Mukaiyama–Michael Reactions with trans‐2,5‐Diarylpyrrolidine Catalysts: Enantioselectivity Arises from Attractive Noncovalent Interactions,Not from Steric Hindrance

The scope of the enantioselective Mukaiyama–Michael reactions catalyzed by trans‐2,5‐diphenylpyrrolidine has been expanded to include both α‐ and β‐substituted enals. However, the rationalization of the observed enantioselectivity is far from obvious since the catalyst is not very sterically hindered. DFT calculations were carried out to rationalize the observed stereoselectivities. Transition states of the C?C bond formation between iminium intermediates and silyloxyfurans were located and their relative energies were used to estimate the stereoselectivity data. We find excellent agreement between the predicted and observed stereoselectivities. The analysis of intermolecular forces reveals that the enantioselectivity is mostly due to stabilizing noncovalent interactions between the reacting partners, not due to steric hindrance. The role of attractive noncovalent interactions in enantioselective catalysis may be underappreciated.     

Formation of carbonium ions on zeolite surfaces

The adsorption and thermal desorption of carbonium ions from surfaces of zeolites, Al₂O₃ and TiO₂ have been investigated spectroscopically. The formation of stable carbonium ions (Φ₃C⁺) of triphenylmethyl compounds (Φ₃CCl and Φ₃COH) occurred at relatively low temperatures, e.g. 100°C. No Φ₃C⁺ ions could be detected after adsorption of triphenylmethane. These findings are in agreement with prior mass spectrometric results. Intensities of the respective IR bands indicate that the molecules (Φ₃CCl, Φ₃COH, Φ₃CH) penetrate into the interior of the zeolite grains, where they are adsorbed. The experiments show that acidic Lewis sites are responsible for the carbonium ion formation in the present system.     

Comparative analysis of the full set of methylated β‐cyclodextrins as chiral selectors in capillary electrophoresis

The chiral separation ability of the full library of methylated‐β‐cyclodextrins towards pharmacologically significant racemic drugs including basic compounds was studied by chiral CE. The syntheses of all the methylated, single isomer β‐cyclodextrins were revised and optimized and the aqueous solubility of the derivatives was unambiguously established. The three most relevant commercially available methylated isomeric mixtures were also included in the screening, so a total of ten various methylated CDs were investigated. The effects of the selector concentration on the enantiorecognition properties at acidic pH were investigated. Among the dimethylated β‐cyclodextrins, the heptakis (2,6‐di‐O‐methyl)‐β‐cyclodextrin isomer (2,6‐DIMEB) resulted to be the most versatile chiral selector. Terbutaline was selected as a model compound for the in‐depth investigation of host‐guest enantiodiscrimination ability. The association constants between the two terbutaline enantiomers and 2,6‐DIMEB were determined in order to support that the enantioseparation is driven by differences is host‐guest binding. The migration order of the enantiomers was confirmed by performing spiking experiments with the pure enantiomers. 1D and 2D NMR spectroscopy was applied to the 2,3‐, and 2,6‐DIMEB/terbutaline systems to rationalize at molecular level the different enantioseparation ability of the dimethylated β‐cyclodextrin selectors.     

Water-repellent acylated and silylated wood samples and their surface analytical characterization

The interest for chemical modification of wood with the aim of preserving it from physical and biochemical deterioration is rapidly increasing. Among the possibilities, acetylation has a great potential for improving the dimension instability of wood against moisture and the durability of wooden objects. Recently, a new acetylating agent, isopropenyl acetate has attracted attention giving an improved acetylating method. By increasing the size of the acyl group, a positive effect on the wood hydrophobicity can be reached. The anhydrides, however, are less reactive. Another applicable surface modification is the silylation of wood that renders the wood surface hydrophobic.

