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Emerging SARS-CoV-2 variants continue to threaten the effectiveness of COVID-19 vaccines, and small-molecule antivirals can provide an important therapeutic treatment option. The viral main protease (Mpro) is critical for virus replication and thus is considered an attractive drug target. We performed the design and characterization of three covalent hybrid inhibitors BBH-1, BBH-2 and NBH-2 created by splicing components of hepatitis C protease inhibitors boceprevir and narlaprevir, and known SARS-CoV-1 protease inhibitors. A joint X-ray/neutron structure of the Mpro/BBH-1 complex demonstrates that a Cys145 thiolate reaction with the inhibitor's keto-warhead creates a negatively charged oxyanion. Protonation states of the ionizable residues in the Mpro active site adapt to the inhibitor, which appears to be an intrinsic property of Mpro. Structural comparisons of the hybrid inhibitors with PF-07321332 reveal unconventional F···O interactions of PF-07321332 with Mpro which may explain its more favorable enthalpy of binding. BBH-1, BBH-2 and NBH-2 exhibit comparable antiviral properties in vitro relative to PF-07321332, making them good candidates for further design of improved antivirals. Three covalent hybrid inhibitors of SARS-CoV-2 main protease (Mpro) have been designed and compared to Pfizer's nirmatrelvir (PF-07321332), providing atomic and thermodynamic details of their binding to the enzyme, and antiviral potency. [ABSTRACT FROM AUTHOR]

The intramolecular catalyst transfer over sterically hindered arenes in Suzuki cross‐coupling reaction was investigated by the reaction of ortho‐substituted dibromoarenes with equimolar ortho‐substituted phenylboronic acid in the presence of NHC based PEPPSI‐IPr as catalyst. The diarylarene species of the form Ar'−Ar−Ar' were observed as major product, which suggested the intramolecular transfer of Pd(0) over sterically hindered arenes proceeded smoothly in Suzuki cross‐coupling reaction. Furthermore, our studies also demonstrated that intramolecular catalyst transfer could be a useful tool to improve the polymerization efficiency, especially in the synthesis of ortho‐linked polyarenes. [ABSTRACT FROM AUTHOR]

Deuterium labeling of semi‐crystalline polymers can dramatically affect their crystallization behaviors. However, the influence of different labeled positions in a partially deuterated polymer on its crystallization is still far from understood. Here, we synthesized a series of selectively deuterated poly(ε‐caprolactones) (PCLs) through ring‐opening polymerization of ε‐caprolactone with controlled deuteration sites, including fully protiated (D0), fully deuterated (D10), tetra deuteration at the 3‐ and 7‐ caprolactone ring positions (D4) and hexa deuteration at the 4‐, 5‐, and 6‐ caprolactone ring positions (D6). All the PCLs showed a similar lamellar structure and parameters. Differential scanning calorimetry (DSC) analysis revealed that the equilibrium melting temperature Tm0, melting temperature Tm, crystallization temperature Tc, and crystallization kinetics changed systemically with the deuterium content except for D4, which indicates that the presence of CD2 moieties on either side of ester group in the polymer chain combined with isotopic inhomogeneity could influence the chain packing. The nonmonotonic trend of Tm as a function of deuterium content could be attributed to the difference in a hydrogen‐bond like intermolecular interaction between different PCLs. Partially deuterated PCLs (D4 and D6) showed an Avrami index near 2. After analyzing the parameters at the same supercooling temperature ΔTc, the existence of two crystallization regimes of PCLs were detected. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2019, 57, 771–779 [ABSTRACT FROM AUTHOR]

Encapsulation behavior, as well as the presence of internal catalytically active sites, has been spurring the applications of a 3 nm hollow spherical metal oxide cluster {Mo132} as an encapsulation host and a nanoreactor. Due to its well-defined and tunable cluster structures, and nanoscaled internal void space comparable to the volumes of small molecules, this cluster provides a good model to study the dynamics of materials under nanoconfinement. Neutron scattering studies suggest that bulky internal ligands inside the cluster show slower and limited dynamics compared to their counterparts in the bulk state, revealing the rigid nature of the skeleton of the internal ligands. NMR studies indicate that the rigid internal ligands that partially cover the interfacial pore on the molybdenum oxide shells are able to block some large guest molecules from going inside the capsule cluster, which provides a convincing protocol for size-selective encapsulation and separation. [ABSTRACT FROM AUTHOR]

