Enantioseparation of 5,5′-Dibromo-2,2′-dichloro-3-selanyl-4,4′-bipyridines on Polysaccharide-Based Chiral Stationary Phases: Exploring Chalcogen Bonds in Liquid-Phase Chromatography

The chalcogen bond (ChB) is a noncovalent interaction based on electrophilic features of regions of electron charge density depletion (σ-holes) located on bound atoms of group VI. The σ-holes of sulfur and heavy chalcogen atoms (Se, Te) (donors) can interact through their positive electrostatic potential (V) with nucleophilic partners such as lone pairs, π-clouds, and anions (acceptors). In the last few years, promising applications of ChBs in catalysis, crystal engineering, molecular biology, and supramolecular chemistry have been reported. Recently, we explored the high-performance liquid chromatography (HPLC) enantioseparation of fluorinated 3-arylthio-4,4′-bipyridines containing sulfur atoms as ChB donors. Following this study, herein we describe the comparative enantioseparation of three 5,5′-dibromo-2,2′-dichloro-3-selanyl-4,4′-bipyridines on polysaccharide-based chiral stationary phases (CSPs) aiming to understand function and potentialities of selenium σ-holes in the enantiodiscrimination process. The impact of the chalcogen substituent on enantioseparation was explored by using sulfur and non-chalcogen derivatives as reference substances for comparison. Our investigation also focused on the function of the perfluorinated aromatic ring as a π-hole donor recognition site. Thermodynamic quantities associated with the enantioseparation were derived from van’t Hoff plots and local electron charge density of specific molecular regions of the interacting partners were inspected in terms of calculated V. On this basis, by correlating theoretical data and experimental results, the participation of ChBs and π-hole bonds in the enantiodiscrimination process was reasonably confirmed.     

Sustainable Protocol for the Synthesis of 2′,3′-Dideoxynucleoside and 2′,3′-Didehydro-2′,3′-dideoxynucleoside Derivatives

An improved protocol for the transformation of ribonucleosides into 2′,3′-dideoxynucleoside and 2′,3′-didehydro-2′,3′-dideoxynucleoside derivatives, including the anti-HIV drugs stavudine (d4T), zalcitabine (ddC) and didanosine (ddI), was established. The process involves radical deoxygenation of xanthate using environmentally friendly and low-cost reagents. Bromoethane or 3-bromopropanenitrile was the alkylating agent of choice to prepare the ribonucleoside 2′,3′-bisxanthates. In the subsequent radical deoxygenation reaction, tris(trimethylsilyl)silane and 1,1′-azobis(cyclohexanecarbonitrile) were used to replace hazardous Bu₃SnH and AIBN, respectively. In addition, TBAF was substituted for camphorsulfonic acid in the deprotection step of the 5′-O-silyl ether group, and an enzyme (adenosine deaminase) was used to transform 2′,3′-dideoxyadenosine into 2′,3′-dideoxyinosine (ddI) in excellent yield.     

Synthesis and Biological Evaluation of 5′-O-Fatty Acyl Ester Derivatives of 3′-Fluoro-2′,3′-dideoxythymidine as Potential Anti-HIV Microbicides

