Long Residence Times Revealed by Aurora A Kinase‐Targeting Fluorescent Probes Derived from Inhibitors MLN8237 and VX‐689

We report the development of three fluorescent probes for protein kinase Aurora A that are derived from the well‐known inhibitors MLN8237 and VX‐689 (MK‐5108). Two of these probes target the ATP site of Aurora A, and one targets simultaneously the ATP and substrate sites of the kinase. The probes were tested in an assay with fluorescence polarisation/anisotropy readout, and we demonstrated slow association kinetics and long residence time of the probes (k_on 10⁵–10⁷ M ^?1 s^?1, k_off 10^?3–10^?4 s^?1; residence time 500–3000 s). The presence of the Aurora A activator TPX2 caused a significant reduction in the on‐rate and increase in the off‐rate of fluorescent probes targeting ATP site. These observations were supported by Aurora A inhibition assays with MLN8237 and VX‐689. Overall, our results emphasise the importance of rational design of experiments with these compounds and correct interpretation of the obtained data.     

Absolute reactivity in the cationic polymerization of methyl and other alkyl vinyl ethers

The cationic polymerizations of methyl-, 2-chloroethyl-, ethyl-, cyclohexyl- and t-butyl- vinyl ethers initiated by cycloheptatrienyl hexachloroantimonate in methylene chloride solutions have been studied in detail. Reaction rates were measured by an adiabatic calorimetric technique and rate constants for propagation of each of the monomers, k_p (obs), were determined by appropriate kinetic analysis of the experimental curves. The results obtained are discussed in terms of current theories regarding ion pair/free ion equilibria in non-aqueous solvents. Although ethyl-, cyclohexyl- and t-butyl- vinyl ethers behave very similarly to isobutyl vinyl ether, and their reactivities are comparable [k_p (obs) ～ 3 × 10³M^?1sec^?1 at 0°C] both methyl- and 2-chloroethyl- vinyl ethers show markedly different characteristics to the others, and in particular exhibit a reactivity approximately one order of magnitude less [k_p (obs) ～ 2 × 10²M^?1sec^?1 at 0°C]. These variations in reactivity are discussed in terms of preferred monomer conformations, and the resulting differences in activation energy which are likely to arise when such conformers are approached by an electrophile.     

A Two-Step Reaction Mechanism of Oxygen Release from Pd/CeO2: Mathematical Modelling Based on Step Gas Concentration Experiments

A mathematical model has been developed to study the transient release of oxygen from a 1wt% Pd/CeO₂ catalyst in the 450–550 °C range based on alternate step concentration switches between CO and O₂. A two-step reaction mechanism that involves the reaction of gaseous CO with the oxygen species of PdO and of the back-spillover of oxygen from ceria to the oxygen vacant sites of surface PdO has been proven to better describe the CO and CO₂ transient response curves. The proposed mathematical model allows the estimation of the transient rates of the CO oxidation reaction and of the back-spillover of oxygen process. It also allows the calculation of the intrinsic rate constant k ₁ (s^–1) of the Eley–Rideal step for the reaction of gaseous CO with surface oxygen species of PdO to form CO₂. An activation energy of 10.1 kJ/mol was estimated for this elementary reaction step. In addition, an apparent rate constant k ₂ ^app (s^–1) was estimated for the process of back-spillover of oxygen.     

Inverse microemulsion copolymerization of butyl acrylate and acrylamide: kinetics,colloidal parameters and some model applications