A convenient and high-yield synthesis for N1-tritylethane-1,1,2,2- d4-1,2-diamine, a novel mono-protected ethylenediamine-C- d4, is reported. N1-tritylethane-1,1,2,2- d4-1,2-diamine was prepared in three steps from ethylene oxide- d4 in a combined yield in the range 68-76%. Also reported is a synthesis of ethylenediamine-C- d4 in two steps from 1,2-dibromoethane- d4 in a combined yield in the range 61-65%. [ABSTRACT FROM AUTHOR]

The ccc stereoisomer-purified tert-butoxycarbonyloxy-protected calix[4]resorcinarene molecular resists blended with photoacid generator exhibit a non-uniform photoacid-catalyzed reaction in thin films. The surface displays a reduced reaction extent, compared with the bulk, with average surface-layer thickness 7.0 ± 1.8 nm determined by neutron reflectivity with deuterium-labelled tert-butoxycarbonyloxy groups. Ambient impurities (amines and organic bases) are known to quench surface reactions and contribute, but grazing-incidence X-ray diffraction shows an additional effect that the protected molecular resists are preferentially oriented at the surface, whereas the bulk of the film displays diffuse scattering representative of amorphous packing. The surface deprotection reaction and presence of photoacid were quantified by near-edge X-ray absorption fine-structure measurements. The ccc stereoisomer-purified tert-butoxycarbonyloxy (t-Boc) protected calix[4]resorcinarene molecular resists for next-generation photolithography exhibit a non-uniform photoacid-catalyzed reaction in thin films. The surface displays a reduced reaction extent with preferential orientation, compared with the amorphous bulk. [ABSTRACT FROM AUTHOR]

Effective alternatives to nitric acid stripping in the Caustic-Side Solvent Extraction (CSSX) solvent have been demonstrated in this work. The CSSX solvent employs calix[4]arene-bis(tert-octylbenzo-18-crown-6) (BOBCalixC6) as the cesium extractant in a modified alkane diluent for decontamination of alkaline high-level wastes, such as those found at the Savannah River and Hanford sites. Results reported in this paper support the idea that replacement of the nitrate anion by a much more hydrophilic anion like borate can substantially lower cesium distribution ratios on stripping. Without any other change in the CSSX flowsheet, however, the use of a boric acid stripping solution in place of the 1 mM nitric acid solution used in the CSSX process marginally, though perhaps still usefully, improves stripping. The less-than-expected improvement was explained by the carryover of nitrate from scrubbing into stripping. Accordingly, more effective stripping is obtained after a scrub of the solvent with 0.1 M sodium hydroxide. Functional alternatives to boric acid include sodium bicarbonate or cesium hydroxide as strip solutions. Profound stripping improvement is achieved when trioctylamine, one of the components of the CSSX solvent, is replaced with a commercial guanidine reagent (LIX® 79). The more basic guanidine affords greater latitude in the selection of aqueous conditions in that it becomes protonated even at mildly alkaline pH values. Under process-relevant conditions, cesium distribution ratios on stripping are approximately 100-fold lower compared with the current CSSX performance. The tolerance to surfactants is good, and the extraction properties of the solvent remain unchanged over three successive extract-scrub-strip cycles. From the point of view of compatibility with downstream processing, boric acid represents an attractive stripping agent, as it is also a potentially ideal feed for borosilicate vitrification of the separated 137Cs product stream. The possibilities for use of these results toward a dramatically better next-generation CSSX process, possibly one employing the more soluble cesium extractant calix[4]arene-bis(2-ethylhexylbenzo-18-crown-6) (BEHBCalixC6) are discussed. [ABSTRACT FROM AUTHOR]

The combined extraction of cesium and strontium from caustic wastes can be achieved by adding a crown ether and a carboxylic acid to the Caustic-Side Solvent Extraction (CSSX) solvent. The ligand 4,4′(5′)-di(tert-butyl)cyclohexano-18- crown-6 and one of four different carboxylic acids were combined with the components of the CSSX solvent optimized for the extraction of cesium, allowing for the simultaneous extraction of cesium and strontium from alkaline nitrate media simulating alkaline high level wastes present at the U.S. Department of Energy Savannah River Site. Extraction and stripping experiments were conducted independently and exhibited adequate results tot mimicking waste simulant processing through batch contacts. The promising results of these batch tests showed that the system could reasonably be tested on actual waste. [ABSTRACT FROM AUTHOR]

