A generalized approach for the calculation and automation of potentiometric titrations Part 2. Redox Titrations

The very fast calculation procedure described earlier is applied to calculate the titration curves of complicated redox systems. The theory is extended slightly to cover inhomogeneous redox systems. Titrations of iodine or 2,6-dichloroindophenol with ascorbic acid are described. It is shown that correspondence between theory and practice is good as long as the relevant stability constants and redox potentials are known with sufficient accuracy

The computerized determination of double-layer capacitance with the use of kalousek-type waveforms and its application in titrimetry

A method for the rapid determination of double-layer capacitance—potential curves of electrodes is described. An on-line computer is used to apply Kalousek-type waveforms to the electrochemical cell and to measure the accompanying current response. The capacitances are determined from the slope of the plots of log current against time. For 0.1 M KCl, the computerized method agrees well with the bridge method, except for the potential range of 0 to –0.15 V. The method is very useful for automating titrations with tensammetric detection of the end-point. The method is applied to the titration of barium with a macrocydic compound (kryptofix 222) and the titration of cetyl-trimethyl-ammonium bromide with bromocresol purple. The accuracy of the titrations is ±2%

Proton and cadmium adsorption by the archaeon Thermococcus zilligii: Generalising the contrast between thermophiles and mesophiles as sorbents

Adsorption by microorganisms can play a significant role in the fate and transport of metals in natural systems. Surface complexation models (SCMs) have been applied extensively to describe metal adsorption by mesophilic bacteria, and several recent studies have extended this framework to thermophilic bacteria. We conduct acid-base titrations and batch experiments to characterise proton and Cd adsorption onto the thermophilic archaeon Thermococcus zilligii. The experimental data and the derived SCMs indicate that the archaeon displays significantly lower overall sorption site density compared to previously studied thermophilic bacteria such Anoxybacillus flavithermus, Geobacillus stearothermophilus, G. thermocatenulatus, and Thermus thermophilus. The thermophilic bacteria and archaea display lower sorption site densities than the mesophilic microorganisms that have been studied to date, which points to a general pattern of total concentration of cell wall adsorption sites per unit biomass being inversely correlated to growth temperature

Lower-rim ferrocenyl substituted calixarenes: new electrochemical sensors for anions

New ferrocene substituted calix[4 and 5]arenes have been prepared and the crystal structure of a lower-rim substituted bis ferrocene calix[4]arene (7) has been elucidated. The respective ferrocene/ferrocenium redox-couples of compounds 6 (a calix[4]arene tetra ferrocene amide) and 8 (a calix[5]arene pentaferrocene amide) are shown to be significantly cathodically perturbed in the presence of anions by up to 160 mV in the presence of dihydrogen phosphate

Two hydroxy pyridinecarboxylic acid derivatives as a possible chelating agents in neurodegenerative disease; equilibrium complexation studies with Cu(II), Zn(II).

The metal ion chelators 4-hydroxy-5-methyl-3-pyridinecarboxylic acid (DQ5) and 1,5-dimethyl-4-hydroxy-3-pyridinecarboxylic acid (DQ715) and Cu(II) and Zn(II) were investigated with the aim to restore the homeostasis of the brain Cu(II) and Zn(II) in neurodegenerative diseases. The proton dissociation constants of the ligands, the stability constants, and the coordination modes of the metal complexes formed were determined by pH-potentiometric, and spectral (UV–Vis and EPR or 1H NMR) methods. The results show that in slightly acidic and neutral pH range mono and bis complexes are formed through bidentate coordination of the ligands. The biological MTT-test reveals that the DQ715 ligand is able to lower the cytotoxic effect of Cu(II) in human embryonic kidney HEK-293 cells. Our studies revealed, however, that none of the chelators were efficient enough to withdraw these metal ions from the amyloid aggregates

Inner-sphere complexation of cations at the rutile-water interface: A concise surface structural interpretation with the CD and MUSIC model

