Search

Two water-soluble piano-stool shaped ruthenium(ii)-arene complexes, [Ru II (η 6 -p-cymene)(L)Cl 2 ] [RuLCl] and [Ru II (η 6 -p-cymene)(L)(PTA)Cl] [RuLPTA], were designed as emissive photocytotoxic agents tagged with morpholine as the lysosome targeting moiety. Here, L = N-(2-morpholinoethyl)-4-(2-aminoethyl)amino-naphthalimide, and PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane. The crystal structure of [RuLCl] exhibits the pseudooctahedral 'three-legged piano-stool' geometry, wherein Ru(ii) is bound to the η 6 -p-cymene moiety as a base and two chlorides and the amine-N of the ligand L occupies the three legs of the stool. The complexes exhibited both the possibility of covalent adduct formation via the hydrolyzed Ru-Cl bond and non-covalent intercalation binding through planar naphthalimide moieties. The complexes showed enhanced photo-cytotoxicity under low-power blue LED light irradiation (λ max = 448 nm) mediated by 1 O 2 , thereby acting as potential PDT agents. Fluorescence microscopy studies revealed that luminescent complexes preferentially localized in both the lysosomes and nucleus for effectively targeting and damaging the nuclear DNA for PDT effects. Due to enhanced lipophilicity of [RuLCl], it showed higher internalization into MCF-7 cell, measured in terms of the ruthenium content using ICP-MS. The interaction of the complexes with human transferrin (hTf) proteins was studied through molecular docking calculations, suggesting favorable binding through histidine residues and possible internalization into cancer cells via TfR-mediated endocytosis. The luminescence properties of the complexes were well-utilized to study their cellular uptake mechanism via endocytosis using fluorescence microscopy.

Two new curcumin containing octahedral ruthenium(ii) polypyridyl complexes, viz. [Ru(NN)2(cur)](PF6) [NN = bpy (1), phen (2)], were designed to explore the antimicrobial activity against ESKAPE pathogens, especially with the Gram-positive drug resistant S. aureus. Solid-state structural characterization by single-crystal X-ray crystallography shows the RuII-center in a distorted octahedral {RuN4O2} geometry. The tested compounds showed significant inhibitory activity and high selectivity (MIC = 1 μg mL-1, SI = 80) against a wide variety of methicillin and vancomycin-resistant S. aureus strains. Compound 1 exhibited strong anti-biofilm activity (48% reduction of biofilm) at 10× MIC compared to the other approved drugs. The murine model of Staphylococcus infection significantly reduced the mean bacterial counts when treated with complex 1 compared to vancomycin, demonstrating its antimicrobial potential in vivo.

Two water-soluble piano-stool shaped ruthenium(II)–arene complexes, [RuII(η6-p-cymene)(L)Cl2] [RuLCl] and [RuII(η6-p-cymene)(L)(PTA)Cl] [RuLPTA], were designed as emissive photocytotoxic agents tagged with morpholine as the lysosome targeting moiety. Here, L = N-(2-morpholinoethyl)-4-(2-aminoethyl)amino-naphthalimide, and PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane. The crystal structure of [RuLCl] exhibits the pseudooctahedral 'three-legged piano-stool' geometry, wherein Ru(II) is bound to the η6-p-cymene moiety as a base and two chlorides and the amine-N of the ligand L occupies the three legs of the stool. The complexes exhibited both the possibility of covalent adduct formation via the hydrolyzed Ru–Cl bond and non-covalent intercalation binding through planar naphthalimide moieties. The complexes showed enhanced photo-cytotoxicity under low-power blue LED light irradiation (λmax = 448 nm) mediated by 1O2, thereby acting as potential PDT agents. Fluorescence microscopy studies revealed that luminescent complexes preferentially localized in both the lysosomes and nucleus for effectively targeting and damaging the nuclear DNA for PDT effects. Due to enhanced lipophilicity of [RuLCl], it showed higher internalization into MCF-7 cell, measured in terms of the ruthenium content using ICP-MS. The interaction of the complexes with human transferrin (hTf) proteins was studied through molecular docking calculations, suggesting favorable binding through histidine residues and possible internalization into cancer cells via TfR-mediated endocytosis. The luminescence properties of the complexes were well-utilized to study their cellular uptake mechanism via endocytosis using fluorescence microscopy. [ABSTRACT FROM AUTHOR]

Two cytotoxic ruthenium(II) polypyridyl complexes containing naproxen (nap) as NSAID, [Ru(NN) 2 (nap)][PF 6 ] (NN = bpy (1), phen (2)) were synthesized and characterized. The physicochemical properties, theoretical aspects, binding interactions with DNA and BSA and antioxidant activities were investigated. The non-steroidal anti-inflammatory drug (NSAID) naproxen (nap) bound to ruthenium(II) in the presence of a bidentate nitrogen donor heterocyclic ligands (bpy = 2,2′-bipyridine and phen = 1,10-phenanthroline), namely, [Ru(bpy) 2 (nap)][PF 6 ] (1) and [Ru(phen) 2 (nap)][PF 6 ] (2) have been synthesized and characterized using various physicochemical methods. Naproxen was coordinated to the Ru(II) center through carboxylato oxygen atoms (–COO−) in a bidentate fashion. The compounds were evaluated for their photophysical properties, stability in solution, reactivity with 5′-guanosine monophosphate (5′-GMP) and GSH, interactions with CT-DNA and BSA. The complexes showed high binding affinity or reactivity towards these biological targets and bioanalytes. Both the compounds 1 and 2 showed moderate antioxidant activity by scavenging DPPH (1,1-diphenyl-picrylhydrazyl) and ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals. The complexes 1 and 2 were highly cytotoxic against PC3 and MCF-7 cancer cells giving IC 50 values ranging from 17 µM to 27 µM. [ABSTRACT FROM AUTHOR]

Two new curcumin containing octahedral ruthenium(ii) polypyridyl complexes, viz. [Ru(NN)2(cur)](PF6) [NN = bpy (1), phen (2)], were designed to explore the antimicrobial activity against ESKAPE pathogens, especially with the Gram-positive drug resistant S. aureus. Solid-state structural characterization by single-crystal X-ray crystallography shows the RuII-center in a distorted octahedral {RuN4O2} geometry. The tested compounds showed significant inhibitory activity and high selectivity (MIC = 1 μg mL−1, SI = 80) against a wide variety of methicillin and vancomycin-resistant S. aureus strains. Compound 1 exhibited strong anti-biofilm activity (48% reduction of biofilm) at 10× MIC compared to the other approved drugs. The murine model of Staphylococcus infection significantly reduced the mean bacterial counts when treated with complex 1 compared to vancomycin, demonstrating its antimicrobial potential in vivo. [ABSTRACT FROM AUTHOR]