Our latest blog series is designed to guide chemists towards a greener, more sustainable laboratory. Each of our blogs will explore one principle. If you missed previous ones, they can be found here.
Tenth Principle: Design for Degradation
Designing Chemicals for a Safe End-of-Life
The tenth principle of green chemistry emphasizes designing chemical products so that, at the end of their functional life, they break down into degradants that do not persist and do not cause harm to the environment. As we approach the final three principles, it becomes clear that many of the first nine focus on prevention and optimal solvent use. Principle 10, in particular, combines both themes.
On the ACS Green Chemistry site, Rich Williams, Founder and President of Environmental Science & Green Chemistry Consulting, LLC, makes a critical distinction:
“Green chemistry practitioners aspire to optimize the commercial function of a chemical while minimizing its hazard and risk.”
Hazard—the inherent ability to cause harm—comes from a chemical’s stereochemistry, just as its function does. While Principles 3, 4, 5, and 12 focus on reducing hazards, Principle 10 is about designing products that degrade after fulfilling their commercial purpose, thereby reducing risk—the probability of harm occurring.¹ ² In cell and gene therapies, this could mean engineering vectors that degrade after delivering their genetic payload. Detection of antidepressants, antibiotics, and other pharmaceutical compounds in rivers has been reported in the recent past.3 While this observation brings human health concerns, the presence of pharmaceuticals in rivers can cause endocrine disruption, decrease fertility, and increase antibiotic resistance in aquatic ecosystems. Therefore, it is the drug designer’s responsibility to design and plan for the degradation of the active ingredient after use.
Planning Is Key
As with the First Principle – Prevention – effective application of Principle 10 begins with early planning. Williams notes that degradation rate must be balanced with business needs, and these considerations are best addressed during the design phase to maintain process flexibility.
He emphasizes that biodegradation, hydrolysis, and photolysis can all be incorporated into product design. Achieving this requires insights from mechanistic toxicology to identify and remove molecular features that cause hazards, and an understanding of degradation mechanisms to introduce features that promote breakdown while avoiding persistence.
Bottom line, this principle tells us that we cannot design a new treatment without evaluating the life cycle of the drug. It is the drug innovator’s responsibility to look beyond just the treatment of an ailment and to assess the long-term impact of the new active molecule in the environment.
References
- 12 Principles of Green Chemistry – ACS
- 12 Design Principles of Green Engineering – ACS
- O.Z. Wada and D.B. Olawade, Recent Occurrence of Pharmaceuticals in Freshwater, Emerging Treatment Technologies, and Future Considerations: A Review, Chemosphere, 374, 144153 (2024). doi.org/10.1016/j.chemosphere.2025.144153
Resources