Chem. Rev.

2007, 107, 2169−2173 2169

Innovations and Green Chemistry

István T. Horváth is a Professor and Vice Director for Science of the

Institute of Chemistry at Eötvös University, Budapest, Hungary. He received Paul T. Anastas joined Yale University as Professor in the Practice of
his Diploma in Chemical Engineering (1977) and his Ph.D. in Chemistry Green Chemistry with appointments in the School of Forestry and
(1979), both at Veszprém University, Veszprém, Hungary. He was a Environmental Studies, Department of Chemistry, and Department of
postdoctoral research associate at Yale University (1982−1984) and a Chemical Engineering. In addition, Prof. Anastas serves as the Director
scientific co-worker at the Swiss Federal Institute of Technology (ETH), of the Center for Green Chemistry and Green Engineering at Yale. From
Zurich, Switzerland (1984−1987). After spending 11 years at Exxon (now 2004 to 2006, Paul Anastas served as Director of the Green Chemistry
ExxonMobil) Corporate Research, Annandale, NJ, as a Senior Staff Institute in Washington, DC. He was previously the Assistant Director for
Chemist, he returned to Hungary at the end of 1998. His research interests the Environment in the White House Office of Science and Technology
center on Green Chemistry with an emphasis on homogeneous transition Policy, where he worked from 1999 to 2004. Trained as a synthetic organic
metal catalysis, organometallic chemistry, and in situ spectroscopy. He chemist, Dr. Anastas received his Ph.D. from Brandeis University and
has published over 150 scientific papers, book chapers, and patents. He worked as an industrial consultant. He is credited with establishing the
is the Editor in Chief of the Encyclopedia of Catalysis and the co-editor field of Green Chemistry during his time working for the U.S. Environmental
of the Handbook of Fluorous Chemistry, based on the fluorous biphasic Protecion Agency as the Chief of the Industiral Chemistry Branch and as
concept he invented in the early 1990s. He was the Chairman of the the Director of the U.S. Green Chemistry Program. Dr. Anastas has
COST Action D29 on Sustainable/Green Chemistry and Chemical published widely on topics of science through sustainability, such as the
Technology (2002−2007). He was awarded a D.Sc. in Chemistry by the books Benign by Design, Designing Safer Polymers, Green Engineering,
Hungarian Academy of Sciences in 1998 and was a Széchenyi Professor and his seminal work with coauthor John Warner, Green Chemistry:
Scholar (2000−2003). He received the first Fluorous Technology Award Theory and Practice.
in 2005 and the Humboldt Research Award in 2006.
of the many topics directly relevant to Green Chemistry being
As we look across the field of Green Chemistry since its pursued by researchers around the world.
emergence as a cohesive field of study beginning with the With all of the research successes realized in Green
development of environmentally friendly processes in the Chemistry over the past 15 years, it is necessary to recognize
early 1990s,1 it is possible to identify certain trends where and understand that the field is in a nascent stage and that
much research has focused and where significant advances some of the most important research questions within it are
have been made. Certainly the area of environmentally only now beginning to be identified and pursued. As a
benign solvents has been one of the leading research areas research community, it is important to accelerate the pursuit
of these research areas by clearly enunciating the great
of Green Chemistry with great advances seen in aqueous
research challenges, the great scientific unknowns within the
(biphase) catalysis2,3 and the use of supercritical fluids4 in
field of Green Chemistry. Only through this exercise will
chemical reactions. While the greenness of ionic liquids5,6 the top institutions, the major funding agencies, and the
and fluorous media7 will ultimately depend on their indi- primary industrial users of these innovations understand the
vidual properties with respect to health and the environment, power and potential of Green Chemistry research discoveries
the sustainability of new biobased solvents8 has to be proven and be willing to provide the support and funding needed to
as well. There has been a renewed focus on the age-old see this field reach its potential.
