Substitution Of Group Research Articles

In vitro nephrotoxicity and structure-toxicity relationships of eight natural aristolactams.

The structural similarity between aristolactams (ALs) and aristolochic acids (AAs) raises constant concerns about the safety of ALs-containing plants. Natural ALs are distributed more extensively than AAs, leading to a higher risk of ALs exposure in daily consumption. This study aimed to evaluate and compare the in vitro nephrotoxicity on human renal tubular epithelial cells (HK-2cells) of eight natural ALs with different substituents on the phenanthrene ring and amide ring, including aristolactam Ⅰ (AL Ⅰ), AL BⅡ, velutinam, AL AⅡ, sauristolactam, AL AⅠa, AL FⅠ and N-methyl piperolactam A. Their IC50 values of cell viability were tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of kidney injury molecule-1 (KIM-1), transforming growth factor-β1 (TGF-β1) and fibronectin (FN). The reactive oxygen species (ROS) assay was used to detect the intracellular oxidative stress level. The results showed that the eight ALs all had specific nephrotoxicity on HK-2cells. Particularly, AL Ⅰ, AL BⅡ and velutinam exhibited more potent cytotoxicity on HK-2cells (IC50=2.49-2.78μM) than the other five ALs (IC50=12.33-43.84μM). The structure-toxicity relationships indicated that both methylenedioxy (-OCH2O-) and methoxy (-OCH3) were positively contributing functional groups of ALs on nephrotoxicity, while the hydroxy group (-OH) and methyl substitution on nitrogen (N-CH3) accounted for a detrimental effect conversely. Consistent with this structure-toxicity relationship, the eight ALs increased KIM-1 levels in the same trend as their cytotoxicity at the same concentration of 2.5μg/mL, associating with different levels of ROS generation. And the four most toxic ALs, AL Ⅰ, AL BⅡ, velutinam and AL AⅡ, could also induce fibrosis by increasing TGF-β1 and FN levels.

Modulation of the Second-Beyond Coordination Structure in Single-Atom Electrocatalysts for Confirmed Promotion of Ammonia Synthesis.

Although microenvironments surrounding single-atom catalysts (SACs) have been widely demonstrated to have a remarkable effect on their catalytic performances, it remains unclear whether the local structure beyond the secondary coordination shells works as well or not. Herein, we employed a series of metal-organic frameworks (MOFs) with well-defined and tunable second-beyond coordination spheres as model SAC electrocatalysts to discuss the influence of long-distance structure on the ammonia synthesis from nitrate, which were synthesized and denoted as Cu12-NDI-X (X = NMe2, H, F). It is first experimentally confirmed that the remote substitution of function groups beyond the secondary coordination sphere can remarkably affect the activity of ammonia synthesis. Meanwhile, the -H endowed Cu12-NND-H exhibits a superior ammonia yield (35.1 mg·h-1·mgcat-1) and FE (98.7%) to those modified with -NMe2 and -F, which also shows good stability at 100 mA·cm-2. The remarkable promotion of the modulated second-beyond coordination structure is unraveled to result from the adjustable d-band center of the Cu active site leading to promoted adsorption of the NO3- and protonation of key intermediates. Encouraged by its extraordinary ammonia yield, we employed the Cu12-NND-H electrode as a cathode to assemble one rechargeable Zn-nitrate battery that exhibits an impressive power density of 34.0 mW·cm-2, demonstrating its promising application in energy conversion and storage.

Total Synthesis of the Conjugation‐Ready Hexasaccharides of Pseudomonas aeruginosa Serotype O17 O‐Antigen via One‐Pot Glycosylation

Comprehensive SummaryThe eradication of Pseudomonas aeruginosa infections is becoming increasingly complex due to the emergence of multidrug‐resistant strains, underscoring the urgent need for novel therapeutic strategies. Currently, no vaccine is available to prevent P. aeruginosa infections and the development of glycoconjugate vaccines based on P. aeruginosa lipopolysaccharides (LPS) presents significant challenges. To explore the immunological activity of the serotype O17 O‐antigen, we present the first chemical synthesis of two hexasaccharides derived from the O17 O‐antigen of P. aeruginosa, which possess distinct sequences. The synthesis of these two target hexasaccharides was accomplished using a chemoselective one‐pot [2+2+2] assembly strategy and a common step‐wise synthesis, respectively. The formation of β‐mannosamine glycosidic linkages in products 1 and 2, was achieved through a direct stereoselective 1,2‐cis‐glycosylation involving 4,6‐O‐benzylidene‐induced conformational locking facilitated by Ph2SO/Tf2O pre‐activation, and an indirect 1,2‐trans‐β‐glycosylation alongside SN2 substitution of azide groups at C2, respectively. The efficient synthesis of these conjugation‐ready oligosaccharides from the O‐antigen of P. aeruginosa serotype O17 will provide foundational materials for identifying key antigens and developing glycoconjugate vaccines.

