Coupling 6-chloro-3-methyluracil with copper: structural features, theoretical analysis, and biofunctional properties

As nucleobases in RNA and DNA, uracil and 5-methyluracil represent a recognized class of bioactive molecules and versatile ligands for coordination compounds with various biofunctional properties. In this study, 6-chloro-3-methyluracil (Hcmu) was used as an unexplored building block for the self-assembly generation of a new bioactive copper(II) complex, [Cu(cmu) 2 (H 2 O) 2 ]·4H 2 O (1). This compound was isolated as a stable crystalline solid and fully characterized in solution and solid state by a variety of spectroscopic methods (UV-vis, EPR, fluorescence spectroscopy), cyclic voltammetry, X-ray diffraction, and DFT calculations. The structural, topological, H-bonding, and Hirshfeld surface features of 1 were also analyzed in detail. The compound 1 shows a distorted octahedral {CuN 2 O 4 } coordination environment with two trans cmu - ligands adopting a bidentate N,O-coordination mode. The monocopper(II) molecular units participate in strong H-bonding interactions with water molecules of crystallization, leading to structural 0D → 3D extension into a 3D H-bonded network with a tfz-d topology. Molecular docking and ADME analysis as well as antibacterial and antioxidant activity studies were performed to assess the bioactivity of 1. In particular, this compound exhibits a prominent antibacterial effect against Gram negative ( E. coli, P. aeruginosa ) and positive ( S. aureus, B. cereus ) bacteria. The obtained copper(II) complex also represents the first structurally characterized coordination compound derived from 6-chloro-3-methyluracil, thus introducing this bioactive building block into a family of uracil metal complexes with notable biofunctional properties.