Beiträge zur Chemie Schiff’scher Basen mit Aminosäuren und deren Metallkomplexe

The presented work describes the synthesis and full characterization of Schiff base ligands derived from ortho-vanillin as an aldehyde source and selected amino acids as amine sources. The ligands, either in pure form or generated in situ, were used in reactions with various metal salts to afford metal complexes. Single crystals suitable for X-ray measurement were grown to allow a confident structure determination. When possible, the biological activity of the ligands as well as the metal were investigated. Ligands derived from L-glutamic acid, L-tyrosine und L-glutamine were successfully synthesized as sodium salts in high yields and fully characterized. Investigations of stability by 1H-NMR revealed partial reversion of the ligands to their respective starting materials in aqueous solution. Antimicrobial studies on the ligands derived from L-glutamic acid and L-tyrosine indicated activity against various microorganisms, in particular against fungi from the genus Candida. However, the activity was traced back to ortho-vanillin, which is released due to decomposition in aqueous solution. No significant antiproliferative activity against cells from the lines L929 and Hep G2 was observed in MTT-assays. The reaction of the L-glutamic acid-containing ligand with various metal salts led to following complexes: • With nickel(II) chloride, a pentadecanuclear wheel-shaped complex was obtained, which is a rare example of an odd-numbered wheel-shaped Ni(II) complexes. The complex was found to be stable in methanol and a water/methanol mixture, and showed only low cytotoxicity against L929 and B16 cells. The investigation of the magnetic properties revealed dominant antiferromagnetic behavior as well as intramolecular interactions below 24 K. • The reaction with copper(II) sulfate and addition of hydrochloric acid at the end of the reaction led to the formation of a tetranuclear Cu(II) complex with a highly distorted heterocubane structure. The complex was found to be stable over the investigated period of 48 h. The amino acid side chains were not involved in complex formation. The complex showed mild to moderate activity against gram-positive bacteria and good antifungal activity against fungi of the genus Candida. Moderate cytotoxic activity was observed against L929 and Hep G2 cells. • Two mononuclear anionic Fe(III) complexes with either sodium or potassium counter ions were produced from the reaction with iron(III) perchlorate. For the potassium-containing complex a reliable crystal structure was not obtained, but XRPD studies suggesting isostructurality. Two ligand molecules coordinate the iron center in a distorted octahedral manner. EPR studies revealed a spin of S = 5/2. • Usage of palladium(II) chloride led to two square-planar Pd(II) complexes, where the Pd center is coordinated by one ligand molecule and one chloride ion. Either a sodium or a potassium ion compensated the negative charge of the complex molecule. Depending on the nature of the counter ion, a different packing within the crystals structure was observed. The potassium-containing complex, which was used for studies of the biologic potential, was found to be stable in DMSO over the investigated period of 72 h. The complex showed moderate to good antimicrobial activity, but was found to be inactive against L929 cells. Continuing studies with further human cancer cell lines are in progress. Complexes with the L-glutamine-containing ligand were only obtained for the reaction with iron(III) perchlorate. These were analogous in structure and properties to the Fe(III) complexes described above. But in this case, crystal structures were obtained for both sodium and potassium salts. The complexes differed in their packing in the solid state. With the L-tyrosine-containing ligand, complexes from nickel and palladium were obtained: • The reaction with nickel(II) chloride led to two isostructural tetranuclear Ni(II) complexes, which differed in the coordinated solvent, methanol or DMF. The complexes did not showed the common Ni-O heterocubane structure, but rather a very rare bowl-shaped motif was observed. The L-tyrosine side chains remained pendant. Both solvates were found to be stable in the liquid and solid state. • Usage of palladium(II) chloride led to two square-planar Pd(II) complexes. The Pd centers were coordinated by one ligand molecule and either one chloride ion, leading to an anionic complex, or a water molecule, leading to a neutral complex. A sodium ion compensated the negative charge. While the neutral complex was found to be stable in DMSO over the investigated period of 72 h, the 1H-NMR spectrum of the anionic complex in d6-DMSO indicated immediate decomposition. Both complexes showed moderate to good antimicrobial activity, but were found to be inactive against L929 cells. Continuing studies with further human cancer cell lines are in progress. The synthesis of a Schiff base from ortho-vanillin and L-cysteine through a condensation reaction was not successful, despite various published claims to the contrary. Instead, the corresponding racemic thiazolidine was produced. The reaction with various metal salts did not lead to crystalline metal complexes, but addition of zinc chloride facilitated the growth of suitable crystals for X-ray measurement of the thiazolidine. Although the bulk material was racemic, in multiple measurements only the crystal structure of the 2R,4R-diastereomer was determined, which exists in a zwitterionic form within the crystal. In conclusion, three Schiff base ligands as sodium salts could be synthesized and fully characterized. The reaction of the ligands with metal salts led to a wide variety of novel metal complexes, possessing a high structural diversity and interesting properties.