Resorc[4]arene-functionalized MWCNTs for the development of new highly sensitive electrochemical immunosensors

One of the main problems in the development of immunosensors is to overcome the complexity of binding antibodies (Abs) onto the sensor surface, thus leading to a loss of sensitivity. 1 In the last twenty years, preorganized macrocycles, i.e. calixarenes, were employed for the site-directed immobilization of Abs to promote the correct end-on orientation. 2 Recently, due to their configuration and unique molecular recognition properties, resorcinol-based cyclooligomes, namely resorcarenes, 3 turned out to be a good option for the construction of highly sensitive immunosensors. 4 In this project, resorc[4]arene architectures decorated with eight methoxy groups at the upper rim and substituted at the lower rim with different functional groups (i.e., 3-bromopropyloxy and 3-azidopropiloxy substituents) were rationally designed and synthesized to tailor their recognition properties towards the Fc portion of Abs and to covalently install the artificial linkers on the multi-walled carbon nanotubes (MWCNTs) surface. Different chemical methods including nucleophilic substitution, click chemistry, or direct cycloaddition via nitrene were exploited. The MWCNTs modified with the resorc[4]arenes were morphologically and electronically characterized by field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), and X-ray photoemission spectroscopy (XPS) before the fabrication of modified electrodes. The latter were electrochemically characterized, and IgG Abs for the SARS-CoV-2 spike protein S1 (SPS1) were immobilized on their surface. The well-designed resorc[4]arene-functionalized MWCNTs-based immunosensors emerged as powerful systems for the development of more efficient immunosensing devices.