Expanded Ligands Based upon Iron(II) Coordination Compounds of Asymmetrical Bis(terpyridine) Domains

The synthesis and characterization of two tritopic ligands containing a 2,2′:6′,2″-terpyridine (tpy) metal binding domain and either a 3,2′:6′,3″- or a 4,2′:6′,4″-tpy domain are detailed. The synthetic routes to these ligands involved the [Pd(dppf)Cl2]-catalyzed coupling of a boronic ester-functionalized 2,2′:6′,2″-tpy with bromo-derivatives of 3,2′:6′,3″-tpy or 4,2′:6′,4″-tpy. The 2,2′:6′,2″-tpy domains of the tritopic ligands preferentially bind Fe2+ in reactions with iron(II) salts leading to the formation of two homoleptic iron(II) complexes containing two peripheral 3,2′:6′,3″-tpy or 4,2′:6′,4″-tpy metal-binding sites, respectively. These iron(II) complexes are potentially tetratopic ligands and represent expanded versions of tetra(pyridin-4-yl)pyrazine.


Introduction
Coordination entities result from the binding of a metal centre to a ligand [1], and the metal centres may be mono-or multinuclear. A ligand is a chemical species with one or more electrons available to bind a metal, and the electrons may be present in 'lone pairs' or chemical bonds of the ligand [1]. Ligands are typically small-to-medium-sized organic or inorganic molecules, ions, or radicals, and the ligand may bind to the metal centres through one or more atoms. The latter case is described as chelating [1], and it is convenient to describe chelating ligands in terms of their metal-binding domains [2]. Typical chelating metal-binding domains include carboxylate (in an O,O'-bidentate binding mode), 1,3-diketonates, 2,2 -bipyridine, 1,10-phenanthroline and 2,2 :6 ,2 -terpyridine.
A special case exists with ligands that possess additional metal-binding capacity after coordination to a metal centre. This additional capacity may be in a binding site that cannot coordinate to the same metal for steric or electronic reasons or, more rarely, when a potentially chelating ligand does not exhibit its maximum denticity. This latter situation is described as a hypodentate coordination mode [3]. A complex containing a ligand exhibiting a hypodentate bonding mode can act as a ligand itself. This new, metal-containing coordination unit has been described as a metalloligand [4][5][6][7][8][9].
The electrospray mass spectra of 1-4 were recorded in MeCN solutions with the addition of a few drops of formic acid. The base peak in each spectrum of 1, 3 and 4 arose from the [M+H] + ion (Figures S1-S3) while for 2, peaks at m/z = 518.21 and 1013.39 ( Figure  S4) were assigned to the [M+Na] + and [2M+Na] + ions, respectively. The 1 H NMR spectra of isomers 1, 3 and 4 are compared in Figure 1, and confirm the characteristic spectroscopic signature of each tpy isomer. The signals arising from the two OMe environments are little affected across the series of compounds. Assignments of the 1 H and 13 C{ 1 H} NMR spectra were made using COSY, NOESY, HMQC, and HMBC methods (Figures S5-S10). Upon going from 1 to 2, the aromatic region of the 1 H NMR spectrum is not significantly affected by the replacement of the bromo substituent by the boron-containing group. The effects of this change are most noticeable for the signals arising from protons H C6 and H C3 , and the OMe groups, as shown in Figure 2. The full 1 H NMR spectrum, and the HMQC and HMBC spectra for 2 are displayed in Figures S11-S13, and full assignments are given in the Materials and Methods section.  The electrospray mass spectra of 1-4 were recorded in MeCN solutions with the addition of a few drops of formic acid. The base peak in each spectrum of 1, 3 and 4 arose from the [M+H] + ion (Figures S1-S3) while for 2, peaks at m/z = 518.21 and 1013.39 ( Figure  S4) were assigned to the [M+Na] + and [2M+Na] + ions, respectively. The 1 H NMR spectra of isomers 1, 3 and 4 are compared in Figure 1, and confirm the characteristic spectroscopic signature of each tpy isomer. The signals arising from the two OMe environments are little affected across the series of compounds. Assignments of the 1 H and 13 C{ 1 H} NMR spectra were made using COSY, NOESY, HMQC, and HMBC methods (Figures S5-S10). Upon going from 1 to 2, the aromatic region of the 1 H NMR spectrum is not significantly affected by the replacement of the bromo substituent by the boron-containing group. The effects of this change are most noticeable for the signals arising from protons H C6 and H C3 , and the OMe groups, as shown in Figure 2. The full 1 H NMR spectrum, and the HMQC and HMBC spectra for 2 are displayed in Figures S11-S13, and full assignments are given in the Materials and Methods section.  The resonance for the CH3 protons in 2 at δ 1.32 ppm is not shown (see Figure S11 for the full spectrum).
