Probing cucurbit[8]uril-mediated supramolecular block copolymer assembly in water using diffusion NMR† Jameel M. Zayed, Frank Biedermann, Urs Rauwald and Oren A. Scherman * Received 30th June 2010, Accepted 18th August 2010 DOI: 10.1039/c0py00197j Diffusion NMR and solution viscometry were used to probe the cucurbit[8]uril-mediated host–guest self assembly of multiple molecular guests to form 5-component supramolecular ABA tri- block copolymers in aqueous solution. Cucurbit[8]uril (CB[8]) is one of the larger homologues of the macrocyclic, barrel-shaped cucurbituril family of molecular hosts. 1,2 Its hydrophobic cavity is large enough to accommodate two molec- ular guests, forming ternary complexes in water. 3 These ternary complexes usually consist of an electron-deficient viologen (paraquat) first guest and an electron-rich aromatic second guest such as naph- thol, 4 associating with the CB[8]-host sequentially in a stepwise manner. 3 The complexes are stable in water (K a ¼ 10 8–12 M 2 ) 4,5 as well as stimuli-responsive. 6 Recently, CB[8]’s complex formation with polymeric guests to form supramolecular copolymers has been demonstrated both in solution 7 and in the gas phase. 8 Supramolec- ular polymers 7,9–13 exhibit intelligent self-assembly akin to that seen with biological building blocks, 14 and have attracted much interest, demonstrating a range of stimuli-responsive properties both in solu- tion 15 and in the bulk. 16,17 Supramolecular polymers therefore combine the material features of macromolecules, such as the ability to form gels, 18 and higher-ordered, compartmentalised structures, 19,20 with the tunability offered by assembling individual small-molecule building blocks. Previously, our group has demonstrated the CB[8]-mediated assembly of supramolecular AB diblock copolymers from viologen- and naphthol-terminated polymers based on the hydrophilic poly- (ethylene glycol) (PEG), and hydrophobic poly(isoprene). 7 In the presence of CB[8], a naphthol guest-terminated PEG, A block, and a low molecular weight ditopic viologen guest, B block (MVdimer), were found to form discrete supramolecular ABA triblock copolymer complexes. 8 The discrete, multi-component assemblies remained stable even in the gas phase as probed by nano-electrospray mass spectrometry (nano-ESI-MS). 8 In tandem with ongoing studies on the self-assembly of CB[8]-complementary polymers in water, we sought to apply the versatility of diffusion-ordered (DOSY) NMR 21 towards probing the CB[8]-mediated ABA triblock copolymer formation in solution. This non-invasive, and in situ technique maps the assembly process as a 2-dimensional NMR spectrum, correlating chemical shift against diffusion coefficient (D). 22,23 Fig. 1 shows the components used in this study; a triethylene glycol (TEG)-spaced viologen dimer MVdimer, and two polymers, a naph- thol-terminated PEG (P1,M n ¼ 1100–8000 g mol 1 ) and a dibenzo- furan-terminated poly(N-isopropylacrylamide) (PNIPAAM) (P2, M n ¼ 19,000 g mol 1 ). The dibenzofuran polymer end-group is used here simply as a suitable alternative second guest to naphthol. 4 A pulsed field-gradient stimulated-echo (PFGSE) sequence with 3- 9-19 water suppression (stebpgp1s19) 24 was used for all DOSY measurements. Fig. 2 shows a 2D DOSY plot of MVdimer and P1 5K (M n ¼ 5000 g mol 1 ) prior to the addition of CB[8] (Fig. 2, top). The diffusion coefficients of the two components are clearly separated as the polymeric and small molecule guests diffuse as single molecular species (log D ¼10.12 and 9.53 m 2 s 1 respectively). Upon adding CB[8] (Fig. 2, bottom), the NMR signals of both MVdimer and P1 5K now share a single diffusion coefficient (log D ¼10.2 m 2 s 1 ), diffusing as one entity. The aromatic signals of MVdimer and P1 5K also showed upfield shifts and significant line-broadening by NMR upon complexation as is typical for CB[8]-binding. 7,8 A 1-dimensional Stejskal-Tanner plot 25,26 (Fig. 3) of decreasing signal intensity (I/I 0 ) over increasing gradient strength (b parameter, Fig. 3, caption) shows the acquired diffusion data instead as a straight line graph where the slope equals the diffusion coefficient. In Fig. 3 a very significant decrease in diffusion of MVdimer is observed upon adding CB[8] to a solution of the high molecular weight P2 (M n ¼ 19,000 g mol 1 ) and MVdimer (2 : 1). The MVdimer then diffuses with the same diffusion coefficient as P2 upon ternary complex formation. Fig. 1 The synthetic building blocks used in this self-assembly study, P1 (M n ¼ 1100–8000 g mol 1 ), P2 (M n ¼ 19,000 g mol 1 ), MVdimer, and CB[8]. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK CB2 1EW. E-mail: oas23@cam.ac.uk; Fax: +44 (0)1223 334866; Tel: +44 (0)1223 334370 † Electronic supplementary information (ESI) available: Experimental details, synthesis of P1 and P2, NMR spectra of the different host–guest complexes (Figs S1–2), variation of D MVdimer with PEG M n (Fig. S3), ITC studies (Fig. S4–7, Table S1), CB[8]’s influence on PEG viscosity (Fig. S8). See DOI: 10.1039/c0py00197j 1434 | Polym. Chem., 2010, 1, 1434–1436 This journal is ª The Royal Society of Chemistry 2010 COMMUNICATION www.rsc.org/polymers | Polymer Chemistry Downloaded on 12 October 2010 Published on 07 September 2010 on http://pubs.rsc.org | doi:10.1039/C0PY00197J View Online