Synthesis, Characterization and Biological Evaluation of Metal Adamantyl 2-Pyridylhydrazone Complexes

Abstract

Four new complexes derived from adamantly containing hydrazone (APH) ligand with Cu(II) (1), Co(II) (2), Ni(II) (3) and Zn(II) (4), have been synthesized and characterized using different physicochemical methods. The structure of the ligand APH and its copper complex 1 have been established by single-crystal X-ray diffraction direct methods, which reveal that complex 1 has distorted square-pyramidal geometry. Complexes 1-4 are screened against seven human cancer cell lines namely, breast cancer cell lines (MCF7, T47D, MDA-MB-231), prostate cancer cell lines (PC3, DU145) and the colorectal cancer cell line Coco-2, for their antiproliferative activities. Complex 1 has shown a promising anticancer activity compared to the other ones. The structural and spectroscopic analysis of APH and its complexes are confirmed by DFT calculations.

Keywords: 2-pyridyl adamantanhydrazone; antitumor; crystal structure; hydrazone complexes.

Scheme 1

Synthesis of the ligand APH.

Scheme 2

Synthesis of the complexes 1–4. All reactions where performed under refluxing condition in ethanol.

Figure 1

Electrostatic potential (ESP) for complex 1a (a) and 1b (b), where red presents the Mulliken negative charge distribution and green represents the positive charge distribution.

Figure 2

Presentation of the HOMO-LUMO atomic orbital for complex 1a and complex 1b, which are obtained at 6–311 + G(2d, p)/B3LYP level of theory (a) HOMO + 1, HOMO, LUMO, and LUMO − 1 for complex 1a (b) HOMO + 1, HOMO, LUMO, and LUMO − 1 for complex 1b.

Figure 3

Molecular units of APH show two different crystallographic molecules in the unit cell. Ellipsoids are drawn at the 30% probability level. The numbered molecule is symmetrically equivalent to the other.

Figure 4

Molecular plot of APH shows the different intermolecular interactions between APH and water moieties. Only one asymmetric unit interaction is shown, as the other unit is symmetrically equivalent.

Figure 5

The packing diagram structures of APH with hydrogen bonds are shown as dotted lines.

Figure 6

Thermal ellipsoid plot for the two possible disorder orientations in the adamantyl moiety (a) and (b) of 1, drawn at the 30% probability level, with atomic labeling and numbering schemes. The crystalline solvent (CHCl₃) and the hydrogen atoms on adamantyl have been omitted for clarity.

Figure 7

Packing diagram along c-axis showing the intermolecular interactions in 1, the hydrogen atoms, disorder in adamantly and crystallization solvents were excluded for clarity purposes.