Structure-Activity Relationships of Dirhodium(II,II) Paddlewheel Complexes with Tethered Thioether Ligands

Dirhodium(II,II) paddlewheel complexes are unique scaffolds used in many applications. Predominately they have been explored in transformations such as cycloadditions, insertion reactions, and ylide formations. They have also been shown to have chromogenic responses when encountered with different species, making them valuable tools for sensing methods. They are also known for their anticancer activities, making them potential alternatives to currently used chemotherapeutics. Generally, complex design has focused on bridging ligands but has recently introduced the addition of tethered ligands. The results highlight the positive influence of modulating said features to achieve various interactions with exogenous ligands in a catalytic and biological context. Due to both rhodium active sites being available, non-tethered dirhodium(II,II) paddlewheel complexes can be more reactive and less selective when binding to exogenous ligands. Further, dirhodium(II,II) paddlewheel complexes have been studied immensely, but their tethered variants are still underrepresented. This work aims to understand better the influence of tethered complexes and how we can use them to control their interactions with exogenous ligands in catalysis and the biological environment. To do this, we have designed an array of complexes that differ at the tether to include variations in electronic and steric properties. To understand structural differences, titration experiments were conducted with pyridine as the binding substrate and followed via UV-vis spectroscopy. Association constants were determined using GraphPad Prism 9 software. A second set of experiments observed the association of biologically relevant species histidine and cysteine to dirhodium(II,II) paddlewheel complexes utilizing UV-vis spectroscopy. The results indicated tethered complexes have an increased affinity for thiol-based amino acid cysteine. Lastly, the chromogenic detection of tethered complexes was tested against nerve agent simulant DCP. The results suggest that tethered complexes can be used as a tool to increase selectivity and sensitivity to exogenous substrates.