Molecular drug design, synthesis and structure elucidation of a new specific target peptide based metallo drug for cancer chemotherapy as topoisomerase I inhibitor

To evaluate the biological preference of metallopeptide drugs in cancer cells, a new dinuclear copper(II) complex [Cu(2)(glygly)(2)(ppz)(H(2)O)(4)]·2H(2)O (1) (glygly = glycyl glycine anion and ppz = piperazine), was designed and synthesized as topoisomerase I inhibitor. The structural elucidation of the complex was done by elemental analysis, spectroscopic methods and single crystal X-ray diffraction. The in vitro DNA binding studies of complex 1 with CT DNA were carried out by employing different optical methods viz. UV-vis, fluorescence and circular dichroism. The molecular docking technique was also utilized to ascertain the mechanism and mode of action towards the molecular target DNA and enzymes. Complex 1 cleaves pBR322 DNA via an oxidative mechanism and strongly binds to the DNA minor groove. Furthermore, complex 1 exhibits significant inhibitory effects on the catalytic activity of topoisomerase I at a very low concentration, ~12.5 μM, in addition to its excellent SOD mimics (IC(50)~0.086 μM).     

Sensitivity of nucleation phenomena on range of interaction potential

Theoretical and computational investigations of nucleation have been plagued by the sensitivity of the phase diagram to the range of the interaction potential. As the surface tension depends strongly on the range of interaction potential and as the classical nucleation theory (CNT) predicts the free energy barrier to be directly proportional to the cube of the surface tension, one expects a strong sensitivity of nucleation barrier to the range of the potential; however, CNT leaves many aspects unexplored. We find for gas-liquid nucleation in Lennard-Jones system that on increasing the range of interaction the kinetic spinodal (KS) (where the mechanism of nucleation changes from activated to barrierless) shifts deeper into the metastable region. Therefore the system remains metastable for larger value of supersaturation and this allows one to explore the high metastable region without encountering the KS. On increasing the range of interaction, both the critical cluster size and pre-critical minima in the free energy surface of kth largest cluster, at respective kinetic spinodals, shift towards smaller cluster size. In order to separate surface tension contribution to the increase in the barrier from other non-trivial factors, we introduce a new scaling form for surface tension and use it to capture both the temperature and the interaction range dependence of surface tension. Surprisingly, we find only a weak non-trivial contribution from other factors to the free energy barrier of nucleation.     

Studies of solvation of ketocyanine dyes in homogeneous and heterogeneous media by UV/Vis spectroscopic method

Solvation characteristics of ketocyanine dyes (I-VI) have been investigated in pure solvents and heterogeneous media by absorption and fluorescence studies. The dyes are good reporters of solvent polarity. In protic solvents they exist as equilibrium mixtures of bare and hydrogen-bonded form in the ground state (S0), the latter being the emitting species. In aprotic solvents of low polarity association of the S1 state of the dye takes place. In aqueous micellar media the dye resides at the micelle water interface. The binding constant for dye-micelle interaction has been determined. Fluorescence data in beta-cyclodextrine solution resemble that for that neutral micellar solution indicating that the interaction between the -OH group of the heterogeneous part (micelle/cyclodextrine cavity) and the carbonyl oxygen of the dye is important in both the cases.     

Comparative study of temperature dependent orientational relaxation in a model thermotropic liquid crystal and in a model supercooled liquid

Recent optical Kerr effect experiments have revealed a power law decay of the measured signal with a temperature independent exponent at short-to-intermediate times for a number of liquid crystals in the isotropic phase near the isotropic-nematic transition and supercooled molecular liquids above the mode coupling theory critical temperature. In this work, the authors investigate the temperature dependence of short-to-intermediate time orientational relaxation in a model thermotropic liquid crystal across the isotropic-nematic transition and in a binary mixture across the supercooled liquid regime in molecular dynamics simulations. The measure of the experimentally observable optical Kerr effect signal is found to follow a power law decay at short-to-intermediate times for both systems in agreement with recent experiments. In addition, the temperature dependence of the power law exponent is found to be rather weak. As the model liquid crystalline system settles into the nematic phase upon cooling, the decay of the single-particle second-rank orientational time correlation function exhibits a pattern that is similar to what has been observed for supercooled liquids.     

