Synthesis and characterization of mixed-ligand diimine-piperonal thiosemicarbazone complexes of ruthenium(II): Biophysical investigations and biological evaluation as anticancer and antibacterial agents

We have used a novel microwave-assisted method developed in our laboratories to synthesize a series of ruthenium-thiosemicarbazone complexes. The new thiosemicarbazone ligands are derived from benzo[d][1,3]dioxole-5-carbaldehyde (piperonal) and the complexes are formulated as [(diimine)2Ru(TSC)](PF6)2 (where the TSC is the bidentate thiosemicarbazone ligand). The diimine in the complexes is either 2,2′-bipyridine or 1,10-phenanthroline. The complexes have been characterized by spectroscopic means (NMR, IR and UV–Vis) as well as by elemental analysis. We have studied the biophysical characteristics of the complexes by investigating their anti-oxidant ability as well as their ability to disrupt the function of the human topoisomerase II enzyme. The complexes are moderately strong binders of DNA with binding constants of 104 M−1. They are also strong binders of human serum albumin having binding constants on the order of 104 M−1. The complexes show good in vitro anticancer activity against human colon cancer cells, Caco-2 and HCT-116 and indeed show some cytotoxic selectivity for cancer cells. The IC50 values range from 7 to 159 μM (after 72 h drug incubation). They also have antibacterial activity against Gram-positive strains of pathogenic bacteria with IC50 values as low as 10 μM; little activity was seen against Gram-negative strains. It has been established that all the compounds are catalytic inhibitors of human topoisomerase II

Anticancer, Biophysical and Computational Investigations of Half-Sandwich Ruthenium(II) Thiosemicarbazone Complexes: The Effect of Arene \u3ci\u3eVersus\u3c/i\u3e Thiacrown Face-Cap

A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h6-p-cymene)Ru(dmabTSC)Cl]PF6, [(h6-benzene)Ru(dmabTSC)Cl]PF6 (arene complexes), and [([9]aneS3(dmabTSC)Cl]PF6 (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 105 M-1. In addition they all bind strongly to human serum albumin with binding constants between 105 and 106 M-1. There appears to be a single binding site on the protein for these complexes. A computational investigation of these complexes and their hydrolysis products was carried out by molecular docking with DNA and topoisomerase II. From this analysis it is noted that the type of face-capping ligand had different effects on the two macromolecules. It is therefore noted that the knowledge gained from this study will be useful in identifying the type of complexes in this class that show useful metallodrug potential

Living Anionic Copolymerization of 1‑(Alkylsulfonyl)aziridines to Form Poly(sulfonylaziridine) and Linear Poly(ethylenimine)

The anionic ring-opening copolymerization of 1-(methylsulfonyl)­aziridine (<b>MsAz</b>) and 1-(<i>sec</i>-butylsulfonyl)­aziridine (^<b>s</b><b>BsAz</b>) produces a soluble random copolymer P­(MsAz-<i>r</i>-^sBsAz), which can subsequently be converted to linear poly­(ethylenimine) (lPEI). The copolymerization of <b>MsAz</b> and ^<b>s</b><b>BsAz</b> is living and allows for the synthesis of copolymers with low molecular weight distributions. Sequential anionic polymerization of <b>MsAz</b> and ^<b>s</b><b>BsAz</b> with 2-methyl-1-(methylsulfonyl)­aziridine (<b>MsMAz</b>) creates P­(MsAz-<i>r</i>-^sBsAz)-<i>b</i>-P­(MeMsAz). Removal of the sulfonyl groups from P­(MsAz-<i>r</i>-^sBsAz)-<i>b</i>-P­(MsMAz) gives lPEI-<i>b</i>-poly­(propylenimine). For the first time, lPEI can be synthesized by a controlled anionic polymerization