Calix[4]pyrrole-based supramolecular assemblies

Abstract

Supramolecular assemblies are known as large-scale and organized structures formed as a result of the self-assembly of smaller molecules through non-covalent interactions such as hydrogen bonding, van der Waals interaction, metal-ion coordination, and cation-π interactions. Within this framework, poly-pseudorotaxanes and micelles are considered as noteworthy examples of supramolecular assemblies that have shown various applications in materials science and drug delivery. The study of such assemblies and attempts to manipulate them to design novel structures can contribute to advancements in these fields. To date, in the field of supramolecular chemistry, numerous macrocyclic structures such as crown ethers, cucurbiturils, calixarenes, and cyclodextrins have been used in the formation of supramolecular amphiphiles and mechanically interlocked molecules. Among these well-known macrocyclic structures, calix[4]pyrrole is known for its remarkable features, including its capability to acquire cone conformation upon binding to an anion, which facilitates ion-pair recognition and anion sensing through hydrogen bonding with anions. Calix[4]pyrrole is a molecule known for its ability to bind various ions in different ways due to its unique conformational features suitable for host-guest interactions. As a result, various types of calix[4]pyrrole systems have been developed to sense or extract ions and can exhibit different binding modes, enabling their use in synthesizing molecular machines. The main goal of this thesis is to demonstrate the applications of calix[4]pyrroles and how they can be used in various areas such as in drug loading and release, in addition to the formation of poly-pseudorotaxane structures, owing to its anion and ion-pair recognition capabilities, respectively. Therefore, in this thesis, we present the innovative synthesis of a non-ionic surfactant built upon the calix[4]pyrrole framework, where a polyethylene glycol (PEG) moiety is introduced at one of its meso positions (C4P-PEG). This surfactant demonstrates the ability to form stable micelles in water. Additionally, it exhibits the capacity to encapsulate a chemotherapeutic cancer drug, doxorubicin hydrochloride (DOX·HCl), by recognizing its counter chloride anion in an aqueous environment. Following the characterization of the synthesized compound using NMR spectroscopy and mass spectrometry, its micelle formation ability in water is confirmed through TEM imaging, DLS and NMR spectroscopy. Furthermore, to assess drug-loading and release capabilities, we employed the nanoprecipitation method and utilized techniques such as TEM and DLS for characterization. Lastly, UV-vis spectroscopy is conducted to determine the compound's drug loading capacity, and its release behavior is examined under different pH conditions, revealing a preference for release under acidic conditions. In addition to the pioneering study of drug delivery applications using the anion recognition property of calix[4]pyrrole, we synthesized the bromide salt of pyridinium-functionalized calix[4]pyrrole (1-Br), which can self-assemble into a supramolecular polymer through ion-pair recognition, serving as the axle of a poly-pseudorotaxane, and perethylated pillar[5]arene (EtP5A) was successfully threaded as the wheels. Moreover, in our anion-controllable molecular motions study, we examined the changes in the properties of the proposed poly-pseudorotaxane by substituting bromide ions in 1-Br with fluoride (1-F), chloride (1-Cl), and hexafluorophosphate (1-PF6) ions using different characterization methods.