Supramolecular purification of mono-adamantane mixtures by enhanced stability in three-shell Matryoshka-type assemblies

The adamantane (Ad) core is widely spread in the pharmaceutical realm since it is considered a lipophilic bullet that boosts the bioactivity of Ad-bearing drugs. However, little is known about the precise recognition modes in confined enzymatic active sites, and poor chromatographic strategies are reported for the purification of mixtures of Ad-derivatives. Here we report on the exquisite supramolecular purification of mono-adamantane mixtures by the development of three-shell supramolecular Matryoshkas featuring an adamantane-cycloparaphenylene (CPP) host-guest adduct encapsulated in a tetragonal prismatic nanocage. The three-shell assembly features an all-in-one strategy, since the encapsulation is inefficient for either [8]CPP or diamondoids alone, and is only formed efficiently when the three components are present. A straightforward solid-state filtration-redissolution protocol allows the purification of diamondoid mixtures, with enhanced preference to amine-bearing adamantane derivatives. This level of supramolecular selectivity among diamondoid complex mixtures is unprecedented, surpassing chromatographic techniques. This deposit includes parameter files of the nanocapsule and the guests studied (diamontoides and CPP rings), output files of the simulations without solvent of the different systems and files releated to the well-tempered metadynamics carried out.