The inverse microemulsion copolymerization of acrylamide and butyl acrylate initiated by ammonium peroxodisulphate, a water‐soluble initiator, and stabilized by anionic emulsifiers sodium bis‐2‐ethylhexylsulfosuccinate and sodium dodecylsulphate (SDS) has been studied. An increase of SDS concentration was observed to increase both the rate of polymerization and the particle size. The average number of radicals per particle (n?) is much below 0.5, which indicates desorption of monomeric radicals from polymer particles. The exit (desorption) rate constants k′_des (cm² s^?1) and k_des (s^?1) were evaluated as a function of SDS concentration (or the particle size) according to the Ugelstad/O'Toole (I), Nomura (II) and Gilbert (III) models. The value of k_des (s^?1) decreases with increasing particle size (or SDS concentration) for all three (I, II and III) models. A complex trend appears for k′_des (cm² s^?1): the Ugelstad/O'Toole model estimates a decrease, the Nomura model finds no variation and the Gilbert model estimates even a slight increase in k′_des with increasing SDS concentration. Copyright © 2006 Society of Chemical Industry     

E‐64c‐Hydrazide: A Lead Structure for the Development of Irreversible Cathepsin C Inhibitors

Cathepsin C is a papain‐like cysteine protease with dipeptidyl aminopeptidase activity that is thought to activate various granule‐associated serine proteases. Its exopeptidase activity is structurally explained by the so‐called exclusion domain, which blocks the active‐site cleft beyond the S2 site and, with its Asp 1 residue, provides an anchoring point for the N terminus of peptide and protein substrates. Here, the hydrazide of (2S,3S)‐trans‐epoxysuccinyl‐L ‐leucylamido‐3‐methylbutane (E‐64c) (k₂/K_i=140±5 M ^?1 s^?1) is demonstrated to be a lead structure for the development of irreversible cathepsin C inhibitors. The distal amino group of the hydrazide moiety addresses the acidic Asp 1 residue at the entrance of the S2 pocket by hydrogen bonding while also occupying the flat hydrophobic S1′–S2′ area with its leucine‐isoamylamide moiety. Furthermore, structure–activity relationship studies revealed that functionalization of this distal amino group with alkyl residues can be used to occupy the conserved hydrophobic S2 pocket. In particular, the n‐butyl derivative was identified as the most potent inhibitor of the series (k₂/K_i=56 000±1700 M ^?1 s^?1).     

Structure and Binding of Peptide‐Dendrimer Ligands to Vitamin B12

The third‐generation peptide‐dendrimer B1 (AcES)₈(BEA)₄(K‐Amb‐Y)₂BCD‐NH₂ (B=branching (S)‐2,3‐diaminopropanoic acid, K=branching lysine, Amb=4‐aminomethyl‐benzoic acid) is the first synthetic model for cobalamin‐binding proteins and binds cobalamin strongly (K_a=5.0×10⁶ M ^?1) and rapidly (k₂=346 M ^?1 s^?1) by coordination of cobalt to the cysteine residue at the dendrimer core. A structure–activity relationship study is reported concerning the role of negative charges in binding. Substituting glutamates (E) for glutamines (Q) in the outer branches of B1 to form N3 (AcQS)₈(BQA)₄(B‐Amb‐Y)₂BCD‐NH₂ leads to stronger (K_a=12.0×10⁶ M ^?1) but slower (k₂=67 M ^?1 s^?1) cobalamin binding. CD and FTIR spectra show that the dendrimers and their cobalamin complexes exist as random‐coil structures without aggregation in solution. The hydrodynamic radii of the dendrimers determined by diffusion NMR either remains constant or slightly decreases upon binding to cobalamin; this indicates the formation of compact, presumably hydrophobically collapsed complexes.     