This work emphasizes the crucial role of polar solvating molecules known as phase modifiers in solvent-extraction systems. The focus of these studies was the extraction of cesium by calix[4tarene-bis(tert-octylbenzo-crown-6) in dodecane modified with various lipophilic alcohols. Results of equilibrium modeling are consistent with aggregation of the alcohol molecules with each other and with the calixarene-cesium nitrate complexes. These modeling results are supported by electrospray mass spectrometry experiments, clearly showing the alcohol:anion adducts containing several alcohol molecules. They are also supported by crystallographic evidence showing the existence of a hexameric aggregate in the solid state for a derivative of one of the alcohol modifiers used for solvent extraction, in agreement with the species giving the best modeling results. [ABSTRACT FROM AUTHOR]

So-called pseudo-hydroxide extraction has been proposed as a method for separating alkali metal hydroxide from alkaline salt solutions by use of weak-acid cation exchangers such as lipophilic phenols or fluorinated alcohols. Under extraction conditions, these lipophilic weak acids (HAs) are converted to their salt forms when dissolved in a suitable water-immiscible polar diluent like 1-octanol. Upon contact with water, the loaded solvents release alkali metal hydroxide to the aqueous phase by hydrolysis, thereby regenerating the extractant. This type of cycle has been demonstrated in previous work, wherein it was shown that bulk concentrations of .sodium hydroxide could be selectively separated from alkaline high-level waste simulants. In the present work, it has been the aim to identify the controlling equilibria and predominant species involved in the extraction process within the framework of a thermochemical model. Using 1 -octanol as the diluent, distribution ratios for sodium (DNa) extraction were measured as a function of organic-phase HA and aqueous-phase NaOH molarity at 25°C. The tested weak acids, 3,5-di-rfr/-butylphenoI (HA-I) and l-trifluoromethyl- 2-(3,5-di-/c;7-butylphenoxy) ethanol (HA-2). significantly enhanced the extraction of NaOH over the minor amount that is extracted by l-octanol alone. The extraction efficiency of HA-I was approximately 10-fold higher than that of HA-2. By use of the equilibrium modeling program SXLSQI. it was shown that a simple model is sufficient to quantitatively explain the observed extraction behavior based upon (a) ion-pair extraction to give Na+OH- ion pairs and corresponding free ions in 1-octanol and (b) cation exchange by monomeric HA molecules to form monomeric organic-phase Na+A- ion pairs and corresponding free organic-phase ions. [ABSTRACT FROM AUTHOR]

Results obtained in this work show that four calix[4]arene mono and bis(benzo-crown-6) ethers functionalized with primary amine groups feature markedly enhanced cesium stripping under acidic conditions compared with nonfunctionalized analogs. The four amine-derivatized calixarenes were surveyed in nitrobenzene diluent at 25°C, demonstrating the effect under controlled conditions, where it was seen that the amino functionalization entailed at most a mild sacrifice of cesium extraction strength or selectivity. Limited solubility of the protonated forms of the extractants appears to be a potential issue for future development, however. In the best case, calix[4]arene bis[4-(2-ethylhexyl)benzo-crown-6], possessing an aminomethyl group on the upper rim, (AMBEHB) exhibited a cesium extraction strength comparable to that of a control system containing calix[4]arene bis(tert-octylbenzo-crown-6) (BOB) under alkaline conditions, whereas stripping of the cesium from AMBEHB was 56-fold more effective than BOB. A proof-of-principle extraction, scrubbing, and stripping (ESS) cycle using AMBEHB in Isopar L modified with 0.75 M 1-(2,2,3,3-tetrafluoropropoxy)-3-(4-sec-butylphenoxy)-2-propanol (Cs-7SB) showed that a greater than three-fold more efficient stripping may be obtained with AMBEHB vs. its nonfunctionalized control BEHB. A slope analysis of systematic extraction data under caustic and acidic conditions confirmed that the extraction of cesium nitrate by AMBEHB in dodecane modified by 0.5 M Cs-7SB involves the formation of a 1:1:1 metal:ligand:nitrate organic species. [ABSTRACT FROM AUTHOR]

