Conformational control of Pd2L4 assemblies with unsymmetrical ligands

With increasing interest in the potential utility of metallo-supramolecular architectures for applications as diverse as catalysis and drug delivery, the ability to develop more complex assemblies is keenly sought after. Despite this, symmetrical ligands have been utilised almost exclusively to simplify the self-assembly process as without a significant driving foa mixture of isomeric products will be obtained. Although a small number of unsymmetrical ligands have been shown to serendipitously form well-defined metallo-supramolecular assemblies, a more systematic study could provide generally applicable information to assist in the design of lower symmetry architectures. Pd2L4 cages are a popular class of metallo-supramolecular assembly; research seeking to introduce added complexity into their structure to further their functionality has resulted in a handful of examples of heteroleptic structures, whilst the use of unsymmetrical ligands remains underexplored. Herein we show that it is possible to design unsymmetrical ligands in which either steric or geometric constraints, or both, can be incorporated into ligand frameworks to ensure exclusive formation of single isomers of three-dimensional Pd2L4 metallo-supramolecular assemblies with high fidelity. In this manner it is possible to access Pd2L4 cage architectures of reduced symmetry, a concept that could allow for the controlled spatial segregation of different functionalities within these systems. The introduction of steric directing groups was also seen to have a profound effect on the cage structures, suggesting that simple ligand modifications could be used to engineer structural properties.


Figure S121
The included solvent was found to be highly disordered, and the best approach to handling this diffuse electron density was found to be the SQUEEZE routine of PLATON. 4 This suggested a total of 662 electrons per unit cell, equivalent to 165.5 electrons per complex. Before the use of SQUEEZE the solvent clearly resembled diethyl ether (C4H10O, 42 electrons), and 4 dichloromethane molecules corresponds to 168 electrons, so this was used as the solvent present. As a result, the atom list for the asymmetric unit is low by 2(C4H10O) = C8H20O2 (and that for the unit cell low by C64H160O16) compared to what is actually presumed to be present.
Crystal data for cis-[Pd2 (4) Both the presumed tetrafluoroborate anions and the included solvent were found to be highly disordered, and the best approach to handling this diffuse electron density was found to be the SQUEEZE routine of PLATON. 4 This suggested a total of 2090 electrons per unit cell, equivalent to 522.5 electrons per complex. Before the use of SQUEEZE, one tetrafluoroborate anion (BF4, 41 electrons) and one dimethylformamide solvent molecule (C3H7NO, 40 electrons) were identified amongst the diffuse electron density. Removing the electron density of the presumed four tetrafluoroborate anions per complex leaves 522.5 -(4 x 41) = 358.5 electrons for the solvent; 9 dimethylformamide molecules corresponds to 360 electrons, so this was used as the solvent present. As a result, the atom list for the asymmetric unit is low by 2(BF4) + 4.5(C3H7NO) = C13.5H31.5B2F8N4.5O4.5 (and that for the unit cell low by C108H252B16F64N36O36) compared to what is actually presumed to be present.

Density Functional Theory Calculations
All models were constructed using Avogadro 5 starting from the crystal structures reported herein. The semi-empirical method GFN2-xTB 6 was used to geometry optimise all structures in implicit solvent before optimisation using density functional theory (DFT). The xTB family of functionals have been shown to reproduce the geometries of metal-containing supramolecular architectures. 7 DFT optimisations were carried out using Gaussian 16. 8 All optimisations were carried out in dimethyl sulfoxide (DMSO) using the polarizable continuum model (PCM), unless stated otherwise. All geometries were optimised at the B3LYP/6-31G(d) level of theory with the D3 empirical dispersion correction. 9 The Stuttgart-Dresden (SDD) effective core potentials were used for the Pd 2+ centres. Each cage has a charge of 4 and a multiplicity of 1. A similar approach has been used by Clever and coworkers on similar cage systems. 10 The total electronic energies are reported in all cases (Tables S1 and S2). Numerical frequency calculations were performed on all optimised structures to confirm that the optimised structure was a minimum. However, there was at most one small negative frequency in some cases. We note that the accuracy of the Hessian calculations was not sufficient in all cases to reliably use the results of the thermochemistry calculations. The geometry of cis-[Pd2(4)4] optimised with DFT matches well with the solid-state structure (Fig. S127).

Table S1
Relative energy (the minimum of each cis-trans pair is set to 0 kJ mol -1 ) and the magnitude of the dipole moment of cis (C) and trans (D) isomers of the cages formed from ligand 1 using two implicit solvent models.

Ligand Distortion Measurements
Ligand distortion measures (Fig. S128) used in this work were adapted from related work reported by Lusby, Duarte and co-workers. 11 The optimised pore diameters were calculated using pyWindow 12 (Python scripts are made available). All guests, ions and solvent molecules were removed from the cages extracted from SCXRD structures for pyWindow analysis.

Figure S137
Alkyne twist angles (φ) were measured as the torsion angle defined by the carbon atoms a, b, c and d for both a) ligands L and 1, and b) 5 and 6. c) Ligand twist angles (θ) were measured as the torsion angle defined by the two Pd-N bonds of an individual ligand.