A number of 5′-O-fatty acyl derivatives of 3′-fluoro-2′,3′-dideoxythymidine (FLT, 1) were synthesized. These conjugates were evaluated for their potential as topical microbicides with anti-HIV activity against cell-free (X4 and R5), cell-associated, and multidrug-resistant viruses. Compared to FLT and 3′-azido-2′,3′-dideoxythymidine (AZT), 5′-O-(12-azidododecanoyl) (5), 5′-O-myristoyl (6), and 5′-O-(12-thioethyldodecanoyl) (8) derivatives of FLT were found to be more active against both cell-free viruses (lymphocytotropic and monocytotropic strains) with EC₅₀ values of 0.4 μM, 1.1 μM, and <0.2 μM, respectively, as well as cell-associated virus with EC₅₀ values of 12.6, 6.4, and 2.3 μM, respectively. Conjugates 5, 6, and 8 exhibited >4 and >30 times better antiviral index than FLT and AZT, respectively. Conjugates 5 and 8 were significantly more potent than FLT against many multidrug-resistant strains. A comparison of the anti-HIV activity with the corresponding non-hydrolyzable ether conjugates suggested that ester hydrolysis to FLT and fatty acids is critical to enable anti-HIV activity. Cellular uptake studies were conducted using fluorescent derivatives of FLT attached with 5(6)-carboxyfluorescein through either β-alanine (23) or 12-aminododecanoic acid (24) spacers. The lipophilic fluorescent analog with a long chain (24) showed more than 12 times higher cellular uptake profile than the fluorescent analog with a short chain (23). These studies further confirmed that the attachment of fatty acids improved the cellular uptake of nucleoside conjugates. In addition, 5, 6, and 8 were the least cytotoxic and did not alter vaginal cell and sperm viability compared to the positive control, a commercial topical spermicide (N-9), which significantly decreased sperm and vaginal cell viability inducing the generation of proinflammatory cytokines.     

Application of HPLC-QQQ-MS/MS and New RP-HPLC-DAD System Utilizing the Chaotropic Effect for Determination of Nicotine and Its Major Metabolites Cotinine,and trans-3′-Hydroxycotinine in Human Plasma Samples

The routine techniques currently applied for the determination of nicotine and its major metabolites, cotinine, and trans-3′-hydroxycotinine, in biological fluids, include spectrophotometric, immunoassays, and chromatographic techniques. The aim of this study was to develop, and compare two new chromatographic methods high-performance liquid chromatography coupled to triple quadrupole mass spectrometry (HPLC-QQQ-MS/MS), and RP-HPLC enriched with chaotropic additives, which would allow reliable confirmation of tobacco smoke exposure in toxicological and epidemiological studies. The concentrations of analytes were determined in human plasma as the sample matrix. The methods were compared in terms of the linearity, accuracy, repeatability, detection and quantification limits (LOD and LOQ), and recovery. The obtained validation parameters met the ICH requirements for both proposed procedures. However, the limits of detection (LOD) were much better for HPLC-QQQ-MS/MS (0.07 ng mL⁻¹ for trans-3′-hydroxcotinine; 0.02 ng mL⁻¹ for cotinine; 0.04 ng mL⁻¹ for nicotine) in comparison to the RP-HPLC-DAD enriched with chaotropic additives (1.47 ng mL⁻¹ for trans-3′-hydroxcotinine; 1.59 ng mL⁻¹ for cotinine; 1.50 ng mL⁻¹ for nicotine). The extraction efficiency (%) was concentration-dependent and ranged between 96.66% and 99.39% for RP-HPLC-DAD and 76.8% to 96.4% for HPLC-QQQ-MS/MS. The usefulness of the elaborated analytical methods was checked on the example of the analysis of a blood sample taken from a tobacco smoker. The nicotine, cotinine, and trans-3′-hydroxycotinine contents in the smoker’s plasma quantified by the RP-HPLC-DAD method differed from the values measured by the HPLC-QQQ-MS/MS. However, the relative errors of measurements were smaller than 10% (6.80%, 6.72%, 2.04% respectively).     

Synthesis,Characterization, and Catalytic Exploration of Mononuclear Mo(VI) Dioxido Complexes of (Z)-1-R-2-(4′,4′-Dimethyl-2′-oxazolin-2′-yl)-eth-1-en-1-ates

The coordination chemistry of the title ligands with Mo metal centers was investigated. Thus, the synthesis and characterization (NMR, X-ray diffraction) of four mononuclear formally Mo(6+) complexes of (Z)-1-R-2-(4′,4′-dimethyl-2′-oxazolin-2′-yl)-eth-1-en-1-ates (L: R = –Ph, –Ph-p-NO₂, –Ph-p-OMe and –t-Bu), derived from the part enols (LH), is described. The resulting air-stable MoO₂L₂ complexes (1–4) exist, as shown by single-crystal X-ray diffraction experiments, in the cis-dioxido-trans(N)-κ²-N,O-L conformation in the solid state for all four examples. This situation was further probed using semi-empirical PM6(tm) calculations. Complexes 1–4 represent the first Mo complexes of this ligand class and, indeed, of Group 6 metals in general. Structural and spectroscopic comparisons were made between these and related Mo(6+) compounds. Complex 1 (R = –Ph) was studied for its ability to selectively catalyze the production of poly-norbornene from the monomer in the presence of MAO. This, unfortunately, only resulted in the synthesis of insoluble, presumably highly cross-linked, polymeric and/or oligomeric materials. However, complexes 1–4 were demonstrated to be highly effective for catalyzing benzoin to benzil conversion using DMSO as the O-transfer agent. This catalysis work is likewise put into perspective with respect to analogous Mo(6+) complexes.     