Model Catalytic Studies on the Thermal Dehydrogenation of the Benzaldehyde/Cyclohexylmethanol LOHC System on Pt(111).

We investigated the dehydrogenation reaction and the thermal robustness of the liquid organic hydrogen carrier (LOHC) couple benzaldehyde/cyclohexylmethanol on a Pt(111) model catalyst in situ in synchrotron radiation photoelectron spectroscopy- and complementary temperature-programmed desorption experiments. The system stores hydrogen in a cyclohexyl group and a primary alcohol functionality and achieves an attractive hydrogen storage capacity of 7.0 mass %. We observed a stepwise dehydrogenation mechanism, characterized by a low temperature dehydrogenation of the alcohol group at 235 K. However, stability limitations challenge the system's application as reversible hydrogen storage solution, as the resultant aldehyde was found to decompose during the dehydrogenation of its cyclohexyl group (between 250 and 350 K). A comparison of cyclohexylmethanol with the structurally related secondary alcohol (1-cyclohexylethanol; 6.3 mass % hydrogen) revealed a parallel stepwise dehydrogenation pattern for both compounds, but a technically relevant superior thermal robustness of the latter, demonstrating the influence of the alcohol-group's substitution degree on the dehydrogenation characteristics of alcohol-functionalized LOHCs. Density functional theory calculations are in agreement with the experimentally observed stability trend.

Uncommon Phosphonylation of Pyrazine‐2,3‐dicarbonitrile Derivatives via C(sp2)−CN Bond Cleavage

AbstractA direct phosphonylation of the C(sp2)−CN bond under mild catalytic and non‐catalytic reaction conditions is disclosed. Pyrazine‐2,3‐dicarbonitriles are readily coupled with HPO(OEt)2 to produce the corresponding dialkoxyphosphoryl‐substituted pyrazines. The phosphonylation reaction occurs in the presence of a base (Et3N, Cs2CO3) as nucleophilic substitution of the CN groups. The yield of target diphosphonates depends on the nature of substituents in the 5,6‐positions of the pyrazine ring: it exceeds 90 % for di‐5,6‐aryl‐substituted pyrazines and is significantly lower when electron‐donating alkyl (n‐propyl) groups are attached to the 5,6‐positions. It should be noted that for pyrazine‐2,3‐dicarbonitriles bearing vicinal 4‐bromophenyl groups, the nucleophilic phosphonylation leading to C−CN/P−H coupling in the pyrazine ring is predominant over Pd‐catalyzed Hirao's C−Br/P−H coupling reaction in phenyl rings. Detailed structural characterization, both in solution by means of 1H, 13C and 31P NMR spectroscopy and in the solid state by single crystal X‐ray diffraction, of a series of newly synthesized pyrazine phosphonates is reported.

Efficient Synthesis of Dihydropyrimidine Hybrids via Guanidine‐Based Biginelli Reaction

AbstractA versatile method has been developed for the synthesis of morpholine‐dihydropyrimidine hybrids, 3‐benzyl‐6‐methyl‐5‐(morpholine‐4‐carbonyl)‐4‐phenyl‐3,4‐dihydropyrimidin‐2(1H)‐one, through the construction of dihydropyrimidine (DHPM) via the guanidine‐based Biginelli reaction followed by sodium tertiary butoxide mediated substitution of the benzyl group at the 3rd position of DHPM ring. This substitution approach represents a novel method for obtaining N‐substituted Biginelli products in good yields (72%–84%). Further, the ester group was subjected to intergroup conversion by morpholine using in situ generated diisobutyl(morpholino)aluminum. Notably, this reaction exhibited tolerance to various functional groups, resulting in the corresponding derivatives of dihydropyrimidine–morpholine hybrids in excellent yield (62%–82%).