The solution absorption spectra of 1-4 ( Figure 3) exhibit intense absorptions in the UV region arising mainly from spin-allowed π*←π transitions. Replacing the bromo by the dioxaborolane group has only a small impact on the absorption spectrum. In contrast, moving across the isomer series 1 to 3 to 4 leads to noticeable changes in the profile of the spectrum (Figure 3).    The resonance for the CH3 protons in 2 at δ 1.32 ppm is not shown (see Figure S11 for the full spectrum).
The solution absorption spectra of 1-4 ( Figure 3) exhibit intense absorptions in the UV region arising mainly from spin-allowed π*←π transitions. Replacing the bromo by the dioxaborolane group has only a small impact on the absorption spectrum. In contrast, moving across the isomer series 1 to 3 to 4 leads to noticeable changes in the profile of the spectrum (Figure 3)  The solution absorption spectra of 1-4 ( Figure 3) exhibit intense absorptions in the UV region arising mainly from spin-allowed π*←π transitions. Replacing the bromo by the dioxaborolane group has only a small impact on the absorption spectrum. In contrast, moving across the isomer series 1 to 3 to 4 leads to noticeable changes in the profile of the spectrum ( Figure 3).
The single crystal structures of 2, 3 and 4 were obtained. X-ray quality crystals of 2 were obtained directly from the isolated crystalline solid of 2 (see Section 3.3). Single crystals of 3 were grown from an EtOH/CHCl 3 solution stored at 2-5 • C for three days, and X-ray quality crystals of 4 were selected from the crystalline solid after the isolation of the bulk compound (see Section 3.5). Due to the similarities in their structures, we discuss the compounds together, starting at a molecular level and then moving on to the packing interactions. Compounds 3 and 4 crystallize in the triclinic space group P1 and monoclinic space group P2 1 /n, respectively, while 2 crystallizes in the orthorhombic space group Pbca. The asymmetric unit in each structure contains one independent molecule, and these are depicted in Figure 4. Bond lengths and angles are unexceptional, and selected parameters are given in the caption to  [21]. The angles between the least squares planes of adjacent pairs of pyridine rings containing N1/N2 and N2/N3 are 28.1 and 25.9 • in 3, 30.3 and 21.6 • in 4, and 26.2 and 9.5 • in 2. In each compound, the arene ring exhibits the typical twist with respect to the pyridine ring containing N2 in order to relieve repulsive H . . . H contacts (angle = 44.1 • in 3, 43.5 • in 4 and 50.3 • in 2). We note that Schwalbe et al. have reported the structure of 4 -(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,2 :6 ,2 -terpyridine (Scheme 4), and that in this compound, the BO 2 C 2 -ring (although slightly puckered) is approximately coplanar with the central pyridine ring of the tpy unit (Cambridge Structural Database [22], CSD, refcode FEKWEZ) [23]. In 4 -[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,2 :6 ,2 -terpyridine (2a, Scheme 4), the angles between the least squares planes of the central pyridine ring and the phenylene spacer, and the phenylene spacer and the BO 2 C 2ring (again, slightly puckered) are 23.5 and 3.4 • , and 39.6 and 10.6 • , respectively, for two independent molecules (CSD refcode NERZAO) [20]. The single crystal structures of 2, 3 and 4 were obtained. X-ray quality crystals of 2 were obtained directly from the isolated crystalline solid of 2 (see Section 3.3). Single crystals of 3 were grown from an EtOH/CHCl3 solution stored at 2-5 °C for three days, and Xray quality crystals of 4 were selected from the crystalline solid after the isolation of the bulk compound (see Section 3.5). Due to the similarities in their structures, we discuss the compounds together, starting at a molecular level and then moving on to the packing interactions. Compounds 3 and 4 crystallize in the triclinic space group 1 and monoclinic space group P21/n, respectively, while 2 crystallizes in the orthorhombic space group Pbca. The asymmetric unit in each structure contains one independent molecule, and these are depicted in Figure 4. Bond lengths and angles are unexceptional, and selected parameters are given in the caption to Scheme 4. Structures of the previously reported compounds 4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,2′:6′,2″-terpyridine [23] and (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,2′:6′,2″-terpyridine (2a) [20].

