Hypervalent Iodine-Catalyzed Fluorination of Diene-Containing Compounds: A Computational Study.

Studies have shown that the incorporation of fluorine into materials can improve their properties, but C-F bonds are not readily formed in nature. Although some researchers have studied the reaction of fluorinating alkenes catalyzed by hypervalent iodine, far too little attention has been paid to its reaction mechanism. This study aimed to explore the mechanism of the hypervalent iodine-catalyzed 1,4-difluorination of dienes. We found that the catalyst is favorable for the activation of C1=C2 double bonds through halogen bonds, and then two HFs interact with one F atom in the catalyst via hydrogen bonds, resulting in the cleavage of I-F bonds and the formation of [F-H∙∙∙F]-. Subsequently, the catalyst interacts with C1, and the roaming [F-H···F]- attacks C4 from the opposite side of the catalyst. After the fluorination step is completed, the nucleophile F- substitutes the catalyst via the SN2 mechanism. Our calculations demonstrated that the interaction between HF and F- is favorable for the stabilization of the transition state within the fluorination process for which the presence of two HFs in the reaction is the best. We also observed that [F-H∙∙∙F]- attacking C4 from the opposite side of the catalyst is more advantageous than attacking from the same side. This study therefore offers a novel perspective on the mechanism of the hypervalent iodine-catalyzed fluoridation of dienes.

Tuning of the Electrostatic Potentials on the Surface of the Sulfur Atom in Organic Molecules: Theoretical Design and Experimental Assessment.

Noncovalent sulfur interactions are ubiquitous and play important roles in medicinal chemistry and organic optoelectronic materials. Quantum chemical calculations predicted that the electrostatic potentials on the surface of the sulfur atom in organic molecules could be tuned through the through-space effects of suitable substituents. This makes it possible to design different types of noncovalent sulfur interactions. The theoretical design was further confirmed by X-ray crystallographic experiments. The sulfur atom acts as the halogen atom acceptor to form the halogen bond in the cocrystal between 2,5-bis(2-pyridyl)-1,3,4-thiadiazole and 1,4-diiodotetrafluorobenzene, whereas it acts as the chalcogen atom donor to form the chalcogen bond in the cocrystal between 2,5-bis(3-pyridyl)-1,3,4-thiadiazole and 1,3,5-trifluoro-2,4,6-triiodobenzene.

ESIPT fluorophores derived from 2,3-dichloro-5,6-dicyano-p-benzoquinone based carbon dots for dual emission and multiple anti-counterfeiting.

Fluorophores and hydrogen bonding interactions play key roles in the fluorescence properties of bottom-up carbon dots. In this work, an excited-state intramolecular proton-transfer (ESIPT) active fluorophore, 5-chloro-6-ethoxy-4,7-dihydroxyisoindoline-1,3-dione (CEDD) and a non-ESIPT 7-cyano-5,8-dihydroxyquinoxaline-6-carboxamide (CDQC) are extracted from 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) based carbon dots. The enol form of CEDD shows a weak blue, small Stokes shift and short lifetime emission under the aprotic or alkali conditions, but the keto form exhibits a strong green, large Stokes shift and long lifetime emission in a protic or an acidic environment. Due to the lack of the ESIPT process, CDQC has no dual emission characteristics, but shows efficient solid-state emission. By virtue of the ESIPT ability of CEDD, multiple anti-counterfeiting methods are achieved by using hydrogen chloride, ammonia, and fluorescence lifetime imaging, as well as dimethyl sulfoxide as the encryption/decryption tools.

Effects of Electronic Structure of Adjacent Carbon on the Strength of C─F⋯H─F Organofluorine Hydrogen Bonds.

