J. Karthikeyan

Water soluble Ru(II)–arene complexes of the antidiabetic drug metformin: DNA and protein binding, molecular docking, cytotoxicity and apoptosis-inducing activity

Two water soluble Ru(II)–arene complexes of the type [Ru(η6-arene)(met)Cl]Cl 1 and 2, where the arene is either p-cymene (1) or benzene (2) and met is metformin (antidiabetic drug) have been isolated and characterized by analytical and spectral methods. The X-ray crystal structure of 1 reveals that the coordination geometry around Ru(II) is described as the familiar pseudo-octahedral “piano-stool” structure. Absorption and emission spectral studies reveal that the complexes interact with calf thymus DNA through hydrophobic and hydrogen bonding interactions of coordinated ligands with the DNA base pairs. Molecular docking studies show that complex 1 effectively docks in the major groove of DNA. The decrease in viscosities of CT DNA upon binding to 1 and 2 suggest the covalent mode of DNA binding of complexes. Further, the covalent mode of binding is validated by the retardation of the mobility of supercoiled (SC) plasmid DNA by the formation of covalent adducts observed in gel electrophoretic mobility studies. The protein binding affinity of the complexes depends upon the arene ligand and follows the order of p-cymene (1) > benzene (2), which is the same as that for DNA binding affinity. Docking studies with BSA and transferrin show that the complex–protein interaction is stabilized by hydrophobic as well as hydrogen bonding interactions. The α-amylase inhibition assay of 1 and 2 indicates that they have the potency to exhibit the antidiabetic activity in vitro. A study of cytotoxicity of 1 and 2 against human breast carcinoma (MDA-MB-231), human lung carcinoma (A549), human ovarian carcinoma (A2780) cell lines and non-tumorigenic human embryonic kidney (HEK293) cells reveals that they are specifically toxic to cancerous cells and non-toxic to normal cells. Remarkably, complexes 1 and 2 exhibit cytotoxicity with potency more than the metformin suggesting that the incorporation of antidiabetic drug with the organometallic Ru-arene frameworks is potential approach to develop effective anticancer drugs. The morphological changes observed by employing AO/EB and Hoechst 33258 staining methods reveal that the complexes 1 and 2 induce an apoptotic mode of cell death in breast cancer cells.

Molecular structure and conformation study of p-[N,N-bis(2-Chloroethyl)amino] benzaldehyde-4-phenyl thiosemicarbazone

The crystal structure of p-[N,N-bis(2-chloroethyl)amino]benzaldehyde-4-phenyl thiosemicarbazone(CEAB-4-PTSC) is described. The compound crystallizes in the monoclinic crystal system, P21/c space group, Z = 4, calculated density = 1.327 mg/cm3, V = 1978.2(6) Å3 with unit cell parameters a = 16.240(3) Å, b = 12.821(2) Å, c = 9.8543(16) Å, β = 105.382(6)°. The crystal structure reveals that the compound exists in the thione form and S1 and N2 are at trans-conformation to each other with respect to the N3-C12 bond. The packing of molecules in the crystal lattice is stabilized by intramolecular hydrogen bonds.

Synthesis, Structural Characterization, and Biological Application of p-[N,N-bis(2-chloroethyl) Aminobenzaldehyde Thiosemicarbazone and Its Nickel (II) Complex

New complex of Ni(II) with p-[N,N-bis(2-chloroethyl)]aminobenzaldehyde thiosemicarbazone (CEABTSC) have been synthesized and characterized by elemental analysis, IR, electronic, and 1H NMR spectroscopy. The crystal structure of the free ligand has been determined by single-crystal X-ray diffraction technique. The compound crystallizes in the Triclinic crystal system with space group P-1, Z = 2, Calculated density = 1.392 mg/m3, V = 761.64(18) A3 with unit cell parameters a = 8.2847(11) Å, α = 99.074°, b = 8.7432(12) Å, β = 94.035(7)°, c = 11.2423(15) Å, γ = 107.337(6)°; final R1 and wR2 are 0.0796 and 0.3021, respectively. The crystal structure reveals that the compound exists in the thione form and C12 and C11 are at E configuration to each other with respect to N2–N3 bond. The packing of the molecules in the crystal lattice is stabilized by intramolecular N(3)-H(3)…S(1) and N(4)-H(4D)…S(1) hydrogen bonds resulting in the formation of edge fused R22(8) ring motif. In the complex, thiosemicarbazone ligand is coordinated to nickel through (1:2 complex) SNNS mode. The complex has been tested for their antibacterial activity against various pathogenic bacteria.