pursuit of the organic chemist to design and successfully The current portfolio of feedstocks that are used today as
apply the ideal synthesis in terms of efficiency, with atom9-11 the basis of the chemical enterprise is likely to be shifting,
and step economy11 being a major goal. New catalytic perhaps dramatically over the coming decades, for reasons
processes continue to emerge to advance the goals of Green related to supply, performance, economics, public pressures,
Chemistry, while techniques such as microwave12-14 and and government policies.8,18-27 The shift toward a more
ultrasonic synthesis15 as well as in situ spectroscopic diverse feedstock base is an important future research area
methods16-17 have been used extensively, leading to spec- in Green Chemistry. While useful breakthroughs have been
tacular results. These research areas are a glimpse of some made in demonstrating how to use biobased materials such
10.1021/cr078380v CCC: $65.00 © 2007 American Chemical Society
Published on Web 06/13/2007
2170 Chemical Reviews, 2007, Vol. 107, No. 6 Editorial

as sugars and starches for basic chemical building blocks, it such as chitin,29 it is again the case that it represents only a
is an important realization that if the scientific innovations fraction of what is possible and necessary to redesign our
are going to be able to be translated to the realm of economic current portfolio of building blocks of the chemical enter-
viability and societal benefit, these feedstocks will have to prise. The utilization of perhaps the world’s greatest waste
be accessed in a way that does not compete with land and product, carbon dioxide, is also a key research area for the
agricultural resources for food and feed production. This future.30 The excellent work on using carbon dioxide in such
likely means that important research challenge for Green applications as the basis for new polymers or as a drilling
Chemistry will be accessing the biobased building blocks aid by a number of groups thus far has provided a glimpse
through the utilization of agricultural waste products. This of what is possible. However, in order for the utilization of
can only be met by systematically exploiting the vast carbon dioxide to truly have an impact, it will need to be
biofeedstocks which Nature graciously provides us, through incorporated on a vastly larger scale in such applications as
broad-scale basic research toward the development of ef- building materials, road surfaces, and synthetic soils. Basic
ficient, environmentally benign, and economical process insight into the development of thermodynamically uphill
methodologies for the large-scale conversion of biomass catalytic systems will likely be needed to deal with the energy
(carbohydrates, proteins, fats, terpenoids) into industrially balance of carbon in a high oxidation state to make it a useful
viable products, such as bulk and intermediate chemicals, starting material.
pharmaceuticals, and polymeric organic materials. In this The synthetic methods that we use to transform our starting
endeavor, national and supranational funding institutions will materials will need to be the focus of basic research in Green
have to play an active role, not only by funding correspond- Chemistry, since those methods that are still widely used
ing activities in a broad time frame (5-10 years) but also are lacking both in terms of material and energy efficiency
by elaborating a concise long-term strategy that takes root as well as in terms of the consequences of the reagents being
in academia and the chemical industry. The basic strategy used for humans and the environment. As we as a chemistry
should be directed not only at the generation of the very community have sought to impart greater reactivity on our
same basic chemicals that are well accessible from petro- reagents and substrates in order to reduce reaction times and
chemical sources but also toward the development of energy requirements, the correlation between reactivity and
products with analogous industrial application profiles, with toxicity31 has often not been incorporated into the design of
as little alteration of the structural framework of the our synthetic methodologies. The insights by leading Green
components of the biomass as possible. Chemistry researchers today take advantage of understanding
The largest material produced in the world every year by biological transformations that impart reactivity both spatially
volume is ligno-cellulose (typically containing 40-50 wt % and temporally through the use of geometric contortion of a
cellulose, 25 wt % hemi-cellulose, and 25 wt % lignin), reaction sight. The generation of catalysts able to carry out
which provides strength to trees and plants. There are these type of transformations will mean being able to
research groups currently striving to take on the important essentially use very unreactive substrates and reagents while
challenge of how to convert ligno-cellulose into a form that achieving the selectivity, low energy, and rapid reaction times
can be exploited as a fundamental building block in a wide desired without the use of substances as hazardous to humans
range of transformations. This is a necessary characteristic and the environment. Currently, the depth of understanding
to be a genuine foundation for the broad scope of products of being able to design these systems based on first principles
in the chemical enterprise. In order for this challenge to be does not exist and should be considered by top catalyst
met, others in the chemistry, biochemistry, and molecular researchers as a challenge for future research.
