Nature achieves impressively strong and selective complexation of small molecule anions through the elaborate binding sites of sophisticated proteins. Inspired by these examples, we have developed an anion templation strategy for the synthesis of mechanically interlocked host structures for anion recognition applications. Upon removal of the discrete anionic templating species, such host systems possess unique, three-dimensional, geometrically restrained cavities containing convergent hydrogen bond donor atoms. Such structures exhibit high affinity binding selectivity toward complementary anions. This Account describes recent advances in this anion templation meth odology, demonstrating the versatility and scope of this approach, and progressing to more diverse architectures. Specifically, we have prepared an expansive range of interlocked hosts with enhanced anion recognition properties, such as the ability to operate effectively in competitive aqueous media. We have produced these structures through the utilization of a new anion templated amide condensation synthetic method and through the incorporation of a range of different anion binding motifs, such as groups capable of effective solution-phase halogen bonding interactions. Importantly, direct comparisons between halogen bonding and hydrogen bonding systems reveal impressively magnified anion recognition properties for halogen bonding interlocked host systems. We have also employed the anion templation strategy successfully to construct selective electrochemical and luminescent anion sensors, as well as architectures of increasing complexity, such as a triply interlocked capsule and a handcuff catenane. The synthesis of these latter examples presents greater challenges; however, such molecules offer additional applications in higher order recognition and sensing and in switchable molecular devices. Having established anion templation as a viable synthetic route to interlocked architectures, we have used this strategy to fabricate a multitude of innovative structures. The key principles of this approach are the ability of anionic species to template the association of carefully designed components, and of the resulting molecular framework with its interlocked host cavity to display impressive anion recognition selectivity. Mechanically interlocked structures have numerous potential applications in nanotechnology. Therefore, the continuing development of effective synthetic methods, especially those which yield functional systems, is of great interest in the broad interdisciplinary field of supramolecular chemistry.

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A macrocyclic tetralactam host is threaded by a highly fluorescent squaraine dye that is flanked by two polyethyleneglycol (PEG) chains with nanomolar dissociation constants in water. Furthermore, the rates of bimolecular association are very fast with kon ~106–107 M−1s−1. The association is effective under cell culture conditions and produces large changes in dye optical properties including turn-on near-infrared fluorescence that can be imaged using cell microscopy. Association constants in water are ~1000 times higher than in organic solvents and strongly enthalpically favored at 27 °C. The threading rate is hardly affected by the length of the PEG chains that flank the squaraine dye. For example, macrocyle threading by a dye conjugate with two appended PEG2000 chains is only three times slower than threading by a conjugate with triethyleneglycol chains that are twenty times shorter. The results are a promising advance towards synthetic mimics of streptavidin/biotin.

The photothermal heating and release properties of biocompatible organic nanoparticles, doped with a near-infrared croconaine (Croc) dye, were compared with analogous nanoparticles doped with the common near-infrared dyes ICG and IR780. Separate formulations of lipid-polymer-hybrid nanoparticles and liposomes, each containing Croc dye, absorbed strongly at 808 nm and generated clean laser-induced heating (no production of 1O2 and no photobleaching of the dye). In contrast, laser-induced heating of nanoparticles containing ICG or IR780 produced reactive 1O2 leading to bleaching of the dye and also decomposition of co-encapsulated payload such as the drug Doxorubicin. Croc dye was especially useful as a photothermal agent for laser controlled release of chemically sensitive payload from nanoparticles. Solution state experiments demonstrated repetitive fractional release of water soluble fluorescent dye from the interior of thermosensitive liposomes. Additional experiments used a focused laser beam to control leakage from immobilized liposomes with very high spatial and temporal precision. The results indicate that fractional photothermal leakage from nanoparticles doped with Croc dye is a promising method for a range of controlled release applications.

The anion-templated synthesis of a rotaxane structure, incorporating the new naphthalimide triazolium motif, is described and the interlocked host shown to exhibit selective, uni-directional, anion-induced shuttling. Initial pseudorotaxane investigations demonstrate the ability of a naphthalimide triazolium threading component to form interpenetrated assemblies with counter-anion-dependent co-conformations. (1)H NMR studies reveal that the shuttling behaviour of the analogous rotaxane host system is controlled by selective anion binding and by the nature of the solvent conditions. Complete macrocycle translocation only occurs upon the recognition of the smaller halide anions (chloride and bromide). The rotaxane solid-state crystal structure in the presence of chloride is in agreement with the solution-phase co-conformation. The sensitivity of the axle naphthalimide absorbance band to the position of the macrocycle component within the interlocked structure enabled the molecular motion to be observed by UV/Vis spectroscopy, and the chloride-induced shuttling of the rotaxane was reversed upon silver hexafluorophosphate addition.