Benign by Design

A wide range of chemicals end up in our water systems, threatening both the environment and our drinking water. And pharmaceuticals are certainly on the hit list. Strategies to prevent APIs entering our water supplies can be expensive but they are not always effective. To that end, Klaus Kümmerer and his team at Leuphana University in Germany are attempting to give medicines a green makeover by redesigning existing pharmaceuticals to be biodegradable (1). Here, Kümmerer tells us more about his ‘benign-by-design’ strategy.

How big is the problem?

Environmentally non-degradable pharmaceuticals can stay in the environment for a long time. In all countries where measurements have been performed, pharmaceuticals have been detected and it has been shown that at least some of them have effects on wildlife at low concentrations. It’s difficult to address the problem because there are so many compounds and environmental processes that often transform the parent compounds into other unknown products, preventing reliable risk assessment. I decided to shift to a more preventative approach – biodegradable drugs.

How do you redesign drugs to be biodegradable?

We use a combination of experimental and computational methods to make small molecular changes to the drug’s structure to allow it to be broken down more easily and safely in the environment, crucially while still retaining the therapeutic activity of the parent. Our study focused on the transformation and degradation of ß-blocker class APIs. ß-blocker Propranolol is a frequently used, nonbiodegradable, and highly persistent pharmaceutical. We used non-targeted synthesis using light – photolysis – to generate safer, more innocuous derivatives for the environment. In fact, we identified the products of photolysis and tested them for biodegradability in the environment. We assessed the drug-like properties of the selected biodegradable drugs and ruled out the mutagenic ones.

What were the main challenges?

The majority of pharmaceuticals have been very well researched; any change to the molecule that disrupts the delicate balance of stability and potency could lead you down a dead end. Trying to redesign a molecule is considered somewhat crazy! At least, that’s the feedback we get from experts in pharmaceutical industries. But it is possible; chemistry is about reactivity under certain conditions – and you can experiment with the options.

Are any biodegradable drugs already on the market?

Yes – but many of those few do not have a targeted design. And I think that most pharma companies aren’t focusing on biodegradable drugs. Nevertheless, those that do exist demonstrate the feasibility of our approach. The new molecules are completely mineralized to innocuous inorganic compounds (e.g., water, carbon dioxide and salts), avoiding the formation of transformation products. There is no need to monitor the byproducts, carry out expensive toxicity studies for them or to follow up with further water treatment – this is at the core of our approach.

Can any drug be made to be biodegradable?

There are many methods that can modify the structures of pharmaceuticals to make them biodegradable so, in principle, there is no limit to how many drugs our approach could be applied to – particularly as we’ve demonstrated that it works for complex molecules. We are currently looking at redesigning antibiotics and even applying our strategy to improve the mineralization of chemicals such as laundry detergents.