Upper rim functionalized calixarenes: from dissipative control to biological applications

Abstract

The present thesis deals with the synthesis of upper rim functionalised calixarenes and the study of their properties under dissipative conditions or in biological media for the recognition of protein and bacteria cell wall constituents. These two apparently distant topics, artificial machines under dissipative control and biomolecular recognition might merge, in a close future, in artificial systems whose recognition properties toward biomolecules is triggered by a chemical fuel. The first chapter of this thesis studies artificial molecular machines whose functions depend on the conformational changes experienced by the macrocycles under dissipative conditions. Among the chemical stimuli used for the modulation of the conformational motion we used 2-cyano-2-phenylpropanoic acid or thrichloroacetic acid as chemical fuels. They allow to change the status of the system for a certain time and when all the fuel is consumed, the system turns back to its original state. The presence of two pyrene nuclei in distal positions at the upper rim of the calixarenes, allows to combine the fuel triggered conformational motion with the switch off/on of the fluorophore. The possibility of modulating the conformation of this calix[4]arene-based molecular machine using trichloroacetic acid as chemical fuel has been studied and the proposed “conformational cycle” will be discussed. In the second chapter it was demonstrated that the host−guest interaction of a trisaminocalix[6]arene receptor with N-methylisoquinolinium trifluoromethanesulfonate can be dissipatively driven by means of 2-cyano-2-(4′-chlorophenyl)propanoicacid used as the most convenient chemical fuel. When the fuel is added to a dichloromethane solution containing the inclusion complex, the host is induced to immediately release the guest in the bulk solution. Consumption of the fuel allows the guest to be re-uptaken by the host. In the third chapter it is reported the progress done in the development of a new approach for the selective identification of different bacterial strains using supramolecular receptors based on calix[4]arenes decorated with zwitterionic amino acids at the upper rim. Amino acids are attached to the upper rim of calixarenes, preserving their zwitterionic structure, using the Mannich reaction. The screening of the recognition properties of these calixarenes towards different bacteria strains was achieved using on-cell STD NMR experiments. The zwitterionic calixarene receptors are able to selectively bind Gram-negative bacteria. It was also evidenced that the selective recognition possibly takes place via recognition of LPS present on the Gram- III negative bacteria cell wall. The rapid and on-site identification of bacteria strains and viruses, using cheap, abiotic and portable devices, is of great appeal and interest also because it will allow a timely selection of the most appropriate antibiotic class to treat the patient, thus avoiding the administration of useless or broad-spectrum antibiotics which are responsible for the continuous and fast growth of antimicrobial resistance (AMR). The last part of this thesis deals with the screening of zwitterionic calix[4]arenes and the p-methylsulfonatocalix[4]arene as molecular glues for proteins. This work has been carried out in a six-month study period at the University of Galway (IE). Surface recognition is shown to drive protein assembly in the solid state only in the case of the p-methylsulfonatocalix[4]arene. The preliminary results of the crystal structure obtained by SOLEIL synchrotron in Paris between this ligand and RSL-KMe2 is discussed.