Spectroscopic, biological, and molecular modeling studies on the interactions of [Fe(III)-meloxicam] with G-quadruplex DNA and investigation of its release from bovine serum albumin (BSA) nanoparticles.

The guanine-rich sequence, specifically in DNA, telomeric DNA, is a potential target of anticancer drugs. In this work, a mononuclear Fe(III) complex containing two meloxicam ligands was synthesized as a G-quadruplex stabilizer. The interaction between the Fe(III) complex and G-quadruplex with sequence of 5'-G3(T2AG3)3-3' (HTG21) was investigated using spectroscopic methods, molecular modeling, and polymerase chain reaction (PCR) assays. The spectroscopic methods of UV-vis, fluorescence, and circular dichroism showed that the metal complex can effectively induce and stabilize G-quadruplex structure in the G-rich 21-mer sequence. Also, the binding constant between the Fe(III) complex and G-quadruplex was measured by these methods and it was found to be 4.53(±0.30) × 10(5) M(-1)). The PCR stop assay indicated that the Fe(III) complex inhibits DNA amplification. The cell viability assay showed that the complex has significant antitumor activities against Hela cells. According to the UV-vis results, the interaction of the Fe(III) complex with duplex DNA is an order of magnitude lower than G-quadruplex. Furthermore, the release of the complex incorporated in bovine serum albumin nanoparticles was also investigated in physiological conditions. The release of the complex followed a bi-phasic release pattern with high and low releasing rates at the first and second phases, respectively. Also, in order to obtain the binding mode of the Fe(III) complex with G-quadruplex, molecular modeling was performed. The molecular docking results showed that the Fe(III) complex was docked to the end-stacked of the G-quadruplex with a π-π interaction, created between the meloxicam ligand and the guanine bases of the G-quadruplex.

Experimental and molecular modeling studies of the interaction of the polypyridyl Fe(II) and Fe(III) complexes with DNA and BSA.

Two mononuclear iron complexes, [Fe(tppz)2](PF6)2·H2O (1) and Fe(tppz)Cl3·2CHCl3 (2) where tppz is (2,3,5,6-tetra(2-pyridyl)pyrazine), have been synthesized and characterized by elemental analysis, spectroscopic methods (UV-Vis and IR) and single crystal X-ray structure analysis. The interaction of (1) as the nitrate salt ([Fe(tppz)2](NO3)2) with calf-thymus DNA (CT-DNA) has been monitored by UV-Vis spectroscopy, competitive fluorescence titration, circular dichroism (CD), voltammetric techniques, viscosity measurement, and gel electrophoresis. Gel electrophoresis of DNA with [Fe(tppz)2](NO3)2 demonstrated that the complex also has the ability to cleave supercoiled plasmid DNA. The results have indicated that the complex binds to CT-DNA by three binding modes, viz., electrostatic, groove and partial insertion of the pyridyl rings between the base stacks of double-stranded DNA. Molecular docking of [Fe(tppz)2](NO3)2 with the DNA sequence d(ACCGACGTCGGT)2 suggests the complex fits into the major groove. The water-insoluble complex (2) can catalyze the cleavage of BSA at 40 °C. There are no reports of the catalytic effect of polypyridyl metal complexes on the BSA cleavage. Molecular docking of (2) with BSA suggests that, when the chloro ligands in the axial positions are replaced by water molecules, the BSA can interact with the Fe(III) complex more easily.

Combined fluorescence spectroscopy and molecular modeling studies on the interaction between harmalol and human serum albumin.

The interaction between harmalol and human serum albumin (HSA) has been studied by fluorescence spectroscopy and molecular modeling methods. The intrinsic fluorescence of HSA was quenched by harmalol, which was rationalized in terms of the static quenching mechanism. The binding parameters, quenching constants and conformation changes were determined by fluorescence quenching method. The thermodynamic parameters, calculated from the temperature dependence of binding constants (i.e., ΔH°=-62.7 kJ mol⁻¹ and ΔS°=-119.3J mol⁻¹ K⁻¹), indicated the major role of van der Waals force and hydrogen bonding in binding process. Site marker competitive experiments revealed that harmalol binds to both the IIA and IIIA sub-domains of HSA with a slight preference toward sub-domain IIA. Finally, the binding of harmalol to HSA was modeled by molecular docking and molecular dynamic simulation methods. Excellent agreement was found between the experimental and theoretical results with respect to the mechanism of binding and binding constants. Molecular dynamic simulation revealed that HSA does not have a significant conformational change when it binds with harmalol.

Quantitative structure-property relationship study of the solvent polarity using wavelet neural networks.

Quantitative structure-property relationship (QSPR) studies based on artificial neural network (ANN) and wavelet neural network (WNN) techniques were carried out for the prediction of solvent polarity. Experimental S' values for 69 solvents were assembled. This set included saturated and unsaturated hydrocarbons, solvents containing halogen, cyano, nitro, amide, sulfide, mercapto, sulfone, phosphate, ester, ether, etc. Semi-empirical quantum chemical calculations at AM1 level were used to find the optimum 3D geometry of the studied molecules and different quantum-chemical descriptors were calculated by the HyperChem software. A stepwise MLR method was used to select the best descriptors and the selected descriptors were used as input neurons in neural network models. The results obtained by the two methods were compared and it was shown that in WNN, the convergence speed was faster and the root mean square error of prediction set was also smaller than ANN. The average relative error in WNN was 7.9 and 6.8% for calibration and prediction set, respectively, and the results showed the ability of the WNN developed here to predict solvent polarity.