Superoxide Reductase: Different Interaction Modes with its Two Redox Partners

Anaerobic organisms have molecular systems to detoxify reactive oxygen species when transiently exposed to oxygen. One of these systems is superoxide reductase, which reduces O₂^.? to H₂O₂ without production of molecular oxygen. In order to complete the reduction of superoxide anion, superoxide reductase requires an electron, delivered by its redox partners, which in Desulfovibrio gigas are rubredoxin and/or desulforedoxin. In this work, we characterized the interaction of Desulfovibrio gigas superoxide reductase with both electron donors by using steady‐state kinetics, 2D NMR titrations, and backbone relaxation measurements. The rubredoxin surface involved in the electron transfer complex with superoxide reductase comprises the solvent‐exposed hydrophobic residues in the vicinity of its metal center (Cys9, Gly10, Cys42, Gly43, and Ala44), and a K_d of 3 μM at 59 mM ionic strength was estimated by NMR. The ionic strength dependence of superoxide‐mediated rubredoxin oxidation by superoxide reductase has a maximum k_app of (37±12) min^?1 at 157 mM . Relative to the electron donor desulforedoxin, its complex with superoxide reductase was not detected by chemical shift perturbation, though this protein is able to transfer electrons to superoxide reductase with a maximum k_app of (31±7) min^?1 at an ionic strength of 57 mM . Competition experiments using steady‐state kinetics and NMR spectroscopy (backbone relaxation measurements and use of a paramagnetic relaxation enhancement probe) with Fe‐desulforedoxin in the presence of ¹⁵N‐Zn‐rubredoxin showed that these two electron donors compete for the same site on the enzyme surface, as shown in the model structure of the complex generated by using restrained molecular docking calculations. These combined strategies indicate that the two small electron donors bind in different manners, with the desulforedoxin complex being a short lived electron transfer complex or more dynamic, with many equivalent kinetically competent orientations.     

Kinetics of leaching of tunisian phosphate ore particles in dilute phosphoric acid solutions

Van der Sluis et al.'s model was used to determine the rate of the partial dissolution of a Tunisian phosphate rock with dilute phosphoric acid (1.5 mass% P₂O₅). When the temperature rises from 25 to 90°C, for a given particle size, the mass-transfer coefficients, k_L°, vary from 3 × 10^?3 to 8 × 10^?3 m ·s^?1. The corresponding diffusion coefficients, D, lies between 6 × 10^?7 and 27 × 10^?7 m²·s^?1. Activation energy is equal to 14 kJ·mol^?1 and values of k_L°, at 25°C, are in the range of 0.28 × 10^?3 and 4 × 10^?3 m·s^?1 when the agitation speed goes from 220 to 1030 rpm, showing that the leaching process is controlled by diffusion rather than by chemical reaction.     

Evaluation of mixed‐conducting lanthanum‐strontium‐cobaltite ceramic membrane for oxygen separation

In this study, La_0.4Sr_0.6CoO_3‐δ (LSC) oxide was synthesized via an EDTA‐citrate complexing process and its application as a mixed‐conducting ceramic membrane for oxygen separation was systematically investigated. The phase structure of the powder and microstructure of the membrane were characterized by XRD and SEM, respectively. The optimum condition for membrane sintering was developed based on SEM and four‐probe DC electrical conductivity characterizations. The oxygen permeation fluxes at various temperatures and oxygen partial pressure gradients were measured by gas chromatography method. Fundamental equations of oxygen permeation and transport resistance through mixed conducting membrane were developed. The oxygen bulk diffusion coefficient (D_v) and surface exchange coefficient (K_ex) for LSC membrane were derived by model regression. The importance of surface exchange kinetics at each side of the membrane on oxygen permeation flux under different oxygen partial pressure gradients and temperatures were quantitatively distinguished from the oxygen bulk diffusion. The maximum oxygen flux achieved based on 1.6‐mm‐thick La_0.4Sr_0.6CoO_3‐δ membrane was ～4.0 × 10^?7 mol cm^?2 s^?1at 950°C. However, calculation results show theoretical oxygen fluxes as high as 2.98 × 10^?5 mol cm^?2 s^?1 through a 5‐μm‐thick LSC membrane with ideal surface modification when operating at 950°C for air separation. © 2009 American Institute of Chemical Engineers AIChE J, 2009     

Kinetic Study of the Scavenging Reaction of the Aroxyl Radical by Eight Kinds of Vegetable Oils in Solution

