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?