| 研究実績の概要 |
The research until now has focused on the challenging synthesis of a proof-of-principle monometallic 2,2’-bipyridine complex. In order to assure a high stability of the targeted complex, we changed the initially proposed design of the dialdehyde unit to a bis-salicylaldehyde unit. The additional hydroxy groups are expected to increase the stability of the aldehyde units against oxidation and furthermore rigidify the envisioned imine bonds via hydrogen bonding. After several failed attempts, the synthesis of 2-bromo-4,6-dihydroxy-5-methylisophthalaldehyde A was achieved in 3 steps, including an Ir-catalyzed meta-selective CH-functionalization. Using a test system, this bromide was shown to be reactive under Suzuki coupling conditions. This is the first report of a bis-salicylaldehyde with a bromo substituent between the aldehyde units. We expect that this building block will be in general useful for the supramolecular community. The corresponding bipyridine-based boronic ester coupling partner B (6,6'-bis(2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2,2'-bipyridine) was also successfully synthesized in 4 steps and the conditions have been adjusted to medium-scale synthesis. Currently, around 450 mg of the borylated bipyridine core are in hand, containing however small amounts of impurities. This versatile building block can in principle be coupled to a wide variety of bromides. If A can be successfully coupled to B, then the synthesis of the targeted monometallic complex could be achieved after subsequent demethylation and metal insertion.
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| 今後の研究の推進方策 |
Next, the synthesis of bromide A will be adjusted to medium scale and the purification conditions will be optimized. After this, the coupling of two molecules of A to the bipyridine core B will be attempted. In the case of problems, protection of the alcohol units might facilitate the coupling reaction. In the case of success, the corresponding product will be demethylated with BBr3 and the metal insertion (Co or Zn) will be attempted. The properties of the targeted complex will then be investigated in detail (UV-vis, fluorescence, NMR, mass spectrometry etc.). Following this, the core idea, i.e., dynamic covalent transformation of the aldehydes into imine units using amino acids and oligopeptides, will be investigated. This will first be performed with the isolated building block A, and after optimization of the imine formation conditions with the monometallic complex. At this point, we will also focus on possible solubility issues in aqueous medium. We will furthermore attempt the synthesis of novel bromide 5-bromo-4,6-dihydroxyisophthalaldehyde C as an alternative to B. Both B and C will be in parallel studied in combination with other boronic esters (e.g., 1,3,5-tris(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzene) to construct new salen complex-type receptors. Since the ultimate goal is a multimetallic receptor, we will also start the modification of the bipyridine core by introducing pyridine groups ortho to the hydroxy groups of the N2O2 metal binding pocket to create a hexavalent N2O2N2-type ligand.
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| 次年度使用額が生じた理由 |
The synthesis of the targeted complex proceeded slower than expected. Since the complex is not synthesized so far, several expensive chemicals were not purchased so far. The planned purchases include mainly carbohydrate cancer biomarkers (e.g., sialic acids) and oligo/polypeptides. We furthermore recently moved into a new research building and were saving some money for purchasing machines in the new building.
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