Molecular storage solutions for incorporating small molecules in crystalline matrices are of interest in the context of structure elucidation, decontamination, and slow release of active ingredients. Here we report the syntheses of 1,3,5,7-tetrakis(2,4-dimethoxyphenyl)adamantane, 1,3,5,7-tetrakis(4-methoxyphenyl)adamantane, 1,3,5,7-tetrakis(4-methoxy-2-methylphenyl)adamantane, and 1,3,5,7-tetrakis(4-methoxy-2-ethylphenyl)adamantane, together with their X-ray crystal structures. All four compounds crystallize readily. Only the octaether shows an unusual level of (pseudo)polymorphism in its crystalline state, combined with the ability to include a number of different small molecules in its crystal lattices. A total of 20 different inclusion complexes with guest molecules as different as ethanol or trifluorobenzene were found. For nitromethane and benzene, schemes for uptake and release are presented.

Tetrakis(dimethoxyphenyl)adamantane (TDA) readily forms crystalline inclusion complexes with reactive, toxic, or malodorous reagents, such as benzoyl chloride, acetyl chloride, cyclohexyl isocyanide, phosphorus trichloride, and trimethylsilyl chloride. The crystals are stable and largely free of the problematic properties of the free reagents. When exposed to solvents such as DMSO or MeOH, the reagents react, and a large portion of the TDA precipitates. The TDA-coated reagents may lead to a safer way of storing, handling, and delivering reagents, and ultimately to synthetic protocols that do not require fume hoods.

Recently, a tetraphenyladamantane octamethylether was shown to encapsulate a wide range of small molecules in its crystals. Uptake and release from the liquid phase were demonstrated, and crystalline inclusion complexes were prepared that act as formulation for obnoxious reagents. However, fewer than two equivalents of guest molecules were found within the crystal structures. Here we report the synthesis of 1,3,5,7-tetrakis(2,4-diethoxyphenyl)adamantane (TEO) and twelve X-ray crystal structures that contain up to 3.5 equivalents of guest molecules. After crystallization and drying, TEO gives a material that absorbs 30 wt % of p-xylene reversibly through the gas phase, and releases it again at 55 °C, suggesting that it may be used for the capture and release of aromatic hydrocarbons.

Oligonucleotide hybrids with organic cores as rigid branching elements and four or six CG dimer strands have been shown to form porous materials from dilute aqueous solution. In order to explore the limits of this form of DNA-driven assembly, we prepared hybrids with three or eight DNA arms via solution-phase syntheses, using H-phosphonates of protected dinucleoside phosphates. This included the synthesis of (CG)8TREA, where TREA stands for the tetrakis[4-(resorcin-5-ylethynyl)phenyl]adamantane core. The ability of the new compounds to assemble in a DNA-driven fashion was studied by UV-melting analysis and NMR, using hybrids with self-complementary CG zipper arms or non-self-complementary TC dimer arms. The three-arm hybrid failed to form a material under conditions where four-arm hybrids did so. Further, the assembly of TREA hybrids appears to be dominated by hydrophobic interactions, not base pairing of the DNA arms. These results help in the design of materials forming by multivalent DNA-DNA interactions.

A linear solution‐phase synthesis of branched oligonucleotides with adamantane as core has been developed. The method uses conventional phosphoramidites only, achieves chain assembly without chromatography of intermediates, and overcomes the low reactivity of adamantane‐1,3,5,7‐tetraol as core. The assembly of four‐arm hybrids with up to 32 nucleotides total was performed, with monodisperse products of up to 10 kDa in size. Overall yields of 20 % over 19 steps (hexamer arms) and 11 % over 25 steps (octamer arms) of HPLC‐purified compounds were obtained. The adamantane‐based hybrids show more DNA‐dominated assembly properties than their analogues with larger lipophilic cores. Reversible formation of macroscopic amounts of materials through hybridization was achieved, both for self‐complementary systems and two‐hybrid systems with two non‐self‐complementary DNA sequences.

Tetrakis(dimethoxyphenyl)adamantane (TDA) readily forms crystalline inclusion complexes with reactive, toxic, or malodorous reagents,such as benzoyl chloride,acetyl chloride,c yclohexyl isocyanide,p hosphorus trichloride,a nd trimethylsilyl chloride.T he crystals are stable and largely free of the problematic properties of the free reagents.W hen exposed to solvents such as DMSO or MeOH, the reagents react, and al arge portion of the TDAp recipitates.T he TDAcoated reagents may lead to as afer way of storing,h andling, and delivering reagents,a nd ultimately to synthetic protocols that do not require fume hoods.

Formulating pharmaceutically active ingredients for drug delivery is a challenge. There is a need for new drug delivery systems that take up therapeutic molecules and release them into biological systems. We propose a novel mode of encapsulation that involves matrices formed through co‐assembly of drugs with adamantane hybrids that feature four CG dimers as sticky ends. Such adamantanes are accessible via inexpensive solution‐phase syntheses, and the resulting materials show attractive properties for controlled release. This is demonstrated for two different hybrids and a series of drugs, including anticancer drugs, antibiotics, and cyclosporin. Up to 20 molar equivalents of active pharmaceutical ingredients (APIs) are encapsulated in hybrid materials. Encapsulation is demonstrated for DNA‐binding and several non‐DNA binding compounds. Nanoparticles were detected that range in size from 114–835 nm average diameter, and ζ potentials were found to be between −29 and +28 mV. Release of doxorubicin into serum at near‐constant rates for 10 days was shown, demonstrating the potential for slow release. The encapsulation and release in self‐assembling matrices of dinucleotide‐bearing adamantanes appears to be broadly applicable and may thus lead to new drug delivery systems for APIs.

Some organic molecules encapsulate solvents upon crystallization. One class of compounds that shows a high propensity to form such crystalline solvates are tetraaryladamantanes (TAAs). Recently, tetrakis(dialkoxyphenyl)-adamantanes have been shown to encapsulate a wide range of guest molecules in their crystals, and to stabilize the guest molecules against undesired reactions. The term ‘encapsulating organic crystals’ (EnOCs) has been coined for these species. In this work, we studied the behavior of three TAAs upon exposition to different guest molecules by means of sorption technique. We firstly measured the vapor adsorption/desorption isotherms with water, tetrahydrofuran and toluene, and secondly, we studied the uptake of methane on dry and wet TAAs. Uptake of methane beyond one molar equivalent was detected for wet crystals, even though the materials showed a lack of porosity. Thus far, such behavior, which we ascribe to methane hydrate formation, had been described for porous non-crystalline materials or crystals with detectable porosity, not for non-porous organic crystals. Our results show that TAA crystals have interesting properties beyond the formation of conventional solvates. Gas-containing organic crystals may find application as reservoirs for gases that are difficult to encapsulate or are slow to form crystalline hydrates in the absence of a host compound. Wet tetraaryladamantane crystals take up methane in form of methane hydrate structure I, even though they appear non-porous to argon.