Modulation of a Supramolecular Figure‐of‐Eight Strip Based on a Photoswitchable Stiff‐Stilbene

Abstract The preparation, assembly and dynamic properties of photoswitchable bisphosphine ligands based on the stiff‐stilbene scaffold are reported. Directional bonding and coordination‐induced assembly allow complexation of these ligands with palladium(II), resulting in the formation of discrete metallo‐supramolecular entities. While the Z isomer forms a simple bidentate metallo‐macrocycle, an intricate double helicate figure‐of‐eight dimer is observed with the E ligand. Topologically 3D complexes can thus be obtained from 2D ligands. Upon irradiation with UV light, isomerization of the ligands allows control of the architecture of the formed complexes, resulting in a light‐triggered modulation of the supramolecular topology. Furthermore, a mechanistic investigation unveiled the dynamic nature of the helicate chirality, where a transmission of motion from the palladium centers yields an „eight‐to‐eight“ inversion.

Molecular structures with ac omplex topology such as figureof-eightstrips have attracted attentionnot only because of the intrinsic aesthetica ppeal, [1] but also for their occurrence in natural compounds such as Lissoclinamide7 ,amarine alkaloid with high cytotoxicity. [2] Furthermore, this structuralm otif was observed in the recombinant structure of circularD NA. [3] Movinga way from the toolbox of biogenic molecules allows for more adaptability in the design of synthetic mimics to create artificial systems following am inimalistic approach compared to complex bio-macromolecules. [4] Various strategies have been introduced to engineer systems adopting this con-formation. [5] These include templatingflexible macromolecules with metals [6,7] and organic effectors, [8,9] or using ar igid core to provide helical chirality [10] andi nduce at wisted conformation. [11,12] This topology can be elusive [13] or persistent, [14] depending on the strategy.
Recently,S auvage and co-workers reportedt he assembly of af lexible macrocycle into am etallo-supramolecular figure-ofeight motif by binding to copper, [6] while the work of Anderson et al. focusedo nt he generation of this topologyu sing organic molecules. [8] However,t he control of structural information in supramolecular entities using externala ctuators in combination with such intricate topologiesi ss till rare. [23] Typically, rigid ligandsw ith well-defineda ngles between the complexing moieties lead to highly defined structures such as pores [17] or cages. [24,25] Alternatively,amore flexible design of the backbone can increase the supramolecular complexity for example, extended (double-) helical structures. [1,26,27] We were interested in designing minimalistic ligands for the photoaddressable self-assembly of complexes with such chiral three-dimensional topology.H erein, we report the forging of intricate chiral assemblies from rigid, structurally simple yet photoresponsive bisphosphinel igands.
Photochemical switches based on overcrowded alkenes [28] such as stiff-stilbenes offer opportunities as templates for supramolecular assemblies (Figure 1a). [29,30] The largegeometrical change induced upon isomerization-withd ihedrala ngles of ca. 08 and 1808 for the Z and E isomers, respectively-yields drastic differences between the molecular architectures. [17] Furthermore, these rigid ligandsw ith encoded directionality are ideal for coordination-drivens elf-assembly using directional bondingw hilem aintaining ar esponsive behavior,a sp roposed by Stang and co-workers. [31] This approachh as been explored to create intricate, polymeric [17] metallo-supramolecular assemblies and generates complexity from simple molecules in adaptive systems. [32] We envisionedt hat using an easily accessible stiff-stilbene skeleton would enable the preparation of self-assembled, neutral palladium complexes with topologically complexa rchitectures (Figure1b). The rigidity of the ligand, combinedw ith the moderate energy of the coordinationb ond, facilitates the generation of discrete metallo-macrocyclic structures, including a figure-of-eight strip, using simple scaffolds.E xploiting their intrinsic responsive nature, switching between these ligands was observedu ponl ight irradiation, allowingt he reversible control of chiral architectures.
Bisphosphinel igands Z-2 and E-2 were prepared in two steps from the corresponding dibromides [33] (Scheme 1), which were readilyc onverted to Z-1/E-1 in an aromatic Finkelstein reaction following ap rocedureb yB uchwald. [34] The resulting iodides proved suitable forp hosphination. While different conditions weren eeded to provide each isomer, Z-2 and E-2 were obtained in moderate to good yields (see Supporting Information).
