A New Mechanically‐Interlocked [Pd2L4] Cage Motif by Dimerization of two Peptide‐based Lemniscates

Abstract Most metallo‐supramolecular assemblies of low nuclearity adopt simple topologies, with bridging ligands spanning neighboring metal centers in a direct fashion. Here we contribute a new structural motif to the family of host compounds with low metal count (two) that consists of a pair of doubly‐interlocked, Figure‐eight‐shaped subunits, also termed “lemniscates”. Each metal is chelated by two chiral bidentate ligands, composed of a peptidic macrocycle that resembles a natural product with two pyridyl‐terminated arms. DFT calculation results suggest that dimerization of the mononuclear halves is driven by a combination of 1) Coulomb interaction with a central anion, 2) π‐stacking between intertwined ligand arms and 3) dispersive interactions between the structure's compact inner core bedded into an outer shell composed of the cavitand‐type macrocycles. The resulting cage‐like architecture was characterized by NMR, MS and X‐ray structure analyses. This new mechanically bonded system highlights the scope of structural variety accessible in metal‐mediated self‐assemblies composed of only a few constituents.

. 1 H NMR spectrum of benzyl bromide S2 (600 MHz) in CDCl3.    COSY contacts are marked with solid lines and NOESY contacts with dashed lines.

[Cl@Pd2L4]
[Cl@Pd2L4](X)3 assemblies were prepared in quantitative yields by mixing ligand L (1.  Besides the major isomer (assigned to the topology as observed in the X-ray structure), all samples contained varying amounts (20 -30%) of a minor isomer (see computational section for a plausible structure), also featuring NMR signal splitting into two sets, in part overlapping with the signals of the major species.
Several signals of the major species that were found to overlap with the minor component, the NBu4 + counter cation and solvent signals in the 1D spectrum could be assigned nevertheless with help of 2D spectra ( Figure S9). The following listing contains all observed signals (including patterns of overlapped signals) above 4 ppm (labels containing * stand for all diastereotopic signals associated with protons carrying the same letter). Signals of the major species that could be assigned are referenced by their proton label and color code (Fig. S9). Estimated contributions to the observed total integrals of overlapping signals are given where appropriate.   The data was cut at 1.1 Å, as the signal to noise ratio has dropped below I/σ(I) < 4.0. Due to high mosaicity and disorder in the solvent region a higher resolution could not be achieved.
Nevertheless, the resolution achieved was sufficient to solve the structure by intrinsic phasing/direct methods using SHELXT. 5 SHELXL 6 (version 2014/7) was used for refinement and ShelXle7 as a graphical user interface. The DSR program plugin was employed for modelling. [8][9] All cycles were refined against F 2 until convergence using the conjugate-gradient algorithm (CGLS). Only for computing the crystallographic information file (CIF) the fullmatrix least-squares routine was employed. All non-hydrogen atoms were refined with anisotropic displacement parameters. The hydrogen atoms were refined isotropically on

Specific refinement details
In order to generate a molecular model and increase robustness of the refinement we have adapted and exploited techniques commonly applied in macromolecular structure refinement.
A theoretical model bases on MMFFS force field was used as input for stereochemical restraints generation by the GRADE program using the GRADE Web Server    isomers were found to be in a similar range (within 11 kJ/mol for the gas phase models),

Comparison of plausible isomers
suggesting that both isomers could be accessible in solution. While the X-ray structurematching topology turned out to feature the higher energy, we denote this to the rather coarse theory level that had to be chosen due to the immense aggregate size (535 atoms) under negligence of solvation effects and further counter anions (also note that BF4 --only containing sample showed a more complex NMR behavior than the Cl --encapsulating species which, however, was not considered in the computational study). In accordance with 2D NMR data for the Cl --encapsulating species, we therefore propose assignment of the major solution species to the diastereomer observed in the X-ray structure and the minor species revealed in the NMR results to the alternative interlocked topology.
Also, a non-interlocked [BF4@Pd2L4] 3+ structure with all four ligands bridging both Pd cations in the classical lantern-shaped geometry was calculated. Although convergence issues were encountered during the geometry optimization, the latter structure turned out to be of significantly higher energy than the interlocked isomers. As such a non-interlocked structure could also be ruled out on the basis of the NMR splitting and NOESY data, the existence of a lantern-shaped Pd2L4 topology can be dismissed in the equilibrated reaction mixture. *geometry optimization terminated prematurely due to convergence issues Figure S11. Three superimposed views, each, comparing the X-ray structure (light blue/green; Pd-Pd distance 8.18 Å) and B97-3c calculated structure (dark blue/green) of top: the interlocked topology as found in the crystal structure (Pd-Pd distance 8.30 Å) and bottom: the interlocked isomer (Pd-Pd distance 8.24 Å). Left and middle: views perpendicular to Pd2-axis, right: view along Pd2-axis.

Dissection of contributions driving dimer formation
In order to get insight into the enthalpic contributions driving dimerization of the mononuclear lemniscates, a number of calculations were performed. Therefore, one of the almost identical [BF4@Pd2L4] 3+ units found in the asymmetric unit of the X-ray structure including the encapsulated BF4anion was chosen for computations carried out in the Spartan '18 software package. 13 First, all nuclear positions except those of the hydrogen atoms were frozen. The latter were then optimized on semiempiric PM6 level of theory to correct CH and XH bond lengths with respect to the ones generated throughout X-ray refinement. Based on this structure, DFT single point calculations on ωB97X-D/6-31G* (LanL2DZ for Pd(II)) and ωB97X-D/def2-TZVP levels of theory were performed for the entire [BF4@Pd2L4] 3+ moiety and the following fragments, cut out from the whole assembly: S18 species E(ωB97X-D/6-31G*- S22 where ze is the ion charge, k B is the Boltzmann constant, µ is the reduced mass of analyte and carrier gas and N 0 is the number density of the neutral gas. For calibration of both the TIMS and TOF analysers, commercially available Agilent ESI tuning mix was used. The instrument was calibrated before each measurement, including each change in the ion mobility resolution mode ("imeX" settings: survey, detect or ultra).
Obtained ion mobility curves as well as derived CCS values are depicted in Figure 3 in the main text.