Designing green derivatives of b-blocker Metoprolol: A tiered approach for green and sustainable pharmacy and chemistry Tushar Rastogi, Christoph Leder, Klaus Kümmerer ⇑ Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, C13, DE-21335 Lüneburg, Germany highlights  Biodegradation test was performed for the mixture of photo transformation products (photo-TPs) of Metoprolol (MTL).  A few derivatives (photo-TPs) were comparatively more aerobically biodegradable.  Better biodegradability due to addition of hydroxyl group on ring or cleavage of redundant moieties of MTL.  Shortlisted derivatives might possess non-inferior pharmacological properties.  A novel direction for designing greener pharmaceuticals. graphical abstract article info Article history: Received 7 February 2014 Received in revised form 26 March 2014 Accepted 27 March 2014 Handling Editor: I. Cousins Keywords: Photolysis (Quantitative) Structure–activity relationships (QSAR) Molecular docking Beta adrenergic receptor Benign by design Metoprolol abstract The presences of micro-pollutants (active pharmaceutical ingredients, APIs) are increasingly seen as a challenge of the sustainable management of water resources worldwide due to ineffective effluent treat- ment and other measures for their input prevention. Therefore, novel approaches are needed like design- ing greener pharmaceuticals, i.e. better biodegradability in the environment. This study addresses a tiered approach of implementing green and sustainable chemistry principles for theoretically designing better biodegradable and pharmacologically improved pharmaceuticals. Photodegradation process cou- pled with LC–MS n analysis and in silico tools such as quantitative structure–activity relationships (QSAR) analysis and molecular docking proved to be a very significant approach for the preliminary stages of designing chemical structures that would fit into the ‘‘benign by design’’ concept in the direction of green and sustainable pharmacy. Metoprolol (MTL) was used as an example, which itself is not readily biode- gradable under conditions found in sewage treatment and the aquatic environment. The study provides the theoretical design of new derivatives of MTL which might have the same or improved pharmacolog- ical activity and are more degradable in the environment than MTL. However, the in silico toxicity predic- tion by QSAR of those photo-TPs indicated few of them might be possibly mutagenic and require further testing. This novel approach of theoretically designing ‘green’ pharmaceuticals can be considered as a step forward towards the green and sustainable pharmacy field. However, more knowledge and further experience have to be collected on the full scope, opportunities and limitations of this approach. Ó 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.chemosphere.2014.03.119 0045-6535/Ó 2014 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. Address: Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, C13, Scharnhorststraße 1, D-21335 Lüneburg, Germany. Tel.: +49 4131 677 2893. E-mail addresses: rastogi@leuphana.de, tushar1909@gmail.com (T. Rastogi), cleder@leuphana.de (C. Leder), Klaus.Kuemmerer@uni.leuphana.de (K. Kümmerer). Chemosphere 111 (2014) 493–499 Contents lists available at ScienceDirect Chemosphere journal homepage: www.elsevier.com/locate/chemosphere