We investigate the effects of the electronic structure of carbon atom on the organofluorine hydrogen bonds, C─F⋯H─F. Our results show that we can modulate the strength of organofluorine hydrogen bonds by adjusting the volume of fluorine atom in C─F via changing the electronic structure of adjacent carbon atoms. Different with the conventional hydrogen bonds, we found that instead of carbon rehybridization and hyperconjugative effects, the magnitude of fluorine atomic volume plays important roles in determining the strength of the C─F⋯H─F organofluorine hydrogen bonds. The lone pair electrons at both the proximal and the vicinal carbon dramatically reinforce the strength of C─F⋯H─F organofluorine hydrogen bond with its interaction energy in the range of about 15-25 kcal/mol, that is, the carbanion-mediated organofluorine hydrogen bond could be very strong. Due to the high electronegativity of fluorine atom, it easily attracts the excess electron from the proximal and vicinal carbon, which results in the increase of its volume and negative charge. The enhanced volume of fluorine atom gives rise to the large polarization energy, and its enhanced negative charge favors the large electrostatic interaction, both of which substantially contribute to making the organofluorine hydrogen bonds strong. © 2019 Wiley Periodicals, Inc.

Tetrel Bond between 6-OTX3-Fulvene and NH3: Substituents and Aromaticity.

Carbon bonding is a weak interaction, particularly when a neutral molecule acts as an electron donor. Thus, there is an interesting question of how to enhance carbon bonding. In this paper, we found that the ⁻OCH3 group at the exocyclic carbon of fulvene can form a moderate carbon bond with NH3 with an interaction energy of about -10 kJ/mol. The ⁻OSiH3 group engages in a stronger tetrel bond than does the ⁻OGeH3 group, while a reverse result is found for both ⁻OSiF3 and ⁻OGeF3 groups. The abnormal order in the former is mainly due to the stronger orbital interaction in the ⁻OSiH3 complex, which has a larger deformation energy. The cyano groups adjoined to the fulvene ring not only cause a change in the interaction type, from vdW interactions in the unsubstituted system of ⁻OCF3 to carbon bonding, but also greatly strengthen tetrel bonding. The formation of tetrel bonding has an enhancing effect on the aromaticity of the fulvene ring.

Insight into the multiple quasi-molecular states in ethylenediamine reduced graphene nanodots.

Recently, graphene nanodots (GNDs) have been frequently considered as inherently heterogeneous systems, leading to multicolor emission under a changeable excitation wavelength. However, an accurate picture of the GNDs and an exhaustive structure-property correlation are still lacking. Using a two dimensional photoluminescence excitation (2D-PLE) map, molecular orbital calculation, reduction level dependent PL analysis, absorption spectroscopy and time-resolved PL spectroscopy, three cases of quasi-molecular PL are determined in ethylenediamine (EDA) reduced GNDs, including the C[double bond, length as m-dash]O related electronic state, graphenol related electronic state and large π-conjugated domains. The graphenol structure is expected to be created via nucleophilic addition-elimination reactions between epoxide groups and EDA, contributing most to the blue-shifted and enhanced PL of GNDs. The multiple quasi-molecular PL provides deeper insights into the commonly called "excitation wavelength dependent PL". An effort is made to utilize the heterogeneous photoluminescence through phosphor-based light-emitting diodes employing reduced GNDs as a phosphor, which are capable of converting blue light into white light.

Experimental and computational studies on molecularly imprinted solid-phase extraction for gonyautoxins 2,3 from dinoflagellate Alexandrium minutum.

An innovative and effective extraction procedure based on molecularly imprinted solid-phase extraction (MISPE) was developed for the isolation of gonyautoxins 2,3 (GTX2,3) from Alexandrium minutum sample. Molecularly imprinted polymer microspheres were prepared by suspension polymerization and and were employed as sorbents for the solid-phase extraction of GTX2,3. An off-line MISPE protocol was optimized. Subsequently, the extract samples from A. minutum were analyzed. The results showed that the interference matrices in the extract were obviously cleaned up by MISPE procedures. This outcome enabled the direct extraction of GTX2,3 in A. minutum samples with extraction efficiency as high as 83 %, rather significantly, without any need for a cleanup step prior to the extraction. Furthermore, computational approach also provided direct evidences of the high selective isolation of GTX2,3 from the microalgal extracts.

