Synthesis and biological properties of palladium(II) cyclometallated compounds derived from ( E )-2-((4-hydroxybenzylidene)amino)phenol

Abstract

( E )-2-((4-hydroxybenzylidene)amino)phenol (iminophenol a ) reacted with Pd(OAc) 2 giving place to com- pound 1a , in which the iminophenol was bonded to palladium(II) in a κ3 - C ortho ,N,O ortho tridentate chelat- ing mode. Thus, 1a was formed by neutral mononuclear units of schematic formula Pd(C,N,O), consisting of two fused five-membered metallacycles. Self-assembly of the Pd(C,N,O) units gave place to the polynu- clear structure of 1a . Treatment of 1a with PPh 3 or PPh 2 CH 2 CH 2 PPh 2 in molar ratio Pd(II)/PPh 3 = 1/1 or Pd(II)/PPh 2 CH 2 CH 2 PPh 2 = 2/1 produced the mononuclear or dinuclear compound of schematic formula [Pd(C,N,O)(PPh 3 )] ( 2a ) or {[P d (C,N,O)] 2 ( μ2 -PPh 2 CH 2 CH 2 PPh 2 )} ( 3a ), respectively. Compounds a were char- acterized by elemental analysis, high resolution ESI-( + ) mass spectrometry, IR, and NMR. In addition, the crystal structure of the adducts 2a ·2(CH 2 Cl-CH 2 Cl) and 3a ·5(dmso) was determined by single crystal X- ray diffraction analysis. Most compounds a were noncytotoxic or poorly cytotoxic. Nonetheless, 2a was moderately cytotoxic against the MCF-7 breast and HCT-116 colon human cancer cell lines, and presented very low cytotoxicity towards normal skin human BJ cells. Compounds a showed moderate antibacterial activity against some Gram-positive ( B. subtilis and S. aureus ) and Gram-negative ( E. coli ) bacterial strains, and displayed also moderate antioxidant activity, producing 3a the best antioxidant activity. 1a changed the electrophoretic mobility of the pBluescript SK + plasmid DNA. This change followed the pattern of cisplatin , but it started at a concentration twenty times higher than with cisplatin . Moreover, compounds 1a - 3a inhibited topoisomerase IIα at concentrations of 10, 50 and 25 μM, respectively.