and materials science communities must engage along with With the successes that catalysts have brought to the
the current leading Green Chemistry researchers in pursuing chemical enterprise over the course of the past 40 to 50
this central challenge. New catalysts, new enzymes, new years,32 we have yet to meet the challenge of designing
processing systems, and new plant hybrids may all be part multifunctional catalysts that are capable of carrying out
of the future solutions to the use of biobased building blocks transformations at more than one site with selectivity. Green
that will be built on the Green Chemistry research starting catalysis particularly could have a key role in maximizing
to be engaged today. Only through this research can we atom efficiency and process simplicity in the manufacture
achieve the benefits of the plentiful, renewable feedstocks of fine, specialty, and pharmaceutical chemicals and materi-
available in ways that take advantage of their intrinsic value. als. In the area of homogeneous catalysis, the integration of
This includes outstanding complexity, as witnessed by the single site catalysis with facile catalyst separation and
high degree of chirality that could and should be exploited recycling should be the primary focus of future research
and the biodegradability that allows the materials to remain activities.33 The design of novel catalysts with preferential
within the carbon cycle on a human time scale rather than a solubility in green solvents could result in commercially
geologic time scale. attractive catalytic systems. The effective utilization of
Alternative feedstocks will not be limited to plant-based enzymes in novel chemical transformations should be another
sources; rather, they will necessarily include a diverse set important objective of green catalyst development.34 The
of cheap, available, benign materials. One of the largely application of the fundamental understanding of the mech-
untapped sources for chemical building blocks is found as anisms of enzymatic reactions in the design of biomimetic
waste in our economy and society today. Another of the analogues could lead to new and effective catalytic systems.35
largest materials produced in the world is chitin, the The development of single site heterogeneous catalysts (e.g.,
substance making up (among other things) the exoskeleton uniform site selectivity and activity)36 could be another
of shellfish. The quantities of chitin unused and disposed of approach to secure sustainable/green industrial catalysts. The
as waste are vast and need to be appropriately exploited.28 incorporation of molecular level shape selectivity in all
While a small number of leaders in the Green Chemistry classes of catalysts could open the way to substrate selective
field have demonstrated the potential of using substances conversion of complex materials including oil-based and/or
Editorial Chemical Reviews, 2007, Vol. 107, No. 6 2171

renewable raw materials. Since most of the chemicals that Alternative energy systems that meet the needs of the
contain chiral centers could interact with our environment, current generation while ensuring the ability of future
the application and/or design and synthesis of chiral catalysts generations to meet their needs is one of the great challenges
should also be included. Finally, the development of novel of our time and a central Green Chemistry research challenge.
catalytic materials, addressing the engineering and com- If discussions of alternative energy futures are to be realized,
mercialization issues, should also be incorporated. whether based on solar energy, biofuels, sustainably produced
During the course of two centuries of synthetic chemistry, hydrogen, or other alternatives and combinations of the
one of the great achievements, perhaps of human history, is above, the materials that will be required for these systems
the mastery of the covalent bond to the point where it can will be designed by chemists who need to ensure that the
be said with considerable confidence that synthetic chemists new materials do not introduce unacceptable problems of
are capable of making virtually any small molecule that can toxicity, persistence, bioaccumulation, and depletion of finite
be drawn. This cannot be said of the mastery of weak bonds. resources as they seek to solve our immediate energy issues.
There have been great advances in the understanding of weak The understanding that we are immersed in a sea of
bond interactions in explaining the performance of certain renewable energy needs to be engrained. Our future energy
molecules and materials.37 There has also been excellent approaches should be focused on the capture and conversion
science conducted that explains particular synthetic interac- of these existing energy reservoirs rather than the so-called
tions through the understanding of weak bond interactions generation of energy from combustion-based depletion of
in the transition states of certain reactions as well as in the finite sources and should be recognized as central to our
reactant-solvent system. For example, hydrogen bonds in Green Chemistry research challenges.