A detailed kinetic study was performed for the reaction of the aroxyl radical (ArO?) with eight vegetable oils 1–8, which contain different concentrations of α‐, β‐, γ‐, and δ‐tocopherols and ‐tocotrienols (‐Tocs and ‐Toc‐3s). The second‐order rate constants (k_s) and aroxyl radical absorption capacity (ARAC) values for the reaction of ArO? with vegetable oils 1–8 (rice bran 1, perilla 2, rapeseed 3, safflower 4, grape seed 5, sesame 6, extra virgin olive 7, and olive oils 8) were measured in ethanol/chloroform/D₂O (50:50:1, v/v/v) solution at 25 °C using stopped‐flow spectrophotometry. The k_s value (16.1 × 10^?3 L g^?1 s^?1) of rice bran oil 1 with the highest activity was 8.0 times larger than that (2.02 × 10^?3) of olive oil 8 with the lowest activity. The concentrations (in mg 100 g^?1) of α‐, β‐, γ‐, and δ‐Tocs and ‐Toc‐3s contained in the vegetable oils 1–8 were determined using high performance liquid chromatography‐mass spectrometry/mass spectrometry (HPLC‐MS/MS). From these results, it was clarified that the ArO?‐scavenging rates (k_s) (i.e., the relative ARAC value) obtained for the vegetable oils 1–8 may be well explained as the sum of the product of the rate constant () and the concentration ([AOH‐i]/10⁵) of AOH‐i (Tocs and Toc‐3s) included in vegetable oils. The results suggest that the ARAC assay method might be used in the evaluation of antioxidant activity of general food extracts.     

Equilibrium and kinetic studies on the extraction of gadolinium(III) from nitrate medium by di‐2‐ethylhexylphosphoric acid in kerosene using a single drop technique

The liquid–liquid extraction of Gd(III) from aqueous nitrate medium was studied using di‐2‐ethylhexylphosphoric acid (HDEHP) in kerosene. On the basis of the slope analysis data, the composition of the extracted species was found to be [Gd A₃(HA)] with the extraction equilibrium constant (K_ex) = (1.48 ± 0.042) × 10^?12 mol dm^?3. The results of the effect of temperature on the value of the equilibrium extraction constant indicated the endothermic character of the extraction system. The kinetics of the forward extraction of Gd³⁺ from nitrate medium by HDEHP in kerosene was investigated using the single drop column technique. The rate of flux (mass transfer per unit area) was found to be proportional to [Gd(III)], [H₂A₂]_(o), [NO₃^?], and [H⁺]^?1 in the liquid drop organic phase. The forward extraction rate constant, k_f, was 2.24 × 10^?3 m s^?1 using the equation: Copyright © 2005 Society of Chemical Industry     

A potential antitumor drug (arginine deiminase) reengineered for efficient operation under physiological conditions

Arginine deiminase (ADI, EC 3.5.3.6) is a potential antitumor drug for the treatment of arginine‐auxotrophic tumors such as hepatocellular carcinomas (HCCs) and melanomas, and studies on human lymphatic leukemia cell lines have confirmed that ADI has antiangiogenic activity. Recent studies showed that a combination of taxane and ADI‐PEG20, which induces caspase‐independent apoptosis, is more effective than taxane monotherapy for prostate cancer. The main limitation of ADI from Pseudomonas plecoglossicida (PpADI) and of many other ADI enzymes lies in their pH‐dependent activity profile. PpADI has a pH optimum at 6.5 and a pH shift from 6.5 to 7.5 results in an ～80 % activity drop (the pH of human plasma is 7.35 to 7.45). In 2010, we reported a proof of concept for ADI engineering by directed evolution that resulted in variant M2 (K5T/D44E/H404R). M2 has a pH optimum of pH 7.0, a fourfold higher k_cat value than the wild‐type PpADI (pH 7.4, 0.5 M phosphate buffer), and an increased K_m value for substrate arginine. In our latest work, variants M5 (K5T/D38H/D44E/A128T/H404R) and M6 (K5T/D38H/D44E/A128T/E296K/H404R) were generated by directed evolution by employing PBS buffer (pH 7.4), which mimics physiological conditions. The S_0.5 value of parent M3 (K5T/D44E/A128T/H404R) decreased from 2.01 to 1.48 mM (M5) and 0.81 mM (M6). The S_0.5 value of M6 (0.81 mM ) is lower than that of wild‐type PpADI (1.30 mM ); the k_cat values improved from 0.18 s^?1 (wild‐type PpADI) to 17.56 s^?1 (M5, 97.6‐fold) and 11.64 s^?1 (M6, 64.7‐fold).     

