Engineering, Materials

The design hierarchy

The problem of toxic substances has roots that can be traced back through the organizational levels of industrial systems: from the design and manufacture of products to the design and manufacture of the materials from which products are fashioned, and ultimately to the level of chemical production and molecular design. The results of design and engineering decisions at each level are taken up as finished products for use in ‘higher’ levels of design and engineering. Product design rarely involves creating new materials or synthesizing new chemicals; rather, it most commonly involves selecting among available existing materials. Those materials, in turn, are made of chemical ingredients selected from already-available options. To a large extent, the entire chemistry-based system of production is shaped by the available transformations of mineral and petrochemical resources.

This view highlights a multi-level hierarchy in the way things are made—we might call it a design hierarchy, illustrated here with the example of a hypothetical PVC-containing building product.

The design hierarchy

We can use the design hierarchy to trace the decisions that have led to the presence of toxic chemicals in products, and to identify opportunities for substitution. This concept is adapted from the ‘nested relationship’ of chemicals, materials, and products that the Lowell Center for Sustainable Production articulated in their Alternatives Assessment Framework. That relationship expressed a hierarchy of inclusion: “products consist of materials and/or chemicals, materials consist of chemicals, and chemicals are constituents of materials or products.” The design hierarchy also expresses the relationships of different actors involved in designing technological artifacts and systems—and these relationships are interesting from the perspective of systems change.

As we follow toxic problems deeper into the design hierarchy, the main actors at each level—the designers, engineers, and manufacturers who make each discrete item what it is—become further and further removed from each other and their respective design goals and knowledge networks. For example, it’s difficult for architects who want to design ‘green’ buildings to influence what goes on in the domains of materials science and chemistry. They lack the resources and technical expertise necessary to delve into issues of the molecular composition of products, and they can’t easily modify products to make them less toxic.

Designers could try to select safer products, by asking what alternatives are available and how these compare in terms of environmental health impacts. But answering such questions is a challenge in itself. There are structural and organizational barriers to information flow in supply chains, especially across different levels of this hierarchy. For any given item, there may be a complex, globally-distributed network of suppliers; who is responsible for its chemical makeup? For that matter, what is its chemical makeup? Product makers don’t necessarily even know. Concerns about chemical risks upstream in the supply chain are simply not negotiable in markets where detailed knowledge of product chemistry is lacking.

One way to advance a safer material economy is to bring more technical resources to bear on the problem at deeper levels of design. This could be approached in a number of ways:

  • Specialized groups of design professionals could take on the challenge of developing innovative technologies that are inherently benign. At the chemical and material design levels, this corresponds to green chemistry and green engineering. Green product design is even more complex and nebulous.
  • Proponents of clean production can develop green design tools—decision support tools intended to inform and guide users in the technical aspects of eliminating toxic substances. Green design tools have been developed and used at all levels of the design hierarchy: to reduce the environmental health impacts of the synthesis and properties of molecules (e.g., the GreenScreen), to optimize the chemical composition of materials and the manufacture of parts and components (e.g. the Sustainable Apparel Coalition’s Higg Index), and to select safer and less environmentally costly products (e.g. Healthy Building Network’s Pharos Project). Different kinds of expertise, and different design tools, are brought to bear at each level. The idea is that well-informed decisions may, in aggregate, help shift production systems to more sustainable trajectories.
  • Stakeholders can advocate for greater access to knowledge of the chemical constituents of products and materials—in other words, transparency of chemical information—to support informed design choices. This idea has gained considerable traction in the green building space, through projects like the Health Product Declaration open standard. Meanwhile, broader initiatives like the BizNGO Guide to Safer Chemicals and the Chemical Footprint Project aim to help companies address systemic problems of supply-chain chemical management.

These are all valid approaches to the challenge of getting toxic substances out of products and production systems. But they all share some common assumptions: that the key problem to solve is a deficit in the technical abilities or knowledge resources of various kinds of design specialists (chemists, architects, etc.); and that these specialists, if well-equipped, could take on all the responsibility for fixing unsustainable technical systems. Taking a different view, we might see the causes and potential solutions to this ‘wicked’ problem as distributed throughout society, in addition to being submerged in technicalities. That will be the subject of another post…

This post originally appeared on the author’s personal blog and is reposted under a Creative Commons Attribution license.