Structural characterization and nonlinear optical properties of 1-phenyl-3-(4-bis(2-chloroethyl)aminophenyl)-2-propen-1-one

A new chalcone derivative 1-phenyl-3-(4-bis(2-chloroethyl)aminophenyl)-2-propen-1-one with the molecular formula C19H19Cl2NO is synthesized by the Claisen–Schmidt condensation reaction. A transparent yellow single crystal was obtained by the slow evaporation solution growth technique using ethanol at room temperature. The compound crystallizes in the triclinic crystal system, P-1 space group, Z = 4, calculated density = 1.332 mg/m3, V = 1736.00(8) Å3 with unit cell parameters a = 7.8899(2) Å, b = 14.1924(4) Å, c = 15.7879(4) Å, α = 83.1280(10)°, β = 81.929(2)°, γ =86.4820°. The second harmonic generation efficiency is found to be 1.5 times higher than that of urea. Thermal stability of the crystal is found to be 250°C determined from the thermogravimetric analysis. The FT-IR spectroscopy is used to identify the functional groups of the synthesized compound. The optical behavior of the grown crystal is examined by the UV-visible spectral analysis, which shows that the absorbance is almost negligible in the wavelength range 400-1300 nm.

Cooked Food Waste—An Efficient and Less Expensive Precursor for the Generation of Activated Carbon

Activated carbon was synthesized from cooked food waste, especially dehydrated rice kernels, by chemical activation method using NaOH and KOH as activating agents. It was then characterized by ultimate and proximate analysis, BET surface analysis, XRD, FTIR, Raman and SEM. The XRD patterns and Raman spectra confirmed the amorphous nature of the prepared activated carbons. Ultimate analysis showed an increase in the carbon content after activation of the raw carbon samples. Upon activation with NaOH and KOH, the surface area of the carbon sample was found to have increased from 0.3424 to 539.78 and 306.83 m2g-1 respectively. The SEM images revealed the formation of heterogeneous pores on the surface of the activated samples. The samples were then tested for their adsorption activity using acetic acid and methylene blue. Based on the regression coefficients, the adsorption kinetics of methylene blue dye were fitted with pseudo-second order model for both samples. Similarly, the Freundlich isotherm was found to be a better fit than Langmuir isotherm for both samples. The activity of thus prepared activated carbons was found to be comparable with the commercial carbon.

Design and in vitro biological evaluation of substituted chalcones synthesized from nitrogen mustards as potent microtubule targeted anticancer agents

A new series of p-[N,N-bis(2-chloroethyl)amino]benzaldehyde substituted chalcone derivatives were designed and synthesized, and their structures were characterized by spectroscopic techniques and single crystal XRD studies. Compounds 3a–f crystallized in the triclinic system with a centrosymmetric space group P, except for crystal 3c which crystallized in the monoclinic crystal system with a centrosymmetric space group P21/c. Molecular docking studies were utilized to reveal the binding mode of the derivatives to identify new tubulin inhibitors. Density functional theory calculations were performed to understand the structural and electronic properties of these chalcones. The DFT results show that the HOMOs of all the chalcones lie in the range of −5.65 to −6.17 eV and the LUMOs in the range of −2.01 to −3.21 eV. The experimental results are well supported by the theoretical structural analysis. The biological activity of these compounds showed high potency of growth inhibitory effects with sub-micromolar IC50 values ranging from 0.089 to 0.200 μM against A549 and HepG2 cancer cell lines. Furthermore, these compounds exhibited a strong inhibitory effect on tubulin polymerization. 3e showed the highest mean activity against both the cancer cells and in tubulin inhibition. This correlated well with the theoretical results from the pharmacophore binding model. Hence, these six compounds, particularly 3e, could be considered as potential leads in the development of new anticancer agents.