemical reactions has been put to good use in the fuel industry for more than a half century, with notable early work that dramatically improved fossil fuels. About 85% of the world's energy today is obtained by burning fossil fuels. At current rates of consumption, we may still be using petroleum as a major source of energy 50 years from now. Natural gas may last 100 years, while coal reserves could last for perhaps four centuries. Despite continuing improvements, atmospheric carbon dioxide produced by combustion of fossil fuels has increased by about one-third since the beginning of the industrial revolution with potentially significant consequences for global warming. The real solution may be in finding fuel alternatives.
Solar energy is currently captured on rooftops by photovoltaic cells that convert as much as 30% of the incident sunlight to electricity. The chemical sciences are challenged to devise materials and processes for photocells that are cheap, long lasting, and efficient in converting sunlight and also devise better means to collect, store, and distribute the energy where it's needed. Another approach to capturing solar energy is to grow special plants that can be converted to electricity either by burning or in a fuel cell.
Nuclear energy is currently the source of 7% of the world's total energy and 20% of U.S. electrical energy. Chemists and chemical engineers devised the processes for producing nuclear fuels and play a critical role in the development of safe methods for dealing with radioactive wastes. A steady decline in the number of university programs in nuclear chemistry and in the graduates they produce poses a significant challenge for the ongoing health of the field.
Chemists and chemical engineers are actively pursuing a viable hydrogen fuel cell, a specific type of electrochemical cell in which the reactants are hydrogen and air that are continuously supplied from outside of the cell. Hydrogen fuel cells were first used in the space program, but they are being developed for land applications, including portable electronics, vehicles, and back-up emergency power systems. Several problems remain to be solved, including speeding up the rate of the reaction at the electrodes and making lightweight cylinders that will hold highpressure hydrogen. If chemists are successful in overcoming these problems and appropriate ways are found to generate and store hydrogen, we could potentially usher in the so-called "hydrogen economy."
National and Personal Security
Chemistry has long played a direct role in personal security applications. Police are protected with strong bulletproof vests made of modern synthetic materials, firemen rely on clothing coated with temperature-resistant polymers, our homes are equipped with smoke detectors, and water purification and chemical testing assures clean water and food. Chemistry has aided the military through radar, synthetic antimalarials, weapons, and other developments.
The September 11 attack on our country has directed tremendous attention to the ways that science and technology could be mobilized for personal security and homeland defense and has shaped new directions in chemistry and chemical engineering. The future will require a better understanding of the actions and time scales of both chemical and biological weapons and an increased focus on detection capabilities. Sensors and other fast analytical techniques must be developed. Chemists can also contribute to developing protective gear for first responders and new approaches for delivering drugs and vaccines.
Part of the root cause of terrorism is the tremendous gap in the standard of living between industrialized and developing countries. Chemists and chemical engineers could help mitigate this difference by applying technology to improve energy, information infrastructure, and medicine and public health infrastructure as well as food, water shelter and clothing in poorer nations.
Public Perception of Chemistry
Chemists and chemistry as a science enjoy a fairly favorable public perception. In a recent survey of 1,012 U.S. adults commissioned by the American Chemical Society (ACS), chemistry as a career option was ranked third on a list of eight scientific professions, and chemists scored high as visionary, innovative, and results oriented. Also, 59% of those surveyed said that chemicals made their lives better. On the other hand, only 43% of the respondents had a favorable opinion of the chemical industry. It was ranked lowest among a list of 10 industries, and only 1 in 10 felt very well informed about the role of chemicals in improving human health.
An ongoing challenge for the chemical sciences is to help the public understand its contribution to applications such as medicine, energy solutions, and microcomputing. When a drug is released, for example, a drug company should more actively recognize the underlying chemistry that made the drug possible. Chemists should make better efforts to describe their work in nontechnical terms so that it is more accessible to the public and the media.
Research and Education
U.S. prosperity depends on high technology, and much of that depends on chemical expertise. For most of the past decade, the chemical industry has been one of the few U.S. manufacturing industries with a positive balance of trade. In fact, the chemical process industries are as much as one-third of the entire U.S. manufacturing sector in terms of value added.
Good chemistry pays off. A recent study carried out by the Council for Chemical Research finds that, on average, every dollar invested in chemical R&D today produces $2 in corporate operating income over six years-an average annual return of 17% after taxes. The study also reported a strong linkage of industrial patents to publicly funded academic research. The chemical industry has a big stake in the health of the chemistry and chemical engineering fields.
U.S. companies swiftly use the new leads from basic research in U.S. universities, in part because they have good contacts and in part because they hire students or even faculty who have played a role in creating basic knowledge. However, support of the research itself is mainly the function of the federal government and to a lesser extent of private foundations. A review of federal funding for the physical sciences shows that, although there has been a steady increase in funding since the 1970's, support for chemistry has lagged considerably behind the overall trend. Support for chemical engineering has actually decreased.
The challenges are so great, and the demand for talent so large, that it is important to attract the best and brightest students to the field. Graduate enrollments in chemistry and chemical engineering have declined slightly over the last decade, despite the need for them. Those already in the field will need to be active ambassadors, recruiting students and describing the rewards of life on the "molecular frontier."
Educators must convey the excitement of the chemical sciences to students, especially those in introductory courses. Education must become increasingly multidisciplinary if it is to keep up with the same trend in the field. The federal government has a clear stake in supporting enhanced education and training of chemical scientists and the recruitment of U.S. students. The government could also provide important support by endorsing the challenges and goals that this book describes.
The Committee on Challenges for the Chemical Sciences in the 21st Century: Ronald Breslow, Columbia University (Co-Chair), Matthew V. Tirrell, University of California, Santa Barbara (Co-Chair), Jacqueline K. Barton, CalTech, Mark A. Barteau, University of Delaware, Carolyn R. Bertozzi, University of California, Berkeley, Robert A. Brown, MIT, Alice P. Gast, MIT, Ignacio E. Grossmann, Carnegie Mellon University, James M. Meyer, E.I. du Pont de Nemours & Co., Royce W. Murray, University of North Carolina, Paul J. Reider, Amgen, Inc., William R. Roush, University of Michigan, Michael L. Shuler, Cornell University, Jeffrey J. Siirola, Eastman Chemical Company, George M. Whitesides, Harvard University, Peter G. Wolynes, University of California, San Diego, Richard N. Zare, Stanford University.
For more information: Contact the National Academies' Board on Chemical Sciences and Technology (BCST) at (202) 334-2156. Beyond the Molecular Frontier: Challenges for Chemistry and the Chemical Sciences is available from the National Academies Press, 500 5th Street, Washington, DC, 20001; (800) 624-6242 or at http://www.nap.edu.
