Synthesis, spectroscopic and crystallographic analysis of the Zn-complex of a di(β,β′-sulfoleno)pyrrin: model for Zn-complexes of bilirubin and of phylloxanthobilins

Abstract A high yield preparation, spectroscopic and crystallographic investigation of the crystalline Zn-complex of a di(β,β′-sulfoleno)pyrrin are reported here. In the brightly green fluorescent Zn-complex of the hardly luminescent di(β,β′-sulfoleno)pyrrin, the metal ion is bound by two di(β,β′-sulfoleno)pyrrin ligands, as revealed first by its mass spectra. The crystal structure of this Zn-complex of the di(β,β′-sulfoleno)pyrrin confirmed a regular 2:1 composition of the bidentate di(β,β′-sulfoleno)pyrrin ligand and the metal ion. The latter was coordinated in a distorted tetrahedral fashion, as found in other dipyrrin Zn-complexes. The here studied Zn-complex of a designed di(β,β′-sulfoleno)pyrrin ligand provides insights into the coordination properties of the proposed (2:1)- and (2:2)-complexes of phylloxanthobilin and bilirubin, respectively, which are two abundant natural bilin-type tetrapyrroles. Graphical abstract


Introduction
Dipyrrins (or dipyrromethenes) feature two conjugated pyrrole rings and represent (formal) dipyrrolic building blocks for the construction of porphyrins and related tetrapyrrolic macrocycles [1]. The complexes of the bidentate dipyrrins with boron (the 'BODIPY'-complexes) [2] or with transition metal ions [3,4] have attracted particular attention due to the 'predictable' coordination properties of dipyrrins, and the tunable emission and absorption properties of their metal complexes [5][6][7][8][9]. Hence, the design of dipyrrin ligands has been attractive, and dipyrrin chemistry has taken advantage of the development of a broad range of strategies for their construction [2-5, 7, 8]. In one approach (used here), dipyrrins are prepared by dehydrogenation of easily accessible corresponding dipyrromethanes [3,4].
In the context of our recent interest in the metal coordination properties of yellow chlorophyll catabolites Dedicated to Prof. Ulrich Schubert on the occasion of his 70th birthday.

Results and discussion
Our synthetic route to di(b,b 0 -sulfoleno)pyrrin 2 relied on the earlier made corresponding di(b,b 0 -sulfoleno)pyrromethane (1), available, in turn, from condensation of 3,5-di-tertbutylbenzaldehyde and b,b 0 -sulfolenopyrrole [13]. Dipyrromethane 1 was oxidized with dicyanodichlorobenzoquinone (DDQ) to furnish bright yellow 2 in 76 % yield, after crystallization in CH 2 Cl 2 /n-C 6 H 14 (see Scheme 1). The UV/Vis spectrum of the dipyrrin 2, displayed in Fig. 1, exhibits characteristic maxima at 436.5 and 327 nm, comparable to the one of bilirubin [14,15], or of a recently described yellow chlorophyll catabolite (YCC, a phylloxanthobilin) [16,17]. A FAB-mass spectrum featured a strong pseudo-molecular ion at m/z = 513.1 [M ? H] ? , confirming its molecular formula as C 27 H 32 N 2 O 4 S 2 . Fragments at m/ z = 448.2 and 384.2 indicated consecutive loss of the two SO 2 -groups. The 1 H NMR spectrum of 2 exhibited two singlets at intermediate field of the two pairs of symmetry equivalent b-methylene groups, a singlet at 7.58 ppm of the pyrrole-a positions, the signals of aryl o-and p-protons at low field, and a broad signal of an NH at 12.76 ppm (see Fig. 2, bottom).
For the preparation of 3, a solution of 15 mg of Zn(OAc) 2 2H 2 O (68.4 lmol, 18 eq) in 0.3 cm 3 MeOH was mixed into a solution of 2 mg 2 (3.8 lmol) in 2.7 cm 3 of CH 2 Cl 2 at room temperature. After 5 min, the reaction mixture was worked up by extraction and evaporation of the solvent (see ''Experimental'' part). The Zn-complex 3 crystallized from CH 2 Cl 2 /n-C 6 H 14 as pink-red crystals (2.0 mg, 94 % yield).
The molecular formula of the dipyrrin Zn-complex 3 was indicated as C 54 H 62 N 4 O 8 S 4 Zn from analysis of its pseudo-molecular ion [M?H] ? at m/z = 1087.2. Corresponding significant fragments occurred at m/z = 1023.3, 894.4, and 830.4, due to consecutive loss of the one, three, and four SO 2 -groups, respectively. The derived molecular formula of the Zn-complex 3 suggested the presence of two dipyrrin ligands 2 and one Zn(II)-ion, i.e. to represent Zn-(2) 2 (see Scheme 2).
The pink-red Zn-complex 3 displayed a UV/Vis-spectrum in CH 2 Cl 2 that featured a maximum at 487 nm (and a shoulder at 463 nm), corresponding to a 51 nm bathochromic shift, when compared with the spectrum of the dipyrrin 2 (see above). Similar bathochromic shifts of the absorption spectrum upon coordination of a Zn(II) ion were observed in Zn-complexes of bilirubin [18], or of phylloxanthobilins [10,12]. Analysis of the Zn-complex 3 by fluorescence spectroscopy showed an intense emission band at 505 nm, whereas the metal-free dipyrrin 2 displayed little luminescence with a maximum around 530 nm (see Fig. 3). The excitation spectrum of dipyrrin Zn-complex 3, observed at 505 nm, fitted the absorption spectrum of 3. As, in contrast, the dipyrrin 2 was essentially nonluminescent in CH 2 Cl 2 , the rapid coordination of Zn ions and formation of 3 lightened up an intense green luminescence with about 200-300-fold higher intensity (see Fig. 3).
In the 1 H NMR spectrum (in CDCl 3 , see Fig. 2) of the Zn-complex 3 [Zn-(2) 2 ], a signal of an HN was lacking (which was found at 12.76 ppm in the spectrum of the dipyrrin 2), consistent with bidentate binding of the dipyrrin ligand 2 to the coordinated Zn(II) ion. Signals of aryl-o hydrogens and aryl-p hydrogen are slightly shifted to lower field while signals of b-methylene groups and pyrrole-a hydrogens are slightly moved to higher field. X-ray diffraction quality crystals of the Zn-complex 3 grew from a solution of 3 in CH 2 Cl 2 when n-C 6 H 14 was