Acid–base reactivity and ion-interaction between mineral surfaces and aqueous solutions is most frequently investigated at the macroscopic scale as a function of pH. Experimental data are then rationalized by a variety of surface complexation models. These models are thermodynamically based which in principle does not require a molecular picture. The models are typically calibrated to relatively simple solid-electrolyte solution pairs and may provide poor descriptions of complex multi-component mineral–aqueous solutions, including those found in natural environments. Surface complexation models may be improved by incorporating molecular-scale surface structural information to constrain the modeling efforts. Here, we apply a concise, molecularly-constrained surface complexation model to a diverse suite of surface titration data for rutile and thereby begin to address the complexity of multi-component systems. Primary surface charging curves in NaCl, KCl, and RbCl electrolyte media were fit simultaneously using a charge distribution (CD) and multisite complexation (MUSIC) model [Hiemstra T. and Van Riemsdijk W. H. (1996) A surface structural approach to ion adsorption: the charge distribution (CD) model. J. Colloid Interf. Sci. 179, 488–508], coupled with a Basic Stern layer description of the electric double layer. In addition, data for the specific interaction of Ca2+ and Sr2+ with rutile, in NaCl and RbCl media, were modeled. In recent developments, spectroscopy, quantum calculations, and molecular simulations have shown that electrolyte and divalent cations are principally adsorbed in various inner-sphere configurations on the rutile 1 1 0 surface [Zhang Z., Fenter P., Cheng L., Sturchio N. C., Bedzyk M. J., Predota M., Bandura A., Kubicki J., Lvov S. N., Cummings P. T., Chialvo A. A., Ridley M. K., Bénézeth P., Anovitz L., Palmer D. A., Machesky M. L. and Wesolowski D. J. (2004) Ion adsorption at the rutile–water interface: linking molecular and macroscopic properties. Langmuir 20, 4954–4969]. Our CD modeling results are consistent with these adsorbed configurations provided adsorbed cation charge is allowed to be distributed between the surface (0-plane) and Stern plane (1-plane). Additionally, a complete description of our titration data required inclusion of outer-sphere binding, principally for Cl- which was common to all solutions, but also for Rb+ and K+. These outer-sphere species were treated as point charges positioned at the Stern layer, and hence determined the Stern layer capacitance value. The modeling results demonstrate that a multi-component suite of experimental data can be successfully rationalized within a CD and MUSIC model using a Stern-based description of the EDL. Furthermore, the fitted CD values of the various inner-sphere complexes of the mono- and divalent ions can be linked to the microscopic structure of the surface complexes and other data found by spectroscopy as well as molecular dynamics (MD). For the Na+ ion, the fitted CD value points to the presence of bidenate inner-sphere complexation as suggested by a recent MD study. Moreover, its MD dominance quantitatively agrees with the CD model prediction. For Rb+, the presence of a tetradentate complex, as found by spectroscopy, agreed well with the fitted CD and its predicted presence was quantitatively in very good agreement with the amount found by spectroscopy

Calibration and comparison of chlorine decay models for a test water distribution system

This paper investigates the kinetics of monochloramine as disinfectant in a 1.3 km water pipe. A novel procedure for the correction of chlorine meter errors is introduced and applied. Parameter estimation using nonlinear optimisation procedures is used to identify decay coefficients for monochloramine models with a single coefficient or two coefficients as used in EPANET. Important difficulties in fitting these parameters which come about because of the model structure are highlighted. Finally, results of decay coefficients are presented and investigated for flow, inlet chlorine concentration and temperature dependence

Complex interplay of kinetic factors governs the synergistic properties of HIV-1 entry inhibitors.

The homotrimeric HIV-1 envelope glycoprotein (Env) undergoes receptor-triggered structural changes that mediate viral entry through membrane fusion. This process is inhibited by chemokine receptor antagonists (CoRAs) that block Env-receptor interactions and by fusion inhibitors (FIs) that disrupt Env conformational transitions. Synergy between CoRAs and FIs has been attributed to a CoRA-dependent decrease in the rate of viral membrane fusion that extends the lifetime of the intermediate state targeted by FIs. Here, we demonstrated that the magnitude of CoRA/FI synergy unexpectedly depends on FI-binding affinity and the stoichiometry of chemokine receptor binding to trimeric Env. For C-peptide FIs (clinically represented by enfuvirtide), synergy waned as binding strength decreased until inhibitor combinations behaved additively. Curiously, this affinity dependence on synergy was absent for 5-Helix-type FIs. We linked this complex behavior to the CoRA dependence of Env deactivation following FI binding. For both FI classes, reducing chemokine receptor levels on target cells or eliminating competent chemokine receptor-binding sites on Env trimers resulted in a loss of synergistic activity. These data imply that the stoichiometry required for CoRA/FI synergy exceeds that required for HIV-1 entry. Our analysis suggests two distinct roles for chemokine receptor binding, one to trigger formation of the FI-sensitive intermediate state and another to facilitate subsequent conformational transitions. Together, our results could explain the wide variety of previously reported activities for CoRA/FI combinations. These findings also have implications for the combined use of CoRAs and FIs in antiviral therapies and point to a multifaceted role for chemokine receptor binding in promoting HIV-1 entry

NMR Line Shapes and Multi-State Binding Equilibria

Biological function of proteins relies on conformational transitions and binding of specific ligands. Protein-ligand interactions are thermodynamically and kinetically coupled to conformational changes in protein structures as conceptualized by the models of pre-existing equilibria and induced fit. NMR spectroscopy is particularly sensitive to complex ligand-binding modes—NMR line-shape analysis can provide for thermodynamic and kinetic constants of ligand-binding equilibria with the site-specific resolution. However, broad use of line shape analysis is hampered by complexity of NMR line shapes in multi-state systems. To facilitate interpretation of such spectral patterns, I computationally explored systems where isomerization or dimerization of a protein (receptor) molecule is coupled to binding of a ligand. Through an extensive analysis of multiple exchange regimes for a family of three-state models, I identified signature features to guide an NMR experimentalist in recognizing specific interaction mechanisms. Results also show that distinct multistate models may produce very similar spectral patterns. I also discussed aggregation of a receptor as a possible source of spurious three-state line shapes and provided specific suggestions for complementary experiments that can ensure reliable mechanistic insight