Half-sandwich Ru(η6-p-cymene) complexes featuring pyrazole appended ligands: Synthesis, DNA binding and in vitro cytotoxicity.

Organometallic Ru(II)-arene complexes have emerged as potential alternatives to platinum appended agents due to their wide range of interesting features such as stability in solution and solid, significant activity, less toxicity and hydrophobic property of arene moiety, etc. Hence, a series of Ru(II)-p-cymene complexes, [(η6-p-cymene)Ru(η2-N,N-L1)Cl]Cl (1), [(η6-p-cymene)Ru(η1-N-L2)Cl2] (2) and [(η6-p-cymene)Ru(η1-N-L3)Cl2] (3) were prepared from pyrazole based ligands [2-(1H-pyrazol-3-yl)pyridine (L1), 3-(furan-2-yl)-1H-pyrazole (L2) and 3-(thiophen-2-yl)-1H-pyrazole (L3)], and [RuCl2-(η6-p-cymene)] dimer. The new Ru(II)-p-cymene complexes were well characterized by elemental analysis, and spectroscopic (FT-IR, UV-Visible, 1H NMR, 13C NMR and mass) and crystallographic methods. The Ru(II)-p-cymene complexes (1-3) were found to adopt their characteristic piano stool geometry around Ru(II) ion. The calf thymus DNA (CT-DNA) binding ability of the new complexes was investigated by electronic absorption spectroscopic titration and viscosity methods. The molecular docking study results showed that complex 1 strongly bound with targeted biomolecules than 2 and 3. Docked poses of bidentate pyrazole based Ru(II)-p-cymene complex 1 revealed that the complex formed a crucial guanine N7 position hydrogen bond with DNA receptor. Complexes 1-3 might hydrolyze under physiological conditions and form aqua complexes 4-8, and docking calculations showed that the aqua complexes bound strongly with the receptors than original complexes. The in vitro cytotoxicity of the Ru(II)-p-cymene complexes and cisplatin was evaluated against triple negative breast cancer (TNBC) MDA-MB-231 cells. Our results showed that the inhibitory effect of bidentate pyrazole based Ru(II)-p-cymene complex 1 on the growth of breast cancer cells was superior to other tested complexes.

Evaluation of the Leaf Essential Oil from Artemisia vulgaris and Its Larvicidal and Repellent Activity against Dengue Fever Vector Aedes aegypti-An Experimental and Molecular Docking Investigation.

Aedes aegypti is a mosquito vector that spreads dengue fever and yellow fever worldwide in tropical and subtropical countries. Essential oil isolated from Artemisia vulgaris is found to have larvicidal and repellent action against this vector. The dried leaves were subjected to hydrodistillation using a clevenger-type apparatus for 4 h. The isolated essential oil was analyzed by using gas chromatography-mass spectrometry, and the major insecticidal compounds were identified as α-humulene (0.72%), ß-caryophyllene (0.81%), and caryophyllene oxide (15.87%). Larvicidal activity results revealed that the essential oil exposure for 24 h period against the third stage larvae was LC50 = 6.87, LC90 = 59.197 ppm and for the fourth stage larvae LC50 = 4.269, LC90 = 50.363 ppm. Highest mortality rates were observed at 24 h exposure period of third and fourth stages, and the exposed A. aegypti larvae were subjected to histo chemical studies, and the studies revealed that larvae cells got totally damaged (midgut and cortex). The repellent activity results revealed that at 50% concentration of the essential oil showed the highest repellent activity at 60 min protection time against the A. aegypti female mosquitoes. To gain further insights into the insecticidal activity, density functional theory and molecular docking calculations were performed with the active components of this essential oil as the ligand and NS3 protease domain (PDB ID: 2FOM) as a receptor. Molecular docking calculation results show that (E)-ß-caryophyllene strongly binds with NS3 protease domain than (Z)-ß-caryophyllene, α-humulene, and ß-caryophyllene oxide and is the major active component for the insecticidal action. It primarily interacts with the receptor through hydrophobic and ionic forces and using water bridges between the amino acid residues in the binding pocket and (E)-ß-caryophyllene.

Structure and Reactivity of Pd Complexes in Various Oxidation States in Identical Ligand Environments with Reference to C-C and C-Cl Coupling Reactions: Insights from Density Functional Theory.

Bonding and reactivity of [(RN4)Pd nCH3X]( n-2)+ complexes have been investigated at the M06/BS2//B3LYP/BS1 level. Feasible mechanisms for the unselective formation of ethane and methyl chloride from mono-methyl PdIII complexes and selective formation of ethane or methyl chloride from PdIV complexes are reported here. Density functional theory (DFT) results indicate that PdIV is more reactive than PdIII and Pd in different oxidation states that follow different mechanisms. PdIII complexes react in three steps: (i) conformational change, (ii) transmetalation, and (iii) reductive elimination. In the first step a five-coordinate PdIII intermediate is formed by the cleavage of one Pd-Nax bond, and in the second step one methyl group is transferred from the PdIII complex to the above intermediate via transmetalation, and subsequently a six-coordinate PdIV intermediate is formed by disproportion. In this step, transmetalation can occur on both singlet and triplet surfaces, and the singlet surface is lying lower. Transmetalation can also occur between the above intermediate and [(RN4)PdII(CH3)(CH3CN) ]+, but this not a feasible path. In the third step this PdIV intermediate undergoes reductive elimination of ethane and methyl chloride unselectively, and there are three possible routes for this step. Here axial-equatorial elimination is more facile than equatorial-equatorial elimination. PdIV complexes react in two steps, a conformational change followed by reductive elimination, selectively forming ethane or methyl chloride. Thus, PdIII complex reacts through a six-coordinate PdIV intermediate that has competing C-C and C-Cl bond formation, and PdIV complex reacts through a five-coordinate PdIV intermediate that has selective C-C and C-Cl bond formation. Free energy barriers indicate that iPr, in comparison to the methyl substituent in the RN4 ligand, activates the cleaving of the Pd-Nax bond through electronic and steric interactions. Overall, reductive elimination leading to C-C bond formation is easier than the formation of a C-Cl bond.

Surfactant-cobalt(III) complexes: The impact of hydrophobicity on interaction with HSA and DNA - insights from experimental and theoretical approach.

To develop surfactant-based metallodrugs, it is very important to know about their hydrophobicity, micelle forming capacity, their interaction with biomacromolecules such as proteins and nucleic acids, and biological activities. Here, diethylenetriamine (dien) and tetradecylamine ligand (TA) based surfactant-cobalt(III) complexes with single chain domain, [Co(dien)(TA)Cl2]ClO4 (1) and double chain domain [Co(dien)(TA)2Cl](ClO4)2 (2) were chosen to study the effect of hydrophobicity on the interaction with human serum albumin and calf thymus DNA. The obtained results showed that (i) single chain surfactant-cobalt(III) complex (1) interact with HSA and DNA via electrostatic interaction and groove binding, respectively; (ii) double chain surfactant-cobalt(III) complex (2) interact with HSA and DNA via hydrophobic interaction and partial intercalation, respectively, due to the play of hydrophobicity by single and double chain domains. Further it is noted that, double chain surfactant-cobalt(III) complex interact strongly with HSA and DNA, compared single chain surfactant-cobalt(III) complex due to their more hydrophobicity nature. DFT and molecular docking studies offer insights into the mechanism and mode of binding towards the molecular target CT-DNA and HSA. Hence, the present findings will create new avenue towards the use of hydrophobic metallodrugs for various therapeutic applications.