Engineering, Environmental Chemistry, Materials, Policy

Chemical Footprinting: New tools for tracking green chemistry business practices

Chemical Footprinting: Identifying Hidden Liabilities in Manufacturing Consumer Products

In an unassuming low-rise in the Boston suburbs, Mark Rossi tinkers with a colorful dashboard on his laptop screen while his border collie putters around his feet. Rossi is the founder of BizNGO and Clean Production Action, two nonprofit collaborations of business and environmental groups to promote safer chemicals. He’s also the creator of tools that he hopes will solve a vexing problem—how to get a handle on companies’ overall toxic chemicals usage.

Consider the screen of Rossi’s laptop. Chances are the company that manufactured the product has crunched the numbers on the total amount of carbon, water, and land associated with getting it into the office—from the manufacturing of the electronic components to the packaging and transportation to retail outlets. But the total amount of toxic chemicals that contributed to the screen’s design and production might be a more difficult question to answer….

Read the entire story, by Lindsey Konkel, at

Engineering, Synthesis

Green Chemistry via Continuous Flow

“Development of a Continuous Flow Scale-Up Approach of Reflux Inhibitor AZD6906” Gustafsson, T.; Sörensen, H.; Pontén, F. Org. Proc. Res. Dev. 2012, ASAP. DOI: 10.1021/op200340c

“Continuous-Flow Synthesis of the Anti-Malaria Drug Artemisinin.” Lévesque, F.; Seeberger, P. H. Angew. Chem. Int. Ed.. 2012, 51, 1706-1709. DOI: 10.1002/anie.201107446

“Monitoring and Control of a Continuous Grignard Reaction for the Synthesis of an Active Pharmaceutical Ingredient Intermediate Using Inline NIR spectroscopy” Cervera-Padrell, A. E.; Nielsen, J. P.; Pedersen, M. J.; Christensen, K. M.; Mortensen, A. R.; Skovby, Dam-Johansen, T. K.; Kiil, S.; Gernaey, K. V. Org. Proc. Res. Dev. 2012, ASAP. DOI: 10.1021/op2002563

A little while back I wrote about an aerobic oxidation which was greatly improved by switching from a traditional round bottom flask setup to a continuous flow reactor – basically, continuous flow reactors are much better at handling oxygen, especially on scale.  But most of the advantages of the flow reactor were specific to that reaction, and it wasn’t clear to me how a flow process would improve a reaction that doesn’t use oxygen, or some other gas.  Fortunately, a lot has been published since then to help me get a handle on how continuous flow reactions can contribute towards greener processes.  In particular, this review covers continuous processing within a green chemistry context, and Organic Process Research and Developement has a continuous flow themed issue in their ASAP section, including this process-oriented review (speaking of OPRD, check out this recent editorial concerning solvent selection and green chemistry).  It turns out that flow chemistry can improve processes in a bunch of different ways, and it’s hard to get a sense for how this can work by just looking at one reaction.  So I’ll cover a few different reactions that illustrate different green aspects of continuous flow reactors.

One benefit of flow reactors is improved control over reaction temperature, due to reduced reaction volume at a given time, higher surface area, and the movement of the reaction mixture.  This is particularly helpful for very exothermic reactions, which often require cryogenic cooling to prevent runaway reactions – this type of cooling is very expensive and resource-intensive on a large scale.  One such reaction is described in a recent paper from AstraZeneca, in which a phosphinate anion adds into a glycine derivative.  The product of this reaction is an intermediate in the synthesis of a gastroesophageal reflux inhibitor drug candidate called AZD6906.

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Engineering, Synthesis

High-Yielding Semi-Synthesis of an Artemisinin Precursor

“Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin” Westfall, P.J.; Pitera, D.J.; Lenihan, J.R.; Eng, D.; Woolard, F.X.; Regentin, R.; Horning, T.; Tsuruta, H.; Melis, D.J.; Owens, A.; Fickes, S.; Diola, D.; Benjamin, K.R.; Keasling, J.D.; Leavell, M.D.; McPhee, D.J.; Renninger, N.S.; Newman, J.D.; Paddon, C.J. Proc. Natl. Acad. Sci. U.S.A. 2012109, E111-E118. DOI: 10.1073/pnas.1110740109.

