Theoretical insights into a turn-on fluorescence probe based on naphthalimide for peroxynitrite detection.

Compared with other reactive oxygen species, peroxynitrite (ONOO-) has diversified reactions and transformations in organisms, and its specific action mechanism is not very clear. The study of reactive oxygen species is of great significance in the field of physiology and pathology. Recently an effective on/off fluorescent probe HCA-OH was designed by Liu et al. through tethering p-aminophenol to 1,8-naphthalimide directly. The probe HCA-OH could release the fluorophore HCA-NH2 with good photostability and high fluorescence quantum yield under oxidation of ONOO- via dearylation process. In this work, the sensing mechanism and spectrum character of probe HCA-OH were studied in detail under quantum chemistry calculation. The electronic structures, reaction sites and fluorescent properties of the probe were theoretically analyzed to benefit us for in-depth understanding the principle of detection on reactive oxygen species (ONOO-) with the fluorescent probe HCA-OH. These theoretical results could inspire the medical research community to design and synthesize highly efficient fluorescent probe for reactive oxygen species detection.

Molecular Docking of Chiral Drug Enantiomers With Different Bioactivities.

Chirality has an important role in the drug design because enantiomers may exhibit different bioactivity when interacting with macromolecules of a living organism. In our previous work, based on the analysis of a set of 100 chiral drugs, a relationship was established between the sign of chirality of enantiomers and their bioactivity. To understand the reasons for the observed patterns of chiral specificity of drug enantiomers, the interaction of 10 enantiomeric pairs of chiral drugs with the corresponding target proteins has been considered using molecular docking and further postprocessing by quantum chemistry methods. The data obtained confirm that the energetic aspect of the interaction between opposite enantiomers and target protein affects the enantiomer biological activity. In addition, the results show that molecular docking is able to distinguish between bioactive and inactive/less active enantiomers, although many docking programs are not accurate enough to distinguish a weak inhibitor from a strong one.

Molecular insights into dicationic versus monocationic ionic liquids as a high hydrophobic alternative for the separation of phenol from waters.

The hydrophobic nature of an extractant is particularly critical in the treatment of wastewater. Considering that dicationic ionic liquids (DILs) are likely to be more hydrophobic, a comparative study of the separation of phenol from waters using [NTf2]- based monocationic ionic liquids (MILs) and DILs is carried out both from experimental and theoretical analysis perspectives. Experimental results revealed that DILs exhibited superior extraction ability compared to MILs, with extraction efficiencies of 93.7% and 97.4% using [BMIM][NTf2] and [C6(MIM)2][NTf2]2 as extractants, respectively. The microscopic examination through theoretical calculations elucidated the higher hydrophobicity and extraction efficiency of DILs over MILs. The results indicated that the DIL showed stronger hydrophobicity than the MIL because the hydrogen bond strength between the DIL and water was lower than that of the MIL. Although the hydrogen bond strength between the DIL and phenol was lower than that of the MIL, the stronger van der Waals forces existed between DIL and phenol, so DIL was more efficient in extracting phenol. In addition, the experimental parameters were optimized to provide basic data for application, such as mass ratio of ILs to water, extraction time and temperature, pH, and initial phenol content. Finally, the DILs were recovered using rotary evaporation apparatus, and the results demonstrated that DILs had good recovery and reuse performance. In brief, this work could provide an effective method for the treatment of phenol-containing wastewater. And the revelation of molecular mechanism is expected to positively impact the design of high-performance task-specific ILs.

Ochrolines A-C, three new indole diketopiperazines from cultures of endophytic fungi Bionectria ochroleuca SLJB-2.

Three new indole diketopiperazines, ochrolines A-C (1-3), along with three known compounds (4-6), were isolated and identified from the EtOAc extract of the solid fermentation of Bionectria ochroleuca SLJB-2. Notably, compound 1 featured a natural rarely-occurring caged skeleton with a 6/5/6/7 heterotetracyclic bridged ring system. The structures including absolute configurations of 1-3 were fully accomplished by extensive spectroscopic analyses, DFT GIAO 13C NMR and electronic circular dichroism (ECD) calculations. The plausible biogenetic pathways of these new indole diketopiperazines were also proposed. Moreover, the cytotoxic activity screening revealed that compound 2 exhibited moderate inhibitory effect against A549 with inhibition rate of 57.44% at the concentration of 50 µM and compound 1 exhibited mild inhibitory activities against A549, Hela and MCF-7.