Synthesis of Alkylated Carbonyl‐Bearing Furans via Acid‐Catalyzed Friedel‐Crafts Reaction

AbstractCarbonyl‐bearing furans, certain pyrroles, and thiophenes were alkylated using alcohols in an acidic medium. Some 5‐alkylated derivatives of 2‐furoic acid with various adamantyls‐, cycloalkyl‐, other 2°‐ and 3°‐alkyl substituents were synthesized using 2‐furoic acid as a biomass‐derived chemical platform. Side reaction resulted in the substitution of the carboxylic group, leading to the formation of 1,5‐dialkyl furans. In the alkylation of acyl and formyl furan, either mono‐ or di‐alkyl products were obtained, depending on the functional group present in the furan nucleus. Pyrroles (or thiophenes) with related functional groups exclusively (or near‐exclusively) yielded mono‐alkyl products. The resultant 5‐substituted carbonyl furans can be used as building blocks and synthetic equivalents for 1 C and 4 C synthons, as demonstrated by a series of reactions involving 5‐adamantan‐1‐yl‐2‐furoic acid.

Accelerating the Gelation of in-Situ Gel Polymer Electrolyte by Lithium Salts-Anion-like Initiator for Lithium-ion Batteries

The demand for high-energy-density batteries is expanding with the rise of EV markets. Moreover, the benefits of solid-state electrolytes are emerging to achieve high energy density. However, the technology of solid-state electrolytes needs to mature further. In the present state, a gel polymer electrolytes (GPEs) could act as a bridge between liquid (LEs) and solid-state electrolytes (SSEs). GPEs under certain conditions can offer the advantages of both LEs and SSEs. Firstly, GPEs should be feasible to create a gel structure with minimal polymer content to ensure high ionic conductivity. Ideally, they should also exhibit a high lithium ion transference number. Secondly, GPEs should ensure safety from the risk of fire. It is essential not only to prioritize the non-flammability of polymer matrix but also to suppress the ignition of the LEs contained within GPEs. Lastly, in the current manufacturing process, the injection of liquid-state GPEs without additional steps should be possible. Also, in-situ gelation is necessary to mitigate interfacial problems. The non-flammable GPEs developed in the previous study satisfied above three conditions but had the disadvantage of long gelation time about one day at 60 oC. The gelation reaction was hindered by the bulky size of the functional groups substituted to enhance the non-flammability. Therefore, the amount of substituted functional groups was inevitably limited.In this study, fully substituted polymers were used to form the GPEs rapidly at room temperature or low temperatures (45 oC) with the addition of a lithium salts-anion-like initiator. The strong CN bonds were allowed to form carbocation due to easily ionized initiators. As a result, generated highly conjugated C=N-C bond great help to the formation of non-flammable polymer matrix compared with conjugated C=N-C bond from LiPF6. Furthermore, thermal degradation of the batteries was minimized because of rapid gelation at room temperature or lukewarm temperature. As the GPEs can undergo gelation without LiPF6, which was employed as an initiator in the previous method, stable operation at 60 oC or higher became possible. In the previous method, the decomposition of LipF6 into hydrogen fluoride at 60 oC resulted in a side reaction at the interphase between the electrolyte and the electrode. However, with the use of an initiator consisting of two anions instead of LiPF6, a stable lithium salt could be employed at high temperatures, ensuring stable operation. Moreover, the absence of hydroxyl groups enables the operation of a lithium metal battery that was previously inoperable when using PVA-CN. Due to the highly potent oxidizing power of the initiator, the gelation could rapidly progress even within a bulky substitute structure. Therefore, bulky flame-retardant structures could be fully incorporated into the polymer instead of the hydroxyl group (OH). Consequently, the side reaction of OH was eliminated. Specifically, the maximized presence of the fluorine functional group with radical scavenging ability ensured enhanced non-flammability of the entire electrolyte compared to previous studies.In summary, the addition of the initiator enabled rapid gelation with minimal energy consumption, facilitating the development of a lithium metal battery suitable for high-temperature operation. Furthermore, complete substitution of the functional group enhanced various functions and the flame retardancy of the electrolyte.