Reactivity of Aliphatic and Phenolic Hydroxyl Groups in Kraft Lignin towards 4,4′ MDI

Several efforts have been dedicated to the development of lignin-based polyurethanes (PU) in recent years. The low and heterogeneous reactivity of lignin hydroxyl groups towards diisocyanates, arising from their highly complex chemical structure, limits the application of this biopolymer in PU synthesis. Besides the well-known differences in the reactivity of aliphatic and aromatic hydroxyl groups, experimental work in which the reactivity of both types of hydroxyl, especially the aromatic ones present in syringyl (S-unit), guaiacyl (G-unit), and p-hydroxyphenyl (H-unit) building units are considered and compared, is still lacking in the literature. In this work, the hydroxyl reactivity of two kraft lignin grades towards 4,4′-diphenylmethane diisocyanate (MDI) was investigated. ³¹P NMR allowed the monitoring of the reactivity of each hydroxyl group in the lignin structure. FTIR spectra revealed the evolution of peaks related to hydroxyl consumption and urethane formation. These results might support new PU developments, including the use of unmodified lignin and the synthesis of MDI-functionalized biopolymers or prepolymers.     

Convenient Synthesis of Pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazoles via Intramolecular Nitrile Oxide Cycloaddition

A simple and efficient synthetic route to the novel 3a,4-dihydro-3H,7H- and 4H,7H-pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazole ring systems from 3-(prop-2-en-1-yloxy)- or 3-(prop-2-yn-1-yloxy)-1H-pyrazole-4-carbaldehyde oximes has been developed by employing the intramolecular nitrile oxide cycloaddition (INOC) reaction as the key step. The configuration of intermediate aldoximes was unambiguously determined using NOESY experimental data and comparison of the magnitudes of ¹J_CH coupling constants of the iminyl moiety, which were greater by approximately 13 Hz for the predominant syn isomer. The structures of the obtained heterocyclic products were confirmed by detailed ¹H, ¹³C and ¹⁵N NMR spectroscopic experiments and HRMS measurements.     

Potential Stereoselective Binding of Trans-(±)-Kusunokinin and Cis-(±)-Kusunokinin Isomers to CSF1R

Breast cancer cell proliferation and migration are inhibited by naturally extracted trans-(−)-kusunokinin. However, three additional enantiomers of kusunokinin have yet to be investigated: trans-(+)-kusunokinin, cis-(−)-isomer and cis-(+)-isomer. According to the results of molecular docking studies of kusunokinin isomers on 60 breast cancer-related proteins, trans-(−)-kusunokinin was the most preferable and active component of the trans-racemic mixture. Trans-(−)-kusunokinin targeted proteins involved in cell growth and proliferation, whereas the cis-(+)-isomer targeted proteins involved in metastasis. Trans-(−)-kusunokinin targeted CSF1R specifically, whereas trans-(+)-kusunokinin and both cis-isomers may have bound AKR1B1. Interestingly, the compound’s stereoisomeric effect may influence protein selectivity. CSF1R preferred trans-(−)-kusunokinin over trans-(+)-kusunokinin because the binding pocket required a ligand planar arrangement to form a π-π interaction with a selective Trp550. Because of its large binding pocket, EGFR exhibited no stereoselectivity. MD simulation revealed that trans-(−)-kusunokinin, trans-(+)-kusunokinin and pexidartinib bound CSF1R differently. Pexidartinib had the highest binding affinity, followed by trans-(−)-kusunokinin and trans-(+)-kusunokinin, respectively. The trans-(−)-kusunokinin-CSF1R complex was found to be stable, whereas trans-(+)-kusunokinin was not. Trans-(±)-kusunokinin, a potential racemic compound, could be developed as a selective CSF1R inhibitor when combined.     