Malaria, caused mainly by the parasite Plasmodium falciparum, leads to nearly a million deaths and 250 million new infections each year. The sesquiterpene lactone endoperoxide artemisinin, derived from Artemisia annua, is very effective as an antimalarial drug, and widespread resistance hasn’t yet developed. Artemisinin is the only high-volume drug that is still isolated by extraction from its native plant producer in a low-yielding (around 10 μg per g plant material), resource-intensive process that uses volatile solvents (most commonly hexane).

Artemisia annua. Photo credit: Jorge Ferreira via Wikimedia Commons.

As a result, supplies of the drug are short, and those who need it often can’t afford it. The development of new processes for artemisinin production would therefore advance both public health and green chemistry interests. Total synthesis of the drug hasn’t been considered as a viable alternative because of low yields, but a lot of effort has been directed toward developing semi-synthetic sources of artemisinin using a combination of microbial fermentation and chemical synthesis. Toward this end, the Keasling lab reported a few years ago that they had constructed a biosynthetic pathway for the artemisinin precursor amorpha-4,11-diene in yeast with yields of ~200 mg/L—already impressive given the complexity of the molecule. Amorphadiene synthase (ADS) comes from Artemisia annua; the rest of the genes are from yeast. Here is the existing pathway:

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Engineering, Synthesis

Chemical Feedstock Production by Fermentation

“Metabolic engineering of Escherichia coli for direct production of 1,4-butanediol” Yim, H.; Haselbeck, R.; Niu, W.; Pujol-Baxley, C.; Burgard, A.; Boldt, J.; Khandurina, J.; Trawick, J. D.; Osterhout, R. E.; Stephen, R.; Estadilla, J.; Teisan, S.; Schreyer, H.B.; Andrae, S.; Yang, T. H.; Lee, S. Y.; Burk, M. J.; Van Dien, S.  Nature Chem. Bio. 2011. 7, 445-452. DOI: 10.1038/nchembio.580

The production of chemicals from biologically-derived feedstocks is a major goal of green chemistry research, but despite a lot of work that’s been done, it’s going to be hard to make the switch from petroleum-derived chemicals to bio-based ones.  This is especially true for high-volume commodity chemicals – many of these chemicals have been produced from petroleum for a hundred years, the processes have been optimized to work efficiently on enormous scale, and they are really, really cheap.  So the bar is set pretty high, and most papers from academic labs on microbial or enzymatic chemical production are too low-yielding to ever be commercialized (although to be fair, the same could be said for most synthetic chemistry papers).  That’s why I was a drawn to this paper published by Genomatica, a company based in San Diego, on the production of 1,4-butanediol by an engineered strain of E. coli – first they got the bug to produce 1,4-butanediol, then they engineered it to produce lots of the stuff.  Currently one million tons of 1,4-butanediol (BDO) are produced each year, virtually all of it derived from petroleum-based feedstock chemicals.

Apparently 40% of this is used in the production of Spandex, and the rest of it is used to make other polymers and THF.  If Genomatica’s BDO production works according to their plan, all those tons of spandex could be bio-based!

The future of spandex?

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Engineering, Synthesis

The Problem with Oxygen

“Development of safe and scalable continuous-flow methods for palladium-catalyzed aerobic oxidation reactions” Ye, X.; Johnson, M. D.; Diao, T.; Yates, M. S.; Stahl, S. SGreen Chemistry, 2010, 12, 1180-1186.  DOI: 10.1039/c0gc00106f

We’ve had a pair of posts recently about using oxygen as an terminal oxidant in cross-coupling and biomass degradation, and as a green oxidant, it’s pretty hard to beat.  So I was a little surprised to learn that of the many cool aerobic synthetic methods that have been developed in the last decade, very few are used in industry.  The big drawback, especially on large scale, is safety – oxygen is usually the limiting reagent in the combustion reaction, and things can get pretty crazy when you have an oxygen-enriched atmosphere (and much crazier with liquid oxygen – check out this awesome video, and this one that Marty had in his last post).  So while stirring 100 mL of toluene under a balloon of pure oxygen might be fine, doing the same thing with 100 L is problematic.

This setup doesn't scale up very well

Safety aside, these reactions suffer because proper gas-liquid mixing is more difficult to achieve as you scale up.  All of this prompted a collaboration between Eli Lilly and Shannon Stahl‘s lab to develop a scalable continuous-flow method for aerobic alcohol oxidation, which avoids these problems. Continue reading