Ten Years of "Green Chemistry"

PCR

(September 8th 2008) Many of the worst aspects of modern industrial pollution result from the unforeseen toxicity of chemicals generated in huge quantities by the chemical industry for use as starting materials, finished products or hard-to-dispose-of deadly waste. The consequences for environmental and human health of this chemical revolution are still being uncovered. However, reports Jeremy Garwood, a growing trend in research chemistry is actively seeking to tackle the problem at its source.

In 1990, the United States' Pollution Prevention Act dealt with pollution in an original and innovative way by aiming to avoid problems before they happen, an initiative that sparked a whole research movement. 'Green Chemistry', also called sustainable chemistry, entails a research philosophy that directly encourages the design of products and processes that reduce or eliminate the use and generation of hazardous substances. This year sees the 10th anniversary of two significant publications in this domain.

In 1998, Paul Anastas (from the US Environmental Protection Agency) and John Warner (founder of the world's first green chemistry course at the University of Massachusetts) published Green Chemistry: Theory and Practice. This book provides the first introductory treatment of the design, development, and evaluation processes central to green chemistry and defines the '12 principles of green chemistry' that have since served as a guide to the ever-increasing numbers of researchers, both in academic institutions and industry, who adhere to its philosophy.

Briefly, the 12 principles that have proved such an inspirational challenge to chemistry researchers over the last decade are:

Pollution prevention. Design chemical syntheses to prevent waste;
Atom economy. The final product should contain the maximum proportion of the starting materials;
Less hazardous synthesis. Design syntheses that use and generate low or non-toxic substances;
Design safer chemicals. Create fully effective, non-toxic chemical products;
Safer solvents and auxiliaries. Avoid solvents, separating agents or auxiliary chemicals but if necessary use innocuous chemicals, especially water as a solvent;
Energy efficiency. Run reactions at ambient temperature and pressure;
Renewable feedstocks. Use raw materials and feedstock that are renewable rather than depleting, e.g. agricultural products or the waste from other processes;
Reduce derivatives. Avoid blocking or protecting groups or any temporary modifications if possible because they generate waste;
Catalysis. Minimise waste by using catalysts that can carry out a single reaction many times;
Design chemicals and products for degradation after use;
Real-time analysis of syntheses minimises or eliminates the formation of by-products;
Accident prevention. Design chemicals that minimise the potential for accidents, such as explosions, fires, or release into the environment.

In 1999, directly inspired by Anastas and Warner's book, the UK's Royal Society of Chemistry launched the journal Green Chemistry, which is currently celebrating its 10th year as the principal research publication in the domain. In its instructions to authors, the journal clearly states that it publishes articles based on the definition of green chemistry outlined in Anastas and Warner's book: "Green chemistry is the utilisation of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design, manufacture and application of chemical products".

So, how successful has this initiative been?

In 2005, the Nobel Prize Committee recognised the importance of green chemistry by awarding Yves Chauvin, Robert H. Grubbs, and Richard R. Schrock the chemistry prize for the development of the metathesis method in organic synthesis. "This represents a great step forward for 'green chemistry', reducing potentially hazardous waste through smarter production. Metathesis is an example of how important basic science has been applied for the benefit of man, society and the environment." Since its discovery, olefin metathesis has gained widespread use in research and industry for making products ranging from medicines and polymers to enhanced fuels. Its advantages include the creation of fewer side products and hazardous wastes.

Ryoji Noyori, the 2001 chemistry Nobel Prize winner is a strong believer in the power of green chemistry: "Our ability to devise straightforward and practical chemical syntheses is indispensable to the survival of our species", adding that, "Researchers must spur public opinions and government policies toward constructing the sustainable society in the 21st century." In 2005, he identified three key developments in green chemistry: use of supercritical carbon dioxide as a green solvent, aqueous hydrogen peroxide for clean oxidations and the use of hydrogen in asymmetric synthesis. Examples of applied green chemistry are supercritical water oxidation and dry media reactions.

Bioengineering is also seen as a promising technique for achieving green chemistry goals. A number of important process chemicals can be synthesized in engineered organisms, such as shikimate, a Tamiflu precursor which is fermented by Roche in bacteria.

The chemical and pharmaceutical industries have also proved remarkably receptive to the concepts of green chemistry. Some observers have wryly suggested that this is because in the USA the colour green symbolises the colour of money with connotations of wealth and capitalism, rather than the European image of political parties focused on environmental issues.

Since 2007, the pharmaceutical giant Merck has marketed Januvia (also known as sitagliptin), a once-a-day pill for type two diabetes that is expected to be a blockbuster drug. Januvia was designed using green chemistry. As Joe Armstrong from the process design team explained: "The new chemistry that we invented to make this molecule removes 80 percent of the waste. The other thing we did is we increased the yield of that process by over 50 percent, and when you increase the yield on a process, that means you use less materials to make the same amount of goods, and therefore, it's going to be much more cost effective and really becomes a sustainable process." Although Merck declined to disclose just how profitable its new green design could be, Berkeley Cue, a retired Pfizer research executive says: "If you have a drug on the market for eight, ten years, and you're saving ten to fifteen million dollars a year, that's as much as a hundred fifty million dollars of manufacturing cost reduction over the lifetime of the patent." He says Pfizer's savings were of this order when his own research team used green chemistry in 2002 to revamp Zoloft (Sertraline hydrochloride), the most popular antidepressant drug in the US.

Green chemistry is also being seen as a powerful tool that researchers must use to evaluate the environmental impact of nanotechnology. As nanomaterials are developed, the environmental and human health impacts of both the products themselves and their manufacturing processes need to be considered to ensure their long-term economic viability.

John Warner, who founded the Green Chemistry programme at the University of Massachusetts, is still concerned at the lack of education: "In 2008, very few, if any graduate or undergraduate programs in materials science and chemistry require students to learn anything about mechanistic toxicology or environmental impacts. Even though worldwide regulatory systems and activist coalitions have changed the way of doing business in R&D labs and manufacturing floors with respect to human health and the environment, our colleges and universities have not yet changed their curricula. "Education can be enabling and transforming. People who go to school to become chemists expect their education to enable them to get a job or to start a career. Environmental problems, while important to them, appear outside their sphere of influence. Green chemistry transforms this perspective. It allows practicing chemists to feel that they themselves can contribute to pollution prevention as individuals. This empowerment is extremely important."