Chalcogen Bonding in Co-Crystals: Activation through 1,4-Perfluorophenylene vs. 4,4′-Perfluorobiphenylene Cores

The ability of alkylseleno/alkyltelluroacetylenes such as bis(selenomethylethynyl)-perfluorobenzene (4F-Se) to act as a ditopic chalcogen bond (ChB) donor in co-crystals with ditopic Lewis bases such as 4,4′-bipyridine is extended here to the octafluorobiphenylene analog, 4,4′-bis(selenomethylethynyl)-perfluorobiphenyl (8F-Se), with the more electron-rich 4,4′-bipyridylethane (bpe), showing in the 1:1 (8F-Se)•(bpe) co-crystal a shorter and more linear C−Se•••N ChB interaction than in (4F-Se)•(bpe), with Se•••N distances down to 2.958(2) Å at 150 K, i.e., a reduction ratio of 0.85 vs. the van der Waals contact distance.     

Microwave-Assisted Extraction of Anticancer Flavonoid, 2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethyl Chalcone (DMC), Rich Extract from Syzygium nervosum Fruits

2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethyl chalcone (DMC) is a biological flavonoid that is present in the fruits of Syzygium nervosum (Ma-Kiang in Thai). Microwave-assisted extraction (MAE), which utilizes microwave radiation to heat the extraction solvent quickly and effectively, was used to recover DMC-rich extract from Syzygium nervosum fruit. To determine the DMC content, a highly accurate and precise HPLC technique was developed. The influences of MAE conditions, including the solid–liquid ratio, microwave power, and microwave duration on the content of DMC, were sequentially employed by a single factor investigation and response surface methodology (RSM) exploratory design. The predicted quadratic models were fitted due to their highly significant (p < 0.0001) and excellent determination coefficient (R² = 0.9944). The optimal conditions for producing DMC-rich extract were a ratio of sample to solvent of 1:35 g/mL, a microwave power of 350 W, and a microwave time of 38 min. Under the optimal MAE setting, the DMC content reached 1409 ± 24 µg/g dry sample, which was greater than that of the conventional heat reflux extraction (HRE) (1337 ± 37 µg/g dry sample) and maceration (1225 ± 81 µg/g dry sample). The DMC-rich extract obtained from MAE showed stronger anticancer activities against A549 (human lung cancer cells) and HepG2 (human liver cancer cells) than the individual DMC substance, which makes MAE an effective method for extracting essential phytochemicals from plants in the nature.     

Effects of 2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone from Syzygium nervosum Seeds on Antiproliferative,DNA Damage,Cell Cycle Arrest,and Apoptosis in Human Cervical Cancer Cell Lines

2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC), a natural product derived from Syzygium nervosum A. Cunn. ex DC., was investigated for its inhibitory activities against various cancer cell lines. In this work, we investigated the effects of DMC and available anticervical cancer drugs (5-fluorouracil, cisplatin, and doxorubicin) on three human cervical cancer cell lines (C-33A, HeLa, and SiHa). DMC displayed antiproliferative cervical cancer activity in C-33A, HeLa, and SiHa cells, with IC₅₀ values of 15.76 ± 1.49, 10.05 ± 0.22, and 18.31 ± 3.10 µM, respectively. DMC presented higher antiproliferative cancer activity in HeLa cells; therefore, we further investigated DMC-induced apoptosis in this cell line, including DNA damage, cell cycle arrest, and apoptosis assays. As a potential anticancer agent, DMC treatment increased DNA damage in cancer cells, observed through fluorescence inverted microscopy and a comet assay. The cell cycle assay showed an increased number of cells in the G₀/G₁ phase following DMC treatment. Furthermore, DMC treatment-induced apoptosis cell death was approximately three- to four-fold higher compared to the untreated group. Here, DMC represented a compound-induced apoptosis for cell death in the HeLa cervical cancer cell line. Our findings suggest that DMC, a phytochemical agent, is a potential candidate for antiproliferative cervical cancer drug development.     

