A M 2 L 2 Redox-Active Metalla-Macrocycle Based on Electron-Rich 9-( 1 , 3-Dithiol-2-ylidene ) Fluorene

A redox-active M2L2 metalla-macrocycle is depicted, of which construction has been achieved through coordination driven self-assembly from an electron-rich 9-(1,3-dithiol-2-ylidene)fluorene bis-pyridyl ligand and a cis-blocked square planar palladium complex (Pd(dppf)OTf2, dppf = 1,1′-Bis(diphenylphosphino)ferrocene). The resulting metalla-macrocycle has been fully characterized in solution, as well as in the solid state (X-ray crystal structure). Its electronic properties show that both constitutive ligands can be oxidized independently through a one-electron process.


Introduction
Since the pioneering example reported by Fujita [1], a plethora of ever more sophisticated metalla-rings and -cages constructed by coordination-driven self-assembly have been reported [2][3][4][5][6][7].This methodology takes advantage of the labile character of the coordination bonds to produce high yields and single step thermodynamically stable architectures, with complex structures that would be challenging to reach through traditional organic chemistry.These self-assembled architectures are usually characterized by an internal cavity that can be exploited in guest encapsulation leading to various applications such as chemistry in confined space [8,9] or drug delivery [10][11][12].Beyond the synthetic challenge in preparing such objects, there is a strong interest in providing them with functionality, as encountered with recently described stimuli responsive rings and cages structures [13][14][15][16].In this context, the preparation of redox-active metalla-rings/cages which allow a redox control over their overall charge appears relevant [17,18] and we described recently the first examples of electron-rich redox-active coordination cages capable of modulating their encapsulation properties through a redox stimulus [19,20].

Results and Discussion
The synthesis of ligand L4Pyr (Scheme 1) was carried out in two steps from 3,6-dibromo-9Hfluoren-9-one 1 adapted from our previous described procedure [29].A pallado-catalyzed Sonogashira cross coupling reaction with 4-ethynylpyridine affords the new compound 2 with 59% yield upon microwave irradiation.The subsequent Horner-Wardsworth-Emmons reaction was carried out with the 4,5-bis(hexylsulfanyl)-1,3-dithiol phosphonate ester 3 to afford the target new ligand L4pyr with 75% yield after purification.Slow evaporation of a CH2Cl2/EtOH solution of ligand L4Pyr allowed for obtaining single crystals suitable for X-Ray analysis.The corresponding solid-state crystal structure is depicted in Figure 1.Remarkably, the presence of two hexylsulfanyl chains did not prevent crystallization.As for its pyridin-3-yl homologous ligand [29], L4Pyr shows a nearly planar geometry with a slight folding of the dithiole rings (6° across the S•••S vector) and a slight twist of the pyridine units relatively to the central planar fluorene core with angles of ca.4.1°.As expected, the angle observed between both ethynyl axes is close to 90°, an angle that is therefore extended to the coordination angle provided by both nitrogen atoms of the pyridine fragments.Slow evaporation of a CH 2 Cl 2 /EtOH solution of ligand L4Pyr allowed for obtaining single crystals suitable for X-Ray analysis.The corresponding solid-state crystal structure is depicted in Figure 1.Remarkably, the presence of two hexylsulfanyl chains did not prevent crystallization.As for its pyridin-3-yl homologous ligand [29], L4Pyr shows a nearly planar geometry with a slight folding of the dithiole rings (6 • across the S•••S vector) and a slight twist of the pyridine units relatively to the central planar fluorene core with angles of ca.4.1 • .As expected, the angle observed between both ethynyl axes is close to 90 • , an angle that is therefore extended to the coordination angle provided by both nitrogen atoms of the pyridine fragments.
Reaction between ligand L4Pyr and complex Pd(dppf)OTf 2 (Scheme 1) was carried out in CD 2 Cl 2 and followed by 1 H-NMR.After 2 h, the reaction converged to a unique structure that could be isolated by precipitation with Et 2 O.The resulting 1 H-NMR spectrum exhibits a single set of well resolved signals as anticipated from a symmetrical discrete self-assembly (Figure 2).H 4 and H 5 signals are upfield shifted compared to ligand L4Pyr due to through-space interactions between the coligand phenyl units (dppf) and the pyridyl groups, confirming coordination to the metal center [22,24].Remarkably, the presence of two hexylsulfanyl chains did not prevent crystallization.As for its pyridin-3-yl homologous ligand [29], L4Pyr shows a nearly planar geometry with a slight folding of the dithiole rings (6° across the S•••S vector) and a slight twist of the pyridine units relatively to the central planar fluorene core with angles of ca.4.1°.As expected, the angle observed between both ethynyl axes is close to 90°, an angle that is therefore extended to the coordination angle provided by both nitrogen atoms of the pyridine fragments.Reaction between ligand L4Pyr and complex Pd(dppf)OTf2 (Scheme 1) was carried out in CD2Cl2 and followed by 1 H-NMR.After 2 h, the reaction converged to a unique structure that could be isolated by precipitation with Et2O.The resulting 1 H-NMR spectrum exhibits a single set of well resolved signals as anticipated from a symmetrical discrete self-assembly (Figure 2).H4 and H5 signals are upfield shifted compared to ligand L4Pyr due to through-space interactions between the coligand phenyl units (dppf) and the pyridyl groups, confirming coordination to the metal center [22,24].High resolution ESI-FTICR-MS spectrometry experiments were carried out to confirm the stoichiometry of the discrete self-assembled complex.Surprisingly, regardless of the instrumental conditions, the solvent and the concentration (10 −5 M < C < 10 −3 M), signal corresponding to the expected M2L2 ([Pd2(L4Pyr)2(OTf)4] − 2OTf] 2+ ; m/z = 1510.1598)was accompanied by mass peaks due to higher nuclearity assemblies.In particular are observed M4L4 ([[Pd4(L4Pyr)4(OTf)8] − 3OTf] 3+ ; m/z = 2064.1986)and sometimes M6L6 species (see Figures 3 and S8 for an illustrative example), whose relative abundances diminish with aggregates size.In accordance with the previously-mentioned DOSY experiment, such MS spectra suggest the presence in solution of M2L2 species that aggregate upon ESI to form dimers and trimers, a phenomenon that is known to occur at high concentration and with soft ionization conditions [33].High resolution ESI-FTICR-MS spectrometry experiments were carried out to confirm the stoichiometry of the discrete self-assembled complex.Surprisingly, regardless of the instrumental conditions, the solvent and the concentration (10 −5 M < C < 10 −3 M), signal corresponding to the expected M 2 L 2 ([Pd 2 (L4Pyr) 2 (OTf) 4 ] − 2OTf] 2+ ; m/z = 1510.1598)was accompanied by mass peaks due to higher nuclearity assemblies.In particular are observed M 4 L 4 ([[Pd 4 (L4Pyr) 4 (OTf) 8 ] − 3OTf] 3+ ; m/z = 2064.1986)and sometimes M 6 L 6 species (see Figure 3 and Figure S8 for an illustrative example), whose relative abundances diminish with aggregates size.In accordance with the previously-mentioned DOSY experiment, such MS spectra suggest the presence in solution of M 2 L 2 species that aggregate upon ESI to form dimers and trimers, a phenomenon that is known to occur at high concentration and with soft ionization conditions [33].Fortunately, single crystals could be grown by slow diffusion of MeOtBu in a CH2Cl2 solution containing [Pd2(L4Pyr)2(OTf)4] (C = 1 mM).X-ray crystallography analyses confirmed unambiguously the expected M2L2 stoichiometry (Figure 4).Two independent discrete assemblies were found in the crystal packing (Figure 4a).They exhibit a similar configuration but differ essentially by the dihedral angle between both dithiafulvenyl mean planes (DTF) (88.7° and 58.1 for blue and turquoise species respectively).The two forms interact through π-π interactions between their respective DTF units with interplanar distance of 3.45 Å, as well as CH-π interactions between DTF units and SHex chains.The geometrical characteristics of the constitutive L4Pyr ligand are mostly preserved in the metalla-macrocycle despite the fact that the average twisting between pyridine units and fluorene core increases to 12.5°.Fortunately, single crystals could be grown by slow diffusion of MeOtBu in a CH 2 Cl 2 solution containing [Pd 2 (L4Pyr) 2 (OTf) 4 ] (C = 1 mM).X-ray crystallography analyses confirmed unambiguously the expected M 2 L 2 stoichiometry (Figure 4).Two independent discrete assemblies were found in the crystal packing (Figure 4a).They exhibit a similar configuration but differ essentially by the dihedral angle between both dithiafulvenyl mean planes (DTF) (88.7 • and 58.1 for blue and turquoise species respectively).The two forms interact through π-π interactions between their respective DTF units with interplanar distance of 3.45 Å, as well as CH-π interactions between DTF units and SHex chains.The geometrical characteristics of the constitutive L4Pyr ligand are mostly preserved in the metalla-macrocycle despite the fact that the average twisting between pyridine units and fluorene core increases to 12.5  Fortunately, single crystals could be grown by slow diffusion of MeOtBu in a CH2Cl2 solution containing [Pd2(L4Pyr)2(OTf)4] (C = 1 mM).X-ray crystallography analyses confirmed unambiguously the expected M2L2 stoichiometry (Figure 4).Two independent discrete assemblies were found in the crystal packing (Figure 4a).They exhibit a similar configuration but differ essentially by the dihedral angle between both dithiafulvenyl mean planes (DTF) (88.7° and 58.1 for blue and turquoise species respectively).The two forms interact through π-π interactions between their respective DTF units with interplanar distance of 3.45 Å, as well as CH-π interactions between DTF units and SHex chains.The geometrical characteristics of the constitutive L4Pyr ligand are mostly preserved in the metalla-macrocycle despite the fact that the average twisting between pyridine units and fluorene core increases to 12.5°.UV-vis absorption spectra of ligand L4Pyr and metalla-macrocycle [Pd 2 (L4Pyr) 2 (OTf) 4 ] were recorded in dichloromethane at C = 1.5 × 10 −5 M (Figure 5).The absorption profile of L4Pyr reveals two high energy absorption bands at 290 nm and 350 nm attributed to π-π* transitions located on the fluorene and pyridines units respectively, whereas the intense low energy band at 460 nm (ε = 46,000 M −1 •cm −1 ) shows an ICT character from the HOMO localized on the DTF unit to the LUMO of the electron accepting pyridyles [34].The absorption spectrum of [Pd 2 (L4Pyr) 2 (OTf) 4 ] complex exhibits a similar profile with maxima shifted to lower energy (λ max = 483 nm) as expected from metal coordination, and ε values twice higher (ε = 102,000 M −1 •cm −1 ) accordingly to the metalla-ring formula.
UV-vis absorption spectra of ligand L4Pyr and metalla-macrocycle [Pd2(L4Pyr)2(OTf)4] were recorded in dichloromethane at C = 1.5 × 10 −5 M (Figure 5).The absorption profile of L4Pyr reveals two high energy absorption bands at 290 nm and 350 nm attributed to π-π* transitions located on the fluorene and pyridines units respectively, whereas the intense low energy band at 460 nm (ε = 46,000 M −1 •cm −1 ) shows an ICT character from the HOMO localized on the DTF unit to the LUMO of the electron accepting pyridyles [34].The absorption spectrum of [Pd2(L4Pyr)2(OTf)4] complex exhibits a similar profile with maxima shifted to lower energy (λmax = 483 nm) as expected from metal coordination, and ε values twice higher (ε = 102,000 M −1 •cm −1 ) accordingly to the metalla-ring formula.The electrochemical properties of ligand L4Pyr and complex [Pd2(L4Pyr)2(OTf)4] were studied by cyclic voltammetry in CH3CN/CH2Cl2 (1/1, v/v) (Figure 6).Ligand L4Pyr exhibits one reversible oxidation wave at E1 ox = 0.57 V vs. Fc/Fc + which is attributed to the formation of the DTF radical-cation [27,28].This potential is higher by 0.15 V compared to the one of the homologous ligand bearing two pyridine-3-yl units [29].This behavior is in accordance to previous observations on pyridine-4-yl (vs.pyridine-3-yl) mono substituted TTF based ligands [35] and accounts for the respective electronic effect of the nitrogen atom.The corresponding metalla-cycle complex presents two reversible oxidation waves.The first one, anodically shifted by 20 mV compared to the uncoordinated ligand is attributed to the oxidation of DTF units (E1 ox = 0.59 V vs. Fc/Fc + ) while the second is centered on the ferrocene moieties at E2 ox = 0.83 V, both processes presenting similar intensities.Altogether, this behavior suggests that both organic redox active DTF units behave independently upon oxidation to their radical cation state and that they do not interact electronically.The electrochemical properties of ligand L4Pyr and complex [Pd 2 (L4Pyr) 2 (OTf) 4 ] were studied by cyclic voltammetry in CH 3 CN/CH 2 Cl 2 (1/1, v/v) (Figure 6).Ligand L4Pyr exhibits one reversible oxidation wave at E 1 ox = 0.57 V vs. Fc/Fc + which is attributed to the formation of the DTF radical-cation [27,28].This potential is higher by 0.15 V compared to the one of the homologous ligand bearing two pyridine-3-yl units [29].This behavior is in accordance to previous observations on pyridine-4-yl (vs.pyridine-3-yl) mono substituted TTF based ligands [35] and accounts for the respective electronic effect of the nitrogen atom.The corresponding metalla-cycle complex presents two reversible oxidation waves.The first one, anodically shifted by 20 mV compared to the uncoordinated ligand is attributed to the oxidation of DTF units (E 1 ox = 0.59 V vs. Fc/Fc + ) while the second is centered on the ferrocene moieties at E 2 ox = 0.83 V, both processes presenting similar intensities.Altogether, this behavior suggests that both organic redox active DTF units behave independently upon oxidation to their radical cation state and that they do not interact electronically.