aqueous systems could be a key designer tool to achieve The solvents that currently remain the basis of our
high selectivity at economical reaction rates.2 Tuning the chemical operations are still largely organic, contain various
attractive interactions between aromatic rings in substrate(s) health and environmental concerns, are derived from petro-
and chiral catalyst(s) or reagent(s) could be a key part of a leum, and are driving much of our solution chemistry and
green process development. This foundation allows us to separation issues. While there have been very notable Green
realize that we are at the beginnings of meeting the great Chemistry successes over the years beginning to address
research challenge of being able to use weak forces as a these issues, there is much fundamental research to be
design tool for imparting new properties and performance conducted. The development of solvents that not only
in molecules and materials and creating new synthetic accomplish heat and mass transfer but also simultaneously
methods and pathways. Again, leading groups are providing catalyze transformations and result in product separation so
a glimpse of the potential of this research challenge if as to drive the chemical equilibrium is still largely a distant
successfully engaged. goal that requires fundamental research. Smart solvents that
On the other end of the spectrum, we recognize the sense certain conditions, such as heat, and are designed to
challenge of being able to manipulate strong bonds in a respond accordingly have been demonstrated and should be
relatively facile manner. The ability to directly derivatize developed. So-called obedient solvents that change basic
carbon-fluorine bonds, as an example, is a great challenge.38 physical and chemical properties as a response to an imparted
An ongoing challenge that a number of researchers are stimulus have also been demonstrated.40,41 Discovering the
undertaking includes the ability to eliminate substitution new applications for ancient solvent systems such as water42
reactions through the application of direct derivatization of will continue to be an important area of investigation for
an otherwise unactivated carbon-hydrogen bond.39 The Green Chemistry researchers. There are major opportunities
consequences for successful research in this area for the goals to extend the use of water as a solvent for organic reactions,
of Green Chemistry are potentially dramatic from the point both at ambient and elevated temperatures. It should be
of view of minimizing waste, energy, and hazard. important to demonstrate the viability of both commercial
The role of energy in the chemical enterprise is of course and technical processes based on fluorous and ionic liquids
multifaceted. One aspect includes every step of a chemical as well as supercritical fluids. Key questions include reaction
process at the industrial level that requires an energy input modeling, scale-up rules, and reactor engineering. At the
either for intrinsic or operational performance. The other same time, there is a need for increased understanding on a
aspect includes the fact the chemistry creates the materials molecular level of reactions in these media and how, if at
and systems needed to generate, store, and transport the all, the reaction mechanisms differ from those in more
energy required by our economy and our society. A central conventional media. The most challenging problem with
goal of Green Chemistry is not only to ensure that energy supercritical CO2 is to develop chemistries which will allow
efficiency is ingrained from the molecular level and through CO2 to be used as both solvent and feedstock for the
our products, processes, and systems, but also to ensure that generation of higher value chemicals. There is also a need
the nature of that energy is sustainable to both humans and to develop “greener” organic solvents, which can be derived
the biosphere. In order to achieve these goals, fundamental from renewable feedstocks or can be designed at the
research is needed on several important areas. The design molecular level to have reduced environmental impact.
of chemical transformations that minimize energy input has The potential environmental and health hazards of both
long been recognized as an important goal for primarily industrial chemicals and chemical based consumer products
economic reasons and needs to continue, likewise with the should be treated as intrinsic properties and should be
tremendously energy intensive area of separations. The minimized during design. First of all, the molecular level
distillation operations alone in the U.S. consume more than understanding of the relationship between structure and
twice the energy than is used by the entirety of the nation of toxicity of chemicals is the only approach to design less or
Switzerland on an annual basis. Designing systems of ideally nontoxic products. While decreasing the intrinsic
separation that minimize energy consumption will be in- toxicity of chemical based consumer products should be the
creasingly important as a Green Chemistry goal. primary focus, understanding the toxicity of secondary
2172 Chemical Reviews, 2007, Vol. 107, No. 6 Editorial

degradation products generated after their use should also ensure that the mechanism of action of the chemical is
be considered. targeted to a specific biological pathway unique to the pest,
In the design of target molecules, materials, composites, thereby reducing the chance of putting other living systems
and formulations, there is a tremendous amount of basic at risk. In addition, it will be necessary to design molecules
research yet to be done. With the tremendous advances that such that they exist and retain structural integrity only as
have been made in understanding the relationship between long as is necessary to accomplish their purpose. For
molecular structure and biological activity as it relates to example, research is needed to ensure that after a pesticide,
drug discovery,43,44 there is a great deal to build on for Green pharmaceutical, or antibiotic performs its desired function,
Chemistry purposes. Currently, there is not a systematic way it will be able to degrade into innocuous products rather than
to design our molecules in a way so as to ensure that the persist, bioaccumulate, and biomagnify after its useful time
molecular structure and the derived physical chemical has passed.
properties do not facilitate adverse consequence in the body The prevention of accidents involving chemicals has
or the biosphere. Basic research on known mechanisms of traditionally been considered as an engineering issue. The
toxic action (and the elucidation of as yet unknown mech- accidental potentials of chemicals can alternatively be
anisms) is central to the ability of future synthetic chemists approached using molecular engineering by selecting inher-
to design safer chemicals. The range of afflictions ranging ently safer chemicals and reaction types during the design
from cancer to endocrine disruption45 to coral bleaching can of green processes.
be minimized as we achieve the fundamental molecular level One of the greatest challenges is the last one percent!
