The Principles of Green Chemistry
Our latest blog series is designed to guide chemists towards a greener, more sustainable laboratory. Each blog explores one principle. If you missed previous ones, they can be found here.
Third Principle: Less Hazardous Chemical Syntheses
This principle states, “Wherever practicable, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment.”
The contributor of this section on the ACS Green Chemistry website, David J. C. Constable, Ph.D., Director, ACS Green Chemistry Institute®, notes that the sentence’s first clause, “whenever possible,” allows for a lot of latitude and interpretation.1 If we draw an analogy with the Hippocratic Oath, which states, “First, do no harm,” there is no optional clause of “whenever possible.” In this case, the harm is associated with performing more hazardous chemical syntheses than is practicable. Just as a doctor must complete the challenging and sometimes agonizing calculation of what harm is, so should a chemist on a much more (seemingly) abstract but possibly no less impactful level. Constable observes that “it’s not that adhering to this principle is particularly difficult to do; it’s more that chemists are disinterested in doing it.” He further states, “For the synthetic organic chemist, effecting a successful chemical transformation in a new way or with a new molecule or in a new order is what matters.”1 To push the analogy with the Hippocratic Oath further, the intent should be combined with the outcome.
However, the synthetic route’s design should also consider the process holistically. More “green” alternatives at one step may cause significant downstream processing to remove impurities that would not have been produced using a more hazardous synthetic route in the first place. As process development chemists, we need to be mindful of that issue and avoid “displacing” the problem to make it greener. At the very least, we should focus on developing recycling/reuse strategies to minimize waste (first principle), avoid depleting resources, and eliminate “trucks on the road.” Therefore, chemists must be conscious of their options in terms of synthetic routes as well as technologies available to achieve their goals. This might involve using non-toxic vectors or carriers for gene delivery in therapies. The complexity of small molecules has increased, and evaluating the impact of the synthesis and the final product on the environment and the end user is even more critical. Peptide chemists face significant challenges as their target molecule complexity has increased. The review article “Sustainability Challenges in Peptide Synthesis and Purification: From R&D to Production” presents some of these alternatives within a historical context.2 Still, as the authors note, two issues are currently hindering the green chemistry in peptide synthesis. First, as we said earlier, peptide complexity has increased significantly in the past decade, with many end products containing >30 amino acids. Secondly, the green formation of amide bonds, especially for long peptides, is still challenging to achieve.2,3 More relevant to solid-phase peptide synthesis, solvent usage remains the most significant waste byproduct.2
In “Evaluation of greener solvents for solid-phase peptide synthesis,” the authors state that it is important “to find a greener solvent alternative that could replace DMF in SPPS manufacturing processes.” The article points towards some achievable resolutions to the dilemma.5 They conclude, “…there’s no one-size-fits-all solution.” While acknowledging that statement, avoiding copious amounts of solvents will eventually be expanded to include other chemical reactions and synthesis.
More than ever, chemists and chemical engineers need to join forces to design and optimize processes using technological advances to provide efficient and nimble processes. This will be good for the planet and also for the bottom line.
References
- https://www.acs.org/content/acs/en/greenchemistry/principles/12-principles-of-green-chemistry.html
- https://pubs.acs.org/doi/10.1021/acs.joc.8b03001
- https://www.proteogenix.science/scientific-corner/peptide-synthesis/challenges-in-chemical-and-recombinant-peptide-production-processes/
- https://pubs.rsc.org/en/content/articlelanding/2017/gc/c7gc00247e#!divCitation
- https://doi.org/10.1080/17518253.2021.1877363
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