Supramolecular Capsule Based on Complementary Adenine-Thymine Base Pairing

Abstract

The harmonious effect of multiple hydrogen bonds plays an essential role in the molecular recognition of many biological systems including well-known cases such as the assembly of duplex DNA and the second structure of proteins. In a similar way, multiple hydrogen bonds have been used in the construction of molecular receptors, onedimensional linear aggregates, two-dimensional planar aggregates, and three-dimensional assemblies. Recently, three-dimensional, self-assembled structures have been designed and synthesized based on self-complementary hydrogen bonds. Only a few artificial systems, however, have utilized DNA-like, complementary, purinepyrimidine base pairing for the construction of selfassembled superstructures. This is because the interaction of adenine (Ade)-thymine (Thy) [or Ade-uridine (Uri)] is too weak (Ka ≈ 10 M−1 in CDCl3), and because cytosine (Cyt) and guanine (Gua) are notoriously hard to handle due to their poor solubility in organic solvents, despite the strong interaction of Cyt-Gua (Ka ≈ 10 M−1 in CDCl3). In spite of these limitations, several groups have tried to achieve the desired molecular assemblies by using Ade-Thy [or AdeUri] or Cyt-Gua base pairing interactions. In this report, we describe the self-assembly of a threedimensional superstructure by using the complementary base-pairing motif. We introduced four Ade and four Thy units into a resorcin[4]arene cavitand, and constructed a selfassembled molecular capsule via multiple hydrogen bonds between the four Ade-Thy pairs in a nonpolar organic solvent (Figure 1). Construction of three-dimensional molecular assemblies requires that the complementary binding partners meet each other with an appropriate curvature of the hydrogen-bond directionality. In order for the two binding partners to associate with each other by hydrogen bonds, we chose a rather long linker, namely the mercaptopropyl group (vide infra). 9-(3-Mercaptopropyl)Ade 1b and 1-(3-Mercaptopropyl)Thy 2b were synthesized from their thiouronium salts (Scheme 1). Treatment of Ade with 1-bromo-3-chloropropane in the presence of NaH gave 9-(3-chloropropyl)Ade 1a. Refluxing EtOH solution of 1a and thiourea and sequential treatment with sodium hydroxide afforded 1b. 1(3-Bromopropyl)Thy 2a was also prepared as shown in Scheme 1. First, Thy was silylated by using hexamethyldisilazane (HMDS) and a catalytic amount of chlorotrimethylsilane (TMSCl). Then, a reaction of the silylated Thy with 1,3-dibromopropane gave 2a. The last step for the synthesis of 2b was the same as that of 1b. Resorcin[4]arene tetramethylbromide 3 was synthesized using Cram’s method. The coupling of 3 and 1b (or 2b) was achieved by a typical SN2 reaction (Scheme 2). The formation of the self-assembled supramolecular heterodimer between 4a and 4b was investigated by H