Tetrel bond of pseudohalide anions with XH3F (X = C, Si, Ge, and Sn) and its role in SN2 reaction.

The complexes of XH3F⋯N3-/OCN-/SCN- (X = C, Si, Ge, and Sn) have been investigated at the MP2/aug-cc-pVTZ(PP) level. The σ-hole of X atom in XH3F acts as a Lewis acid forming a tetrel bond with pseudohalide anions. Interaction energies of these complexes vary from -8 to -50 kcal/mol, mainly depending on the nature of X and pseudohalide anions. Charge transfer from N/O/S lone pair to X-F and X-H σ* orbitals results in the stabilization of these complexes, and the former orbital interaction is responsible for the large elongation of X-F bond length and the remarkable red shift of its stretch vibration. The tetrel bond in the complexes of XH3F (X = Si, Ge, and Sn) exhibits a significant degree of covalency with XH3F distorted significantly in these complexes. A breakdown of the individual forces involved attributes the stability of the interaction to mainly electrostatic energy, with a relatively large contribution from polarization. The transition state structures that connect the two minima for CH3Br⋯N3- complex have been localized and characterized. The energetic, geometrical, and topological parameters of the complexes were analyzed in the different stages of the SN2 reaction N3- + CH3Br → Br- + CH3N3.

Origin of selenium-gold interaction in F2CSe⋯AuY (Y = CN, F, Cl, Br, OH, and CH3): Synergistic effects.

Selenium-gold interaction plays an important role in crystal materials, molecular self-assembly, and pharmacochemistry involving gold. In this paper, we unveiled the mechanism and nature of selenium-gold interaction by studying complexes F2CSe⋯AuY (Y = CN, F, Cl, Br, OH, and CH3). The results showed that the formation of selenium-gold interaction is mainly attributed to the charge transfer from the lone pair of Se atom to the Au-Y anti-bonding orbital. Energy decomposition analysis indicated that the polarization energy is nearly equivalent to or exceeds the electrostatic term in the selenium-gold interaction. Interestingly, the chalcogen-gold interaction becomes stronger with the increase of chalcogen atomic mass in F2CX⋯AuCN (X = O, S, Se, and Te). The cyclic ternary complexes are formed with the introduction of NH3 into F2CSe⋯AuY, in which selenium-gold interaction is weakened and selenium-nitrogen interaction is strengthened due to the synergistic effects.

Bioaccessibility and Health Risk Assessment of Cu, Cd, and Zn in "Colored" Oysters.

Bioaccessibility describes the fraction of contaminants released from the food matrix into the digestive tracts of humans, which is beneficial for improving the health risk assessment of contaminants. In this study, the bioaccessibilities of cadmium (Cd), copper (Cu), and zinc (Zn) in two severely contaminated green oyster (Crassostrea angulate) and blue oyster (Crassostrea hongkongensis) populations were investigated. A human health risk assessment of these metals was then performed based on bioaccessibility measurements. Among the three metals, the bioaccessibility was the highest for Cu (42-95%), and Cd and Zn had comparable bioaccessibility (13-58%). There was no major difference in the bioaccessibility between green and blue oysters. A significant correlation between the tissue Cu and Zn concentrations was found in these highly contaminated oysters. A health risk assessment showed that all three metals in both oyster species seriously exceeded the levels recommended by the United States Environmental Protection Agency. Thus, oysters from these locations, and the metals contained therein, presented quite high risks for human consumption, which should be a great cause of concern. A significant relationship was only found between metal bioaccessibility and its tissue concentration instead of between metal bioaccessibility and subcellular distribution. In addition, a significant relationship was only observed between metal health risks and its tissue concentration. The influence of metal bioaccessibilities on the health risks was limited. This may suggest that in the case of the colored oysters examined in this study, metal concentration instead of metal subcellular distribution could be the driving factor of the metal bioaccessibility, and metal concentration, instead of metal bioaccessibility, could be the driving factor of the metal health risks.

