Based on their ability to form organised structures, macrocyclic systems are being designed for multiple applications, e.g., as photoswitches, molecular machines, catalysts and molecular and drug delivery and discovery systems. Our attention has especially been gained by the application of these systems as drug delivery devices to suppress undesirable side effects and release the desired guest molecule in response to external stimuli. Hence, we develop new macrocycles with the opportunity of backbone modification for complexation with larger guest molecules, which are able to respond to external stimuli, such as pH of the environment, temperature or light.

So far, we have synthesised and investigated oxacalixarene macrocycles with up to eight repeating units and added carboxylic acid functionalities for solubility in water.

Scheme of a flexible host molecule and initiated guest release.

In addition to these studies, we are interested in constructing multicomponent systems, which profit from the chemical and photophysical properties of its components.

How do we design the macrocycles of our interest?

The design of a flexible macrocycle can be achieved by the introduction of a responsive moiety in the cyclic frame. Further, the binding or release of the guest can be influenced by changing the physical or chemical environment of the complex. Those host molecules are able to change their geometry, triggered by photochemical or thermal isomerisation and can thereby easily change their shape, size and physical properties. The spectral properties and function of the macrocycles strongly depend on their substituents, enabling the access to tailored responses of the molecule. Host-guest binding studies of the isolated compounds, e.g., in the form of titration experiments, with a guest molecule provide information about the binding ability of the synthesised macrocycles for ion or drug molecule classes and therefore application possibilities. For the macrocycles to operate as drug vehicles, the testing of the host-guest complexes’ biocompadibility and finding the suitable conditions for the human body are needed.

Possible reaction set up for the synthesis of the macrocycles.

NMR samples to characterize the compounds.

Column chromatography can be used to separate and purify the reaction mixture.

Isolated column fractions contain the separated macrocycles.

Our research is generously supported by

TK134 Emerging orders in quantum and nanomaterials by the Archimedes Foundation (1.08.2015−31.08.2023)

PSG400 Functional cavitands for drug discovery and delivery by the Estonian Research Council (1.01.2020−31.12.2023)