Recycling Compatible Organic Electrode Materials Containing Amide Bonds for Use in Rechargeable Batteries.

Organic rechargeable batteries that do not use any scarce heavy metals are candidates for the next generation of rechargeable batteries; although, it is not easy to realize both high capacity and long cycle life. Organic compounds linked by amide bonds are expected to have superior recycling properties after battery degradation, since they will become a single monomer upon hydrolysis. In this study, anthraquinone was chosen as a model redox active unit, and dimeric and trimeric compounds were synthesized, their cycle performances as electrode materials for use in rechargeable batteries were compared, and a trend in which oligomerization improves cycle properties was confirmed. Furthermore, quantum chemistry calculations suggest that oligomerization decreases solubility, which would support a longer life for oligomerized compounds. This methodology will lead to the development of organic rechargeable batteries with further environmental benefits.

Photolysis and photo-enhanced toxicity of three novel designed neonicotinoids: Impact of novel modifying groups.

Three novel neonicotinoids (cycloxaprid, flupyradifurone and sulfoxaflor) were designed to reduce the biotoxicity for non-target organisms. These neonicotinoids were photolyzed under light radiation, but it was unclear for the photo-enhanced toxicity and influences of the novel modifying group of the three neonicotinoids. The photolysis and photo-enhanced toxicity experiments were performed for the three neonicotinoids, coupled with quantum chemistry calculation, the mechanisms of photolysis, photo-enhanced toxicity and the influences of novel modifying groups were analyzed. The results showed the photolysis pathways were enriched as compared with previous neonicotinoids due to the composition of modifying groups, singlet oxygen and hydroxyl participated the photolysis of cycloxaprid and flupyradifurone. All tested neonicotinoids exhibited photo-enhanced toxicity to Vibrio fischeri. Due to the difference of photolysis mechanism and toxicity to V. fischeri, the photo-enhanced toxicity curves showed diverse variation when histidine, tert-butanol or dissolved organic matters was in presence of the test solutions. The impact of novel modifying groups over photolysis and photo-enhanced toxicity were analyzed based on the comparison with previous neonicotinoids, theoretically predicted UV-Vis spectra and photo-physical/chemical property descriptors. The data showed the composition of novel modifying group increased the light absorption and photo-chemical activities for the three neonicotinoids.

Novel Cytotoxic Sesquiterpene Ester Derivatives from the Roots of Ferula mervynii.

This study is the first chemical investigation of Ferula mervynii M. Sagiroglu & H. Duman, an endemic species to Eastern Anatolia. The isolations of nine compounds including six previously undescribed sesquiterpene esters, 8-trans-cinnamoyltovarol (1), 8-trans-cinnamoylantakyatriol (3), 6-acetyl-8-trans-cinnamoyl-3-epi-antakyatriol (5), 6-acetyl-8-trans-cinnamoylshiromodiol (6), 6-acetyl-8-trans-cinnamoylfermedurone (7), and 6-acetyl-8-trans-cinnamoyl-(1S),2-epoxyfermedurone (8), were described along with three known sesquiterpene esters, 6-acetyl-8-benzoyltovarol (2), 6-acetyl-8-trans-cinnamoylantakyatriol (4), and ferutinin (9). The structures of novel compounds were elucidated through extensive spectroscopic analyses and quantum chemistry calculations. The putative biosynthetic pathways for compounds 7 and 8 were discussed. The extracts and isolated compounds were tested for cytotoxic activity against the COLO 205, K-562, MCF-7 cancer cell lines, and Human Umbilical Vein Endothelial Cell (HUVEC) lines using MTT assay. Compound 4 showed the highest activity against the MCF-7 cell lines with an IC50 value of 16.74±0.21 µM.

Interstellar Benzene Formation Mechanisms via Acetylene Cyclotrimerization Catalyzed by Fe+ Attached to Water Ice Clusters: Quantum Chemistry Calculation Study.

