Transition Metal Complexes with 1‐Adamantoyl Hydrazones – Cytotoxic Copper(II) Complexes of Tri‐ and Tetradentate Pyridine Chelators Containing an Adamantane Ring System

Abstract

Five pentacoordinate copper(II) complexes with 2‐acetylpyridine or di(2‐pyridyl) ketone 1‐adamantoyl hydrazone ligands (Adpy and Addpy, respectively) of the formulae [CuCl2(Adpy)] (1), [Cu2(μ‐Cl)2(Adpy‐H)2] (2), [Cu(NCS)2(Adpy)] (3), [Cu2(μ‐Cl)2(Addpy‐H)2] (4), and [Cu2(NCS)2(μ‐Addpy‐H)2] (5) were synthesized and characterized by spectral, electrochemical, and X‐ray structural analysis. Flow cytometry and morphological analysis confirmed that the copper(II) complexes 2 and 5 induced accumulation of a sub‐G1 phase population, and fluorescence microscopy indicated the presence of large cells in apoptosis. The interaction of the copper(II) complexes with calf thymus DNA (CT‐DNA) was monitored by changes in their UV/Vis spectra. The observed intrinsic binding constants for 2 and 5 (Kb = 1.77 × 106 and 3.58 × 106 M–1, respectively) together with ethidium displacement fluorescence experiments indicate intercalative binding. Complexes 2 and 5 showed nuclease activity against pUC19 plasmid DNA.

Synthesis, spectroscopic and X-ray crystallographic properties of manganese compounds of keto- and enol-coordinated di-2-pyridyl ketone benzoyl hydrazone (dpkbh). Reactions of [Mn(CO)5Br] with dpkbh

“…Previous studies have shown high tendency of dpk-h's and their metal complexes to undergo solvolysis [22-24, 26, 29]. For example, when [Mn(CO) 5 Br] reacted with dtktsc in refluxing CH 3 [22]. In the case of dpkbh, an equilibrium between dpkbh and its amide-deprotonated conjugate base (dpkbh-H) − was established from a series of spectrophotometric titrations [22].…”

“…The ligand (dpkbh) and its conjugate base (dpkbh-H) − coordinate to Mn(II) in these compounds in a κ 3 pyridyl ring and the oxygen and imine of the hydrazone backbone. This coordination leaves a nitrogen of one pyridyl ring for potential binding to other moieties.…”

“…When (i) was carried out at room temperature for 1 h a redbrown precipitate was isolated from the reaction mixture. Infrared spectra of the red-brown precipitate showed a significant decrease in the intensity of ν(C≡O) of the carbonyl groups of fac-[Mn(CO)3 (κ 2 -N py ,N im -dpkbh)Br] pointing to thermal instability of fac-[Mn(CO) 3 (κ 2 -N py ,N imdpkbh)Br]. No attempt was made to separate the mixture.…”

“…Infrared spectra of dpkbh, fac-[Mn I (CO)3 (κ 2 -N py ,N im -dpkbh)Br]·H 2 O, [Mn II Br 2 (κ 3 -N py ,N im ,O-dpkbh)] and [Mn II (κ 3 -N py ,N im ,O-dpkbh-H) 2 ]·0.5H 2 O are shown in figure 1. In the spectrum of fac-[Mn I (CO) 3 (κ 2 -N py ,N im -dpkbh)Br]·H 2 O, peaks assignable to ν(N-H), ν(C≡O), ν(C=O), combined ν(C=N and C=C) of the pyridyl group, and ν(N-N) appeared, consistent with the coordination of dpkbh to fac-[Mn(CO) 3 Br].…”

Transition metal complexes with cage-opened diamondoid tetracyclo[7.3.1.14,12.02,7]tetradeca-6.11-diene

“…Such molecules find applications in the development of new metal-organic materials for nanoelectronics. Since lipophilic hydrocarbon moieties are considered highly "pharmacophoric" [34,35], such Cu-complexes may also find applications as pharmaceutically active agents [36,37]. …”