Hydrogen Bonding and Anticancer Properties of Water‐Soluble Chiral p‐Cymene Ru^II Compounds with Amino‐Oxime Ligands

Abstract

The investigation of the hydrogen-bonding effect on the aggregation tendency of ruthenium compounds [(η6-p-cymene)Ru(κNHR,κNOH)Cl]Cl (R = Ph (1a), Bn (1b)) and [(η6-p-cymene)Ru(κ2NH(2-pic),κNOH)][PF6]2 (1c), [(η6-p-cymene)Ru(κNHBn,κNO)Cl] (2b) and [(η6-p-cymene)Ru(κNBn,κ2NO)] (3b), has been performed by means of concentration dependence 1H NMR chemical shifts and DOSY experiments. The synthesis and full characterization of new compounds 1c, [(η6-p-cymene)Ru(κNPh,κ2NO)] (3a) and 3b are also reported. The effect of the water soluble ruthenium complexes 1a-1c on cytotoxicity, cell adhesion and cell migration of the androgen-independent prostate cancer PC3 cells have been assessed by MTT, adhesion to type-I-collagen and recovery of monolayer wounds assays, respectively. Interactions of 1a-1c with DNA and human serum albumin have also been studied. Altogether, the properties reported herein suggest that ruthenium compounds 1a-1c have considerable potential as anticancer agents against advanced prostate cancer.

Novel enantiopure cyclopentadienyl Ti(IV) oximato compounds as potential anticancer agents

“…In contrast, IR spectra of 1a , 2a–2c show sharp absorptions at ū 3374 ( 1a ), 3370 ( 2a ), 3370 ( 2b ) and 3304 ( 2c ) cm −1 , assigned to amino ν(-NH) bands. C=N stretching frequencies of oximato group [54,56,59] are observed in the 1638–1646, 1570–1602 cm −1 regions, with similar wavenumbers relative to those bands found in the spectra of organic derivatives a–c [48]. …”

“…Recently, we published a family of cytotoxic ruthenium oxime compounds able to modulate both adhesion and migratory capabilities of PC-3 cells using concentrations of only 5 μm [48]. Thus, we evaluated the effect of the novel chiral cyclopentadienyl oximato Ti(IV) compounds on cytotoxicity, cell adhesion and migration of the human androgen-independent prostate cancer PC-3.…”

“…We reported recently a new family of chiral, water soluble and stable p -cymene ruthenium(II) compounds with amino-oxime ligands. The compounds show significant effects on cytotoxicity, cell adhesion to collagen and migration of androgen-independent prostate cancer cells while they do not exhibit strong interactions with plasmid (pBR322) DNA [48]. …”

“…Encouraged by our previous results on the enantiomerically pure amino-oxime ruthenium compounds [48], we hypothesized that oximato ligands could increase the water solubility and stability of the resulting titanium derivatives [52]. Thus, we explored reactions of [(η 5 -C 5 H 5 )TiCl 2 ] and [(η 5 -C 5 H 5 ) 2 TiCl 2 ] with the previously described enantiopure amino-oxime derivatives (2 S , R )-{NOH,(R)NH} (R = phenyl a , benzyl b , 2-picolyl c , see Fig.…”

“…Thus, we explored reactions of [(η 5 -C 5 H 5 )TiCl 2 ] and [(η 5 -C 5 H 5 ) 2 TiCl 2 ] with the previously described enantiopure amino-oxime derivatives (2 S , R )-{NOH,(R)NH} (R = phenyl a , benzyl b , 2-picolyl c , see Fig. 2) [48,63,64], derived from R-limonene. This naturally occurring terpene is an inexpensive starting reagent, commercially available in optically pure form and easily tailored by stereoselective functionalization [63–65].…”