Natural Products as Benign Substitutes for Synthetic Chemicals - the Example of Flavonoids

Chemicals improve health and living standards of humans while at the same time causing severe environmental pollution. Therefore, the aim of this thesis was to explore the potential of flavonoids, a class of natural products studied for a variety of applications, to substitute persistent and harmful synthetic chemicals in line with the Benign by Design concept. This overarching goal was pursued by performing research on three important aspects of a potential benign substitute. Firstly, as example of the functionality, the application of flavonoids as biopesticides was investigated with a systematic literature review. Secondly, the environmental effects and fate of several flavonoids were explored by investigating their ecotoxicity based on algae growth inhibition and their environmental biodegradability. The applied standard tests according to Organization for Economic Co-operation and Development (OECD) guideline 201 and 301 D were accompanied by further analytical methods including High Performance Liquid Chromatography coupled with an ultraviolet and visible light detector (HPLC-UV/vis) or coupled with High Resolution Mass Spectrometry (HPLC-HR-MS) to gain a better understanding of the processes taking place during these tests e.g. abiotic degradation and the formation of transformation products. The results of the systematic literature review revealed that many different pesticidal activities of flavonoids were investigated, but more cohesive knowledge, e.g. on the effectiveness of flavonoid-based biopesticides and their target spectrum is required. Regarding the environmental effects and fate of a chemical, the observed moderate algae growth inhibition of flavonoids and of the identified abiotic transformation products as well as the readily biodegradability of most tested flavonoids support their utilization as benign substitutes with low ecotoxicity and non-persistence in the environment. Additionally, this thesis highlights the importance to consider the limited abiotic stability of many flavonoids and identified it as one of the major challenges for the application of flavonoids in e.g. agriculture or pharmacy. However, this thesis showed that structural features known to enhance the abiotic stability (lacking hydroxy group at C3, C2-C3 single bond, and O-methylation) do not hinder environmental biodegradation. Therefore, these structural features can be used to select or design flavonoids with sufficient abiotic stability for application while being readily biodegradable. These obtained new insights show that selected flavonoids have the potential to substitute persistent and harmful chemicals. Among the tested flavonoids, hesperetin was identified as the most promising candidate. All in all, this thesis showed that a combination of algae growth inhibition and environmental biodegradability screening is a suitable approach to apply the Benign by Design concept to natural products. The chosen approach can be used to investigate the environmental effects and fate of other natural products, but small improvements of the experimental setup could be made. Generally, this thesis further promotes the idea to use natural products as substitutes for synthetic chemicals in order to tackle environmental pollution.