Synthesis,Neuroprotection, and Antioxidant Activity of 1,1′-Biphenylnitrones as α-Phenyl-N-tert-butylnitrone Analogues in In Vitro Ischemia Models

Herein, we report the neuroprotective and antioxidant activity of 1,1′-biphenyl nitrones (BPNs) 1–5 as α-phenyl-N-tert-butylnitrone analogues prepared from commercially available [1,1′-biphenyl]-4-carbaldehyde and [1,1′-biphenyl]-4,4′-dicarbaldehyde. The neuroprotection of BPNs 1-5 has been measured against oligomycin A/rotenone and in an oxygen–glucose deprivation in vitro ischemia model in human neuroblastoma SH-SY5Y cells. Our results indicate that BPNs 1–5 have better neuroprotective and antioxidant properties than α-phenyl-N-tert-butylnitrone (PBN), and they are quite similar to N-acetyl-L-cysteine (NAC), which is a well-known antioxidant agent. Among the nitrones studied, homo-bis-nitrone BPHBN5, bearing two N-tert-Bu radicals at the nitrone motif, has the best neuroprotective capacity (EC₅₀ = 13.16 ± 1.65 and 25.5 ± 3.93 μM, against the reduction in metabolic activity induced by respiratory chain blockers and oxygen–glucose deprivation in an in vitro ischemia model, respectively) as well as anti-necrotic, anti-apoptotic, and antioxidant activities (EC₅₀ = 11.2 ± 3.94 μM), which were measured by its capacity to reduce superoxide production in human neuroblastoma SH-SY5Y cell cultures, followed by mononitrone BPMN3, with one N-Bn radical, and BPMN2, with only one N-tert-Bu substituent. The antioxidant activity of BPNs 1-5 has also been analyzed for their capacity to scavenge hydroxyl free radicals (82% at 100 μM), lipoxygenase inhibition, and the inhibition of lipid peroxidation (68% at 100 μM). Results showed that although the number of nitrone groups improves the neuroprotection profile of these BPNs, the final effect is also dependent on the substitutent that is being incorporated. Thus, BPNs bearing N-tert-Bu and N-Bn groups show better neuroprotective and antioxidant properties than those substituted with Me. All these results led us to propose homo-bis-nitrone BPHBN5 as the most balanced and interesting nitrone based on its neuroprotective capacity in different neuronal models of oxidative stress and in vitro ischemia as well as its antioxidant activity.     

Heterobimetallic [Ru(II)/Fe(II)] complexes: On the formation of trans- and cis-[RuCl2(dppf)(diimines)]

The synthesis and characterization of trans/cis-[RuCl₂(dppf)(diimines)], dppf = 1,1′-bis(diphenylphosphino)ferrocene; diimines = 2,2′-bipyridine (trans/cis-(1)), the new complexes with 4,4′-dimethyl-2,2′-bipyridine (trans/cis-(2)) and 1,10-phenanthroline (cis-(3)) are presented. The complexes were synthesized using two routes and the trans/cis-isomer formation is dependent upon conditions and the precursor applied. The trans-isomer (kinetic) readily isomerizes to the cis-isomer (thermodynamic) when exposed to light (fluorescent) and this process was followed by cyclic voltammetry and UV-vis. The electrochemical studies on these complexes reveal that Fe^(III)/Fe^(II) couples are insensitive to the isomer (trans/cis) formed, but the Ru^(III)/Ru^(II) couples are dependent on the isomer. Transfer-hydrogenation reactions for reduction of acetophenone were conducted using complexes cis-(1) and cis-(2) and the results are compared with that obtained for similar complexes. X-ray structure for cis-(3) are presented and discussed.     