Benzene is the simplest building block of polycyclic aromatic hydrocarbons and has previously been found in the interstellar medium. Several barrierless reaction mechanisms for interstellar benzene formation that may operate under low-temperature and low-pressure conditions in the gas phase have been proposed. In this work, we studied different mechanisms for interstellar benzene formation based on acetylene cyclotrimerization catalyzed by Fe+ bound to solid water clusters through quantum chemistry calculations. We found that benzene is formed via a single-step process with one transition state from the three acetylene molecules on the Fe+(H2O)n (n = 1, 8, 10, 12 and 18) cluster surface. Moreover, the obtained mechanisms differed from those of single-atom catalysis, in which benzene is sequentially formed via multiple steps.

Stabilizing Halogen-Bonded Complex between Metallic Anion and Iodide.

Halogen bonds (XBs) between metal anions and halides have seldom been reported because metal anions are reactive for XB donors. The pyramidal-shaped Mn(CO)5- anion is a candidate metallic XB acceptor with a ligand-protected metal core that maintains the negative charge and an open site to accept XB donors. Herein, Mn(CO)5- is prepared by electrospray ionization, and its reaction with CH3I in gas phase is studied using mass spectrometry and density functional theory (DFT) calculation. The product observed experimentally at m/z = 337 is assigned as [IMn(CO)4(OCCH3)]-, which is formed by successive nucleophilic substitution and reductive elimination, instead of the halogen-bonded complex (XC) CH3-I···Mn(CO)5-, because the I···Mn interaction is weak within XC and it could be a transient species. Inspiringly, DFT calculations predict that replacing CH3I with CF3I can strengthen the halogen bonding within the XC due to the electro-withdrawing ability of F. More importantly, in so doing, the nucleophilic substitution barrier can be raised significantly, ~30 kcal/mol, thus leaving the system trapping within the XC region. In brief, the combination of a passivating metal core and the introduction of an electro-withdrawing group to the halide can enable strong halogen bonding between metallic anion and iodide.

Virtual Screening and Quantum Chemistry Analysis for SARS-CoV-2 RNA-Dependent RNA Polymerase Using the ChEMBL Database: Reproduction of the Remdesivir-RTP and Favipiravir-RTP Binding Modes Obtained from Cryo-EM Experiments with High Binding Affinity.

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as the pathogenic cause of coronavirus disease 2019 (COVID-19). The RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 is a potential target for the treatment of COVID-19. An RdRp complex:dsRNA structure suitable for docking simulations was prepared using a cryo-electron microscopy (cryo-EM) structure (PDB ID: 7AAP; resolution, 2.60 Å) that was reported recently. Structural refinement was performed using energy calculations. Structure-based virtual screening was performed using the ChEMBL database. Through 1,838,257 screenings, 249 drugs (37 approved, 93 clinical, and 119 preclinical drugs) were predicted to exhibit a high binding affinity for the RdRp complex:dsRNA. Nine nucleoside triphosphate analogs with anti-viral activity were included among these hit drugs, and among them, remdesivir-ribonucleoside triphosphate and favipiravir-ribonucleoside triphosphate adopted a similar docking mode as that observed in the cryo-EM structure. Additional docking simulations for the predicted compounds with high binding affinity for the RdRp complex:dsRNA suggested that 184 bioactive compounds could be anti-SARS-CoV-2 drug candidates. The hit bioactive compounds mainly consisted of a typical noncovalent major groove binder for dsRNA. Three-layer ONIOM (MP2/6-31G:AM1:AMBER) geometry optimization calculations and frequency analyses (MP2/6-31G:AMBER) were performed to estimate the binding free energy of a representative bioactive compound obtained from the docking simulation, and the fragment molecular orbital calculation at the MP2/6-31G level of theory was subsequently performed for analyzing the detailed interactions. The procedure used in this study represents a possible strategy for discovering anti-SARS-CoV-2 drugs from drug libraries that could significantly shorten the clinical development period for drug repositioning.

Self-polishing antifouling coatings based on benzamide derivatives containing capsaicin.