The Effects of Molecular Properties on Ready Biodegradation of Aromatic Compounds in the OECD 301B CO2 Evolution Test.

Ready biodegradation is the primary biodegradability of a compound, which is used for discriminating whether a compound could be rapidly and readily biodegraded in the natural ecosystems in a short period and has been applied extensively in the environmental risk assessment of many chemicals. In this study, the effects of 24 molecular properties (including 2 physicochemical parameters, 10 geometrical parameters, 6 topological parameters, and 6 electronic parameters) on the ready biodegradation of 24 kinds of synthetic aromatic compounds were investigated using the OECD 301B CO2 Evolution test. The relationship between molecular properties and ready biodegradation of these aromatic compounds varied with molecular properties. A significant inverse correlation was found for the topological parameter TD, five geometrical parameters (Rad, CAA, CMA, CSEV, and N c), and the physicochemical parameter K ow, and a positive correlation for two topological parameters TC and TVC, whereas no significant correlation was observed for any of the electronic parameters. Based on the correlations between molecular properties and ready biodegradation of these aromatic compounds, the importance of molecular properties was demonstrated as follows: geometrical properties > topological properties > physicochemical properties > electronic properties. Our study first demonstrated the effects of molecular properties on ready biodegradation by a number of experiment data under the same experimental conditions, which should be taken into account to better guide the ready biodegradation tests and understand the mechanisms of the ready biodegradation of aromatic compounds.

Nearly exclusive growth of small diameter semiconducting single-wall carbon nanotubes from organic chemistry synthetic end-cap molecules.

The inability to synthesize single-wall carbon nanotubes (SWCNTs) possessing uniform electronic properties and chirality represents the major impediment to their widespread applications. Recently, there is growing interest to explore and synthesize well-defined carbon nanostructures, including fullerenes, short nanotubes, and sidewalls of nanotubes, aiming for controlled synthesis of SWCNTs. One noticeable advantage of such processes is that no metal catalysts are used, and the produced nanotubes will be free of metal contamination. Many of these methods, however, suffer shortcomings of either low yield or poor controllability of nanotube uniformity. Here, we report a brand new approach to achieve high-efficiency metal-free growth of nearly pure SWCNT semiconductors, as supported by extensive spectroscopic characterization, electrical transport measurements, and density functional theory calculations. Our strategy combines bottom-up organic chemistry synthesis with vapor phase epitaxy elongation. We identify a strong correlation between the electronic properties of SWCNTs and their diameters in nanotube growth. This study not only provides material platforms for electronic applications of semiconducting SWCNTs but also contributes to fundamental understanding of the growth mechanism and controlled synthesis of SWCNTs.

Synthesis and Anticancer Activities of Glycyrrhetinic Acid Derivatives.

A total of forty novel glycyrrhetinic acid (GA) derivatives were designed and synthesized. The cytotoxic activity of the novel compounds was tested against two human breast cancer cell lines (MCF-7, MDA-MB-231) in vitro by the MTT method. The evaluation results revealed that, in comparison with GA, compound 42 shows the most promising anticancer activity (IC50 1.88 ± 0.20 and 1.37 ± 0.18 µM for MCF-7 and MDA-MB-231, respectively) and merits further exploration as a new anticancer agent.

[Research advances on medical genetics in China in 2015].

