Protein Binding of a Novel Platinum-Based Anticancer Agent BP-C1 Containing a Lignin-Derived Polymeric Ligand

Platinum (Pt) antineoplastic agents remain indispensable for the treatment of oncological disease. Pt-based drugs are mainly used in the therapy of ovarian cancer and non-small-cell lung carcinoma. A novel platinum-containing antineoplastic agent BP-C1 is a complex of diamminoplatinum with an oxygen-donor polymeric ligand of benzene-polycarboxylic acids, isolated from natural lignin. The aim of the study was to investigate ex vivo protein binding of BP-C1. Protein binding of BP-C1 was tested using equilibrium dialysis. Pooled blood plasma was used in the study. Control solutions contained the same dosages of BP-C1 in PBS (pH 7.2). Plasma and control solutions were submitted to equilibrium dialysis across a vertical 8 kDa cut-off membrane for 4 h at 37 °C under gentle shaking. Platinum was quantified in dialysis and retained fractions using inductively coupled plasma mass spectrometry after microwave digestion. The dialysis system was tested and validated; this showed no protein saturation with platinum. A medium degree of binding of platinum to macromolecular species of ca. 60% was observed. The study showed the maintenance of a high fraction of free BP-C1 in the bloodstream, facilitating its pharmacological activity.

Substrate binding in the processive cellulase Cel7A: Transition state of complexation and roles of conserved tryptophan residues

Cellobiohydrolases effectively degrade cellulose and are of biotechnological interest because they can convert lignocellulosic biomass to fermentable sugars. Here, we implemented a fluorescence-based method for real-time measurements of complexation and decomplexation of the processive cellulase Cel7A and its insoluble substrate, cellulose. The method enabled detailed kinetic and thermodynamic analyses of ligand binding in a heterogeneous system. We studied WT Cel7A and several variants in which one or two of four highly conserved Trp residues in the binding tunnel had been replaced with Ala. WT Cel7A had on/off-rate constants of 1 × 105m−1 s−1 and 5 × 10−3 s−1, respectively, reflecting the slow dynamics of a solid, polymeric ligand. Especially the off-rate constant was many orders of magnitude lower than typical values for small, soluble ligands. Binding rate and strength both were typically lower for the Trp variants, but effects of the substitutions were moderate and sometimes negligible. Hence, we propose that lowering the activation barrier for complexation is not a major driving force for the high conservation of the Trp residues. Using so-called Φ-factor analysis, we analyzed the kinetic and thermodynamic results for the variants. The results of this analysis suggested a transition state for complexation and decomplexation in which the reducing end of the ligand is close to the tunnel entrance (near Trp-40), whereas the rest of the binding tunnel is empty. We propose that this structure defines the highest free-energy barrier of the overall catalytic cycle and hence governs the turnover rate of this industrially important enzyme.

Catalytic Performances of Platinum Containing PLLA Macrocomplex in the Hydrogenation of α,β-Unsaturated Carbonyl Compounds

The synthesis of a bipyridine poly(lactic acid) carboxylic end-capped macroligand coordinated to a platinum center was reported. The reaction between the metal ion and the polymeric ligand was run in a very efficient way through a one-step synthesis and the complex was tested for selective hydrogenation of α,β-carbonyl compounds. High selectivity was proven for double bond hydrogenation of 2-cyclohexen-1-one (up to 99%) and the production of 1-butanol from (E)-but-2-enal. Moreover, the catalytic system was still active after three catalytic cycles.

Catalyst shuttling enabled by a thermoresponsive polymeric ligand: facilitating efficient cross-couplings with continuously recyclable ppm levels of palladium

A thermoresponsive polymeric Pd-complex was synthesized, enabling highly efficient cross-couplings and continuous catalyst-recycling flow reactions with ultralow Pd usages.

Functional nanoscale metal–organic particles synthesized from a new vinylimidazole-based polymeric ligand and dysprosium ions

Bimodal magneto-fluorescent metal–organic nanoparticles were synthesized from a new vinylimidazole-based polymer ligand and Dy3+, which further develop an anti-disassembling ability by silica-coating.

Efficient adsorption, removal and recovery of phosphate and nitrate from water by a novel lanthanum(iii)-Dowex M4195 polymeric ligand exchanger

A novel polymeric ligand exchanger (PLE) can selectively remove phosphate and nitrate from water down to <0.1 ppm.