The dynamic covalent synthesis, structure and conformational dynamics of a chiral polyimine nanocapsule 1a are reported. Reaction of four tetraformyl cavitands and eight H2N(CH2)2NH2 yields quantitatively 1a, which has a compact, asymmetrically folded, pseudo-C2-symmetric structure, as determined by X-ray crystallography, and encapsulates four CHCl3 and three CH3OH guests in the solid state. In solution, 1a enantiomerizes by passing over a barrier of ΔG298⧧ = 21.5 ± 0.7 kcal mol−1 via a refolding process.

The thermodynamically controlled reaction of six tetraformylcavitands with twelve rigid, linear diamines yields quantitatively polyimine octahedrons with diameters of up to 5 nm. The cavitands are optimized to match the ideal geometry of a 60° tetratopic vertex unit and are connected along the octahedron edges with the diamines through 24 newly formed imine bonds.

Several dynamic hexaimine cryptophanes, that are built up from two triformylcyclotribenzylene cavitands and three diamino linkers and spontaneously assemble in water in the presence of a suitable templating guest, are reported. X-ray structure, kinetics and thermodynamics of assembly and molecular recognition properties are discussed.

Laser flash photolysis of fluorophenyldiazirine incarcerated in hemicarcerand 2 affords incarcerated fluorophenylcarbene [2⊙3], which forms a metastable, innermolecular π-complex with aryl moieties of 2. This carbene complex can be observed spectroscopically. Extensive computational studies provide insights into the structure, spectroscopy, energetics, and kinetics of the 2⊙3 carbene complex.