Blue fluorescent conductive poly(9,10‐di(1‐naphthalenyl)‐2‐vinylanthracene) homopolymer and its highly soluble copolymers with styrene or 9‐vinylcarbazole

A new blue fluorescent monomer, 9,10‐di(1‐naphthalenyl)‐2‐vinylanthracene, was designed and synthesized in good yield. Its homopolymer poly(9,10‐di(1‐naphthalenyl)‐2‐vinylanthracene) (P(ADN)) and soluble conductive vinyl copolymers poly[(9,10‐di(1‐naphthalenyl)‐2‐vinylanthracene)‐co‐styrene] (P(ADN‐co‐S)) and poly[(9,10‐di(1‐naphthalenyl)‐2‐vinylanthracene)‐co‐(9‐vinylcarbazole)] (P(ADN‐co‐VK)) were synthesized using free radical solution polymerization. All the polymers showed high glass transition mid‐point temperatures (203 to 237 °C) and good thermal stabilities. The photoluminescence emission of the copolymers was similar to that of P(ADN) (with two maxima at 423 and 442 nm). The lifetimes of P(ADN‐co‐S) (6.82 to 7.91 ns) were all slightly less than that of P(ADN) (8.40 ns). The lifetime of P(ADN‐co‐VK) increased from 7.8 to 8.8 ns with an increase in VK content. The fluorescence quantum yields of P(ADN‐co‐S) showed an overall increasing tendency from 0.42 to 0.58. The quantum efficiencies of P(ADN‐co‐VK) decreased from 0.36 to 0.19 with an increase of VK fraction. With increasing S/VK content, the highest occupied molecular orbital of P(ADN‐co‐S)/P(ADN‐co‐VK) ranged from ?5.58 to ?5.73 eV, which was similar to that of P(ADN) (?5.71 eV). The band gaps of P(ADN‐co‐S) and P(ADN‐co‐VK) were about 2.97 eV, which were equal to that of P(ADN), and smaller than that of 2‐methyl‐9,10‐di(1‐naphthalenyl)anthracene (MADN) (3.04 eV) and poly(9‐vinylcarbazole) (3.54 eV). Preliminary electroluminescence results were obtained for a homojunction device with the configuration ITO/MoO₃ (20 nm)/P(ADN)/LiF (1 nm)/Al (100 nm), which achieved only 30–50 cd m^?2, due to P(ADN) having a low mobility of 4.7 × 10^?8 cm² V^?1 s^?1 compared to that of its model compound MADN of 6.5 × 10^?4 cm² V^?1 s^?1. © 2013 Society of Chemical Industry     

An evaluation of the impact of SG1 disproportionation and the addition of styrene in NMP of methyl methacrylate

A kinetic modeling study is presented for batch nitroxide mediated polymerization (NMP) of methyl methacrylate (MMA; nitroxide: N‐tert‐butyl‐N‐[1‐diethylphosphono‐(2,2‐dimethylpropyl)] (SG1)). Arrhenius parameters for SG1 disproportionation (A = 1.4 10⁷ L mol^?1 s^?1; E_a = 23 kJ mol^?1) are reported, based on homopolymerization data accounting for unavoidable temperature variations with increasing time, that is, nonisothermicity. For low targeted chain lengths (TCLs ≤ 300), this nonisothermicity is also relevant for NMP of MMA with a small amount of styrene. Parameter tuning to copolymerization data confirms a penultimate monomer unit effect for activation (s_a2 = k_a12/k_a22=6.7; 363 K; 1: MMA; 2: styrene). To obtain, for a broad TCL range (up to 800), a dispersity well below 1.3 an initial styrene mass fraction of ca. 10% is required. An interpretation of the comonomer incorporation is performed by calculating the fractions of activation‐growth‐deactivation cycles with a given amount of monomer units and the copolymer composition distribution. © 2018 American Institute of Chemical Engineers AIChE J, 64: 2545–2559, 2018     