Synthesis of Polyanionic C5-Modified 2′-Deoxyuridine and 2′-Deoxycytidine-5′-Triphosphates and Their Properties as Substrates for DNA Polymerases

Modified 2′-deoxyribonucleotide triphosphates (dNTPs) have widespread applications in both existing and emerging biomolecular technologies. For such applications it is an essential requirement that the modified dNTPs be substrates for DNA polymerases. To date very few examples of C5-modified dNTPs bearing negatively charged functionality have been described, despite the fact that such nucleotides might potentially be valuable in diagnostic applications using Si-nanowire-based detection systems. Herein we have synthesised C5-modified dUTP and dCTP nucleotides each of which are labelled with an dianionic reporter group. The reporter group is tethered to the nucleobase via a polyethylene glycol (PEG)-based linkers of varying length. The substrate properties of these modified dNTPs with a variety of DNA polymerases have been investigated to study the effects of varying the length and mode of attachment of the PEG linker to the nucleobase. In general, nucleotides containing the PEG linker tethered to the nucleobase via an amide rather than an ether linkage proved to be the best substrates, whilst nucleotides containing PEG linkers from PEG₆ to PEG₂₄ could all be incorporated by one or more DNA polymerase. The polymerases most able to incorporate these modified nucleotides included Klentaq, Vent(exo-) and therminator, with incorporation by Klenow(exo-) generally being very poor.     

A Tail Does Not Always Make a Difference: Assembly of cds Nets from Co(NCS)2 and 1,4-bis(n-Alkyloxy)-2,5-bis(3,2′:6′,3″-terpyridin-4′-yl)benzene Ligands

The consistent assembly of a (6⁵.8) cds net is observed in reactions of cobalt(II) thiocyanate with 1,4-bis(n-alkyloxy)-2,5-bis(3,2′:6′,3″-terpyridin-4′-yl)benzene ligands in which the n-alkyloxy substituents are n-propyl (ligand 3), n-butyl (4), n-pentyl (5), n-hexyl (6), n-heptyl (7), and n-octyl (8). Crystals were grown by layering a methanol solution of Co(NCS)₂ over a 1,2-dichlorobenzene solution of each ligand. The choice of crystallization solvents is critical in directing the assembly of the cds net. Single-crystal structures of [Co(NCS)₂(3)]_n^.3.5nC₆H₄Cl₂, [Co(NCS)₂(4)]_n^.5.5nC₆H₄Cl₂, [Co(NCS)₂(5)]_n^.4nC₆H₄Cl₂, [Co(NCS)₂(6)]_n^.3.8nC₆H₄Cl₂, [Co(NCS)₂(7)]_n^.3.1nC₆H₄Cl₂, and [Co(NCS)₂(8)]_n^.1.6nC₆H₄Cl₂^.2nMeOH (C₆H₄Cl₂ = 1,2-dichlorobenzene) are presented and compared. The n-alkyloxy chains exhibit close to extended conformations and are accommodated in cavities in the lattice without perturbation of the coordination framework.     

Ochratoxin A and 2′R-Ochratoxin A in Selected Foodstuffs and Dietary Risk Assessment

The aim of this study was to estimate the contamination of grain coffee, roasted coffee, instant coffee, and cocoa purchased in local markets with ochratoxin A (OTA) and its isomerization product 2′R-ochratoxin A (2′R-OTA), and to assess risk of dietary exposure to the mycotoxins. OTA and 2′R-OTA content was determined using the HPLC chromatography with immunoaffinity columns dedicated to OTA. OTA levels found in all the tested samples were below the maximum limits specified in the European Commission Regulation EC 1881/2006. Average OTA concentrations calculated for positive samples of grain coffee/roasted coffee/instant coffee/cocoa were 0.94/0.79/3.00/0.95 µg/kg, with the concentration ranges: 0.57–1.97/0.44–2.29/0.40–5.15/0.48–1.97 µg/kg, respectively. Average 2′R-OTA concentrations calculated for positive samples of roasted coffee/instant coffee were 0.90/1.48 µg/kg, with concentration ranges: 0.40–1.26/1.00–2.12 µg/kg, respectively. In turn, diastereomer was not found in any of the tested cocoa samples. Daily intake of both mycotoxins with coffee/cocoa would be below the TDI value even if the consumed coffee/cocoa were contaminated with OTA/2′R-OTA at the highest levels found in this study. Up to now only a few papers on both OTA and 2′R-OTA in roasted food products are available in the literature, and this is the first study in Poland.     