In this study, N-hydroxymethylbenzamide was alkylated with various aromatic compounds to obtain five novel benzamide derivatives containing capsaicin (BDCC), and the BDCC were incorporated into coatings as auxiliary agents. The relationships between properties and structures were discussed based on experimental and theoretical results. The theoretical results showed the optimized configurations of BDCC and confirmed that the benzene ring, phenolic hydroxyl, ester and amide groups were active sites. Experimental results indicated that the antimicrobial and antifouling effects of compounds b1, b2 and b3 were better than those of chlorothalonil, their MIC and MBC values were no more than 64 and 512 µg·mL-1, and their test panels were covered only with small amounts of dirt and biofilms; they worked well as green antifouling additives. The experimental and theoretical results showed that BDCC and BDCC antifouling coatings were effective and eco-friendly.

Dual aggregation in ground state and ground-excited state induced by high concentrations contributes to chlorophyll stability.

Chlorophyll (Chl) has great application potential in food colouring and nutritional supplementation. Since Chl is easily degraded, stability protection is vital to its application. Herein, a dual aggregation mechanism induced by high concentrations to improve Chl stability was proposed. As a result, the Chl retention at high concentrations increased to 323.92% of that at low concentrations. To explain aggregation, the Chl dimer was observed by atomic force microscopy, and a stable structural model of the Chl a "sandwich" dimer was established. It was proven that Chl dimer stability was dominated by van der Waals (vdW) interactions, while monomer orientation during aggregation was dominated by electrostatic interactions. Charge transfer (CT) was also shown to be a key interaction in the dimer. Excitation at 393 nm was first proposed for CT identification. This research hopes to provide new ideas for the design of food ingredients in human health promotion.

Comparative analysis on the photolysis kinetics of four neonicotinoid pesticides and their photo-induced toxicity to Vibrio Fischeri: Pathway and toxic mechanism.

Neonicotinoids are widely used pesticides all over the world and pose severe water pollution. Although they can be degraded via absorbing sunlight, few attentions have been paid to the environmental risks of their photolysis products. In this paper, the photo-toxicity was investigated for four neonicotinoids (dinotefuran, nitenpyram, thiamethoxam and clothianidin) based on a series of experiments (i.e., photolysis kinetics, radical scavenging, bioluminescent inhibition test to Vibrio Fischeri and intermediate identification) and in-silico calculation of photolysis pathway. The results show that direct photolysis dominates the photolysis of the four neonicotinoids under simulated sunlight radiation. The bioluminescent inhibition kinetics shows that all four neonicotinoids have photo-induced toxicity to V. fischeri, but with different light-induced responses. Scavenging radicals (·OH and 1O2) will decrease the photo-induced toxicity of all the four neonicotinoids, indicating radicals play important roles to the photo-chemical reactions of intermediates. Dissolved organic matters exhibit slightly shading effect to the photolysis rates of four parent compounds. However, the ROSs generated by DOM can accelerate the photo-chemical reactions of intermediates, leading to different photo-induced toxicity in present of DOM. According to the detected intermediates and Gaussian calculations, there are different photolysis pathways and mechanisms for the four neonicotinoids. The calculation for photo-sensitization reactions with 3O2 indicates that both energy transfer reactions and electron transfer reactions can be produced under simulated sunlight radiation, which further consolidate that reactive oxygen species are involved in the photolysis process. A theoretical model has been developed to explain the toxicity variations of four neonicotinoids in different aqueous conditions.

Insight into the defluorination ability of per- and polyfluoroalkyl substances based on machine learning and quantum chemical computations.

UV-generated hydrated electrons play a critical role in the defluorination reaction of poly- and perfluoroalkyl substances (PFAS). However, limited experimental data hinder insight into the effects of the structural characteristics of emerging PFAS on their defluorination abilities. Therefore, in this study, we adopted quantity structure-activity relationship models based on machine learning algorithms to develop the predictive models of the relative defluorination ability of PFAS. Five-fold cross-validations were used to perform the hyperparameter tuning of the models, which suggested that the gradient boosting algorithms with PaDEL descriptors as the best model possessed superior predictive performance (R2test = 0.944 and RMSEtest = 0.114). The importance of the descriptor indicated that the electrostatic properties and topological structure of the compounds significantly affected the defluorination ability of the PFAS. For the emerging PFAS the best model showed that most compounds, such as potential alternatives of perfluorooctane sulfonic acid, were recalcitrant to reductive defluorination, whereas perfluoroalkyl ether carboxylic acids had relatively stronger defluorination abilities than perfluorooctanoic acid. The theoretical calculations implied that additional electrons on PFAS could cause molecular deconstruction, such as changes in the dihedral angle involved in the carbon chain, as well as C-F bond and ether C-O bond cleavages. In general, the current computational models could be useful for screening emerging PFAS to assess their defluorination ability for the molecular design of fluorochemical structures.