Effect of substituting CaO with BaO on the viscosity and structure of CaO‐BaO‐SiO2‐MgO‐Al2O3 slags

In this study, the effect of CaO and BaO substitution on the viscosity and structure of CaO‐BaO‐SiO₂‐MgO‐Al₂O₃ slags was investigated. The results showed that the viscosity increased with an increase in the BaO substitution concentration, which was correlated to an increase in the degree of polymerization (DOP) of the slag structural units as the activation energy increased from 207.9 to 263.8 kJ/mol for viscous flow. Deconvolution and area integration of the Raman spectrum of the slag revealed that the ratio of Q³/Q² (Qⁱ, i is the number of O⁰ in a [SiO₄]‐tetrahedral unit) increased and NBO/Si (nonbridging oxygen per unit silicon atom) decreased with higher BaO content. It was also observed from the ²⁷Al magic angles pinning nuclear magnetic resonance (²⁷Al MAS‐NMR) spectrum that the relative proportion of Al^IV increased, while that of Al^V decreased because of the decrease in the percentage of nonbridging oxygen (O^?), indicating the polymerization of the slag. O_1s X‐ray photoelectron spectroscopy (XPS) was also carried out to semi‐quantitatively analyze the various types of oxygen anions present in the slag. The XPS results correlated well with the results obtained from the analysis of the Raman and ²⁷Al MAS‐NMR spectra of the slags and its viscous behavior.     

Measurement of mass transfer coefficient in an airlift reactor with internal loop using coalescent and non‐coalescent liquid media

In this work the sulfite oxidation (SOM), dynamic pressure‐step (DPM) and gassing‐out (GOM) methods were compared for volumetric mass transfer coefficient measurement in an airlift reactor with internal loop. As a liquid phase both, non‐coalescent and coalescent media were used. Among the methods discussed here, the mass transfer coefficient (k_La) values obtained by the DPM appear as the most reliable as they were found to be independent of oxygen concentration in the inlet gas, which confirmed the physical correctness of this method. The difference between data measured using air and oxygen was not higher than 10%, which was comparable to the scatter of experimental data. It has been found that the sulfite oxidation method yielded k_La values only a little higher than those obtained by the DPM and the difference did not exceed 10%. Up to an inlet gas velocity (U_GC) of ?0.03 m s^?1 the GOM using oxygen as a gas medium gave k_La values in fact identical with those obtained by the DPM. At higher flows of the inlet gas, the GOM yielded k_La values as much as 15% lower. The enhancement in oxygen mass transfer rate determined in non‐coalescent media was estimated to be up to +15%, when compared with a coalescent batch. The experimental dependence of k_La vs the overall gas hold‐up was described by an empirical correlation. 1 Copyright © 2004 Society of Chemical Industry     

A three‐phase fluidized bed reactor in the combined anaerobic/aerobic treatment of wastewater

Aerobic degradation or polishing is an essential step in the combined anaerobic/aerobic treatment of wastewater. In this study, a type of porous glass beads was used for immobilization of microbial cells in a three‐phase aerobic fluidized bed reactor (AFBR) with an external liquid circulation. The effects of superficial gas and liquid velocities on bed expansion, solid and gas hold‐ups and specific oxygen mass transfer rate, k_La, were investigated. A tracer study showed that the mixing and flow pattern in the 8 dm³ reactor could be simulated by a non‐ideal model of two continuous stirred tank reactors (CSTRs) in series. By treating an effluent from an upflow anaerobic sludge blanket (UASB) digester, the distribution of suspended and immobilized biomass in the reactor as well as the kinetics of COD removal were determined. The specific oxygen mass transfer rate, k_La, at a superficial gas velocity of 0.7 cm s⁻¹ dropped by about 30% from 32 h⁻¹ in tap water to 22 h⁻¹ after a carrier load of 15% (v/v) was added. The measured k_La further dropped by about 20% to 18 h⁻¹ in the wastewater, a typical value of the bubbling fermenters with no stirring. Compared with the aerobic heterotrophs under optimum growth conditions, the microbes in this reactor which was fed with anaerobic effluent plus biomass behaved like oligotrophs and showed slow specific COD removal rates. This might be attributed to the presence of a significant amount of obligate anaerobes and facultative organisms in the aerobic reactor. This was confirmed by a relatively low intrinsic oxygen uptake rate of the microbial population in the reactor, 94 mg O₂ dm⁻³ h⁻¹ or 19 mg O₂g VS⁻¹ h⁻¹. © 1999 Society of Chemical Industry     

Advanced oxidation with ozone of 1,3,6‐naphthalenetrisulfonic acid in aqueous solution

The kinetics of oxidation with ozone of 1,3,6‐naphthalenetrisulfonic acid was analysed by studying the influence of different experimental parameters such as the concentration of tert‐butyl alcohol (2‐methyl‐2‐propanol), initial concentration of the acid, pH, and temperature. The rate constant of the direct reaction at 25 °C was calculated (k_D = 6.72 M ^?1s^?1). The constant of the free radical reaction was determined with the competitive kinetics method, using sodium 4‐chlorobenzoate as reference compound, obtaining a value of k_OH = 3.7 × 10⁹ M ^?1s^?1. It was demonstrated that even at very acid pH values, 80% of the 1,3,6‐naphthalenetrisulfonic acid was degraded by free radical reactions, so that the ozonation of this acid may be considered an advanced oxidation process. © 2002 Society of Chemical Industry     

Probing the Peptidylglycine α‐Hydroxylating Monooxygenase Active Site with Novel 4‐Phenyl‐3‐butenoic Acid Based Inhibitors

Specific inhibition of the copper‐containing peptidylglycine α‐hydroxylating monooxygenase (PHM), which catalyzes the post‐translational modification of peptides involved in carcinogenesis and tumor progression, constitutes a new approach for combating cancer. We carried out a structure–activity study of new compounds derived from a well‐known PHM substrate analogue, the olefinic compound 4‐phenyl‐3‐butenoic acid (PBA). We designed, synthesized, and tested various PBA derivatives both in vitro and in silico. We show that it is possible to increase PBA affinity for PHM by appropriate functionalization of its aromatic nucleus. Compound 2 d , for example, bears a meta‐benzyloxy substituent, and exhibits better inhibition features (K_i=3.9 μM , k_inact/K_i=427 M ^?1 s^?1) than the parent PBA (K_i=19 μM , k_inact/K_i=82 M ^?1 s^?1). Docking calculations also suggest two different binding modes for PBA derivatives; these results will aid in the development of further PHM inhibitors with improved features.     

Automated measurements of gas‐liquid mass transfer in micropacked bed reactors

Gas‐liquid mass transfer in micropacked bed reactors is characterized with an automated platform integrated with in‐line Fourier transform infrared spectroscopy. This setup enables screening of a multidimensional parameter space underlying absorption with chemical reaction. Volumetric gas‐liquid mass‐transfer coefficients (k_La) are determined for the model reaction of CO₂ absorption in a methyl diethanolamine/water solution. Parametric studies are conducted varying gas and liquid superficial velocities, packed bed dimensions and packing particle sizes. The results show that k_La values are in the range of 0.12～0.39 s^?1, which is about one‐to‐two orders of magnitude larger than those of conventional trickle beds. An empirical correlation predicts k_La in micropacked bed reactors in good agreement with experimental data. © 2017 American Institute of Chemical Engineers AIChE J, 64: 564–570, 2018