PdII 2L4-type coordination cages up to three nanometers in size

The utilization of easily accessible metalloligands allows the construction of PdII 2L4-type coordination cages of unprecedented size.


General
All chemicals were obtained from commercial sources (see below) and used without further purification unless stated otherwise. Bis(bromophenyl)methane (A) was synthesized following a literature procedure. 1 Solvents were dried using a solvent purification system from Innovative Technologies, Inc.. Reactions were carried out under an atmosphere of dry N2 using standard Schlenk techniques.
NMR spectra were obtained on a Bruker DRX ( 1 H: 400 MHz, 13 C: 100 MHz) equipped with a BBO 5 mm probe and a Bruker Avance III spectrometer ( 1 H: 400 MHz) equipped with a 5 mm BBFO-Plus probe.
The chemical shifts are reported in parts per million δ (ppm) referenced to the residual solvent signal. All spectra were recorded at 298 K, unless stated otherwise. The analysis of NMR spectra was performed with MestreNova and for the DOSY analysis the Baysian DOSY transform from MestreNova was used.
Routine ESI-MS data were acquired on a Q-TOF Ultima mass spectrometer (Waters) operated in the positive ionization mode and fitted with a standard Z-spray ion source equipped with the Lock-Spray interface. Data were processed using the MassLynx 4.1 software.
High resolution mass spectra were acquired for pure, pre-synthesized samples of all cages. The analytes were diluted in acetonitrile to a final concentration of ~10-20 μM. High resolution mass spectrometry experiments were carried out using a hybrid ion trap-Orbitrap Fourier transform mass spectrometer, Orbitrap Elite (Thermo Scientific) equipped with a TriVersa Nanomate (Advion) nano-electrospray ionization source. Mass spectra were acquired with a minimum resolution setting of 120,000 at 400 m/z. To reduce the degree of analyte gas phase reactions leading to side products unrelated to solution phase, the transfer capillary temperature was lowered to 50 °C. Experimental parameters were controlled via standard and advanced data acquisition software. Post-acquisition analysis was performed using vendor software, Xcalibur (Thermo Scientific), and ChemCalc (http://www.chemcalc.org/) web tool. 2  4-Bromophenol (10 g, 57.8 mmol, 2 eq.), 1,5-dibromopane (5.8 g, 28.9 mmol 1 eq.) and K2CO3 (60 g, 780 mmol 7.5 eq.) were added to acetone (250 mL) and the mixture was heated under reflux overnight. The reaction mixture was cooled to r.t. and the white solid was filtered and washed with acetone (200 mL) and DCM (100 mL). The organic layer was evaporated under reduced pressure to obtain the dibromo compound C as a white powder (7.2 g, 18.7 mmol, 65%).

Synthesis of double clathrochelate (L1-L6)
General Anhydrous FeCl2 (4 eq.) and the respective dioxime (12 eq.) were dissolved in MeOH (15 mL). In a separate flask, the respective diboronic acid (100 mg, 1 eq.) and 3-pyridine boronic acid (6 eq.) were dissolved in methanol (130 mL), acetone (5 mL), and water (2 mL) and heated to reflux and stirred for 30 min. The pre-prepared mixture of dioxime and FeCl2, was added to the boronic acid mixture, the mixture was heated to reflux for an additional 2 h, before the solvent was removed under reduced pressure. The remaining solid was dissolved in CHCl3 (100 mL), filtered and washed with a saturated aqueous solution of sodium EDTA and 5% ammonia (100 mL). The organic phase was dried over MgSO4, and evaporated under reduced pressure. The solid was pre-purified by a short silica column (150 g silica, 10% MeOH in DCM) to remove any polymeric material. The dark red fractions were evaporated under reduced pressure, the solid was dissolved in DCM (10 mL), filtered over H-PTFE 20/25 syringe filters and separated on a size exclusion column (200 g, dry weight, Bio-Beads S-X3 in DCM). The pure fractions (checked by MS, pos. mode), were combined and washed with saturated NaHCO3 solution, dried over MgSO4 and the solvent was removed under reduced pressure to yield a red powder as the double clathrochelate.

General synthesis procedure for Pd2L4 coordination cages.
To the double clahtrochelate ligand (see Table S2 for amounts, 2.2 µmol, 2 eq.) and [Pd(CH3CN)4](BF4)2 (0.5 mg, 1.1 µmol, 1 eq.) 0.6 mL of solvent (CD3CN or DMSO-d6) was added. The solution was heated at 70 °C for 17 h, in which the solution went from turbid to a clear red solution with everything dissolved. NMR shows full conversion to yield the Pd2L4 coordination cages. (except in the cases of double clatrhochelate (5) and (6) where there was a small amount of precipitate).  Figure S1. 1 H NMR spectrum of the diboronic acid B in DMSO-d6.

Single crystal X-ray analysis
Single crystals of sufficient quality for X-ray analysis were obtained by using slow diffusion with the following solvents: Intensity data for all ligands and cages were collected on a Rigaku SuperNova dual system in combination with an Atlas CCD detector using Cu-Kαradiation (λ = 1.54178 Å) at 140.0(2) K. The solutions were obtained by SHELXT [S3] ; and the refinements were carried out by SHELXL-2014 [S4] and OLEX2 [S5] programs. The crystal structures were refined using full-matrix least-squares based on F 2 with anisotropically refined non-hydrogen atoms (except some disordered -nioxime fragments and solvent molecules which were refined in isotropic approximation). The anions in cages (all disordered and some ordered ones) were refined isotropically with Uiso and B-F and B...B distances fixed. Hydrogen atoms were placed in calculated positions by means of the "riding" model. Additional electron density found in the difference Fourier map of cage 1-3, 5, 6 was treated by the SQUEEZE algorithm of PLATON [S6] and refined using ABIN instruction because of presence of a twinned component. Unfortunately, weak reflection ability and presence of a twinned component resulted in poor convergence factors for 2 and 5. Nevertheless, the quality of the data is clearly sufficient to establish the connectivity of these structures. Intense disorder affected solvent molecules of L1, L2, 1, 3, 6 and several moieties of crystal structures 1, 2 and 5 tough restraints/constraints (involving SHELX commands: DFIX, SADI, SIMU, RIGU, EADP and ISOR) were used to handle it. Crystallographic data have been deposited with the CCDC no. 1511090−1511096. Copies of the data can be obtained free of charge on application to the CCDC, 12 Union Road, Cambridge, CB2 1EZ, U.K. (fax, (internet.) +44-1223-336033) or via https://summary.ccdc.cam.ac.uk/structure-summary-form.