understanding of the basis of hazard. This complex challenge Today’s scientific and technological establishment (or pro-
for Green Chemistry may only be possible with the collab- fessors and managers) gives high rewards to those that
oration of other disciplines such as toxicology and ecosystem discover and develop new chemical reactions or processes
biologists. As an example, the molecular-level understanding with high yields, mostly between 95 and 99%. While
of hazard currently does not begin to address the impacts of achieving “100%” or an enzyme-like performance is remark-
synergistic chemicals that have a multiplicative biological ably difficult, no rewards are given to those who get the last
consequence when in the presence of their complementary 1%.
chemicals. Basic research in collaboration with other disci- Finally, the success of Green Chemistry ultimately depends
plines will be needed to develop the beginnings of heuristic on the practicing chemists who will use the same brilliance
design rules for safer chemicals to be used by chemical and creativity that is the long tradition of chemistry and use
designers. Even the simplest of these challengessto target it with the new perspective for transformative innovations
molecular design to minimize the ability of a chemical to for sustainability.
cross biological interfaces and manifest hazardsis something
generally not incorporated into a design protocol, with the References
important exception of the pharmaceutical industry.
(1) Benign by Design: AlternatiVe Synthetic Design for Pollution
Another approach to increase the sustainability of both PreVention; Anastas, P., Farris, C., Eds.; American Chemical
industrial chemicals and chemical based consumer products Society: Washington, DC, 1994.
is the minimization of materials needed to achieve the same (2) Li, C. Chem. ReV. 1993, 93, 2023 and 2005, 105, 3095.
(3) Aqueous Organometallic Chemistry and Catalysis; Horváth, I. T.,
performance. Therefore, the fundamental understanding of Joó, F., Eds.; Kluwer Academic Publishers: Dordrecht, 1995.
achieving the same or better product performance with less (4) Jessop, P.; Leitner, W. Chemical Synthesis Using Supercritical Fluids;
material (e.g., thinner polymers, higher biological activity, Wiley-VCH: Weinheim, 1999.
(5) Welton, T. Chem. ReV. 1999, 99, 2071.
better stability, etc.) should be developed. (6) Earle, M.; Seddon, K. Pure Appl. Chem. 2000, 72, 1391.
The development of recyclable chemical based consumer (7) Horváth, I. T. Acc. Chem. Res. 1998, 31, 641.
products could significantly reduce the use of virgin raw (8) Dale, B. J. Chem. Technol. Biotechnol. 2003, 78, 1093.
(9) Trost, B. Science 1991, 254, 1471.
materials in the chemical and allied industries and lower the (10) Trost, B. Acc. Chem. Res. 2002, 35, 695.
amount waste generated. The key challenge in this area is (11) Wender, P. A.; Croatt, M. P.; Witulski, B. Tetrahedron 2006, 62,
to develop a molecular level understanding of the relationship 7505.
between the structure and the recyclability of the product (12) Bose, A. K.; Manhas, M. S.; Ganguly, S. N.; Sharma, A. H.; Banik,
B. K. Synthesis 2002, 1578.
without compromising the performance of the product. For (13) Nuchter, M.; Ondruschka, B.; Bonrath, W.; Gum, A. Green Chem.
example, the introduction of molecular functionalities (or 2004, 6, 128.
switches) that would be resting during the normal use of the (14) Topics in Current Chemistry: MicrowaVe Methods in Organic
Synthesis; Larhed, M., Olofsson, K., Eds.; Springer: Berlin, 2006.
product but could be turned on during the recycling processes (15) Mason, T. J. Sonochemistry; Oxford University Press: Oxford, 1999.
is an attractive approach for consideration. (16) Chalmers, J. M. Spectroscopy in Process Analysis; CRC Press: Boca
If the development of recyclable chemical based consumer Raton, FL, 2000.
(17) In situ NMR Methods in Catalysis; Bargon, J., Kuhn, L. T., Eds.;
products is limited by the intrinsic nature of the chemical Springer: Dordrecht, 2007.
used, the replacement of components of the products that (18) van Bekkum, H. In Renewable Resources and Renewable Energy:
are persistent with biodegradable chemicals should be A Global Challenge; Graziani, M., Fornasiero, P., Eds.; CRC Press:
Boca Raton, FL, 2006.
preferred. While the intrinsic biodegradability of chemical (19) Carbohydrates as Organic Raw Materials; Lichtenthaler, F. W.. Ed.;
based consumer products should be the primary focus, VCH: Weinheim, 1991.
understanding the biodegradability of secondary degradation (20) Feedstocks for the Future: Renewables for the Production of
products generated after their use should also be considered. Chemicals and Materials; Bozell, J. J., Patel, M. K., Eds.; Oxford
University Press: New York, 2006.
