Synthesis, X-ray structure, Hirshfeld, DFT studies and biological activity of 2-((E)-((E)-(1-(thiazol-2-yl)ethylidene)hydrazono)methyl)phenol and its dinuclear Cu(II) complex

The new bioactive [Cu(L)(NO3)]2 complex of 2-((E)-((E)-(1-(thiazol-2-yl)ethylidene)hydrazono)methyl)phenol (HL) is synthesized. Their structural characteristics are discussed at molecular and supramolecular levels using single crystal X-ray diffraction and Hirshfeld calculation. In [Cu(L)(NO3)]2 complex, the Cu(II) is coordinated by a mononegative NNO-tridentate ligand (L-), one bidentate nitrate anion, in addition to an O-atom from another L- unit in a neighboring [Cu(L)(NO3)] molecule. Hence, the geometry around Cu(II) is distorted octahedron. Hirshfield analysis reveals that the O center dot center dot center dot H (32.0 %), O center dot center dot center dot S (3.4 %), O center dot center dot center dot C (0.8 %), N center dot center dot center dot H (10.4 %), C center dot center dot center dot C (3.4 %), and C center dot center dot center dot N (2.0 %) for [Cu(L)(NO3)]2, and O center dot center dot center dot H (7.1 %) for HL are the most important close contacts. Energy framework results proved that the dispersion energy dominates for both compounds. Transition state calculations support the interconversion of HL from the stable anti-isomer to the syn one in the [Cu(L)(NO3)]2 complex is promoted by chelate effect. Antimicrobial study indicated a large diameter of inhibition zone (DIZ) towards E. coli (DIZ = 23 mm), S. aureus (DIZ = 22 mm), B. subtilis (DIZ = 21 mm), and P. vulgaris (DIZ = 18 mm) for [Cu(L) (NO3)]2 compared to HL. Interestingly, the Cu(II) complex (IC50 = 5.66 f 0.20 and 1.64 f 0.08 mu M) is superior to the reference medication cis-platin (IC50 = 27.90 f 2.66 and 62.44 f 1.99 mu M) and HL (IC50 = 990.30 f 33.10 and 154.46 f 4.24 mu M) against HCT-116 and HepG-2 cells, respectively. Furthermore, the selectivity indices (SI) of the Cu(II) complex (SI = 2.2 and 7.5) indicate higher safety for normal cells compared to HL (SI = 0.3 and 1.6) and cis-platin (SI = 11.1 and 5.0) against both cell lines and HepG-2, respectively.