Functional G‐Quartet Macroscopic Membrane Films

Abstract

G-quartets, formed by the hydrogen-bonding self-assembly of four guanosine (G) residues and stabilized by alkali-metal cations, play an important role in biology, in particular in nucleic acid telomers of potential interest to cancer therapy. The G-quartet architecture represents a nice example of a dynamic supramolecular system that has been used as a building block for gelators, columnar polymeric aggregates, self-organized surfaces, and prototypes of chemical dynamic devices. 5] . In the last few decades, G-quartets and the similar folic acid quartet have also been proposed as powerful scaffolds for building synthetic ion channels. Although stable in organic solvents, they do not seem to have defined transport functions in hydrophobic membranes. Barrel-stave, lipophilic, calix[4]arene, and 8-aromatic–guanosine conjugates have been used to stabilize the formation of G-quartets. Recently, a new strategy based on reversible metathesis was successfully used by Davis et al. to generate a rich array of interconverting ionchannel conductance states of a unimolecular G-quartet in a phospholipid membrane. Despite such impressive progress, considerable challenges still lie ahead and the more significant one is to improve the stability of G-quartet dynamic aggregates in polymeric devices, such as films or membranes, to extend (address) the transport studies to the macroscopic level. Several earlier studies reported the preparation of discrete supramolecular assemblies of nucleobases embedded in synthetic polymers and hybrid materials. However, the “dynamic communication” between the supramolecular self-assembly of nucleobases and the polymerization processes, which kinetically and stereochemically might communicate, is not so trivial. For all these reasons, in this study building blocks of guanosine (1; Scheme 1), 2-formylphenylboronic acid (2), and bis(3-aminopropyl)polytetrahydrofuran (PTHF, 3 ; numberaverage molecular weight Mn ca. 1100 gmol ) are used as molecular precursors to conceive G-quartet polymeric membrane materials at the macroscopic scale. Our efforts involve the successive synthesis of the ditopic bisiminoboronic 4 and bisiminoboronate-guanosine 5macromonomers, and then the self-assembly of 5 into G-quartet-type supramolecular superstructures (Scheme 1). The main strategy consists of generating (amplifying) dynamic supramolecular G-quartets by K ion templating, from a dynamic pool of oligomeric ribbon-type or cyclic supramolecular architectures. Then, the G-quadruplex architectures are fixed in self-supporting polymeric membrane films. A standard sample without potassium chloride, which resulted in the formation of an H-bond ribbon-type superstructure of the guanine moieties, was prepared as reference under the same conditions as described above (Figure 1). Scheme 1. Synthesis of bisiminoboronic 4 and bisiminoboronate-guanosine 5 macromonomers, and the self-assembly of 5 into G-quartettype superstructures.