In this paper, we report about the acylation and silylation of different wood samples. A new manufacturing process is tested in which low-value Eucalyptus wood is mixed acylated. The reagent mixture contains at least two kinds of acyl group. One of them is acetyl group; the other(s) can be user-defined. We also report about a silylation method, in which catalyst facilitates the chemisorption process. The extent of modification of the treated wood samples was evaluated by means of weight percent gain, ATR-FTIR, and pyrolysis-gas chromatography–mass spectrometry (Py-GC/MS). Methylene blue adsorption of selected samples was also studied. The result of analytical measurements was in agreement with that of wettability studies.     

Visible Light Conjugation with Triazolinediones as a Route to Degradable Poly(ethylene glycol)–Lipids for mRNA Lipid Nanoparticle Formulation

Polyethylene glycol (PEG) is considered as the gold standard for colloidal stabilization of nanomedicines, yet PEG is non-degradable and lacks functionality on the backbone. Herein, we introduce concomitantly PEG backbone functionality and degradability via a one-step modification with 1,2,4-triazoline-3,5-diones (TAD) under green light. The TAD-PEG conjugates are degradable in aqueous medium under physiological conditions, with the rate of hydrolysis depending on pH and temperature. Subsequently, a PEG-lipid is modified with TAD-derivatives and successfully used for messenger RNA (mRNA) lipid nanoparticle (LNP) delivery, thereby improving mRNA transfection efficiency on multiple cell cultures in vitro. In vivo, in mice, mRNA LNP formulation exhibited a similar tissue distribution as common LNPs, with a slight decrease in transfection efficiency. Our findings pave the road towards the design of degradable, backbone-functionalized PEG for applications in nanomedicine and beyond.     

Enantioseparation of solriamfetol and its major impurity phenylalaninol by capillary electrophoresis using sulfated gamma cyclodextrin

R-solriamfetol is a recently approved drug used for the treatment of excessive sleepiness associated with narcolepsy and sleep apnea. Herein, a capillary electrophoretic method was developed, enabling the simultaneous analysis of the API and its S-enantiomer in addition to the enantiomers of its major impurity phenylalaninol. Twenty-nine different cyclodextrins (CDs), including native, neutral, and charged ones were screened as potential chiral selectors, and the best results were obtained with sulfated CDs. Randomly sulfated-β-CD exhibited outstanding enantioresolution, the peaks of phenylalaninol enantiomers inserted between the two peaks of solriamfetol enantiomers, while sulfated-γ-CD (S-γ-CD) showed remarkable resolution values in a much shorter analysis time with the optimal enantiomer migration order. Among the single isomer sulfated CD derivatives, substituent dependent enantiomer migration order reversal could also be observed in the case of heptakis(6-O-sulfo)-β-CD (HS-β-CD) or heptakis(2,3-O-dimethyl-6-O-sulfo)-β-CD (HDMS-β-CD) with R-,S-solriamfetol, and heptakis(2,3-O-diacetyl-6-O-sulfo)-β-CD (HDAS-β-CD) resulting S-,R-solriamfetol migration order. The sulfated-γ-CD system was chosen for method optimization applying orthogonal experimental design. The optimized method (45 mM Tris-acetate buffer, pH 4.5, 4 mM S-γ-CD, 21°C, +19.5 kV) was capable for the baseline separation of solriamfetol and phenylalaninol enantiomers within 7 min. The optimized method was validated according to the ICH guidelines and successfully applied for the analysis of pharmaceutical preparation (Sunosi^® 75 mg tablet), thus it may serve as a routine procedure for the laboratories of regulatory authorities as well as in Pharmacopoeias.     

Determination of <Superscript>129</Superscript>I using volatilization method and liquid scintillation spectrometry

A simple and rapid separation method for ¹²⁹I determination in radioactive waste samples was developed. Suitable conditions for iodine volatilization were tested. Iodine was trapped in 1.5 mol L^?1 NaOH and precipitated as PdI₂·H₂O by addition of PdCl₂ with recoveries higher than 80%. The method was applied for analysis of contaminated soil, radioactive sludge, evaporator concentrate and heterogeneous waste samples from nuclear power plants in Slovak Republic. ¹²⁹I was measured on liquid scintillation counter TRI CARB 2900 TR using Ultima Gold AB scintillation cocktail.