13820 DOI: 10.1021/la9020806 Langmuir 2009, 25(24), 13820–13832 Published on Web 08/14/2009 pubs.acs.org/Langmuir © 2009 American Chemical Society Self Aggregation of Supramolecules of Nitroxides@Cucurbit[8]uril Revealed by EPR Spectra † Nithyanandhan Jayaraj, ‡ Mintu Porel, ‡ M. Francesca Ottaviani,* ,§ Murthy V. S. N. Maddipatla, ‡ Alberto Modelli, ) Jos e P. Da Silva, ^ Balakrishna R. Bhogala, ‡ Burjor Captain, ‡ Steffen Jockusch, # Nicholas J. Turro, # and V. Ramamurthy* ,‡ ‡ Department of Chemistry, University of Miami, Coral Gables, Florida 33124, § Department of Geological Sciences, Chemical and Environmental Technologies (GeoTeCA), University of Urbino, Campus ex-Sogesta, Loc. Crocicchia, 61029 Urbino, Italy, ) Universit  a di Bologna, Dipartimento di Chimica “G. Ciamician”, via Selmi 2, 40126 Bologna, Italy, and Centro Interdipartimentale di Ricerca in Scienze Ambientali (CIRSA), via S. Alberto 163, 48123 Ravenna, Italy, ^ Faculdade de Ci^ encias e Tecnologia, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal, and # Department of Chemistry, Columbia University, New York, New York 10027 Received June 10, 2009. Revised Manuscript Received July 13, 2009 Supramolecular complexation behavior of cucurbiturils with paramagnetic nitroxide spin probes was examined by 1 H NMR, X-ray diffraction studies of crystals, computation, and EPR. Both cucurbit[7]uril (CB7) and cucurbit[8]uril (CB8) form a 1:1 complex with 4-(N,N,N-trimethylammonium)-2,2,6,6-tetramethylpiperidinyl-N-oxy bromide (CAT1). The structure of the complex in the solid state was inferred by X-ray diffraction studies and in the gas phase by computation (B3LYP/6-31G(d)). Whereas ESI-MS data provided evidence for the existence of the complex in solution, indirect evidence was obtained through 1 H NMR studies with a structural diamagnetic analogue, 4-(N,N,N-trimethylammonium)- 2,2,6,6-tetramethyl-N-methylpiperidine iodide (DCAT1). The EPR spectrum of the CAT1@CB7 complex consisting of three lines suggested that probe CAT1 is associated with host CB7 such that the nitroxide part is exposed to water. The spectral pattern was independent of the concentration of the complex and the presence of salt such as NaCl. The most interesting observation was made with CB8 as the host. In this case, in addition to the expected three-line spectrum, an additional spectrum consisting of seven lines was recorded. The contribution of the seven-line spectrum to the total spectrum was dependent on the concentration of the complex and added salt (NaCl) to the aqueous solution. The coupling constant for the seven-line spectrum for 14 N-substituted CAT1 is 5 G, and that for the four-line spectrum for 15 N- substituted CAT1 is 7.15 G. The only manner by which we could reproduce the observed spectra by simulation for both 14 N- and 15 N-substituted CAT1@CB8 was by assuming a spin exchange among three nitroxide radicals. To account for this observation, we hypothesize that three CAT1 molecules included within CB8 interact in such a way that there is an association of three supramolecules of CAT1@CB8 (i.e., [CAT1@CB8] 3 ) in a triangular geometry that leads to spin exchange between the three radical centers. We have established, with the help of 13 additional examples, that this is a general phenomenon. We are in the process of understanding this unusual phenomenon. Introduction The recent ready availability of cucurbiturils (CBs) has prompted studies that explore them as hosts for carrying out selective reactions, vehicles for drug delivery, containers for gas storage, transporters of antibacterial agents, deaggregators of dyes, and light-driven molecular switches, sensors, and motors. 1,2 In addition to such targeted studies, investigations oriented toward a fundamental understanding of the host-guest com- plexes of cucurbiturils and organic and inorganic guest molecules continue, a category to which this report belongs. Cucurbit[7]uril (CB7) and cucurbit[8]uril (CB8) (Scheme 1 and Figure 1), host molecules with cavities similar to β- and γ-cyclodextrins, are water-soluble, although CB8 is less so than CB7. In this study, three EPR-active cationic nitroxide probes CAT1, CAT8, and CAT12 (1-3) (Scheme 1) have been utilized to understand the aggregation characteristics of supramolecular complexes of CB7 and CB8 with organic guests in water. 3 Spin probes CAT8 and CAT12 were briefly investigated to establish the generality whereas extensive studies have been performed with CAT1. We provide support for our hypothesis that CAT1 forms 1:1 (host/ guest) complexes with both CB7 and CB8 through X-ray crystal structure analysis, ESI-MS data, and computations carried out at the B3LYP/6-31G(d) level. The hindrance to direct 1 H NMR spectral support for complex formation in aqueous solution due to the paramagnetic nature of probe CAT1 was circumvented by indirect information gleaned from the line broadening of 1 H NMR signals of the host. Further information was obtained by using diamagnetic structural analog DCAT1 (4) (Scheme 1). The EPR results presented here suggest that all three probes CAT1, CAT8, and CAT12 interact with the CB7 and CB8 cages; the mobility and polarity sensed were dependent on the relative concentrations of the host, guest, and host-guest complex and the presence of a salt (sodium chloride). The most exciting observation was the noticeable aggregation of supramolecules of CB8 and CATn (i.e., formation of [CATn@CB8] n ). Very recently, while this study was in progress, the unusual behavior † Part of the “Langmuir 25th Year: Molecular and macromolecular self- assemblies” special issue. *Corresponding author. E-mail: murthy1@miami.edu. (1) Lagona, J.; Mukhopadhyay, P.; Chakrabarti, S.; Isaacs, L. Angew. Chem., Int. Ed. 2005, 44, 4844–4780. (2) Lee, J. W.; Samal, S.; Selvapalam, N.; Kim, H.-J.; Kim, K. Acc. Chem. Res. 2003, 36(8), 621–630. (3) Franchi, P.; Lucarini, M.; Pedulli, G. F. Curr. Org. Chem. 2004, 8, 1831– 1849.