Stimuli-Responsive Host-Guest Systems Decorated with Hemithioindigo and Spiropyran Units

Synthetic host-guest systems lead to the formation of supramolecular complexes between two or more chemical entities, held together by non-covalent, weak intermolecular forces, usually referred as molecular recognition interactions. Simple host-guest systems may be decorated with fragments that display a selective and controllable response to an external stimulus: light, pH, temperature, solvation, metal ions, redox potential and mechanical force. Photochromic compounds are nearly ideal candidates for this purpose: light is a privileged external input given its non-damaging and non-invasive nature, and its high spatial and temporal resolution. In particular, organic photoswitches offer a higher ease of preparation with respect to other photochromic systems and they have been employed in the functionalization of smart materials, nanostructures, biopolymers and photopharmacophores.

We focused our attention on fundamental research involving host-guest systems based on hemithioindigo (HTI) or spiropyran (SP) photoswitches. Several synthetic receptors (hosts) covalently functionalized with HTI or SP units and their use in molecular recognition studies of organic and biological molecules in solution are found in literature. Examples of photoswitchable guests equipped with HTI or SP units are also reported. The intermolecular interactions involved in the stabilization of the host-guest complexes can be modulated by the structural changes experienced by the photoswitches upon light-irradiation. In some cases, the light-induced structural change experienced by the photoswitch does not translate into significant changes in the stability constants of the complexes. Nevertheless, other examples do reveal that it is possible to couple the photoprocess to dramatic changes in the composition of the host-guest systems.

This doctoral thesis deals with the design and synthesis of stimuli-responsive host-guest systems in which the photoactive unit is covalently incorporated into either the receptor’s or the guest’s scaffold. We use two photoswitches with distinct properties, hemithioindigos and spiropyrans, and two types of macrocyclic scaffolds based on calix[4]arene and calix[4]pyrrole. We study how light-irradiation and acid-base treatments induce the isomerization of the molecular switch. We were especially interested in coupling the isomerization of the molecular switch with the binding affinity and the encapsulation properties of the synthesized molecular receptors and supramolecular capsules, respectively.

We describe the synthesis and photochemical characterization of two hemithioindigos featuring a terminal N-oxide moiety. We probe their Z/E reversible photoisomerization with visible light (λ = 450 nm) and we provide a detailed study of the 1:1 binding and its effect on the switching of the Z- and E-HTI isomers into the polar aromatic cavity of a super aryl-extended calix[4]pyrrole receptor in organic solvent.

Next, we designed and synthesized two tetraurea calix[4]arenes decorated with four hemithioindigo units at the upper rim. We describe the synthetic efforts to obtain these receptors and we investigate their dimerization in a variety of non-polar organic solvents and in the presence of tetramethyl phosphonium salts. We also report the tentative photoisomerization of the tetraureas in the monomeric state and involved in aggregates.

In a sequel, we synthesized a stimuli-responsive tetraurea calix[4]arene featuring four appended spiropyran groups at its upper rim, which self-assembles into a homocapsule in chloroform solution. We probe the dimerization in dichloromethane solution with tetramethyl phosphonium and ammonium cations acting as templating guests. Finally, the tetraspiropyran tetraurea self-assembles exclusively into a heterodimeric capsule in the presence of a calix[4]pyrrole counterpart and a suitable N-oxide template. The self-assembly, self-sorting, photo- and acidochromic studies of the capsular systems in chlorinated solvents are investigated. Our results suggest that the light-irradiation and acid-base treatments are reversible and augur well for the transport and release of molecular cargo.