During the use phase of a chemical, it should be recognized (21) Hong, C. K.; Wool, R. P. J. Appl. Polym. Sci. 2005, 95, 1524.
that certain substances are designed to be toxic and cause (22) Kim, S.; Dale, B. J. Ind. Ecol. 2003, 7, 147.
adverse consequence to a living thing, such as a pest being (23) Kim, S.; Dale, B. Biomass Bioenergy 2004, 26, 361.
(24) Lynd, L. R.; Cushman, J. H.; Nichols, R. J.; Wyman, C. E. Science
the target of a pesticide. While some advances are being 1991, 251, 1318.
made in this area, much fundamental research is needed to (25) Petrus, L.; Noordermeer, M. A. Green Chem. 2006, 8, 861.
Editorial Chemical Reviews, 2007, Vol. 107, No. 6 2173

(26) Bio-based polymers and composites; Wool, R., Sun, X. S., Eds.; (38) Perutz, R. N.; Braun, T. In ComprehensiVe Organometallic Chemistry
Elsevier: St. Louis, MO, 2005. III; Crabtree, R. H., Mingos, D. M. P., Eds.; Elsevier: Oxford, 2007.
(27) Drumright, R.; Henton, P. G. AdV. Mater. 2000, 12, 1841. (39) ActiVation and Functionalization of C-H Bonds; Goldberg, K. I.,
(28) Knorr, D. Food Technol. 1991, 45, 114. Goldman, A. S., Eds.; ACS Symposium Series 885; American
(29) Clark, J. H.; Budarin, V.; Deswarte, F. E. I.; Hardy, J. J.; Kerton, F. Chemical Society: Washington, DC, 2004.
M.; Hunt, A. J.; Luque, R.; Macquarrie, D. J.; Milkowski, K.; (40) Eckert, C. A.; Liotta, C. L.; Bush, D.; Brown, J. S.; Hallett, J. P. J.
Rodriguez, A.; Samuel, O.; Tavener, S. J.; White, R. J.; Wilson, A. Phys. Chem. B 2004, 108, 18108.
J. Green Chem. 2006, 8, 853. (41) Jessop, P. G.; Heldebrant, D. J.; Li, X.; Eckert, C. A.; Liotta, C. L.
(30) Carbon Dioxide Utilization for Global Sustainability; Park, S.-E., Nature 2005, 436, 1102.
Lee, K.-W., Chang, J.-S., Eds.; Elsevier: Amsterdam, 2004. (42) Breslow, R. Acc. Chem. Res. 1991, 24, 7816.
(31) A ComprehensiVe Guide to the Hazardous Properties of Chemical (43) Jorgensen, W. Science 2004, 303, 1813.
Substances, 3rd ed.; Patnaik, P., Ed.; Wiley: Hoboken, NJ, 2007. (44) Jorgensen, W.; Duffy, E. AdV. Drug DeliVery ReV. 2002, 54, 355.
(32) Encyclopedia of Catalysis; Horváth, I. T., Iglesia, E., Klein, M. T., (45) Colborn, T.; Dumanoski, D.; Myers, J. P. Our Stolen Future; Dutton,
Lercher, J. A., Russel, A. J., Stiefel, E. I., Eds.; Wiley: New York, Penguin Books: New York, 1996.
2003.
(33) Gladysz, J. A. Chem. ReV. 2002, 102, 3215.
(34) BRENDA, The Comprehensive Enzyme Information System, Cologne István T. Horváth
University BioInformatics Center (http://www.brenda.uni-koeln.de/
), Cologne, Germany. Eötvös University, Budapest, Hungary
(35) Holliday, G. L.; Almonacid, D. E.; Bartlett, G. J.; O’Boyle, N. M.;
Torrance, J. W.; Murray-Rust, P.; Mitchell, J. B. O.; Thornton, J.
M. Nucl. Acids Res. 2007, 35, D515 (http://www.ebi.ac.uk/thornton- Paul T. Anastas
srv/databases/MACiE/). Yale University, New Haven, CT, USA
(36) Thomas, J. M.; Raja, R. Top. Catal. 2006, 38, 3 and 40, 3.
(37) Lehn, J.-M. Supramolecular Chemistry; VCH: Weinheim, 1995. CR078380V