Face and edge directed self-assembly of Pd12 tetrahedral nano-cages and their self-sorting

A di-tetrazole ligand was used to occupy the edges of a tetrahedron to generate an edge-directed self-assembled Pd12 water soluble cage which was used as a vessel to encapsulate aromatic nitro-olefins. A face directed Pd12 tetrahedral cage was also constructed occupying the triangular faces of the tetrahedron by a tri-tetrazole ligand.

and used without further purification. NMR spectra were recorded on a Bruker 400 MHz spectrometer and the chemical shifts (δ) in the 1 H NMR spectra are reported in ppm relative to tetramethylsilane (Me 4 Si) as an internal standard (0.0 ppm) or proton resonance resulting from incomplete deuteration of the solvents (CD 3 ) 2 SO (2.51 ppm) and D 2 O (4.79 ppm).
Electrospray ionization mass spectrometry (ESI-MS) experiments were carried out on a ESI-MS spectra were recorded on a Q-TOF electrospray instrument. Dynamic rheological measurements were carried out with the gels and an AR 1000 rheometer (TA instruments) with a plate-plate (the rotor was serrated) geometry (20 mm diameter,400 μm gap). Scanning electron micrographs were recorded on an SERION instrument. Prior to the measurements a thin layer of the gels was taken on a silicon wafer and dried under vacuum and finally coated with a thin gold layer.

Synthesis of L 1 , L 2 and L 3 :
All the ligands L 1 , L 2 and L 3 were synthesized following the reported procedure 1 . In a clean and dried round bottom flask 1,4-dicyanobenzene (10.0 mmol, 1.28 g), NaN 3 (60.0 mmol, 3.90 g) and trimethylamine hydrochloride (60.0 mmol, 8.25 g) were taken, to which 100 mL of toluene and 30 mL of methanol were added and the mixture was refluxed for 4 days. The resulting precipitate was filtered and dissolved in aqueous NaOH (1M). The clear colourless solution was then titrated with 1M HCl until it reached at pH ~4. The precipitated product was washed with water and methanol followed by drying under vacuum. Isolated yield 1.70 g (79%). 1 H NMR(DMSO-d 6 ) δ (ppm): 8.22 (s, 4H). L 2 and L 3 were also synthesized following the above-mentioned procedure. L 2 : Isolated yield 84%. 1

Synthesis of G1:
In a cleaned and dried glass vial cis-(tmeda)Pd(NO 3 ) 2 (M) (0.04 mmol, 13.8 mg) and [1,4-di(1H-tetrazol-5-yl)benzene (L 1 ) (0.04 mmol, 8.6 mg) were taken followed by the addition of 1 mL water. The mixture was heated at 50 °C with stirring until all the solids dissolved. The solution was then heated at 50 °C for 6 h to form the hydrogel. Subsequently, the DMSO gel was synthesized by taking the exact amount of the reagents in 1 mL DMSO and heating it at 60 °C for 5 h.

Synthesis of G2:
In a dried glass vial M (0.04 mmol, 13.8 mg), 1,3,5-tri(1H-tetrazol-5-yl)benzene (L 2 ) (0.026 mmol, 7.5 mg) and 1 mL of water were taken. The heated at 50 °C with continuous stirring until L 2 consumed completely. The solution was then heated at 50 °C for 8 h to produce the hydrogel. Similarly, the DMSO gel was synthesized by taking the exact amount of the reagents in 1 mL DMSO and heating it at 60 °C for 8 h.

