D,L-Citrullinato-bipyridine Copper Complex: Experimental and Theoretical Characterization

Abstract

Citrulline is a non-protein amino acid that acts as a metabolic intermediate in the urea cycle and arginine synthesis. It is present in some foods, although its name derives from watermelon (Citrullus vulgaris), from which it was first identified. Under normal conditions, Citrulline exists as a zwitterion in aqueous solutions since its carboxylic and amine groups can act as Lewis donors to chelate metal cations. In addition, Citrulline possesses in the aliphatic chain a terminal ureide group, which could also coordinate. Although Citrulline is comparable to other classical amino acids, its coordination chemistry has yet to be explored. Only two metal complexes have been reported, and the copper complex is a polymeric and insoluble material. As part of our search for active Casiopeina® analogs, we created a more soluble complex by combining 2,2′-Bipyridine into a new mixed material, resulting in the mononuclear complex [Cu(Bipy)(Citr)(H2O)(NO3)]·H2O. Single-crystal X-ray diffraction, spectroscopic methods (FT-IR, UV-Vis, Raman), and mass spectrometry characterized the material. Interestingly, both isomers of Citrulline, R(D), and S(L) are present in the same crystal. In addition, the molecular structure and electronic properties of the complex were calculated using density functional theory (DFT). Non-covalent interactions were characterized using the atoms-in-molecules (AIM) approach and Hirshfeld surface (HS) analysis. This ternary complex containing Citrulline and 2,2′-Bipyridine will be used for docking calculations and preliminary biological studies using calf thymus DNA (CT-DNA) and plasmid pUC19 as a first approximation to cytotoxic activity against cancer cell lines.

Keywords

• citrulline
• 2,2′-Bipyridine
• copper complex
• DFT
• AIM
• Hirshfeld surface