Scheme 4.
Structures of the previously reported compounds 4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,2′:6′,2″-terpyridine [23] and (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2,2′:6′,2″-terpyridine (2a) [20]. A trans,trans-conformation of the 2,2′:6′,2″-tpy unit is observed in 2 (Figure 4c), typical of non-coordinated tpy ligands. The conformation of the 3,2′:6′,3″-tpy unit in 3 ( Figure  4a) is one of three possible, limiting planar conformations (Scheme 5) and appears to be adopted in the crystal structure of 3 because of the assembly of the centrosymmetric motif shown in Figure 5. This features a combination of face-to-face π-stacking of pyridine rings containing N3 and N1 i (symmetry code i = 2 − x, 1 − y, 1 − z) and C23-H23...N1 i hydrogen A trans,trans-conformation of the 2,2 :6 ,2 -tpy unit is observed in 2 (Figure 4c), typical of non-coordinated tpy ligands. The conformation of the 3,2 :6 ,3 -tpy unit in 3 (Figure 4a) is one of three possible, limiting planar conformations (Scheme 5) and appears to be adopted in the crystal structure of 3 because of the assembly of the centrosymmetric motif shown in Figure 5. This features a combination of face-to-face π-stacking of pyridine rings containing N3 and N1 i (symmetry code i = 2 − x, 1 − y, 1 − z) and C23-H23 . . . N1 i hydrogen bonds (C23 is in one of the methyl groups, see Figure 4a). For the π-stacking interaction (Figure 5a), the centroid . . . centroid distance is 3.93 Å, and the angle between the ring planes is 29.2 • . While these parameters are not optimal [24], the interaction is supplemented by CH methyl . .    [25] for compounds containing a Bpin unit with a trigonal planar boron atom attached to an aryl of alkenyl unit (see Figure S14 in the Supporting Materials for the search motif) gave 487 compounds, 261 of which contained C-H . . . B contacts in which the H . . . B distance was less than or equal to the sum of the van der Waals radii; normalized H coordinates were applied within the program Conquest [25] to make the bond length equal to the average neutron diffraction value. Disordered structures were excluded. The range of CH . . . B distances was 2.58-3.02 Å with a mean value of 3.02 Å, and the C-H . . . B angles ranged from 100.6 to 177.9 • with a mean value of 145.1 • . The parameters for the interactions in 2 are comparable to these mean values. The nature of the interaction is ambiguous: the boron atom could act as a Lewis acid with the C-H bond as a donor, or the C-H σ* orbital could accept electron density from the π-bonding orbitals of the B-O or B-C aryl/alkenyl bonds.

Synthesis and Characterization of the Asymmetrical Bis(Terpyridine) Ligands 5 and 6
Compounds 5 and 6 were prepared using palladium-catalyzed cross coupling reactions of the boronic ester 2 with the two bromo-derivatives 3 and 4 (Scheme 6). The asymmetric bis(terpyridines) 5 and 6 were isolated in 57.4 and 36.2% yields, respectively, after purification. Both electrospray and high-resolution ESI mass spectra were recorded and showed peaks assigned to [M+H] + . For 5, the base peak in the HR ESI-MS arose from the [M+H] + ion (m/z 737.2869) and the [M+Na] + ion was also observed at higher mass ( Figure S15 in the Supporting Materials). For 6, peaks at m/z 369.1476 and 737.2871 arose from the [M+2H] 2+ and [M+H] + ions, with the former corresponding to the base peak as shown in Figure S16. The assignments of the 1 H and 13 C{ 1 H} NMR spectra of 5 and 6 were made with the aid of COSY, NOESY, HMQC and HMBC experiments, and by comparing the spectra of 5 and 6 with those of compounds 1, 3 Figure 6 displays a comparison of the 1 H NMR spectra of 5 and 6. In addition to the signatures of the 2,2 :6 ,2 -and 3,2 :6 ,3 -tpy domains in the spectrum of 5, and of the 2,2 :6 ,2 -and 4,2 :6 ,4 -tpy domains in that of 6, both spectra show a clean separation of the signals for the four chemically and magnetically different OMe environments. The absorption spectra of 5 and 6 are discussed in the next section.
145.1°. The parameters for the interactions in 2 are comparable to these mean values. The nature of the interaction is ambiguous: the boron atom could act as a Lewis acid with the C-H bond as a donor, or the C-H σ* orbital could accept electron density from the πbonding orbitals of the B-O or B-Caryl/alkenyl bonds.