Conversion of G1 to T1:
To the vial containing hydrogel G 1 (synthesized as mentioned above) solid M (0.04 mmol, 13.8 mg) was added and the mixture was stirred at 60 °C for 3 h to give a clear light yellow solution. The solution was concentrated and treated with excess acetone to give a faint yellow precipitate. The precipitate was then washed with acetone and dried under vacuum. Yield: 23.5 mg (75%). For the organogel, the same procedure was followed to get the yellow DMSO solution. It was then treated with excess ethyl acetate to get a faint yellow precipitate.
Isolated yield: 25 mg (80%). The solid product was dissolved in water and kept for acetone vapor diffusion which allowed the isolation of single crystals suitable for XRD analysis. 1

Conversion of G2 to T2:
Following the above-mentioned procedure, G2 was treated with M (0.04, 13.8 mg) to get the nanocage T2 as light yellow powder. Yield: 22.2 mg (73%). This solid was dissolved in water and allowed diffusion of acetone vapor to get single crystals. 1

Cage (T1) to gel (G1) conversion:
To a 1 mL aqueous solution of T1 (0.003 mmol, 15.6 mg), L 1 (0.02 mmol, 4.3 mg) was added and the mixture was stirred at 50 °C until all solid L 1 was consumed. Then the solution was heated further at 50 °C for 6 h to obtain the hydrogel. Similar procedure was followed to prepare the organogel with DMSO. pH monitored self-assembly:

Gage (T2) to gel (G2) conversion:
1 mL aqueous solution of T2 (0.003 mmol, 15.1 mg) was added to solid L 2 (0.013 mmol, 3.7 mg) in a clean glass vial and the mixture was stirred at 50 °C until L 1 was consumed. Then the solution was heated at 50 °C for 8 h to obtain the hydrogel. Similar procedure was followed to prepare the organogel in DMSO.

Synthesis of the prism P:
A 2 mL aqueous solution of M (0.1 mmol, 34.6 mg) was added to the solid ligand L 3 (0.05 mmol, 10.7 mg) and heated at 55 °C for 2 h to give a light yellow solution. The resulting solution was then concentrated under reduced pressure and treated with 10 mL of acetone to obtain a white precipitate. The precipitate was then washed with acetone and dried under vacuum. Yield: 33 mg (84%). 1

Self-sorting experiment:
To a D 2 O solution of M (0.04 mmol, 13.8 mg), solid ligand L 1 (0.01 mmol, 2.1 mg) and L 2 (0.006 mmol, 1.9 mg) were added and the reaction mixture was heated and stirred at 50 °C S5 for 6 h. The resulting clear solution was used for 1 H NMR spectral analysis. The same solution was further treated with excess KPF 6 salt to get a white precipitate, which was isolated, dried and dissolved in acetonitrile for mass spectral analysis for better ESI-MS result.

Michael addition reactions:
To a solid nitro-alkene 2 (0.02 mmol), 1 mL aqueous solution of the cage T1 (2 mol %) was added followed by an addition of 3 (0.02 mmol, 3.1 mg). The mixture was stirred at room temperature for the time periods as mentioned in Table 1. Then the reaction mixtures were extracted with chloroform and finally the pure product was obtained from preparative TLC, which was characterized by 1 H NMR spectroscopy.

Single crystal XRD structures of T1, T2 and P:
All the cages were crystallized by diffusion of acetone vapour to an aqueous solution of the corresponding cages. Single crystal X-ray data were collected on a Bruker SMART APEX (D8 QUEST) CMOS diffractometer using the SMART/SAINT software. 2 Intensity data were collected using graphite-monochromatized Mo-Kα radiation (0.71073 Å) at 110 K. The structure was solved by direct methods and Fourier analyses and refined by the full-matrix least-squares method based on F 2 with all observed reflections. 3-4 using the SHELX-97 5 program incorporated into WinGX 6 . All non-hydrogen atoms were refined with anisotropic displacement coefficients. The hydrogen atoms bonded to carbon were included in geometric positions and given thermal parameters equivalent to 1.2 times those of the atom to which they were attached. In addition, the structure contains a huge void of disordered solvent molecules and anions, so Squeeze program 7 was applied to account for embedded solvent molecules seriously disordered. Crystallographic data and refinement parameter are given in Table S1.  Figure S1: 1 H NMR spectra of the linker L 1 in DMSO-d 6 .           Coordinates of the optimized geometry of 1⊂T1: