Screening for New Inhibitors of Glycine Transporter 1 and 2 by Means of MS Binding Assays

A straightforward screening of a compound library comprising 2439 substances for the identification of new inhibitors for the neurotransmitter transporters GlyT1 and GlyT2 is described. Screening and full-scale competition experiments were performed using recently developed GlyT1 and GlyT2 MS Binding Assays. That way for both targets, GlyT1 and GlyT2, ligands were identified, which exhibited affinities (pK_i values) in the low micromolar to sub-micromolar range. The majority of these binders exhibit new chemical scaffolds in the class of GlyT1 and GlyT2 inhibitors, which could be of interest for the development of new ligands with improved affinities for the target proteins. Additionally, compounds with excellent fluorescent properties were found for GlyT2, which renders them promising compounds for future fluorescence-based techniques. All in all, this study demonstrates that MS Binding Assays represent a powerful technology platform also well suited for the screening of compound libraries in a highly reliable and effective manner.     

Simultaneous Multiple MS Binding Assays for the Dopamine,Norepinephrine, and Serotonin Transporters

In this work, we present label‐free, mass‐spectrometry‐based binding assays (MS Binding Assays), targeting the human dopamine, norepinephrine, and serotonin transporters (hDAT, hNET, and hSERT) in simultaneous binding experiments. Using a validated LC–ESI‐MS/MS method for quantification of the selective dopamine transporter inhibitor (R,R)‐4‐(2‐benzhydryloxyethyl)‐1‐(4‐fluorobenzyl)piperidin‐3‐ol ((R,R)‐D‐84), the selective norepinephrine transporter inhibitor (S,S)‐reboxetine, and the selective serotonin reuptake inhibitor (S)‐citalopram, binding affinities at the three monoamine transporters could be characterized simultaneously in a single binding experiment. The performed simultaneous saturation and competition experiments yielded results that are in good accordance with those determined in MS Binding Assays addressing the monoamine transporters individually. The results obtained from this study underscore the potential of MS Binding Assays for simultaneous affinity determination at different targets, which is difficult to accomplish with conventional radioligand binding assays.     

MS Binding Assays for D1 and D5 Dopamine Receptors

MS Binding Assays are a label‐free alternative to radioligand binding assays. They provide basically the same capabilities as the latter, but an unlabeled reporter ligand is used instead of a radioligand. The study presented herein describes the development of MS Binding Assays that address D₁ and D₅ dopamine receptors. A highly sensitive, rapid and robust LC–ESI‐MS/MS quantification method for the selective D₁ dopamine receptor antagonist SCH23390 ((5R)‐8‐chloro‐3‐methyl‐5‐phenyl‐1,2,4,5‐tetrahydro‐3‐benzazepin‐7‐ol) was established and validated, using its 8‐bromo analogue SKF83566 as an internal standard. This quantification method proved to be suitable for the characterization of SCH23390 binding to human D₁ and D₅ receptors. Following the concept of MS Binding Assays, saturation experiments for D₁ and D₅ receptors were performed, as well as competition experiments for D₁ receptors. The results obtained are in good agreement with results from radioligand binding assays and therefore indicate that the established MS Binding Assays addressing D₁ and D₅ receptors are well‐suited substitutes for radioligand binding assays, the technique that has so far dominated affinity determinations toward these targets.     

Synthesis and Biological Evaluation of Nipecotic Acid and Guvacine Derived 1,3-Disubstituted Allenes as Inhibitors of Murine GABA Transporter mGAT1

A new class of nipecotic acid and guvacine derivatives has been synthesized and characterized for their inhibitory potency at mGAT1–4 and binding affinity for mGAT1. Compounds of the described class are defined by a four-carbon-atom allenyl spacer connecting the nitrogen atom of the nipecotic acid or guvacine head with an aromatic residue. Among the compounds investigated, the mixture of nipecotic acid derivatives rac-{(R_a)-1-[4-([1,1′:2′,1′′-terphenyl]-2-yl)buta-2,3-dien-1-yl](3R)-piperidine-3-carboxylic acid} and rac-{(S_a)-1-[4-([1,1′:2′,1′′-terphenyl]-2-yl)buta-2,3-dien-1-yl](3R)-piperidine-3-carboxylic acid} ( 21 p ), possessing an o-terphenyl residue, was identified as highly selective and the most potent mGAT1 inhibitor in this study. For the (R)-nipecotic acid derived form of 21 p , the inhibitory potency in [³H]GABA uptake assays was determined as pIC₅₀=6.78±0.08, and the binding affinity in MS Binding Assays as pK_i=7.10±0.12. The synthesis of the designed compounds was carried out by a two-step procedure, generating the allene moiety via allenylation of terminal alkynes which allows broad variation of the terminal phenyl and biphenyl subunit.     

A Single Second Shell Amino Acid Determines Affinity and Kinetics of Linagliptin Binding to Type 4 Dipeptidyl Peptidase and Fibroblast Activation Protein

Drugs targeting type 4 dipeptidyl peptidase (DPP-4) are beneficial for glycemic control, whereas fibroblast activation protein alpha (FAP-α) is a potential target for cancer therapies. Unlike other gliptins, linagliptin displays FAP inhibition. We compared biophysical and structural characteristics of linagliptin binding to DPP-4 and FAP to better understand what differentiates linagliptin from other gliptins. Linagliptin exhibited high binding affinity (K_D) and a slow off-rate (k_off) when dissociating from DPP-4 (K_D 6.6 pM; k_off 5.1×10⁻⁵ s⁻¹), and weaker inhibitory potency to FAP (K_D 301 nM; k_off>1 s⁻¹). Co-structures of linagliptin with DPP-4 or FAP were similar except for one second shell amino acid difference: Asp663 (DPP-4) and Ala657 (FAP). pH dependence of enzymatic activities and binding of linagliptin for DPP-4 and FAP are dependent on this single amino acid difference. While linagliptin may not display any anticancer activity at therapeutic doses, our findings may guide future studies for the development of optimized inhibitors.     

Effect of processing parameters on microstructure and ablation behavior of SiC/ZrB2 coating for graphite

In this research, a SiC/ZrB₂ coating was produced on graphite by reactive melt infiltration and plasma spraying method. The coating characterization was performed using XRD analysis, electron microscopy equipped with energy dispersive spectrometer (EDS), and supersonic flame ablation test at 2073 K. The results indicated that the dense C/SiC coating with good ablation resistance can be obtained at 1873 K. The coating thickness decreased with increasing infiltration temperature. The results of ablation test showed that by increasing the infiltration temperature and holding time, weight loss and mass ablation rate decreased from 22.63% to 9.83% and 3.63 × 10⁻³ g cm⁻² s⁻¹ to 1.34 × 10⁻³ g cm⁻² s⁻¹, respectively. The results showed that by using the ZrB₂ as outer coating the ablation resistance improved remarkably. The weight loss and mass ablation rates for the SiC/ZrB₂ coating were 12.79% and 1.857 × 10⁻³ g cm⁻² s⁻¹, respectively.     

MS Binding Assays for the Three Monoamine Transporters Using the Triple Reuptake Inhibitor (1R,3S)‐Indatraline as Native Marker

We herein present label‐free, mass‐spectrometry‐based binding assays (MS Binding Assays) for the human dopamine, norepinephrine, and serotonin transporters (hDAT, hNET, and hSERT). Using this approach both enantiomers of the triple reuptake inhibitor indatraline as well as its cis‐configured diastereomer were investigated toward hDAT, hNET, and hSERT in saturation experiments. The dissociation rate constants for (1R,3S)‐indatraline binding at hDAT, hNET, and hSERT were determined in kinetic studies. These experiments revealed an allosteric effect of clomipramine on the dissociation of (1R,3S)‐indatraline from hSERT. Finally, a comprehensive set of known monoamine transport inhibitors and substrates was studied in competition experiments at hDAT, hNET, and hSERT, using (1R,3S)‐indatraline as nonlabeled marker. The results are in excellent agreement with those reported for radioligand binding assays. Therefore, the established MS Binding Assays are a promising alternative to the latter for the characterization of new monoamine reuptake inhibitors at DAT, NET, and SERT.     

Two-resistance mass transfer models for the adsorption of dyestuffs from aqueous solutions using activated carbon

The adsorption of telon blue (acid blue 25) dye and deorlene yellow (basic yellow) dye on to carbon has been studied. A two-resistance mass transfer model has been developed based on film resistance and homogeneous solid phase diffusion. The model may be applied over a wider range of operating conditions than previous models since it has more extensive analytical components. The variables investigated were initial dye concentration and solid: liquid ratio, and the experimental and theoretical results were in good agreement. The adsorption of telon blue on to carbon has been described using an external mass transfer coefficient of 2.0 × 10⁻³ cm s⁻¹ and a homogeneous solid phase diffusion coefficient of 2.0 × 10⁻⁹ cm² s⁻¹. The adsorption of deorlene yellow has been described using an external mass transfer coefficient of 1.0 × 10⁻³ cm s⁻¹ and a homogeneous solid phase diffusion coefficient of 3.0 × 10⁻¹⁰ cm² s⁻¹.     

Reactions of Photoexcited Triplet States of Zinc Porphyrin with Transient Radicals in Aqueous Solutions

The technique of simultaneous pulse radiolysis and photolysis, PRAP, has been utilized to study the reactions of various radicals with ground state ZnTPPS and the triplet state ZnTPPS^T in aqueous solutions. The radicals H and OH add to both states with k ∼ 1 × 10¹⁰ M⁻¹ s⁻¹. The CH₂C(CH₃)₂OH radical from t-BuOH is relatively inert toward ZnTPPS but reacts rapidly (k = 1.8 × 10⁹ M⁻¹ s⁻¹) with ZnTPPS^T to form an adduct. Electron transfer reactions are found to be about an order of magnitude faster with the triplet than with the ground state. The (CH₃)₂COH radical reduces both ZnTPPS (k = 1 × 10⁸ M⁻¹ s⁻¹) and ZnTPPS^T (k = 3 × 10⁹ M⁻¹ s⁻¹) to the anion radical (ZnTPPS)⁻. The radical Br⁻₂ oxidizes both states to the cation radical (ZnTPPS)⁺ with k = 8 × 10⁸ M⁻¹ s⁻¹ for the ground state and 5 × 10⁹ M⁻¹ s⁻¹ for the triplet. The transient cation Cd⁺ reduces both states with a diffusion-controlled rate (k = 1 × 10¹⁰ M⁻¹ s⁻¹) to produce the anion radical. The above mechanisms of radical addition and electron transfer are also supported by the product spectra.     

Preparation of a modified crosslinked chitosan/polyvinyl alcohol blended affinity membrane for purification of His-tagged protein

Based on a crosslinked chitosan (CS)/polyvinyl alcohol (PVA) matrix membrane, an immobilized metal ion affinity membrane (IMAM) using Cu²⁺ and Ni²⁺ ions as affinity ligands was prepared for purification of the His-tagged recombinant protein. The affinity membrane possessed a favorable membrane structure including 1.39 μm average pore size and 0.33 mL·cm⁻²·s⁻¹ water flux under 0.08 MPa pressure at 25 °C. The Cu²⁺ and Ni²⁺ ions capacities immobilized on the IMAM were 155.6 and 137.3 μmol·disk⁻¹, respectively. The IMAM had an excellent specific affinity to His-tagged protein. About 10-fold purification factor for the model protein was obtained in a batch adsorption, and serine hydroxymethyl transferase could be purified to a single band in sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis from its crude extract solution with an affinity membrane cartridge by a dynamic purification process. This work provides a promising IMAM for the purification of His-tagged recombinant proteins. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47347.     

Kinetic and thermodynamic studies on oxidative desulphurisation of organic sulphur from Indian coal at 50–150°C

This paper reports a relatively simple low-temperature non-isothermal oxidative desulphurisation of coal organic sulphur by weakening the CS bond using HgCl₂ solution to an inorganic sulphur-free high-sulphur Indian coal. When oxidised from 50°C to 150°C in air under normal atmospheric pressure, there is continuous decrease of organic sulphur content in the samples of the feed and Hg-treated coals. Desulphurisation is more in the Hg-treated coal (4.97–14.53 wt.%) than in the feed coal (3.72–10.93 wt.%). Kinetic study reveals that the oxidative desulphurisation process follows pseudo-first order kinetics and the rate constants have been found to be in the range (3.09–5.06)×10⁻⁵ s⁻¹ for feed coal and (4.19–6.80)×10⁻⁵ s⁻¹ for Hg-treated coal. The activation energies for the sulphur loss reaction in the oxidative desulphurisation process by using the pseudo-first order kinetic (feed coal: 2.21×10² J mol⁻¹; Hg-treated coal: 1.53×10² J mol⁻¹) have been found to be almost similar to those calculated by applying the Coats and Redfern's equation (feed coal: 2.19×10² J mol⁻¹; Hg-treated coal: 1.53×10² J mol⁻¹). However, the value is higher (feed coal: 3.50×10² J mol⁻¹; Hg-treated coal: 2.70×10² J mol⁻¹) when Horowitz and Metzger's equation is applied. The frequency factors computed by the pseudo-first order kinetics are very low and have been found to be 2.66×10⁻⁵ s⁻¹ for feed coal and 3.96×10⁻⁵ s⁻¹ for Hg-treated coal, suggesting very low rate of successful collisions for the formation of the activated complex. Evaluation of thermodynamic parameters viz., ΔH, ΔU, ΔS and ΔG, reveals that this oxidative desulphurisation process is non-spontaneous in nature and the degree of non-spontaneity of such a process in the feed coal is more relative to that of the Hg-treated coal.     

Plasmonic organic bulk–heterojunction solar cells based on hydrophobic gold nanorod insertion into active layers

In this work, we fabricated plasmonic organic bulk–heterojunction solar cells by inserting hydrophobic gold nanorods (GNRs) into the active layers. Power conversion efficiency was improved from 7.43% to 8.22% because the plasmonic effect of GNRs improved the light harvesting efficiency. Maximum exciton generation rate was increased from 1.35 × 10⁻²⁶ to 1.51× 10⁻²⁶m⁻³ s⁻¹, and the electron mobility was also increased from 8.6 × 10⁻⁵ to 1.5× 10⁻⁴cm⁻² V⁻¹ s⁻¹. As a result, the short circuit current density was improved from 15.5 to 16.7 mA cm⁻²—the dominant reason for performance enhancement. The open circuit voltage and fill factor were improved simultaneously. The plasmonic device showed a highest PCE of 8.43%, indicating that doping GNRs into active layers is a simple and effective way to fabricate high‐performance organic solar cells. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45920.     

Radiolytic Studies of the Cumyloxyl Radical in Aqueous Solutions

Formation and reactions of the cumyloxyl radical in aqueous solutions were studied by steady-state and pulse radiolytic techniques. Cumene hydroperoxide reacts with e⁻_aq (k = 4.4 × 10⁹ M⁻¹s⁻¹) to yield the cumyloxyl radical. The spectrum recorded after the pulse indicates formation of a species absorbing at 250 nm. This product was identified as acetophenone, which is formed by the fragmentation of the cumyloxyl radical. By comparison of the pseudo-first-order rates of e⁻_aq decay at 600 nm with the rate of production of acetophenone at 245 nm at increasing concentrations of cumene hydroperoxide, it was possible to derive a rate constant of 1.0 × 10⁷ s⁻¹ for the cleavage of cumyloxyl to acetophenone and methyl radical. This value is higher than that measured previously in organic solvents (1 × 10⁶ s⁻¹), as expected. HPLC analysis of the radiation products acetophenone and cumyl alcohol permitted determination of rate constants for hydrogen abstraction by the cumyloxyl radical, in competition with the fragmentation. The rate constants for H abstraction from i-PrOH, EtOH, and MeOH by CmO were found to be 9.9 × 10⁶, 3.8 × 10⁶, and 8.5 × 10⁵ M⁻¹ s⁻¹, respectively.     

Pharmacological Evidence on Augmented Antiallodynia Following Systemic Co-Treatment with GlyT-1 and GlyT-2 Inhibitors in Rat Neuropathic Pain Model

The limited effect of current medications on neuropathic pain (NP) has initiated large efforts to develop effective treatments. Animal studies showed that glycine transporter (GlyT) inhibitors are promising analgesics in NP, though concerns regarding adverse effects were raised. We aimed to study NFPS and Org-25543, GlyT-1 and GlyT-2 inhibitors, respectively and their combination in rat mononeuropathic pain evoked by partial sciatic nerve ligation. Cerebrospinal fluid (CSF) glycine content was also determined by capillary electrophoresis. Subcutaneous (s.c.) 4 mg/kg NFPS or Org-25543 showed analgesia following acute administration (30–60 min). Small doses of each compound failed to produce antiallodynia up to 180 min after the acute administration. However, NFPS (1 mg/kg) produced antiallodynia after four days of treatment. Co-treatment with subanalgesic doses of NFPS (1 mg/kg) and Org-25543 (2 mg/kg) produced analgesia at 60 min and thereafter meanwhile increased significantly the CSF glycine content. This combination alleviated NP without affecting motor function. Test compounds failed to activate G-proteins in spinal cord. To the best of our knowledge for the first time we demonstrated augmented analgesia by combining GlyT-1 and 2 inhibitors. Increased CSF glycine content supports involvement of glycinergic system. Combining selective GlyT inhibitors or developing non-selective GlyT inhibitors might have therapeutic value in NP.     

A Shock Tube Study of the Reactions of H Atoms with COS,CS2, and H2S

Reactions of H atoms with COS, CS₂, and H₂S were studied behind reflected shock waves at temperatures between 1170 K and 1830 K and pressures around 1.0 bar by applying atomic resonance absorption spectroscopy (ARAS) for time-resolved measurements of H atoms at L_α. The thermal decomposition of a few ppm ethyl iodide (C₂H₅I) was used as a H-atom source. In the presence of a large excess of the molecular reactant COS, CS₂, or H₂S, a consumption of H was observed which follows a pseudo first-order rate law. Rate coefficients for the reactions: were determined to be: k₁ = 2.4 × 10¹⁴exp(–3415 K/T) cm³mol⁻¹s⁻¹ k₂ = 1.4 × 10¹⁵exp(–9250 K/T) cm³mol⁻¹s⁻¹ k₃ = 2.5 × 10¹⁴exp(–2890 K/T) cm³mol⁻¹s⁻¹     

Influence of different reactor types on Nannochloropsis oculata microalgae culture for lipids and fatty acid production

Greenhouse gases emitted into the atmosphere by burning of fossil fuels cause global warming. One option is obtaining biodiesel. Nannochloropsis oculata was cultured under different light intensities and reactors at 25°C for 21 days with f/2 medium to assess their effects on cell density, lipid, and fatty acids (FAs). N. oculata improved cell density on fed-batch glass tubular reactor (7 L) at 200 μmol E m⁻² s⁻¹, yielding 3.5 × 10⁸ cells ml⁻¹, followed by fed-batch Erlenmeyer flask (1 L) at 650 μmol E m⁻² s⁻¹ with 1.7 × 10⁸ cells ml⁻¹. The highest total lipid contents (% g lipid × g dry biomass⁻¹) were 44.4 ± 0.8% for the reactor (1 L) at 650 μmol E m⁻² s⁻¹ and 35.2 ± 0.2% for the tubular reactor (7 L) at 200 μmol E m⁻² s⁻¹, until twice as high compared with the control culture (Erlenmeyer flask 1 L, 80 μmol E m⁻² s⁻¹) with 21.2 ± 1%. Comparing the total lipid content at 200 μmol E m⁻² s⁻¹, tubular reactor (7 L) and reactor 1 L achieved 35.2 ± 0.2% and 28.3 ± 1%, respectively, indicating the effect of shape reactor. The FAs were affected by high light intensity, decreasing SFAs to 2.5%, and increased monounsaturated fatty acids + polyunsaturated fatty acids to 2.5%. PUFAs (20:5n-3) and (20:4n-3) were affected by reactor shape, decreasing by half in the tubular reactor. In the best culture, fed-batch tubular reactor (7 L) at 200 μmol E m⁻² s⁻¹ contains major FAs (16:0; 38.06 ± 0.16%), (16:1n-7; 30.74 ± 0.58%), and (18:1n-9; 17.15 ± 0.91%).     

Cholesterol interaction with recombinant human sterol carrier protein-2

The interaction of human recombinant sterol carrier protein-2 (SCP-2) with sterols was examined. Two independent ligand binding methods, Lipidex 1000 binding of [³H]cholesterol and a fluorescent dehydroergosterol binding assay, were used to determine the affinity of SCP-2 for sterols. Binding analysis indicated SCP-2 bound [³H]cholesterol and dehydroergosterol with aK _d of 0.3 and 1.7 μM, respectively, and suggested the presence of a single binding site. Phase fluorometry and circular dichroism were used to characterize the SCP-2 sterol binding site. Alterations in dehydroergosterol lifetime, SCP-2 tryptophan lifetime, and SCP-2 tryptophan quenching by acrylamide upon cholesterol binding demonstrated a shielding of the SCP-2 tryptophan from the aqueous solvent by bound sterol. Differential polarized phase fluorometry revealed decreased SCP-2 tryptophan rotational correlation time upon cholesterol binding. Circular dichroism of SCP-2 indicated that cholesterol elicited a small decrease in SCP-2 alpha helical content. The data suggest that SCP-2 binds sterols with affinity consistent with a lipid transfer protein that may act either as an aqueous carrier or at a membrane surface to enhance sterol desorption.     

MS Binding Assays—with MALDI toward High Throughput

A novel type of MS binding assay, a substitute for radioligand binding, in which the quantification of the MS marker is performed by MALDI‐MS–MS (FlashQuant) has been established. Because conventional MS binding assays can only be carried out by LC–ESI‐MS–MS, the use of the FlashQuant system substantially increases the throughput capacity of this method. The study was performed for mGAT1 as a model system. First, a method was developed to quantify NO 711 as a marker for mGAT1 in a range from 208 pM to 16.7 nM using [²H₁₀]NO 711 as an internal standard. On this basis, MS binding assays for mGAT1 could be implemented. Affinity constants determined in both saturation and competition experiments were in excellent agreement with those obtained in MS binding assays based on LC–ESI‐MS–MS quantification. As the MALDI‐MS system takes only a few seconds for quantification per sample, and the whole assay procedure is executed in a 96‐well format, this technique is amenable to high‐throughput screening.     

The Oxidation of Coated SOFC Interconnects in Fuel Side Environments

This study focuses on examining the effect of PVD coatings on the oxidation performance of interconnects in fuel (anode) side environments. A Fe‐22Cr ferritic steel was coated with (i) Ce 10 nm (ii) La 10 nm and (iii) Co 600 nm. The samples were exposed at 850 °C in Ar‐5% H₂‐3% H₂O in a tubular furnace over 500 h. Additionally, the effect of a pre‐oxidation step was investigated by exposure in air prior to the simulated fuel gas environment. Chemical analysis on the samples was subsequently performed with SEM/EDX and XRD. It was established that the Ce and La coatings brought about a factor 2–3 reduction (k_p values of 2.16 × 10⁻¹⁴ ± 3.6 × 10⁻¹⁵ g² cm⁻⁴ s⁻¹ for the La 10 nm coated steel compared to 7.72 × 10⁻¹⁴ ± 5.86 × 10⁻¹⁵ g² cm⁻⁴ s⁻¹ for the uncoated steel) in the oxidation rate while the Co coating disintegrated into metallic islands in and on the thermally grown oxide after exposure. Additionally, the La coating resulted in the formation of a continuous perovskite layer by reaction with the thermally grown oxide.     

Fluorescence Quenching in Three to Zero Dimensions: Effect of Dimensionality on a Diffusion-Limited Reaction

The diffusion-limited fluorescence quenching of pyrene by a hydrophobic benzophenone derivative, 1-(4-benzoyl)-phenylhexane, was investigated in the different phases of the binary system hexaethyleneglycol-mono-n-dodecylether (C₁₂E₆)-water, from the normal homogeneous solution of the neat surfactant, via a sequence of liquid crystalline phases, to the aqueous micellar solution. These phases provide nonpolar domains of various dimensionality for the reactants: three dimensions in the neat surfactant, two in the lamellar phase, one in the hexagonal phase, and zero in the small micelles. The results were evaluated using models with appropriate dimension for the diffusion-controlled reaction. The resulting diffusion coefficients at 20°C were obtained as 3 × 10⁻¹¹ m² s⁻¹ in the neat surfactant, around 6 × 10⁻¹¹ m² s⁻¹ in the lamellar phase, and 10 × 10⁻¹¹ m² s⁻¹ in the hexagonal phase. The activation energy for the diffusion process increased from 32 kJ mol⁻¹ in the neat surfactant to 42 kJ mol⁻¹ in the hexagonal phase. The differences between the phases may be due to the uncertainty in the values of the size parameters for the structures; in any case, they are not large, indicating that it is mainly the geometry that is important for the deactivation kinetics, whereas the mobilities of the reactants are less affected by changes in packing.