Synthesis and Characterization of the Asymmetrical bis(terpyridine) Ligands 5 and 6
Compounds 5 and 6 were prepared using palladium-catalyzed cross coupling reactions of the boronic ester 2 with the two bromo-derivatives 3 and 4 (Scheme 6). The asymmetric bis(terpyridines) 5 and 6 were isolated in 57.4 and 36.2% yields, respectively, after purification. Both electrospray and high-resolution ESI mass spectra were recorded and showed peaks assigned to [M+H] + . For 5, the base peak in the HR ESI-MS arose from the [M+H] + ion (m/z 737.2869) and the [M+Na] + ion was also observed at higher mass ( Figure  S15 in the Supporting Materials). For 6, peaks at m/z 369.1476 and 737.2871 arose from the [M+2H] 2+ and [M+H] + ions, with the former corresponding to the base peak as shown in Figure S16. The assignments of the 1 H and 13 C{ 1 H} NMR spectra of 5 and 6 were made with the aid of COSY, NOESY, HMQC and HMBC experiments, and by comparing the spectra of 5 and 6 with those of compounds 1, 3 (5) (5)2][NO3]2 was prepared from the corresponding chloride. Ligand 5 was dissolved in a mixture of MeOH and CHCl3, and addition of FeCl2·4H2O followed by an excess of aqueous NaNO3 (see Section 3.8) led to the
The electrospray and HR-ESI mass spectra of both iron(II) complexes were recorded, and each spectrum exhibited a peak arising from the [M-2BF 4 ] 2+ ion (m/z 764.67). The characteristic isotope pattern and half-mass peak separations are depicted in Figures S21  and S22. In the HR-ESI mass spectrum of [Fe(6) 2 ][BF 4 ] 2 , a low intensity peak was observed at m/z 1615.4979 corresponding to the [M-BF 4 ] + ion. The 1 H and 13 C{ 1 H} NMR spectra were recorded in CD 3 CN; the addition of a few grains of solid K 2 CO 3 to the solutions in the NMR tubes led to a sharpening of the signals. The spectra were assigned using NOESY, COSY, HMQC, and HMBC methods and through comparison with the corresponding uncoordinated 5 and 6. Figures S23-S26 show the HMQC and HMBC. Coordination of ligands 5 and 6 to iron(II) results in significant changes in the chemical shifts of the signals for protons H A6 , H B3 and H C6 (Figure 7 and Figure S27). These protons are all associated with the 2,2 :6 ,2 -tpy metal-binding domain (see Scheme 6). The large shift to lower frequency for H A6 is typical of the formation of {M(2,2 :6 ,2 -tpy) 2 } n+ units as the H A6 protons of one ligand experience shielding since these protons lie over the aromatic system of the second ligand. Protons H B3 and H C6 are both influenced by the change in conformation of the 2,2 :6 ,2 -tpy from trans,trans to cis,cis upon coordination to Fe(II).    concentration of 2.0 × 10 -5 mol dm -3 using MeCN. MeCN solutions were used for the other three compounds. The spectra of 5 and 6 exhibit intense absorptions in the UV region arising mainly from spin-allowed π*←π transitions. The approximate doubling of the extinction coefficients in the high-energy region on going from free ligand to complex is consistent with the formation of [FeL2] 2+ species. The spectra of [Fe (5)   Attempts to grow X-ray quality crystals of [Fe (5) 2+ , and with mixtures of the two counterions. In the absence of a single crystal structure, the structure of the [Fe(6) 2 ] 2+ ion was optimized at a molecular mechanics level (MM2) using the program Spartan 18 (v. 1.4.8) [26], and the dimensions of this "expanded ligand" were compared with a related 'simple ligand'. The simplest analogue is tetra(pyridin-4-yl)pyrazine. While structures of two zinc(II) complexes of this ligand have been reported [27], the structure of the ligand itself has not. The modelled structure (MM2 level [26]) is shown in Figure 9a

General
1 H, 13 C{ 1 H} and 2D NMR spectra were recorded at 298 K on a Bruker Avance III-50 spectrometer (Bruker BioSpin AG, Fällanden, Switzerland) equipped with a BBFO probe head. The 1 H and 13 C NMR chemical shifts were referenced with respect to residual so vent peaks (δ TMS = 0). A Shimadzu LCMS-2020 instrument (Shimadzu Schweiz GmbH 4153 Reinach, Switzerland) was used to record electrospray ionization (ESI) mass spectra and a Bruker maXis 4G QTOF (Bruker BioSpin AG, Fällanden, Switzerland) instrumen for HR ESI mass spectra. A PerkinElmer UATR Two instrument (PerkinElmer, 860 Schwerzenbach, Switzerland) and a Shimadzu UV2600 (Shimadzu Schweiz GmbH, 415 Reinach, Switzerland) spectrophotometer were used to record FT-IR and absorption spec

Compound 2
A 100 mL Schlenk tube was charged with compound 1 (1.00 g, 2.23 mmol), B 2 pin 2 (0.680 g, 2.68 mmol), KOAc (0.657 g, 6.69 mmol) and [Pd(dppf)Cl 2 ] (0.049 g, 0.067 mmol). The reaction vessel was flushed with nitrogen, then degassed DMSO (25 mL) was added, and the mixture was stirred and heated at 110 • C for 24 h. After allowing it to cool to room temperature, the mixture was diluted with toluene (100 mL) and was washed with brine (4 × 50 mL). The toluene layer was dried over Na 2 SO 4 and was then filtered. The solvent was removed by rotary evaporation, yielding a brown residue, which was redissolved in CH 2 Cl 2 and filtered through a celite pad. The brown portion was retained by the celite, while the colorless solution was dried, giving 2 (0.555 g, 1.