The new cesium-selective macrocycle calix[4]arene-bis[4-(2-ethylhexyl) benzo-crown-6] (“BEHBCalixC6”) has been found to have improved solubility in a modified alkane diluent over calix[4]arene-bis(4-tert-octylbenzo-crown-6) (“BOBCalixC6”). The synthesis of this new calixcrown extractant, together with its solubility and extraction properties, is described in this report. The solubility, cesium extraction, and potassium loading behavior are compared with those of BOBCalixC6, the macrocycle currently employed in the caustic-side solvent extraction (CSSX) process for extracting cesium from alkaline nitrate solutions such as high-level nuclear waste. Replacement of the tert-octyl alkyl chains on the benzo-crown portion of the calixcrown by 2-ethylhexyl chains improves the equilibrium solubility of the free calixcrown in aliphatic diluents while not affecting the cesium extraction strength. Equilibrium concentrations of BEHBCalixC6 in Isopar L diluent modified with 0.5 M 1-(2,2,3,3-tetrafluoropropoxy)-3-(4-sec-butylphenoxy)-2-propanol (Cs-7SB) over the course of 41 weeks of gentle agitation at 25°C maintained the initial concentration of 57 ± 2 mM, with no evidence of precipitation or third-phase formation. In contrast, 57 ± 2 mM solutions of BOBCalixC6 prepared using sonication were not stable, with precipitation occurring to afford an equilibrium concentration of only 6.7 ± 0.2 mM after 41 weeks. Third-phase tests showed that BEHBCalixC6 resists third-phase formation as well as, or better than, BOBCalixC6. With increasing potassium loading from an alkaline sodium nitrate solution, both calixcrowns at 20 mM in modified Isopar L exhibited comparable onset of third-phase formation, gauging by the decreasing mass balance in cesium extraction from the same solutions. However, the BEHBCalixC6 solvent exhibited no visible indications of third-phase formation until the aqueous potassium concentration reached 0.75 M, whereas the BOBCalixC6 suffered visible third-phase formation when the aqueous potassium nitrate concentration reached 0.25 M. Calixcrowns with higher solubility in alkane diluents may find application in cesium extraction from waste matrices containing moderate (≥0.2 M) quantities of potassium, such as that stored at the US Department of Energy's Hanford Site, where higher concentrations of the calixcrown extractant may be required to obtain practical cesium distribution coefficients for process flowsheets. [ABSTRACT FROM AUTHOR]

Investigates the effectiveness of alkylphenoxy fluorinated alcohols as modifiers in solvents for the extraction of cesium from alkaline nitrate media. Experimental details; Influence of the fluorinated portion of the modifier on chemical stability; Impact of the structure of the alkyl substituent of the alkylphenoxy moiety on the phase behavior of the solvent.

We report a facile approach to control the shape memory effects and thermomechanical characteristics of a lignin-based multiphase polymer. Solvent fractionation of a syringylpropane-rich technical organosolv lignin resulted in selective lignin structures having excellent thermal stability coupled with high stiffness and melt-flow resistance. The fractionated lignins were reacted with rubber in melt-phase to form partially networked elastomer enabling selective programmability of the material shape either at 70 °C, a temperature that is high enough for rubbery matrix materials, or at an extremely high temperature, 150 °C. Utilizing appropriate functionalities in fractionated lignins, tunable shape fixity with high strain and stress recovery, particularly high-stress tolerance were maintained. Detailed studies of lignin structures and chemistries were correlated to molecular rigidity, morphology, and stress relaxation, as well as shape memory effects of the materials. The fractionation of lignin enabled enrichment of specific lignin properties for efficient shape memory effects that broaden the materials' application window. Electron microscopy, melt-rheology, dynamic mechanical analysis and ultra-small angle neutron scattering were conducted to establish morphology of acrylonitrile butadiene rubber (NBR)-lignin elastomers from solvent fractionated lignins. [ABSTRACT FROM AUTHOR]

The nanoconfinement effect defined by the polyoxometalate nanocage renders the encapsulated bulky ligands rigid properties by significantly limiting and slowing down their diffusive motions. These ligands that partially cover the interfacial pore on the molybdenum oxide shells are able to block some large guest molecules from going inside the capsule cluster, which provides a convincing protocol for size‐selective encapsulation and separation. More information can be found in the Communication by P. Yin et al. on page 14131 ff. [ABSTRACT FROM AUTHOR]

Invited for the cover of this issue are Panchao Yin and collaborators at Oak Ridge National Laboratory. The image depicts a 2.9 nm molybdenum oxide molecular cluster for the size-selective encapsulation of small alkane molecules. Read the full text of the article at . [ABSTRACT FROM AUTHOR]