4 Summary BINOL = 24 Biphenol = 31 Figure 4.1:

Transcription

1 4 Summary The main aim of this work was the synthesis of lanthanide cryptates that can be used as building blocks in solid phase peptide synthesis. The latter is a promising method for the construction of multinuclear lanthanide complexes, which combine the unique physical properties of several lanthanide ions. This requires lanthanide complexes, which are, on the one hand, stable under relatively acidic conditions and, on the other hand, provide the necessary functionalization. Another goal was the synthesis of anionic ligands, which can reduce the overall charge of the lanthanide complexes and consequently minimize the repulsion interaction between them. For both synthetic strategies, it was taken into account that the cryptates should contain a chromophore to sensitize lanthanide emission. The starting point for the first part was the synthesis of several sodium cryptates and their characterization. a S S a 15 BIL = 24 Biphenol = 31 Figure 4.1: Investigated anionic cryptates. The depicted cryptates in figure 4.1 are based on the commercially available aza crownether 9. Three different units, which were thought to provide anionic charges and also a chromophore, were introduced to bridge this macrocycle. Formation of lanthanide cryptates of 15 could not be confirmed by ESI-MS. Therefore, this cryptand was considered to be not suitable for this work and hence, were not studied further. In contrast, cryptates 24 and 31 indeed formed complexes with lanthanide ions with a reduced charge (1) which was confirmed by ESI-MS. They both exhibit an axial chirality which emerges from the BIL and biphenol units. owever, both cryptates were synthesized in racemic mixtures. The triplet energy levels of both cryptands were determined using the corresponding gadolinium cryptates. While the biphenol cryptate exhibits a triplet energy level sufficiently high for sensitization of Tb(III) and Eu(III), the triplet energy of the BIL 73

2 cryptand is too low to sensitize emission from terbium. Unfortunately, all lanthanides cryptates containing the macrocycle 9 showed low kinetic stabilities under acidic conditions. This observation was true for all lanthanide cryptates containing macrocycle 9. a a 2 33 Figure 4.2: Promising cryptates with high kinetic stabilities. To improve the stability, the more flexible macrocycle 9 was replaced with the rigid bpy.bpy macrocycle 10. Therefore, sodium cryptate 33 was synthesized and, as intended, its lanthanide cryptates showed high kinetic stability under acidic conditions. These results were comparable to those for the isostructural cryptate 2 that was also found to form high kinetically stable complexes with all lanthanides. Moreover, cryptand 33 exhibits a higher triplet energy and consequently, sensitizes emission of both Tb(III) and Eu(III). With these two stable cryptates in hand (Figure 4.2), which both possess promising photophysical properties, further functionalization was performed. Two approaches were attempted by introduction of a functional group either to the bipyridine macrocycle 10 or to the respective bridging moieties (Figure 4.3). Approach I () () =, 2, CMe Approach II () () Figure 4.3: Retro synthesis of the mono substituted Cryptands. 74

3 For approach I, a bromide, a nitro and a carboxylic acid methyl ester group were introduced to the macrocyle 10. The corresponding sodium cryptates were synthesized by addition of either a biphenol or bipyridine, -oxide (Figure 4.4). The cryptates were obtained in diastereomeric mixtures due to the axial chirality of the bridging moieties. In addition the existence of three different arms with one being unsymmetrical, which cause an unusual chirality of the whole molecule. Although the introduction of different functional groups to the cryptates following approach I was found to be synthetically accessible, approach II offered the possibility to circumvent the formation of diastereomeres. a a = -CMe 58 = -CMe 60 = 62 = 2 63 Figure 4.4: Funcionalized cryptate based on biphenol(right) and biypridine dioxide (left). For approach II, synthetic efforts started with the application of two different strategies to obtain a functionalized biphenol moiety. owever, functionalization of phenol derivatives or directly of the 2,2 -biphenol remained unsuccessful. In contrast, introduction of the carboxylic acid methyl ester to bipyridine, -dioxide could be obtained in satisfactory yield and purity. It was then successfully reacted with the bipyridine macrocyle 10 to afford the corresponding functionalized cryptate 66 (Figure 4.5). The latter was obtained as racemic mixture due to the axial chirality of the bipyridine, -dioxide. The triplet energy level of this compound was shifted slightly towards low energies which is expected to decrease the ability of this cryptand to sensitize Tb(III). a Me 66 Figure 4.5: Methyl ester functionalized cryptate

4 All carboxylic acid methyl ester functionalized cryptates were successfully saponified to the corresponding carboxylic acids, which were coupled to Fmoc-lysine- in solution (Figure 4.6). The coupling product 93 was isolated and characterized with MR and ESI-MS. Remarkably, the europium complex of 93 proved to be stable even under harsh acidic conditions. In contrast, cryptate 94 could be observed in ESI-MS but isolation of the pure compound was not possible despite several attempts to optimize this reaction. Fmoc a Fmoc a Figure 4.6: The prepared building blocks for solid phase synthesis. In summary, building blocks for solid phase peptide synthesis were prepared from stable cryptates based on biphenol and bipyridine-, -dioxide. Therefore, different synthetic strategies for the incorporation of functional groups to cryptates were developed, and the relation between structure and photopysical properties were revealed. While coupling of these cryptates to an amino acid was shown to be possible, the optimization of these reactions still remain a challenging task for the continuation of this project. Within this work, the influence of the number of 2,2 -bipyridine moieties on the luminescence properties of europium was also investigated. Therefore, a series of cryptates with increasing number of 2,2 -bipyridine units was studied (Figure 4.7). While the cryptates 101 and 103 are already literature-known, cryptates 102 was synthesized and characterized to complete the series Ln Ln Ln little investigated unknown well investigated Ln = Gd 101a = Eu 101b Ln = Gd 102a = Eu 102b Ln = Gd 103a = Eu 103b Figure 4.7: Investigated 2,2 -bipyridine-based lanthanoid cryptates. 76

5 Triplet energy measurements using the gadolinium cryptate and lifetime as well as quantum yield determinations using the europium cryptate were performed in aqueous solution. It was found that with increasing number of bipyridine units, the intersystem crossing (ISC) efficiencies and the number of bound water molecules also increase. In contrast, a decrease was found in the same direction for overall quantum yields, triplet energies, and sensitization efficiencies. In the last part of this work, the synthesis and characterization of novel cryptates with unusual chirality was reported (Figure 4.8). These cryptates were based on an unsymmetrical unit which is a requirement for the molecule to be chiral and was synthesized applying a coupling reaction between pyridine and furane derivatives. This unit was added into two unsymmetrical macrocycles 108 and 118. The resulting crpytates with three different arms were both synthesized as racemic mixtures. a Three different arms ne unsymmetrical arm a chiral cryptates Figure 4.8: Synthesized sodium cryptands 109 and 110 with unusual chirality. 77