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Green Chemistry
Definition of Green Chemistry
The design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances
Benefits of Green Chemistry• Environment• Human Health• Economics and
Competitiveness• Sustainability • New scientific
knowledge
Green Chemistry across Industrial Sectors
• Defense and aerospace• Adhesives, coatings, corrosion
inhibitors
• Automotive• Solvents, polymers, fuels
• Household cleaners• Surfactants, fragrances, dyes
• Cosmetics• Builders, chelating agents, dyes
• Agriculture• Pesticides, fungicides, fertilizers
• Electronics• Solder, housings, displays
• Pharmaceuticals
GREEN CHEMISTRY is a fundamental Change in Thinking
• Green Chemistry moves our consideration of how to deal with environmental problems from the circumstantial to the intrinsic.
• Hazard must be recognized as a design flaw
Circumstantial vs. Intrinsic• Circumstantial
• Use• Exposure• Handling• Treatment• Protection• Recycling• Costly
• Intrinsic• Molecular design for
reduced toxicity• Reduced ability to
manifest hazard• Inherent safety from
accidents or terrorism• Increased potential
profitability
Risk = Hazard x Exposure
Principles of Green Chemistry1. It is better to prevent waste than to treat or clean up waste after it is formed.2. Synthetic methods should be designed to maximize the incorporation of all materials used in the process
into the final product.3. Wherever practicable, synthetic methodologies should be designed to use and generate substances that
possess little or no toxicity to human health and the environment.4. Chemical products should be designed to preserve efficacy of function while reducing toxicity.5. The use of auxiliary substances (e.g. solvents, separation agents, etc.) Should be made unnecessary
wherever possible and, innocuous when used.6. Energy requirements should be recognized for their environmental and economic impacts and should be
minimized. Synthetic methods should be conducted at ambient temperature and pressure.7. A raw material of feedstock should be renewable rather than depleting wherever technically and
economically practicable.8. Reduce derivatives - Unnecessary derivatization (blocking group, protection/ deprotection, temporary
modification) should be avoided whenever possible.9. Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.10. Chemical products should be designed so that at the end of their function they do not persist in the
environment and break down into innocuous degradation products.11. Analytical methodologies need to be further developed to allow for real-time, in-process monitoring and
control prior to the formation of hazardous substances.12. Substances and the form of a substance used in a chemical process should be chosen to minimize
potential for chemical accidents, including releases, explosions, and fires.
Green Chemistry Design FrameworkAcross the life-cycle
Waste Prevention
Atom Economy
Design ForDegradation
Less HazardousReagents
Renewable Feedstocks
Design for Safety and Security
Green AnalyticalMethods
Benign Solvent Systems
Use of Catalysis
Benign Product Design
Unnecessary Derivatives
Energy Considerations
OriginsOf Materials Manufacturing Distribution Use End of Life
Journals
Articles
1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
Headlines
Research
AqueousSolvents
BiobasedTransformations
Biobased materials
Alternative Energy Science
Synthetic Methodologies
Next Gen Catalysts
Molecular Self-Assembly
Breakthroughs
Green Nano
RT Ionic Liquids
Degradable Polymers
Molecular Design
Biofuels Reactor Design
SCF
Business?
Conferences
Networks
2010, Bloomberg NewsWegmans stops selling reusable bags after lead tests
2010, Bloomberg NewsWegmans stops selling reusable bags after lead tests
2010, NY TimesHydrocarbons in Cereal Stoke New Debate Over Food Safety
2010, The Sun Chronicle
Toxic Beauty
2010, Maine Public Broadcasting NetworkReport: Cosmetic Products Contain High Levels of Toxic Chemicals
2009, The Charleston GazetteStudy finds food-wrapper chemicals in blood
Design for Inherency• “The term ‘intrinsic nature’ does not
indicate a factor’s temporal status, but rather refers to its underlying and defining nature.”
--Aristotle
References• Towards Molecular Design for Hazard Reduction
- Fundamental Relationships Between Chemical Properties and Toxicity. Tetrahedron 2010, 66 (5), 1031-1039.
• Toward a Comprehensive Molecular Design Framework for Reduced Hazard. Chemical Reviews 2010, 110 (10), 5845-5882.
• Anastas, P. T.; Beach, E. S., Green chemistry: the emergence of a transformative framework. Green Chemistry Letters and Reviews 2008, 1 (1), 9-24.
Circumstantial vs. Intrinsic• Circumstantial
• Use• Exposure• Handling• Treatment• Protection• Costly
• Intrinsic• Molecular design
for reduced toxicity
• Reduced ability to manifest hazard
• Inherent safety from accidents or terrorism
Hazards• Physical: explosivity, flammability,
particulate-biological interactions, reactivity, corrosives
• Toxicological: acute, chronic toxicity, carcinogenicity, ecotoxicity
• Global: stratospheric ozone depletion, global climate change, global toxics dispersion, resource depletion
ADME and Design
MolecularWeight
Solubility Electronic Charge
Volatility
ReactiveFunctional
Groups
Bioaccumulation/Persistence
Particlesize
Receptorbinding
Key events
Shape/Molar
Volume
Toxicokinetics
Toxicodynamics
Toxicokinetic methodologies• Reduce potential for undesirable
ABSORBTION.
• Limit DISTRIBUTION to potential target organs.
• Enhance METABOLISM to non-toxic products.
• Facilitate EXCRETION of xenobiotics.
OVERARCHING FRAMEWORK
•Flammability•Radioactivity• Explosivity•Chemical Reactivity
Chemical and Physical PropertiespKa chain branching log P molecular refractivity mol. wt. hydrolyzable groups
EHOMO ELUMO electronegativity hardness dipole log D7.4 # H-bond acceptor/donor
•Pollution•Persistence•Depletion of natural resources
Physiochemical Property Desired value
Particle size Increased particle size (for nanoparticles) Ideally >100 nm
Ionization Keeping substance in unionized form (ionization increases solubility), with the exception of nano particles,
Unionized or ionized at pH 2 (e.g. –SO3
-)
log P High log P implies too lipid soluble to dissolve in GI tract, and low log P means increased water solubility and elimination
0>log P>5
Molecular weight Increased molecular weight decreases chance of absorption in GI tract
> 500 Da
Melting point Liquids are absorbed faster than the corresponding solids, so solids at room temperature are preferred
>150 °C
Hydrogen bonds Increased number of hydrogen bond donors and acceptors limits absorption (unless transported by specific active transport carrier proteins, e.g. erythromycin, methotrexate).
>5 H-bond donors or >10 H-bond
Hydrolyzable linkages Ability to be hydrolyzed by acidic flora of stomach or biotransformed by intestinal enzymes or bacterial intestinal flora, and toxicity of products
Avoidinghydrolysable esterand amidelinkages
Desirable physiochemical properties for decreased GI absorption and bioavailability of chemicals in humans.
DERIVING PROPERTY CRITERIA TO REDUCE BIOAVAILABILITY
Acidic substance
pKa<7
Unionized at pH>pKa
Basic substance
pKa>7
Un-ionized at pH>pKa
Lipid soluble
Absorbed across intestine membrane
into blood
Chemicall
Example: Influence of pKa and ionization on absorption of chemicals in the GI tract.
Can We Define Toxic Chemical Space & Safer Chemical Space?
What do we mean by “performance”?
• Is it enough to accomplish a narrow definition of function?• Color?• Strength?• Adhesion?
• Does performance also require that the substance does not cause harm?• Cancer?• Endocrine disruption?• Neurotoxicity?