Exploring flavonoids as potent SLC46A3 inhibitors: Insights from the structural characteristics of flavonoid–SLC46A3 interactions

SLC46A3, a transporter for lysosomal steroid conjugates and bile acids, plays a pivotal role in the pharmacological effects of noncleavable antibody–drug conjugates using maytansine as a payload. SLC46A3 may exert negative effects on various phenomena, including copper homeostasis, mitochondrial function in the liver, and the uptake of lipid-based nanoparticles (NPs) in tumor cells. Consequently, inhibiting SLC46A3 may be a promising strategy for treating hepatic disease or enhancing lipid NP delivery to tumor cells, although the underlying mechanisms remain unknown. This study investigates flavonoids, the largest subgroup of polyphenols characterized by a simple C6-C3-C6 structure, as potential SLC46A3 inhibitors and provides insights into the structural requirements for flavonoid–SLC46A3 interactions. Screening revealed several flavonoids, including dihydrochalcones, flavonols, isoflavones, flavanones, and flavones, as effective inhibitors of 5-carboxyfluorescein (5-CF) uptake in MDCKII (Mardin-Darby canine kidney type II) cells stably expressing a mutant SLC46A3 localized to the plasma membrane. Notably, apigenin and luteolin exhibited marked 5-CF uptake inhibition, with IC50 values of 10.8 and 8.7 µM, respectively. Additionally, 4′,7-dihydroxyflavone significantly inhibited 5-CF uptake, exhibiting an IC50 value of 9.3 µM, whereas acacetin and genkwanin possessing methoxy group substitutions for the hydroxy group at the 4′- or 7-position of apigenin, respectively, did not affect the uptake. Luteolin’s inhibition mechanism was found to be of a mixed type involving increased Km and decreased Vmax. These findings emphasize the importance of hydroxy groups at 4′- and 7-positions in flavone–SLC46A3 interactions.

Triphenylamine-based D-A-π-A dyes for DSSC applications: Theoretical study on the impact of auxiliary acceptor groups and π-bridges on photovoltaic performance using DFT and TD-DFT calculations

In this study, a series of eight D-Ai-πi-A organic dyes designed by chemically modifying a previously synthesized D-π-A-type organic dye, called DPA-azo-A (R), were examined to assess the impact of the inclusion of different auxiliary acceptor groups (Ai, i = 4) and the substitution of the anthracene π-spacer group by thionothiophene/furofuran πi-bridge on their performance in dye-sensitized solar cells (DSSCs). Density functional theory (DFT) and time-dependent DFT (TD-DFT) computational methods were used to investigate geometrical structures, optoelectronic properties, and some key short-circuit current-related parameters, such as light-harvesting efficiency (LHE), electron injection driving force (ΔGinject), electron regeneration energy (ΔGreg), excitation lifetime (τ) and chemical reactivity. In addition, we identified the most stable TiO2-dye complex. The results showed that these new dyes show a reduced gap, significant absorption, strong adsorption, excellent light harvesting efficiency and better intramolecular charge transfer properties than the reference dye, translating into better photovoltaic performance. Consequently, this theoretical study breaks new ground by offering valuable guidance for the experimental synthesis of highly efficient triphenylamine-based organic dyes for DSSC applications.

Influence of core fluorination on the phase properties of fan-like azobenzene based supramolecules, their cis-trans photoisomerization and photoluminescence dynamics

The stimuli-responsive, low molecular weight, dynamically tunable photophysical features have long been an important objective that challenges chemists in synthesizing liquid crystal (LC) compounds. Herein, the effect of core fluorination on the mesomorphic behavior of fan-like azobenzene derivatives was reported. Two new series of azobenzene derivatives which differ from each other in the length of the terminal alkoxy side chain as well as fluorine (-F) group substitution on the azobenzene moiety were synthesized (3a-3c, 4a-4c) and molecular structures of the compounds were confirmed using various analytical techniques. Absorption spectra of the LC compounds 3b and 3c are characterized by ππ∗ transitions around 350–410 nm. The self-assembly of these LC compounds was investigated using polarized optical microscope (POM) and differential scanning colorimetry (DSC). The trans-to-cis photoisomerization of the LC compounds 3b and 3c occurs in these absorption bands. The trans-to-cis photoisomerization of LC compounds 3b and 3c showed 4 h and 24.5 h whereas, thermal cis-to-trans isomerization rates were found to be 90s and 100s resulting in tuning of mesophases. Room temperature photoluminescence (RTPL) of LC compounds 3b and 3c when excited at 220 nm, 230 nm and 240 nm showed several sharp/weak emission intensity bands. Both the LC compounds (3b, 3c) showed sharp blue emission bands and yellow/green/orange colored bands correspond to weak emission spectra when excited at 220 nm. Further, steady state photoluminescence (SSPL) spectra of these both LC compounds revealed sharp near edge emission bands and broad violet emission peaks with higher Stoke's shift as well as full width half maximum (FWHM). Fluorescence lifetime decay (FLD) studies of compound 3 b unveiled an average lifetime (τ) shuttle between 17.24 ns and 103.60 ns at various excitation wavelengths. However, FLD of LC compound 3c unveiled that the τ fluctuates between 27.00 ns and 102.56 ns at various excitation wavelengths. Quantum yield (QY) decreases for both the LC compounds with an increase in excitation wavelengths. The study proved the importance of the alkoxy side chain at one end of the aromatic ring and core fluorination as a significant tool to modify the LC behavior of azobenzene derivatives. Thus, synthesized azobenzene derivatives are potentially useful for developing permanent optical storage and display devices.