Molecular container compounds are hollow spherical hosts with cavities that allow accommodation of one or multiple guest molecules1, 2, 3. They are of great interest as nanoreactors4, 5, in which fleeting intermediates are stabilized6, 7, 8, 9, reactions accelerated10, 11 and regio- and stereochemistry altered12, 13, 14, as well as for solar energy conversion15, nanodevice fabrication16, drug delivery17, storage and separation technology18. The discovery of self-assembly processes involving hydrogen bonding or metal coordination, in which multiple building blocks spontaneously assemble to form spherically and cylindrically shaped molecular capsules held together by hydrogen bonding or metal–ligand interactions, has tremendously increased the diversity of capsules with respect to shape and size19, 20, 21, 22, 23. The efficiency of such self-assembly approaches is best demonstrated in the quantitative multicomponent synthesis of structurally well-defined molecular spheres with cavity diameters that reach 5 nm (see refs. 24,25). The synthesis of similar-sized nanocapsules, in which building blocks are covalently linked, is especially desirable for biomedical applications. We recently reported a nearly quantitative one-pot 18-component synthesis of an octahedral nanocontainer that is built up from six bowl-shaped cavitands and 12 linker units held together by 24 newly formed imine bonds (Fig. 1) (ref. 26). Our approach strongly surpasses earlier multistep covalent synthesis of related nanocontainers in its simplicity and efficiency, which should facilitate applications in medicinal, analytical, chemical and material sciences27, 28. Important was the choice of imine bonds to connect building blocks during the synthesis. Imine bond formation is reversible, which provides an error correction mechanism such that ultimately the thermodynamically most stable product—in this case 1—is obtained29, 30. A subsequent reduction of all 24 imine bonds fixes the structure and produces amino groups that allow further functionalization of the nanocapsule. From molecular mechanics calculations, a cavity volume of approximately 1,700 Å3 was estimated for 1 and 4, which is sufficient for encapsulation of multiple small organic molecules or a small biomacromolecule. We see potential use of suitably functionalized or immobilized nanocapsules in drug delivery, wastewater detoxification, separation technology or as building blocks for new sensors.The synthesis of 1 involves condensation of six tetraformylcavitands 2 with twelve 1,2-ethylene-diamines 3 in chloroform in the presence of catalytic amounts of trifluoroacetic acid (TFA). Cavitand 2 can be prepared in gram quantities in four steps from resorcinol and hexanal according to the literature procedures (Fig. 2) (see refs. 31–34 and Boxes 1,2,3,4). It is stable in the solid state but the formyl groups slowly oxidize in aerated solution, which substantially lowers the yield of its condensation reaction with 3. Upon mixing 2 and 3, hexamer 1 forms slowly at room temperature (22 °C). Equilibrium is reached after 2–3 days. The reaction is best monitored by 1H NMR spectroscopy (Fig. 3).Spectra taken at an early stage of the reaction show substantial amounts of tetramer 8, which subsequently converts into 1 (Figs. 3b and 4). After full equilibration, the hexamer to tetramer ratio is approximately 15:1 (Fig. 3c). We have carried out this reaction on a half-gram scale and do not find a decrease in the yield of 1 as long as the reactants are of high purity. On the other hand, the condensation reaction is remarkably solvent dependent35. In solvents other than chloroform, the yield of 1 is considerably lower and other nanocages form preferentially. For example, in tetrahydrofuran (THF), tetramer 8 is the major condensation product and octamer 9 in dichloromethane (Fig. 4). For a discussion of the solvent effect on the outcome of the condensation reaction between 2 and 3, the reader is referred to ref. 35.The reduction of all imine bonds of 1 with NaBH4 is quantitative and leads initially to boramines -CH2N(BH2)-, which have to be hydrolyzed under acidic conditions. Hydrolysis is slow and should be carried out at room temperature. We observe substantial acetal cleavage if hydrolysis is carried out at elevated temperature. An intramolecular acid catalysis by the ammonium groups might contribute to this side reaction (Fig. 5) (ref. 35).Support for this cleavage mechanism comes from the observation of substantial acetal cleavage, if solid 4·24CF3CO2H is heated to 80 °C under vacuum for 24 h. At room temperature, side reactions are minimized and 4·24CF3CO2H is obtained in 50–65% yield after purification by reversed-phase high-pressure liquid chromatography (HPLC). Nanocontainer 4·24HCl is soluble in methanol:water 9:1, but precipitates if the water content is increased.Step 1: 1.5 hSteps 2–7: 1 hSteps 8 and 9: 1 hStep 10: 41 hSteps 11 and 12: 8 hSteps 13 and 14: 1 hSteps 15 and 16: 0.5 hStep 17: 3.5 daysSteps 18–21: 1.5 hSteps 22–25: 8 hTroubleshooting advice can be found in Table 1. 13C NMR (100 MHz, CDCl3, 22 °C;) δ 157.7, 153.6, 138.8, 124.5, 121.7, 100.5, 63.2, 36.7, 32.3, 30.1, 27.9, 23.0, 14.4.FT-IR (CHCl3) v 2,956.8 (s), 2,929.6 (s), 2,872.1 (sh), 2,855.6 (s) 1,641.5 (s), 1,602.6 (m), 1,587 (m), 1,361.3 (m), 1,112.3 (w), 1,088.9 (m), 980 (s).ESI-MS (CH2Cl2/CH3CN (1:5) (m/z) 1,954.9 (100%, [M+3H]3+); 1,466.9 (13%, [M+4H]4+); 1,173.7 (3%, [M+5H]5+).Final product 4: 1H NMR (CD3OD; 0.4 vol% CF3COOD; 7 °C; 300 MHz) δ 7.55 (s, 24H, Haryl); 6.16 (d, J = 6.9 Hz, 24H, OCH outHO); 4.85 (t, J = 7.6 Hz, 24H, CH(CH2)4CH3); 4.43 (d, J = 6.9 Hz, 24H, OCH inHO); 4.16 (sb, 48H, NCH 2Ar); 3.59 (sb, 48H, N(CH 2)2N); 2.38 (sb, 48H, CHCH 2(CH2)3CH3); 1.6–1.2 (m, 144H, CHCH2(CH 2)3CH3); 0.92 (t, J = 7.1 Hz, 72H; CHCH2(CH2)3CH 3). 13C NMR (CD3OD; 0.4 vol% CF3COOD; 22 °C; 75 MHz) δ 160.5 (q; J = 37.8 Hz), 155.1, 139.9, 124.6, 119.9, 101.2, 44.4, 42.7, 38.5, 33.1, 30.9, 29.1, 24.0, 14.6.ESI-MS (CH3OH/H2O/TFA (98/2/0.1) (m/z) 1,478.9 ([M+4H]4+); 1,507.3 ([M+4H+TFA]4+); 1,535.5 ([M+4H+2TFA]4+); 1,564.1 ([M+4H+3TFA]4+); 1,592.5 ([M+4H+4TFA]4+); 1,620.7 ([M+4H+5TFA]4+); 1,649.1 ([M+4H+6TFA]4+); 1,677.4 ([M+4H+7TFA]4+); 1,706.0 ([M+4H+8TFA]4+). MALDI-TOF MS (m/z) 5912.28 ([M+H]+, 100%).

The thermodynamically controlled reaction of six tetraformylcavitands with twelve rigid, linear diamines yields quantitatively polyimine octahedrons with diameters of up to 5 nm. The cavitands are optimized to match the ideal geometry of a 60° tetratopic vertex unit and are connected along the octahedron edges with the diamines through 24 newly formed imine bonds.

Several dynamic hexaimine cryptophanes, that are built up from two triformylcyclotribenzylene cavitands and three diamino linkers and spontaneously assemble in water in the presence of a suitable templating guest, are reported. X-ray structure, kinetics and thermodynamics of assembly and molecular recognition properties are discussed.