Chemicals
Compound 1 [36] and 3 [37] were synthetized as described in the literature.All reagents were of commercial reagent grade and were used without further purification.Silica gel chromatography was performed with a SIGMA Aldrich Chemistry SiO2 (pore size 60 Å, 40-63 µm technical grades) (Sigma-Aldrich, Steinheim, Germany).

Chemicals
Compound 1 [36] and 3 [37] were synthetized as described in the literature.All reagents were of commercial reagent grade and were used without further purification.Silica gel chromatography was performed with a SIGMA Aldrich Chemistry SiO 2 (pore size 60 Å, 40-63 µm technical grades) (Sigma-Aldrich, Steinheim, Germany).

X-ray Crystallographic Analysis
X-ray single-crystal diffraction data for L4Pyr and [Pd 2 (L4Pyr) 2 (OTf) 4 ] were collected at 150 K on an Agilent Technologies SuperNova diffractometer equipped with an Atlas CCD detector and micro-focus Cu Kα radiation (λ = 1.54184Å).Both structures were solved by direct methods and refined on F 2 by full matrix least-squares techniques using SHELX (G.M. Sheldrick, 2013-2016) package.All non-hydrogen atoms were refined anisotropically and the H atoms were included in the calculation without refinement.Multiscan empirical absorption was corrected using CrysAlisPro program (CrysAlisPro 1.171.38.41r,Rigaku Oxford Diffraction, 2015).
The structure refinement for [Pd 2 (L4Pyr) 2 (OTf) 4 ] showed disordered electron density that could not be reliably modeled, therefore PLATON/SQUEEZE was used to remove the corresponding scattering contribution from the intensity data.This electron density can be attributed to solvent molecules (methyl tert-butyl ether) and anions missing atoms (CF 3 SO 3 anions).The assumed solvent composition and missing anions atoms were used in the calculation of the empirical formula, formula weight, density, linear absorption coefficient, and F(000).
A 1 H-NMR DOSY experiment revealed a single set of signals that confirms the formation of a unique discrete species.From the corresponding diffusion value of D = 10 −10 m 2 •s −1 , a hydrodynamic radius of ca. 10 Å was estimated from the Stokes-Einstein equation (T = 298 K) [30], a value which is compatible with the formation of the expected tetracationic M 2 L 2 architecture [Pd 2 (L4Pyr) 2 (OTf) 4 ] [31,32].

Figure 1 .
Figure1.Remarkably, the presence of two hexylsulfanyl chains did not prevent crystallization.As for its pyridin-3-yl homologous ligand[29], L4Pyr shows a nearly planar geometry with a slight folding of the dithiole rings (6° across the S•••S vector) and a slight twist of the pyridine units relatively to the central planar fluorene core with angles of ca.4.1°.As expected, the angle observed between both ethynyl axes is close to 90°, an angle that is therefore extended to the coordination angle provided by both nitrogen atoms of the pyridine fragments.
A 1 H-NMR DOSY experiment revealed a single set of signals that confirms the formation of a unique discrete species.From the corresponding diffusion value of D = 10 −10 m 2 •s −1 , a hydrodynamic radius of ca. 10 Å was estimated from the Stokes-Einstein equation (T = 298 K) [30], a value which is compatible with the formation of the expected tetracationic M2L2 architecture [Pd2(L4Pyr)2(OTf)4] [31,32].