Spontaneous Formation of Hexameric Resorcinarene Capsule in Chloroform Solution as Detected by Diffusion NMR Liat Avram and Yoram Cohen* School of Chemistry, The Sackler Faculty of Exact Sciences, Tel AViV UniVersity, Ramat AViV 69978, Tel AViV, Israel Received June 12, 2002 In recent years, molecular capsules of different kinds were prepared. 1 Among those capsules, molecular capsules held together by hydrogen bonds attracted much attention. 2,3 Substituted calix- arenes, 2-4 and more recently resorcinarenes, 5 were shown to form such molecular capsules. The recent interest in resorcinarene capsule stems from the pioneering work of MacGillivray and Atwood who demonstrated that resorcinarene (1a, Chart 1) forms a large cap- sule consisting of six 1a units and eight water molecules (i.e., [(1a) 6 (H 2 O) 8 ]) in the solid state and suggested its possible role for molecular recognition in solution. 6 Very recently Shivanyuk and Rebek demonstrated that under certain experimental conditions, that is, water-saturated CDCl 3 as solvent and a suitable guest such as tetrahexylammonium bromide (THABr, 2a) or Bu 4 SbBr, 1b (Chart 1) forms a stable hexameric molecular capsule in solution. 5a,b The pulse gradient spin-echo (PGSE) technique is a powerful NMR method for measuring molecular diffusion. 7 In recent years NMR diffusion measurements were used to probe complexation of different complexes, 8a,b to study ion-pairing aggregation 8c and the structure of organometallic compounds, 8d and to probe rotax- ane formation. 8e Recently, we were able to show that NMR dif- fusion is a powerful tool for probing encapsulation. 9a,b We there- fore thought to use this technique to probe the structure of 1b in CDCl 3 solutions. Here, we report that NMR diffusion measure- ments show unequivocally that, surprisingly, 1b, assembles into a hexameric capsule in chloroform spontaneously without the aid of any guest by encapsulating several chloroform molecules, which seems to occupy different chemical environments on the NMR time scale. Compound 1b was prepared according to the literature 10 and afforded the expected spectrum as shown in Figure 1A. Indeed, addition of 2a to the water-saturated CDCl 3 solution of 1b gave the spectrum shown in Figure 1B which is identical to that reported previously for the hexameric capsule of 1b. 5a Interestingly, when we measured the diffusion coefficients for the two species shown in Figure 1, A and B, we found the same diffusion coefficient 11 (0.28 ( 0.02 × 10 -5 cm 2 s -1 ) for both molecular species which is inconsistent with the assignment of these spectra to the monomer and the hexameric capsule of 1b, respec- tively. This assignment is not probable since it is reasonable to assume that the very large difference in the molecular weight of the monomeric and the hexameric forms of 1b (molecular weights of 1104 g/mol vs 6624 g/mol) should be reflected in their diffusion coefficients. However, the diffusion coefficients of the peaks of 1b, in water-saturated CDCl 3 and in commercial CDCl 3 before and after addition of 2a, were found to be the same within experimental errors (Table 1). Taking into account the previous assignment of Shivanyuk and Rebek 5a and the low diffusion coefficients measured in the CDCl 3 solution, we began to suspect that the spectrum of 1b shown in Figure 1A in CDCl 3 represents mostly a hexameric capsule. It should be noted that the diffusion coefficient of 1b is significantly lower than that of the dimeric capsule of the teraureacalix[4]arene derivative (3) having a molecular weight of 3152 g/mol, which was found to be 0.40 ( 0.01 × 10 -5 cm 2 s -1 (CDCl 3 , 5 mM, 298 K). 9c To further challenge this result the following experiments were performed: First 1b was dissolved in CHCl 3 , and indeed the same spectrum was obtained with additional singlets (298 K, 400 MHz), which were found in the range of 4.8-5.1 ppm. 12 These peaks, which are 2.1-2.4 ppm upfield compared with the “free” CHCl 3 , were attributed to the encapsulated chloroform molecules (see * To whom correspondence should be addressed. E-mail: ycohen@ ccsg.tau.ac.il. Figure 1. 1 H NMR spectra (400 MHz, 298 °K) in a water-saturated solution of (A) 1b in CDCl3, (B) 1b and 2a in CDCl3, (C) 1b in CHCl3, (D) same as (C) after addition of 2a. The inset shows the peaks attributed to the encapsulated chloroform molecules observed when 1b is dissolved in CHCl3. Chart 1 Published on Web 11/26/2002 15148 9 J. AM. CHEM. SOC. 2002, 124, 15148-15149 10.1021/ja0272686 CCC: $22.00 © 2002 American Chemical Society