Scheme 1
Fig. 1 UV-Vis spectra of the dipyrrin 2 and of its Zn-complex 3 (=Zn-(2) 2 ) in CH 2 Cl 2 (4 9 10 -6 mol/dm 3 ) mixed in slowly at 4°C. The Zn-complex 3 crystalized in the triclinic system with space group P-1 (no. 2). A unitcell contained four molecules of 3. The crystal structure of 3 showed two bidentate dipyrrin moieties wrapped around one Zn(II) center leading to coordination in a distorted tetrahedral fashion with N-Zn-N angles of about 94, 113, and 121° (Fig. 4). The bonds of the four N atoms to the coordinated Zn ion are 1.98 Å long, consistent with crystallographic data from other Zn-dipyrrin complexes (1.96-1.98 Å ) [19][20][21]. The structure of 3 in the triclinic crystal deviates slightly from the symmetric model reported for crystals of other bis(dipyrrinato) Zn-complexes [19]. The planes of the two dipyrrin ligands are roughly vertical to each other (82°dihedral angle), as are the aryl groups at the 5-position with respect to the conjugated pyrrole system in the same ligand moiety (85°). Thus, the plane defined by one aryl group at the meso-position is observed at 3.8°with respect to the plane of the conjugated pyrrole system in the other ligand. In contrast, the other aryl group at 5-position is inclined by 17.1°with respect to the conjugated pyrrole system in the second dipyrrin unit. Probably, these small symmetry-deviations are consequences of the packing in the triclinic crystal. The bond lengths and bond angles within the dipyrrin ligands in 3 are similar to those of other bis(dipyrrinato) Zn-complexes [19][20][21]. The crystal structure of 3 reflects the symmetric, bidentate coordination behavior of the dipyrrin 2. Thus, the Zn-complex 3 may represent a valuable model for the chelation pattern in non-crystalline Zn(II)-complexes of natural oligopyrroles with similar chromophores, e.g. of bilirubin [18] or of the phylloxanthobilin YCC [10].

Scheme 2
Synthesis, spectroscopic and crystallographic analysis of the Zn-complex of a di(b,b 0 -… Conclusion Dipyrrin 2 is a yellow dipyrrole that possesses two conjugated pyrrolic rings and shows negligible luminescence. It may be considered a simple model compound for the chromophore part of some natural tetrapyrroles, such as the heme-derived bilirubin (BR) [14,15] and phylloxanthobilins [17] or yellow chlorophyll catabolites (YCCs) [10,16]. Binding of Zn(II) ions to the bidentate 2 furnishes the 2:1 complex 3, the crystal structure of which exhibited a distorted tetrahedral structure. This type of coordination pattern was derived for the (2:1)-complex of a YCC with Zn(II) ions [10]. Similar, furthermore, to observation with the Zn(II)-complex of the YCC [10], the bis(dipyrrinato) Zn-complex 3 displays intensive green luminescence. Hence, the present study helps to model the coordination behavior of Zn-complexes of natural oligopyrroles with similar conjugated chromophores, e.g. of BR [18] or of YCC [10,12], and to gain basic insights into their luminescence properties. Bis(dipyrrinato) Zn-complexes, and related boron complexes of dipyrrins (BODIPYs) [2], exhibit intensive and tunable absorption and emission properties, which make them useful in various optical applications [5][6][7]9]. In contrast to BODIPYs, bis(dipyrrinato) Zn-complexes exhibit a tetrahedral coordination pattern in 2:1 assemblies (ligand: Zn), giving them considerable potential in supramolecular structuring [21,22]. The sulfoleno-units of the dipyrrin 2 and of the bis(dipyrrinato) Zn-complex 3 are, furthermore, 'programmed' for introduction of covalent modifications at the pyrrole b-positions by [4?2]-cycloaddition reactions. As was recently developed with porphyrinoids, such as tetrasulfolenoporphyrins [23][24][25] and a tetra-sulfolenocorrole [13], the dipyrrinato-units of 2 and 3 could, thus, also open up efficient access to further designed functionalized supramolecular assemblies.

5-(3,5-Di
To the solution of 2 mg dipyrromethane 1 (3.8 lmol) [13] in 1 cm 3 CH 2 Cl 2 1.4 mg DDQ (6.2 lmol, 1.6 equiv) was added. After 20 h at room temperature, the reaction mixture was diluted to 20 cm 3 with CH 2 Cl 2 and washed with saturated aq. NaHCO 3 (3 9 15 cm 3 ). The organic phase was filtered through a plug of dry cotton-wool and evaporated to dryness under reduced pressure to give a brown residue. The residue was dissolved in 1.5 cm 3 CH 2 Cl 2 and loaded on a silica gel column (1.5 9 10 cm). The product was washed down with CH 2 Cl 2 /EtOAc 10/1 (v/v). The collected product fractions were combined and concentrated to dryness under reduced pressure to furnish 2     (2)  Copies of the data can be obtained free of charge from the Cambridge Crystallographic Data Centre via http:// summary.ccdc.cam.ac.uk/structure-summary-form.