The electron density of the isomeric phosphines was compared via the corresponding selenide,p repared by refluxing the phosphine compounds with an excesso fs eleniumi n chloroform (see Supporting Information), and analyzed using 31 PNMR. The resulting phosphorouss ignal appeared at 32.5 ppm and 33.0 ppm for the Z and E compounds, respectively.The 1 J( 77 Se-31 P) spin-spin coupling wasfound to be equal in both isomers (364 Hz), suggesting similard onor properties of the phosphine lone pair of both ligands Z-2 and E-2. [35] The photoswitching of the isolated bisphosphines was studied in N 2 -purged benzene (or [D 6 ]benzene) solutionst hrough UV-vis and NMR spectroscopy.T he absorption spectrumo fZ-2 (l max = 356 nm) showedadistinct bathochromic shift compared to that of E-2 (l max = 338 and 356 nm), hence wavelengths of 365 and 385 nm were used to inducet he E!Z and Z!E isomerization,r espectively.I nb oth cases, the photostationary states were reached by prolonging the irradiation until no further spectralc hanges wereo bserved. Consequently,t he E-isomer was convertedi nto the Z with a3 65 nm LED at 20 8C resultingi nt he decrease of the absorption bands with maxima at 338 and 356 nm. The photostationary distribution associated to this conversion was 54:46 E:Z (Figure 2a). Irradiating the sample at shorter wavelengths did not improve the photostationary state (PSS). On the other hand, the Z isomer was converted quantitativelyi nto the E form via irradiation with l = 385 nm light, restoringt he 338 and 356 nm absorption bands (Figure 2b). The presence of isosbestic points corroborates the unimolecular nature of the photochemical transition, while the possibility to cyclem any times between the two irradiation wavelengths provided evidenceo ft he stabilityo ft he photoswitch( Figure 2a).  Upon complexation of each bisphosphine ligand 2 with Pd(CH 3 CN) 2 Cl 2 in toluene at room temperature, as ingle product was observedb y 1 Ha nd 31 PNMR. Z-2 formed the symmetrical complex Z-3 in excellent yield (Figure 3, see Supporting Information). In [D 6 ]benzene, ad eshielded aromatic signal at 10.41 ppm appeared as at riplet, suggesting the presence of virtual couplingb yc omplexation of palladium in a trans fashion. [36] Trans complexation with palladium was also supported by the downfield shift of the phosphine signal by 31 PNMR at 20.6 ppm. [37] Diffusion Ordered Spectroscopy (DOSY) NMR confirmed the presence of as ingle compound with ad iffusion coefficient of 5.50 10 À6 cm 2 s À1 in [D 6 ]benzene. This corresponds to ar adius of about6 .68 ,i nl ine with the formation of a monomeric bidentate palladium complex. Finally,asingle species was observed by Electrospray Ionisation Mass Spectroscopy (ESI-MS) for the [Z-3-Cl] + ion. Treatment of Z-2 with one equivalent of K 2 PtCl 4 in am ixture of benzene, ethanol and water formed as imilars pecies (see Supporting Information), as confirmed by 1 H, 31 PNMR, as well as ESI-MS.P resumably, Z-2 chelates Pt II in a trans-spanning bidentate complex in as imilar fashion to Pd II .
Single crystalss uitablef or X-ray diffraction were grown from as aturated solutiono fZ-3 in CDCl 3 .T he structure obtained confirmed the trans arrangement of the phosphine atoms, with the chloride atoms pointing perpendicularly to the ligand's plane (Figure 3d). The palladiuma tom was found to be slightly out of planarity (ffPPdP' = 164.88)i no rdert oa rrange for chelation, while the ligand adopts as kewed conformation, with adihedral angle of 29.48 between the two phosphines.
Interestingly,t he 1 HNMR spectrum of the only product of the reactiono fE-2 and Pd(CH 3 CN) 2 Cl 2 included diastereotopic signals in the CH 2 region, while the 31 PNMR showedo nly one phosphine signala ta round 21.8 ppm (Figure 3). This, together with the highly deshielded 1 Ht riplet at 9.61 ppm, indicated the formation of an alternative complex E-3.W hile the 31 PNMR suggested the formation of ad iscrete metallo-supramolecular entity,t he 1 HNMR pointedt owardsachiral complex. ESI-MS of the product revealed the presence of as ingle ion of am ass corresponding to [E-3-Cl] + .S imilarly,D OSY NMR confirmed the presence of as ingle species with ad iffusion coefficiento f3 .56 10 À6 cm 2 s À1 in [D 6 ]benzene, supporting the formation of a dimer.R emarkably,w hile the group of Stang and co-workers described the formation of metallo-supramolecular polymers using stiff stilbene incorporating pyridine ligands, [17] we only observed the discrete dimeric species E-3 with the phosphorus-based system. Ligand E-2 also formed dimericc omplexes when reactedw ith platinum(II) (see Supporting Information). However,d ue to the preference of platinum for cis-chelation,a conformationally heterogenous mixture of dimers was observed by 31 PNMR (see the Supporting Information). This configurational inhomogeneity prevented furthera nalysis( vide infra).