1-Alkylamino-3H-naphtho[1,2,3-de]quinoline-2,7-diones. Visualization of lipid droplets in living cells

A series of previously unknown 1-alkylamino-3H-naphtho[1,2,3-de]quinoline-2,7-diones, 1-alkylamino-6-nitro-3H-naphtho[1,2,3-de]quinoline-2,7-diones, and 1-alkylamino-6-amino-3H-naphtho[1,2,3-de]quinoline-2,7-diones was obtained by nucleophilic substitution of the tosyl group of 1-tosyl-3H-naphtho[1,2,3-de]quinoline-2,7-dione with aliphatic amines. Among the synthesized compounds, fluorophores emitting light from the blue-green to orange-red region of the visible spectrum with fluorescence quantum yields up to 0.39 were found. Some of the synthesized compounds showed phototoxic effects on human breast carcinoma cell line BT474. It was shown that 3-butyl-1-(butylamino)-6-nitronaphthoquinolinedione stains exclusively lipid droplets, has a large Stokes shift and can be used for visualization of these organelles.

Study on the electrochemical oxidation mechanism of sulfamethoxazole using three-dimensional boron-doped diamond

In this study, we prepared a novel three-dimensional boron-doped diamond (BDD) electrode. Subsequently, we systematically conducted an electrochemical oxidation reaction on sulfamethoxazole (SMX) using a BDD anode and a platinum plate (Pt) cathode. The effects of initial concentration, current density, initial pH, and carrier electrolyte on SMX degradation were investigated. The SMX was completely removed after 4 h of electrolysis at a current density of 30 mA/cm2, 0.1 mol sodium sulphate as the supporting electrolyte, and a pH of 7. Additionally, the COD removal rate was 65.6 %, while the energy consumption was 40.1 %. Compared with two-dimensional BDD electrode degradation, the energy saving was 54 %. Density functional theory (DFT) and high-performance liquid chromatography (HPLC) were used to analyse the SMX degradation mechanism. Three possible degradation pathways were proposed: ·OH substitution of the amino group in the aromatic ring, oxidation of the amino group to nitrogen dioxide, and addition of ·OH to the isoxazole ring. The active sites detected in the reaction corresponded closely with the calculated results using DFT. Moreover, ECOSAR toxicity analysis was applied to evaluate the toxicity of the intermediates produced during electrolysis. We discovered that the toxicity of SMX and its intermediates decreased significantly during electrolysis.

Design, synthesis and antitumor activity of triphenylphosphonium-linked derivatives of quinazolinone

Cancer is the leading cause of human death. Quinazolinone heterocyclic compounds have a variety of biological activities and have been extensively studied in recent years, especially for their potential anticancer activity. The triphenylphosphonium moiety (TPP+) has become a very important lipophilic cation, especially concerning its application the development of anticancer agents. In this work, we designed and synthesised 24 new TPP+ -conjugated quinazolinone derivatives, which have alkylated TPP+ at the N-3 position and different small group substitutions at the C-6 position, and their antiproliferative activity was evaluated in three cancer cell lines (human alveolar adenocarcinoma cells (A549), human hepatoblastoma cells (HepG2) and human breast cancer cells (MCF-7)) and human normal liver cells (QSG-7701). The cytotoxicity screening results showed that some derivatives exhibited effective inhibitory effects in cancer cells. Among them, the compound 5k–o showed better antiproliferative activity than the positive control drug gefitinib on MCF-7 and A549 cells. The most active compounds being 5o, with IC50 values of 6.56, 14.52 and 7.51 µM in MCF-7 cells, HepG2 cells and A549 cells, respectively. Compound 5o may be a promising compound for cancer treatment worthy of further study.

