The Effect of Mechanical Interlocking on Crystal Packing: Predictions and Testing Fabio Biscarini, † Massimiliano Cavallini, † David A. Leigh,* ,‡ Salvador Leo ´ n, § Simon J. Teat, | Jenny K. Y. Wong, ‡ and Francesco Zerbetto* ,§ Contribution from the Consiglio Nazionale delle Ricerche, Istituto di Spettroscopia Molecolare, Via P. Gobetti 101, 40129, Bologna, Italy, Centre for Supramolecular and Macromolecular Chemistry, Department of Chemistry, UniVersity of Warwick, CoVentry CV4 7AL, U.K., Dipartimento di Chimica “G. Ciamician”, UniVersita ` degli Studi di Bologna, V. F. Selmi 2, I-40126, Bologna, Italy, and CLRC Daresbury Laboratory, Warrington, Cheshire, WA4 4AD, U.K. Received April 3, 2001. Revised Manuscript Received September 18, 2001 Abstract: The first statistical analyses of the X-ray crystal structures of mechanically interlocked molecular architectures, the first molecular mechanics-based solid-state calculations on such structures and atomic force microscopy (AFM) experiments are used in combination to predict and test which types of benzylic amide macrocycle-containing rotaxanes possess mobile components in the crystalline phase and thus could form the basis of solid-state devices that function through mechanical motion at the molecular level. The statistical studies and calculations show that crystals formed by rotaxanes possess similarities and unanticipated differences with respect to the crystal packing of noninterlocked molecules. Trends in the rotaxane series correlate quantities related to crystal packing, molecular size, stoichiometry, and H-bonding. In accordance with the findings of Gavezzotti et al. for conventional molecular architectures, a principal component analysis (PCA) showed that three vectors related to the size, packing parameters, and stoichiometry are sufficient to describe the crystal properties of benzylic amide macrocycle-containing rotaxanes. When hydrogen bond-related quantities are included in a second PCA, they combine with the size and the stoichiometry vectors but not with packing-related parameters, indicating that the intramolecular “saturation” of the H-bonds (between the interlocked components) takes precedence over crystal assembly (i.e., intermolecular packing) in these systems. However, cluster analyses also suggest a major role for the energy of interaction between the macrocycle and its crystal environment. The identification of such a “privileged” interaction is of fundamental importance to the development of rotaxanes with in-crystal mobility of one or more of their interlocked components, a prerequisite for the exploitation of molecular level mechanical motion in the solid state. The set of trends found, together with the calculated energies, was used to propose guidelines for which benzylic amide macrocycle-containing rotaxanes are best suited to become building blocks for systems with mobile submolecular units in the crystalline phase. An experimental test of the predictive power of such guidelines was carried out using AFM on a rotaxane and its thread, identified by the study as a promising candidate for solid-state mobility. Intuitively, the rotaxane should be less mobile in the solid state since it has multiple sets of both hydrogen bond donors and acceptors that can form strong inter- and intramolecular H-bonds. Conversely, the thread has no hydrogen bond donors and cannot form such bonds. The AFM experiments, however, confirm the statistical analysis prediction that the rotaxane is considerably more mobile in the solid than the thread. Introduction Molecules crystallize as the result of relatively weak interac- tions between the crystallizing components; noncovalent binding during the crystal assembly process ultimately yields a lower total energy than the individual components have with a solvent or at infinite distances. When considering molecules with mechanically interlocked molecular architectures, catenanes (interlocked rings) and rotaxanes (where a macrocycle is locked onto a linear thread by two bulky “stoppers”), 1 the picture is somewhat altered because the separation of the interlocked components is intrinsically restricted. The presence of a me- chanical bond often enables the interlocked components to interact together in a very efficient manner, altering the mode of binding they could have on external species, in general, and * To whom correspondence should be addressed. D.A.L.: E-mail, David.Leigh@ed.ac.uk. F.Z.: E-mail, gatto@ciam.unibo.it. † Istituto di Spettroscopia Molecolare. ‡ University of Warwick. Present address: Department of Chemistry, University of Edinburgh, The King’s Buildings, West Mains Road, Edinburgh EH9 3JJ, U.K. § Universita ` degli Studi di Bologna. | CLRC Daresbury Laboratory. (1) (a) Amabilino, D. B.; Stoddart, J. F. Chem. ReV. 1995, 95, 2725-2828. (b) Sauvage, J.-P., Dietrich-Buchecker, C., Eds.; Molecular Catenanes, Rotaxanes, and Knots; Wiley-VCH: Weinheim, 1999. Published on Web 12/13/2001 10.1021/ja0159362 CCC: $22.00 © 2002 American Chemical Society J. AM. CHEM. SOC. 9 VOL. 124, NO. 2, 2002 225