Calculation of the structure of E-3 by DFT (wB97X-D/def2-TZVP(def2-TZVPP,SDD)//M06-L/6-31G*(LANL2DZ)) confirmed the existence of ad imeri nw hich each palladium center binds with one phosphine atom of each ligand in a trans fashion (see the Supporting Information). The stiff-stilbenes were found to lie antiparallel to one another,generating ab is-helical structure. Thes ame structure was found by X-ray diffraction of crystalso fE-3 grown by vapor diffusion of diisopropyl ether into as aturated solution of this compound in tetrahydrofuran (Figure 3h). In this structure, the bisphosphine ligands are slightly twisted out of planarity, with ad ihedral angle of 175.38 aroundt he double bond. The figure-of-eight motif was thus confirmedb yt he presence of at ightly packed double helicate, connected at each extremity by coordination with ap alladium atom. [38] The increase of three-dimensionalityu pon complexation was demonstrated by analysiso ft he Potential Moment of Inertia of Z-2 and E-2 compared to Z-3 and E-3 using LLAMA (see the Supporting Information). [39] The conformationald ynamics of complex E-3 were then investigated by Chiral Stationary Phase HPLC. Twod istinct peaks were observed (Figure 4a). Thorough analysis of the chromatogram at 25 8Cr evealed that full resolution could not be achieved as ap lateau waso bserved. This suggested the dynamic nature of the system,t hat is, enantiomeric interconversion of the double helicate. Dynamic HPLC was used to probe the kinetic profile of this interconversion. [40] The column temperature was adjusted to control on-columni nterconversion from 22 to 37 8C. Retention times were kept as low as possible to prevent interaction with the stationaryp hase to have an impacto nt he barriert oi nterconversion. [41] When raising the temperature, the height of the plateauw as found to increase, at ypical characteristic of chiral compoundsr acemizing within minutes at room temperature. [42] Using the unifiede quationd eveloped by Trapp, [42] the kinetics of enantiomerization could be calculated by Eyring analysis.
Complex E-3 readily interconverts at 25 8Cw ith an oncolumn barrier to racemization DG ¼ 6 293 K = 92.7 AE 0.6 kJ mol À1 , corresponding to ah alf-life of racemization of ca. 32 min at 20 8C. The enthalpy of activation was found to be DH ¼ 6 = 46.9 kJ mol À1 with an entropy value DS ¼ 6 = À155.5 Jmol À1 K À1 . The negative entropic factor suggestst he absence of ad issociative mechanism. Racemization therefore likely occur by gear slippage via ah ighly symmetrical transition state where the palladium centers serve as midpoints of molecular motion. [43] This reaction plausibly populatest he meso form intermediate E-3' whichc ould not be observed due to its intrinsic instability compared to E-3 (calculated DG ¼ 6 293 K = 36.5 kJ mol À1 ,s ee Figure 4b). The enantiomers of the corresponding dimers, formed with platinum insteado fp alladium, could not be separated under similar conditions even at 0 8C( See SupportingI nformation). The stronger PtÀPb ond, together with the larger Van der Waals radius of platinum vs. palladium and the seemingly lower interconversion barrier of the Pt II dimers suggests indeed that enantiomerization of E-3 occurs through an associative mechanism.
In conclusion, we prepared and characterized photoswitchable bisphosphine ligands based on as tiff-stilbenes caffold. Complexation of each isomer with palladium(II) resulted in the selectivef ormation of discrete palladamacrocycles.W hile the Z ligand complexed in ab identate fashion, the E isomer formed ad imerics pecies. Interestingly,t he rigidity and directionality of this compound forced at opologically complex figure-of-eight strip, as demonstrated by DOSY NMR, mass spectrometry and X-ray diffraction. Both enantiomerso ft his supramolecule were observed by CSP-HPLC. Enantiomerici nterconversion readily occurred at room temperature as demonstrated by on-column helix inversion. Most likely,e nantiomerization happens through ar igid transition state produced via gear slippage where the palladium(II) centers act as transmitters of molecular motion. This study demonstrates that the degree of three-dimensionality of higher-order structures obtainedb yc oordination-driven self-assembly can be controlledb yi somerization of simple, rod-like planar ligands featuring directional bonding.