Two-dimensional infrared investigation of N-acetyl tryptophan methyl amide in solution

The linear infrared and two-dimensional infrared (2D IR) spectra in the amide-I region of N-acetyl tryptophan methyl amide (NATMA) in solvents of varying polarity are reported. The two amide-I transitions have been assigned unambiguously by using 13C isotopic substitution of the carbonyl group. The amide unit at the amino end shows a lower transition frequency in CH2Cl2 and methanol, while the acetyl end has a lower transition frequency in D2O. Multiple conformers exist in CH2Cl2 and methanol, but only one conformer is evident in D2O. The 2D IR cross peaks from the intermode coupling yield off-diagonal anharmonicities 2.5 +/- 0.5, 3.25 +/- 0.5, and 3.0 +/- 0.5 cm(-1) in CH2Cl2, methanol, and D2O, respectively, which by simple matrix diagonalization yield the coupling constants 8.0 +/- 0.5, 8.0 +/- 1.0, and 5.5 +/- 1.0 cm(-1). The major conformer in CH2Cl2 corresponds to a C7 structure, in agreement with that found in the gas phase [Dian, B. C.; Longarte, A.; Mercier, S.; Evans, D. A.; Wales, D. J.; Zwier, T. S. J. Chem. Phys. 2002, 117, 10688-10702] with intramolecular hydrogen bonding between the acetyl end C=O and the amino end N-H. The backbone dihedral angles (phi, psi) are determined to be in the ranges of (-55 +/- 5 degrees , 30 +/- 5 degrees ), (120 +/- 10 degrees , -20 +/- 10 degrees ), and (+/-160 +/- 10 degrees , +/-75 +/- 10 degrees ) in CH2Cl2, methanol, and D2O, respectively.     

Spectroscopic study of association of a hemicyanine dye in mixed aqueous binary solvents

Electronic absorption and steady state emission properties of a hemicyanine dye [4-[4-(dimethylamino)styryl]-1-docosylpyridinium bromide], have been studied in several pure solvents and two mixed binary solvents (water+ethanol and water+acetonitrile). In pure solvents the band-width of the absorption spectrum correlates well with the Stoke's shift. In mixed aqueous solvents two different molecular forms of the solute, viz. the monomer and the dimer of the solute exists in equilibrium. Thermodynamic parameters (e.g. the Delta G degrees and Delta H degrees ) characterizing the equilibrium have been determined. While the value of Delta G degrees changes very slightly with the composition of the binary mixture, the value of Delta H degrees has been observed to depend significantly with solvent composition.     

Electrocatalytic activity of binary Palladium Ruthenium anode catalyst on Ni-support for ethanol alkaline fuel cells

In search for a cheaper anode catalyst for the oxidation of ethanol for development of direct alcohol fuel cells, Pd has been considered here as an interesting substitute for Pt in Pt Ru binary electrodeposite. The binary catalyst when co-deposited on nickel support has been found to increase the current density and decrease the anodic overvoltage significantly with respect to pure Pt, Pd and Ni. Its electrocatalytic capability is also comparable with that of the Pt-Ru binary electrocatalyst on Ni-support, when studied in 1 M EtOH containing 1 M NaOH solution. The effect of loading of Pd Ru electrocatalyst on Ni support has also been tested. The electrocatalytic activity of the electrodes for oxidation of ethanol has been explained by studies of cyclic voltammetry, chronopotentiometry, steady-state polarization, and conjugated scanning electron microscopy–energy dispersion X-ray spectroscopy. It has been found that electrode containing the higher amount of deposit are less affected by carbonaceous poisons.     

Novel fluorescent probe as aggregation predictor and micro-polarity reporter for micelles and mixed micelles

Aggregational behaviour of micelles sodium dodecyl sulphate (SDS and Triton X-100, TX-100 both in pure and mixed form) and micelle like aggregates such as polymer-surfactant system [polymer poly(vinyl pyrrolidone), PVP]-SDS have been studied by using fluorescence characteristics of a newly synthesized probe. The critical micelle concentration (CMC) values determined at various surfactant compositions are lower than the ideal values indicating a synergistic effect. The value of the interaction parameter for the surfactant mixture has been determined which agrees well with the value calculated according to molecular thermodynamic theory. The total aggregation number of surfactant in mixed micelle shows a drastic variation in the SDS mole fraction range 0 < or = alpha1 < or = 0.3 and beyond the range it remains practically constant. Molar-based partition coefficients for the dye between the micellar and aqueous phase have been determined and a non-linear variation is obtained for the mixed micellar system. Variations of micro-polarity in the mixed micellar region have been investigated as a function of surfactant composition and results have been explained in terms of a suitable realistic model.     

Simplified,interpretable graph convolutional neural networks for small molecule activity prediction

Journal of Computer-Aided Molecular Design - We here present a streamlined, explainable graph convolutional neural network (gCNN) architecture for small molecule activity prediction. We first...     

A study of preferential solvation of N-alkyl pyridinium iodides in mixed solvents containing acetonitrile

The charge transfer (CT) band maximum of N-alkyl pyridinium iodide (NAPI) has been studied as a function of the composition of binary mixed dipolar aprotic solvents. The deviation from linearity of the energy maximum (E₁₂) and the mole fraction (of a component solvent) plot is explained as due to a preferential solvation by the more polar cosolvent in the binary mixture. The extent of preferential solvation has been observed to vary with the composition, the maximum being towards the less-polar end. The role of hydrogen bond donating ability of a solvent in preferential solvation is discussed.