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New, Different....Better? Enabling Innovation through a Diversified Chemical Library

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Contributed by Ashley Baker, Research Assistant, ACS Green Chemistry Institute®

Some dedicated researchers literally look high and low for new compounds to be used in products like pharmaceuticals. The vast majority of chemical building blocks, however, rely on a common set of seven bulk organic chemicals.  These seven precursor chemicals – methanol, ethylene, propylene, butadiene, xylenes, benzene and toluene - are not only produced in some of the highest volumes worldwide, they’re also derived almost exclusively from petroleum.

Computational analysis has shown that the more times a chemical has been used in synthesis, the more it becomes a molecular “celebrity.”  A set of core molecules, which represents only 4% of all organic compounds, are involved in over 35% of known reactions, and give rise to more than 78% of the known organic chemical universe.  This results in a low level of chemical diversity, and doesn’t make apparent other options that may be less intrinsically hazardous.  And the data show a troubling trend to boot – as developing countries produce and use more chemicals, they’re relying on the same petroleum-derived starting materials.


Of course, it’s only natural that chemists use the building blocks they’re familiar with. They ensure thermodynamically and kinetically favorable reactions, result in the highest yields, react in predictable ways, are “easily” obtained (i.e. lowest cost), and generally don’t require sophisticated reactors or laboratory technology. Yet, a look at our standard set of chemical building blocks begs the question: are chemists inherently limiting their ability to innovate with their loyalty to the familiar?  Certainly there are molecules with unique biological properties for treating disease, for example, which have yet to be discovered.

As technologies emerge to produce chemicals biosynthetically, another question arises: should the focus be on creating these same chemicals – and wedding ourselves to their associated risks – or are there other kinds of chemicals available to us, but hidden, tucked away in common things like mangroves and dairy products, that are waiting to be put to a different use? Not only do these new molecules need to be discovered, but it’s imperative that chemists adopt synthetic biology as just another synthesis tool to broaden their ability to make useful and more sustainable chemical transformations.  In 2013, annual production capacity for renewably-sourced chemicals was approximately 113 MMT, including nearly 89 MMT of ethanol capacity. That’s less than a third of the global production of the seven bulk organic chemicals mentioned earlier.

What will it take for renewable and sustainably-derived chemical building blocks to replace the large volumes of petroleum-derived chemicals currently used? There are a wide range of initiatives and research projects that are building a revised chemical library consisting of biobased and renewable alternatives.  Simple bio-based chemical building blocks like ethylene derived from ethanol hold promise for replacing their naphtha-derived counterparts. In addition to avoiding the use of fossil fuels, a larger chemical library means more options as we explore and design alternative chemicals and chemical processes that are safer for humans and the environment.  As biosynthetic chemistry advances, it will enable the development and utilization of an enzyme’s high selectivity to functionalize molecules in ways that are not practical through conventional organic synthetic chemistry routes.

Combining biological approaches with traditional synthetic organic chemistry will give us access to molecules with new functionality in fewer, more efficient steps. Broad approaches to finding different chemicals are helping to define new classes of compounds that may offer interesting alternatives to standard synthetic route strategies.  An Australian biodiscovery company, for example, is working to discover new chemical structures and families from a vast array of microbial outputs.  The potential for discovering new functionalities from microbes that can be added to existing chemical structures is, for all practical purposes, endless. Another implication of research into the use of synthetic biology is the possibility of producing unique, highly tailored products and materials.

On the other hand, there are a large number of projects aimed at tackling one chemical challenge at a time, as for example replacing synthetic styrene-butadiene latex with a biodegradable lignin-based adhesive.  Materials such as plant proteins are also being explored for a variety of different end use applications.  The results of studies like these is that in many cases the new materials have improved properties over their petroleum-based counterparts, like plastic films with better strength and elasticity.  While these examples are many and compelling, it is unfortunate that the path to commercialization continues to be challenging.

Still, expanding our chemical library is an incredible opportunity for entrepreneurs. Bio-based, renewable and potentially more sustainable chemicals from small start-ups are working to develop markets to increase the demand for novel and more sustainable chemical alternatives. The ACS GCI recently started the ACS GCI Biochemical Technology Leadership Roundtable, uniquely devoted to catalyzing and enabling the bio-based and renewable chemicals economy by promoting the underlying science required for the development and implementation of bio-based and renewable chemical technologies.  However, with petroleum at such a low cost, these start-ups are struggling and many technical challenges remain.

From pine trees to yeast, there are huge possibilities for a  more sustainable chemistry enterprise in the future.  It seems that every day there’s another breakthrough in a biosynthetic method, or another start-up has begun making chemicals from waste, or from some other bio-based source.  Although the widespread adoption may be slow-going, more researchers and businesses continue to pursue success in creating safer, financially beneficial, and more robust products through an increasingly diverse and more sustainable chemical library.

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