Molecular recognition in aqueous media within modularly constructed molecular tweezers

Supramolecular chemistry is a field that has been growing rapidly for over half a century and supramolecular hosts have found wide-spread application both in fundamental research and "real-life" problems. Especially at the junction of supramolecular chemistry and biological chemistry, the development of the past two decades showcases the vast potential of tailor-made synthetic hosts. One particularly interesting class of supramolecular hosts is called molecular tweezers which can be differentiated from the majority of hosts in that they are structurally not macrocyclic but can be described as two recognition sites connected but kept apart from each other via a spacer unit. Several water-soluble tweezers have been shown to strongly interact with important biogenic targets in vitro and in vivo but a framework that can be used for facile and diverse derivatization to assess the SAR in detail has not been presented so far.
In this thesis, a general synthetic platform towards phosphorylated tweezers of the structure 81 has been developed that allows for rapid derivatization at multiple different positions of the carbon skeleton and construction of non-symmetric tweezers. Based on this synthetic platform, five derivatives have been synthesized. The investigation of the first-generation tweezer 90 led to the conclusion that hosts with the general structure 81 are a promising entry into molecular recognition of organic diamine guests in aqueous media with unique binding properties. A second generation of tweezers was synthesized with varying substitution patterns. These tweezers 127–130 provided insight into the effect of variation of the position of the phosphate groups and the derivatization of the tips of the tweezers on the recognition patterns.
Overall, in the substitution patterns of these first two generations, either a readily accessible entrance into the cavity of the tweezer for sterically hindered guests or strong binding via ionic interactions of the guest with the phosphate groups of the host has been achieved. However, very strong binding to sterically demanding guests will necessitate further research. The understanding of the binding properties of these five tweezers may be seen as a guide towards future generations of molecular tweezers that are based on the structure 81 and can be tailor- made for guests based on their steric hindrance and chemical surroundings.