The mainly agricultural input of NO3- and compliance with drinking water guideline values pose major challenges for many water suppliers. Additionally, associated changes in hydrochemistry, especially concerning products of NO3- reduction (Fe2+/3+, Mn2+/4+, Ca2+, Mg2+, SO42-, HCO3-) and subsequent reactions, can have a major influence on mineral saturation states and well yield: well productivity can be strongly reduced by mineral precipitation and silting. To evaluate hydrogeochemical evolution and clogging potential for a given well field, thorough hydrochemical and geochemical investigations are required. Therefore, time-dependent and depth-specific ion concentrations in water samples (n = 818) were analysed in a catchment area of a waterworks in western Germany. The sediments of the aquifers were extensively investigated for their geochemistry (CS, scanning electron microscope, aqua regia digestion and dithionite solution; n = 253). In addition, PhreeqC was used to model saturation indices in order to identify possible mineral precipitation in the wells. Results show a high NO3- input into deep wells screened in Tertiary sediments due to an admixture of Quaternary groundwater. Directly at the Quaternary-Tertiary boundary, chemolithotrophic NO3- reduction consuming pyrite occurs. Protons released during the process are pH-buffered by dissolving carbonate minerals. Overall, the hydrochemistry and especially the saturation indices are strongly influenced by NO3- reduction and its degradation products. A change in well yield has not yet been observed, but future clogging by ochre formation or sintering cannot be excluded.

The aim of this study was to identify small molecule compounds that inhibit the kinase activity of the IGF1 receptor and represent novel chemical scaffolds, which can be potentially exploited to develop drug candidates that are superior to the existing experimental anti-IGF1R therapeuticals. To this end, targeted compound libraries were produced by virtual screening using molecular modeling and docking strategies, as well as the ligand-based pharmacophore model. High-throughput screening of the resulting compound sets in a biochemical kinase inhibition assay allowed us to identify several novel chemotypes that represent attractive starting points for the development of advanced IGF1R inhibitory compounds.