Synthesis, biological evaluation, and in silico studies of lantadene-derived pentacyclic triterpenoids as anticancer agents targeting IKK-β

We report the anticancer activity, structure-activity relationships (SAR), molecular mechanism, and in silico docking studies of nine pentacyclic triterpenoids derived from lantadene A. The NCI-60 cytotoxicity screening of synthesized compounds on 60 human tumor cell lines, representing nine different cancers revealed that compound 6, bearing dual C-3 and C-22 butyryloxy substitutions at the pentacyclic triterpenoid scaffold, displays remarkable potency with mean growth inhibition of 98.7% at 10 μM. The SRB five-dose assay of compound 6 exhibited that it suppresses the growth of all NCI-60 cell lines with a GI50 value in the single-digit micromolar range, except for one. The Western blot analysis revealed that compound 6 inhibits the expression of IKK-β and its down-stream effector NF-κB (p65). Molecular docking analysis of compound 6 with IKK-β showed hydrogen bond interactions with GLN425 and ARG427 and hydrophobic contact with PHE424 residues as the prominent interactions. Molecular dynamics simulation of the docked complex suggested that the complex was fairly stable. Compound 7, possessing the isobutyryloxy groups at the analogous positions of compound 6 was the second-favorable anticancer agent. Conversely, the substitution of the hydroxy group in compounds emerged as the least favorable substitution at both the C-3 and C-22 positions of the pharmacophore. The presence of the 22β-angeloyloxy side-chain, akin to the natural product lantadene A, exhibited moderate favorability for enhanced activity. As a whole, the cytotoxicity data of compounds underscores the preference for linear and extended substitutions at both the C-3 and C-22 positions of the pharmacophore for heightened activity.

Blue Thermally Activated Delayed Fluorescent OLEDs With EQE up to 25% via 3MMLCT‐Induced and Short‐Lived Phosphorescent Dinuclear Pt(II) Sensitizers

AbstractThe novel dinuclear Pt(II) complexes, Di‐Pt‐CH3 and Di‐Pt‐CD3 with non‐fluorinated n‐hetero cyclic (NHC) ligands are developed. They exhibit phosphorescent emission in the range of 440–460 nm in film state with ≈60% photoluminescence quantum yield (PLQY) and a shorter lifetime due to a moderate Pt‐Pt distance of 3.21 Å. By suitably combining with blue multiresornance thermally activated delay fluorescence ( MR‐TADF) emitters, t‐DABNA and ν‐DABNA, efficient energy transfer is achieved from the triplet intraligand state (3IL) and triplet metal ligand change transfer (3MLCT) mixed states of Pt(II) complexes to the singlet state of the emitters. Importantly, the delayed triplet lifetime of the TADF emitter is shortened through the fast relaxation of triplet metal‐metal to ligand charge transfer (3MMLCT) states, possessing 0.07 eV lower energy compared to the triplet states of the TADF emitters. Di‐Pt‐CH3 and Di‐Pt‐CD3 are employed in phosphorescent and phosphorescent sensitized TADF (PS‐TADF) blue OLEDs, resulting in high external quantum efficiency (EQE) of 18.8% and 25.4%, respectively. An extremely low roll‐off characteristic of 9.8% is observed in the PS‐TADF OLED. Additionally, deuterium substitution of the methyl group improved phosphorescent device lifetime by 2.6 times. Notably, Di‐Pt‐CD3 resulted in significant lifetime enhancements: 4.7 times in phosphorescent devices and 6.6 times in PS‐TADF devices, compared with Ir(cb)3‐based devices. The mechanism for the increased lifetime is extensively studied through the magneto‐electroluminescence (MEL) and transient electroluminescence (TrEL) measurements.

Optimization of synthesis of cationic starches for wastewater sludge and microalgae separation

The implementation of stricter water protection legislation requires the development of novel environmentally friendly water treatment materials. A new method for the preparation of water soluble cationic starch flocculants using potato starch, 3-chloro-2-hydroxypropyltrimethylammonium chloride and CaO additive was developed and surface response methodology was successfully utilized for the optimization of degree of substitution in the cationization of potato starch with and without CaO additive. Based on the results of destabilization studies of model kaolin, wastewater sludge, and microalgae dispersion systems, optimized conditions ware proposed for obtaining an efficient, soluble, and biodegradable cationic starch flocculant with optimal structure. The duration of starch etherification reaction was reduced to <12 h to obtain soluble cationic starch derivatives with a degree of substitution of quaternary ammonium groups of 0.25, which retained the granular structure during synthesis. An efficient flocculation technology using anionic polymer and high content of biodegradable cationic flocculant was proposed. The highly efficient flocculation of microalgae suspensions using developed cationic starch derivative with the degree of substitution of cationic groups of 0.25 has been also achieved. The developed environmentally friendly cationic starches with tailored flocculation properties proofed to have a great potential in various water cleaning and separation technologies with prospects in wastewater treatment, agriculture or energy sectors.

