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(H2O)2]·4H2O (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 {CuN2O4} 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.