Cationic copolymerization of anethole: Reactivity of geometric isomers of α,β-disubstituted ethylenes

Cationic copolymerizations of anethole were carried out under various conditions in order to confirm the relative reactivities of its geometric isomers. trans-Anethole was more reactive than cis-anethole in copolymerizations with p-methoxystyrene or styrene, but less reactive in the mutual copolymerization of cis- and trans-anethole; i.e., the trans isomer was more reactive to a growing chain end with little steric hindrance. Thus the intrinsic reactivity of an olefinic double bond to carbonium ion is greater for the trans isomer than for the cis isomer. This idea is supported by ¹³C NMR spectra, since the signal of the olefinic β-carbon of the trans isomer is at higher field than that of the cis isomer. The behavior of anethole was compared with the results observed in vinyl ethers, where the cis isomer was always more reactive irrrspective of the structure of the growing chain end. In addition, the dependence of monomer reactivity ratios on polymerization conditions is discussed.     

A Study on Synthesis and Upscaling of 2′-O-AECM-5-methyl Pyrimidine Phosphoramidites for Oligonucleotide Synthesis

2′-O-(N-(Aminoethyl)carbamoyl)methyl-modified 5-methyluridine (AECM-MeU) and 5-methylcytidine (AECM-MeC) phosphoramidites are reported for the first time and prepared in multigram quantities. The syntheses of AECM-MeU and AECM-MeC nucleosides are designed for larger scales (approx. 20 g up until phosphoramidite preparation steps) using low-cost reagents and minimizing chromatographic purifications. Several steps were screened for best conditions, focusing on the most crucial steps such as N³ and/or 2′-OH alkylations, which were improved for larger scale synthesis using phase transfer catalysis (PTC). Moreover, the need of chromatographic purifications was substantially reduced by employing one-pot synthesis and improved work-up strategies.     

Adsorption of N,N,N′,N′-Tetraoctyl Diglycolamide on Hypercrosslinked Polysterene from a Supercritical Carbon Dioxide Medium

The work considers for the first time the preparation of sorbents based on hypercrosslinked polysterene (HCP) and chelating agent N,N,N′,N′-tetraoctyl diglycolamide (TODGA) by impregnation in the supercritical (SC) CO₂ medium. Such sorbents can be applied for further isolation and separation of lanthanides, actinides and other metals. They are usually prepared by impregnation in toxic organic solvents (e.g., methanol, dichloromethane). Our study shows that application of SC CO₂ instead of organic solvents can significantly speed up the impregnation, perfom it in one stage and make the process more eco-friendly. At the same time, the obtained sorbents are close in their parameters to the classical ones. This article presents the results of measuring the TODGA adsorption isotherms on two HCP sorbents (MN202 and MN270) on a wide range of SC fluid parameters. Adsorption measurements were carried out using on-line supercritical fluid chromatography and gravimetry. Based on the sorption capacity parameter, MN202 sorbent was selected as the better carrier for TODGA. An impregnation temperature increase within the range 313–343 K in isochoric conditions (ρ = 0.780 g/mL) reduces the maximum of TODGA adsorption from ~0.68 mmol/g to ~0.49 mmol/g.     

Meeting key synthetic challenges in amanitin synthesis with a new cytotoxic analog: 5′-hydroxy-6′-deoxy-amanitin

Appreciating the need to access synthetic analogs of amanitin, here we report the synthesis of 5′-hydroxy-6′-deoxy-amanitin, a novel, rationally-designed bioactive analog and constitutional isomer of α-amanitin, that is anticipated to be used as a payload for antibody drug conjugates. In completing this synthesis, we meet the challenge of diastereoselective sulfoxidation by presenting two high-yielding and diastereoselective sulfoxidation approaches to afford the more toxic (R)-sulfoxide.

Elucidating a highly diastereoselective sulfoxidation of S-deoxy-amanitin to afford α-amanitin and a more synthetically accessible analog of near-native toxicity.