Fast, Regioselective Aminolysis of Tetrasubstituted Cyclic Carbonates and Application to Recyclable Thermoplastics and Thermosets.

Herein, the long-standing challenge of the ring-opening aminolysis of CO2-derived tetrasubstituted cyclic carbonates at room temperature (r.T) is overcome under catalyst-free conditions. Molecular design of the cyclic carbonate by substitution of an alkyl group by a thioether unlocks quantitative conversion at r.T and ensures total regioselectivity toward highly substituted oxazolidone scaffolds. An in-depth rationalization of the high reactivity of these cyclic carbonate structures and of the aminolysis reaction mechanism is provided by a computational study supporting experimental observations. The high efficiency of the reaction is then translated to the deconstruction of high-performance thermoplastics containing tetrasubstituted cyclic carbonate linkages to deliver building blocks that are reused for designing recyclable thermosets bearing dynamic N,S-acetal linkages.

Remdesivir triphosphate is a valid substrate to initiate synthesis of DNA primers by human PrimPol

Remdesivir is a broad-spectrum antiviral drug which has been approved to treat COVID-19. Remdesivir is in fact a prodrug, which is metabolized in vivo into the active form remdesivir triphosphate (RTP), an analogue of adenosine triphosphate (ATP) with a cyano group substitution in the carbon 1’ of the ribose (1’-CN). RTP is a substrate for RNA synthesis and can be easily incorporated by viral RNA-dependent RNA polymerases (RdRp). Importantly, once remdesivir is incorporated (now monophosphate), it will act as a delayed chain terminator, thus blocking viral RNA synthesis. It has been reported that mitochondrial Polγ is also blocked in vitro by RTP, but the low impact in vivo on mitochondrial DNA replication stalling is likely due to repriming by the human DNA-directed DNA Primase/Polymerase (HsPrimPol), which also operates in mitochondria. In this work, we have tested if RTP is a valid substrate for both DNA primase and DNA polymerase activities of HsPrimPol, and its impact in the production of mature DNA primers. RTP resulted to be an invalid substrate for elongation, but it can be used to initiate primers at the 5´site, competing with ATP. Nevertheless, RTP-initiated primers are abortive, ocassionally reaching a maximal length of 4–5 nucleotides, and do not support elongation mediated by primer/template distortions. However, considering that the concentration of ATP, the natural substrate, is much higher than the intracellular concentration of RTP, it is unlikely that HsPrimPol would use RTP for primer synthesis during a remdesivir treatment in real patients.

Developing Allosteric Inhibitors of SARS-CoV-2 RNA-Dependent RNA Polymerase.

The use of Fpocket and virtual screening techniques enabled us to identify potential allosteric druggable pockets within the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Of the compounds screened, compound 1 was identified as a promising inhibitor, lowering a SARS-CoV-2 RdRp activity to 57 % in an enzymatic assay at 10 μM concentration. The structure of compound 1 was subsequently optimized in order to preserve or enhance inhibitory activity. This involved the substitution of problematic ester and aromatic nitro groups with more inert functionalities. The N,N'-diphenylurea scaffold with two NH groups was identified as essential for the compound's activity but also exhibited high toxicity in Calu-3 cells. To address this issue, a scaffold hopping approach was employed to replace the urea core with potentially less toxic urea isosteres. This approach yielded several structural analogues with notable activity, specifically 2,2'-bisimidazol (in compound 55 with residual activity RA=42 %) and (1H-imidazol-2-yl)urea (in compounds 59 and 60, with RA=50 and 28 %, respectively). Despite these advances, toxicity remained a major concern. These compounds represent a promising starting point for further structure-activity relationship studies of allosteric inhibitors of SARS-CoV-2 RdRp, with the goal of reducing their cytotoxicity and improving aqueous solubility.