The determination of antibacterial mode for cationic lipopeptides brevibacillins against Salmonella typhimurium by quantum chemistry calculation.

Brevibacillins are broad-spectrum cationic antimicrobial lipopeptides produced by Brevibacillus laterosporus fmb70 CGMCC 18426. The antibacterial mode of brevibacillins against Salmonella typhimurium CICC 21493 was investigated by quantum chemistry calculation in this study. The addition of LPS, Mg2+, and Ca2+ partially reduced the antimicrobial activity of brevibacillin and brevibacillin V against S. typhimurium, which indicated that the two cationic lipopeptides could bind to LPS and displaced the divalent cations on the LPS network. Release of LPS from S. typhimurium by brevibacillin and brevibacillin V resulted in destroying the dense LPS network and increasing the permeability of the outer membrane. Quantum chemistry calculation analysis revealed that Lys7 is the most critical amino acid residue to destroy the outer membrane. The total average N-H charge difference of the three protonated amino groups (Orn3-NH3, Lys7-NH3, and Lys10-NH3) determined the ability of brevibacillin V to bind LPS stronger than brevibacillin. Calcein complete leakage from liposomes and release of DiSC3-5 from the cytoplasmic membrane (CM) indicated that brevibacillin and brevibacillin V may destroy the CM. Brevibacillin and brevibacillin V exhibited their antimicrobial activities through membrane damages, where the OM permeability with high concentration of 64-256 µg/mL and membrane damage of CM with a low concentration of 4 µg/mL. Our finding might be helpful to understand the broad-spectrum antimicrobial mechanism of cationic lipopeptide and to design the novel antimicrobial peptide. KEY POINTS: • Brevibacillin V had stronger affinity for LPS than brevibacillin. • The N-H charge difference was the key of the difference in the affinity to LPS. • Brevibacillins inhibited Salmonella by displacing the divalent cations on the LPS.

Interpretation of the differential UV-visible absorbance spectra of metal-NOM complexes based on the quantum chemical simulations for the model compound esculetin.

In this study, the model compound esculetin that has functional groups typical for natural organic matter (NOM) was used to ascertain the nature of the characteristic bands in the differential UV-visible absorbance spectra (DAS) associated with the formation of metal-NOM complexes. The binding of ten different metal ions (Cu(II), Ni(II), Co(II), Fe(III), Cr(III), Al(III), Zn(II), Ca(II), Mg(II) and Pb(II)) with esculetin generate four bands in the DAS. These bands are similar to those present in the DAS of metal-NOM complexes. The UV-visible absorbance spectra of the metal-esculetin systems were calculated using time-dependent density functional theory (TD-DFT). The TD-DFT results demonstrate that the prominent features of the DAS of esculetin are primarily associated with the electron transitions between the molecular orbitals near the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) in the metal-esculetin complex. Charge decomposition analysis (CDA) results demonstrated that these electron transitions originate from the esculetin fragment to the Zn(II) fragment in the complex. Covalent indexes [(χm)2rc] of the metal ions were found to be correlated with the metal-specific features of the DAS of metal-esculetin systems. The strength of the linear correlations between the quantitative parameters of the electron density of the bond critical points (BCP) is indicative of the strength of the metal-esculetin interactions.

Computational study of the substituent effect of halogenated fused-ring heteroaromatics on halogen bonding.

Halogen bonding (XB) has been applied in many fields from crystal engineering to medicinal chemistry. Compared with the well-studied XB of simple halogenated aromatics, little research has been done on the XB of halogenated fused-ring heteroaromatics, a prevalent substructure in organic compounds. With 1H-pyrrolo[3,2-b]pyridines (PPs) as examples of novel fused-ring heteroaromatics with hydrogen bond donor and acceptor and XB donor, the XB formed by the halogenated heteroaromatics was explored in this study. With 4 different substituents, viz., -CH3, -NH2, -F, and -CONH2, at different positions, 339 derivatives of brominated PP (Br-PP) were designed for calculating their electrostatic potential of the σ-hole of the halogen atom (VS,max) and binding energy with ammonia as XB acceptor (Eint) at M06-2X/6-311++G(d,p) level by PCM model in dichloromethane. The calculated VS,max values ranging from -1.3 to 35.1 kcal/mol and the calculated Eint ranging from -0.82 to -2.37 kcal/mol demonstrated that the XB is complicated and highly tunable. Noticeably, the electron-withdrawing substituents, especially at ortho-position, do not always increase the values of VS,max, while the electron-donating substituents do not always decrease VS,max. Similar results were observed from the calculation on 339 iodinated PPs at M06-2X/6-311++G(d,p) level. The complexity of the XB formed by the halogenated fused ring heteroaromatics indicated a great potential of tuning its strength by different substituents at different positions and revealed a necessity of quantum chemistry calculation for predicting the XB.Graphical abstract.

Tetra-proline modified calix[4]arene bonded silica gel: A novel stationary phase for hydrophilic interaction liquid chromatography.

Calixarenes and their derivatives have been widely used in chromatographic studies due to unique host-guest recognition properties. However, stationary phases in hydrophilic interaction chromatography associated with them have yet to be studied because of their general hydrophobicity. In this paper, a tetra-proline modified calix[4]arene bonded stationary phase (DTPCSP) was prepared and characterized by FT-IR spectra, elemental analysis, solid state 13C NMR, SEM, EDS and thermogravimetric analysis. The chromatographic performance and retention mechanism of the developed stationary phase were validated in hydrophilic interaction mode and compared with a commercial column using a variety of hydrophilic or hydrophobic compounds including phenols, nucleosides and sulfonamides. The developed stationary phase exhibited better selectivity than conventional calixarene phases, and the retention behaviors of phenols on DTPCSP column were elucidated by the calculation of quantum chemistry using ODS as contrast. All the results indicate that the developed DTPCSP stationary phase can be beneficial for simultaneously separating complex hydrophilic samples with high selectivity.

Experimental and Theoretical Studies on the Adsorption Mechanisms of Uranium (VI) Ions on Chitosan.

An experiment on the adsorption of uranium (VI) by chitosan was conducted to investigate the efficiency of chitosan as an adsorbent for U(VI). The adsorption potential of U(VI) by chitosan was investigated with ICP-MS by varying the experimental conditions such as the pH in order to obtain the optimum conditions. Adsorption dependence on the pH was confirmed, and the highest uptake of U(VI) was observed at pH 5. In addition, to scrutinize the experimental results, quantum chemistry calculations were performed. The results, taking into account the experimental conditions, show that the adsorption efficiency increases as the total charge of the adsorbent and adsorbate species decreases if both of them are positively charged. It was also found that a slight change in the adsorption geometric configuration controls the adsorption efficiency.

Experimental and Theoretical Studies on the Adsorption and Desorption Mechanisms of Chromate Ions on Cross-Linked Chitosan.

In this work, chitosan bead materials were modified by cross-linking with epichlorohydrin (EP) and glutaraldehyde (GA) for the removal of heavy metals in wastewater. Using these cross-linked chitosan materials, the dependence of adsorption of chromate anions on pH was investigated experimentally and theoretically. The experimental results show that the adsorption process of the chromate (Cr) ions greatly depends on the pH of the solution, with the chitosan modified by cross-linking being an efficient adsorbent for chromate. On the other hand, quantum chemistry calculations were conducted to find out the factor determining the pH dependence of the adsorption efficiency of chromate ions on the dimer chitosan molecule, and show results similar to those found in the experiment. Both the experimental and numerical results show that the total charge numbers of the adsorbent and the adsorbate species and their relative molecular geometries are crucial in determining the adsorption efficiency.