Steady progress has been achieved in the medical genetics in China in 2015, as numerous original researches were published in the world's leading journals. Chinese scientists have made significant contributions to various fields of medical genetics, such as pathogenicity of rare diseases, predisposition of common diseases, somatic mutations of cancer, new technologies and methods, disease-related microRNAs (miRNAs), disease-related long non-coding RNAs (lncRNAs), disease-related competing endogenous RNAs (ceRNAs), disease-related RNA splicing and molecular evolution. In these fields, Chinese scientists have gradually formed the tendency, from common variants to rare variants, from single omic analyses to multipleomics integration analyses, from genetic discovery to functional confirmation, from basic research to clinical application. Meanwhile, the findings of Chinese scientists have been drawn great attentions of international peers. This review aims to provide an overall picture of the front in Chinese medical genetics, and highlights the important findings and their research strategy.

Quantum Chemical Simulation of Carbon Nanotube Nucleation on Al2O3 Catalysts via CH4 Chemical Vapor Deposition.

We present quantum chemical simulations demonstrating how single-walled carbon nanotubes (SWCNTs) form, or "nucleate", on the surface of Al2O3 nanoparticles during chemical vapor deposition (CVD) using CH4. SWCNT nucleation proceeds via the formation of extended polyyne chains that only interact with the catalyst surface at one or both ends. Consequently, SWCNT nucleation is not a surface-mediated process. We demonstrate that this unusual nucleation sequence is due to two factors. First, the π interaction between graphitic carbon and Al2O3 is extremely weak, such that graphitic carbon is expected to desorb at typical CVD temperatures. Second, hydrogen present at the catalyst surface actively passivates dangling carbon bonds, preventing a surface-mediated nucleation mechanism. The simulations reveal hydrogen's reactive chemical pathways during SWCNT nucleation and that the manner in which SWCNTs form on Al2O3 is fundamentally different from that observed using "traditional" transition metal catalysts.

Tetrel-hydride interaction between XH3F (X = C, Si, Ge, Sn) and HM (M = Li, Na, BeH, MgH).

A tetrel-hydride interaction was predicted and characterized in the complexes of XH3F···HM (X = C, Si, Ge, Sn; M = Li, Na, BeH, MgH) at the MP2/aug-cc-pVTZ level, where XH3F and HM are treated as the Lewis acid and base, respectively. This new interaction was analyzed in terms of geometrical parameters, interaction energies, and spectroscopic characteristics of the complexes. The strength of the interaction is essentially related to the nature of X and M groups, with both the larger atomic number of X and the increased reactivity of M giving rise to a stronger tetrel-hydride interaction. The tetrel-hydride interaction exhibits similar substituent effects to that of dihydrogen bonds, where the electron-donating CH3 and Li groups in the metal hydride strengthen the binding interactions. NBO analyses demonstrate that both BD(H-M) → BD*(X-F) and BD(H-M) → BD*(X-H) orbital interactions play the stabilizing role in the formation of the complex XH3F···HM (X = C, Si, Ge, and Sn; M = Li, Na, BeH, and MgH). The major contribution to the total interaction energy is electrostatic energy for all of the complexes, even though the dispersion/polarization parts are nonnegligible for the weak/strong tetrel-hydride interaction, respectively.

A σ-hole interaction with radical species as electron donors: does single-electron tetrel bonding exist?

A single-electron tetrel bond was predicted and characterized in FXH3···CH3 (X = C, Si, Ge, and Sn) complexes by performing quantum chemical calculations, where the methyl radical acts as the Lewis base and the σ-hole on the X atom in FXH3 as the Lewis acid. The interaction between the methyl radical and FXH3 is characterized by a red shift of F-X stretching frequency. The strength of the tetrel bond becomes stronger by not only increasing the atomic number of the central atom X (X = C, Si, Ge, and Sn) but also by enhancing the electron-withdrawing ability of substituents in the Lewis acid. The energy decomposition analysis highlights the importance of the electrostatic interaction in the formation of the tetrel bond, although the dispersion part is also non-negligible for the weak tetrel bond. There is a competition between the formation of single-electron tetrel bonds and hydrogen bonds for the complexes composed of the methyl radical and CNCH3 or NCCH3. Furthermore, the single-electron tetrel bond exhibits the cooperative effect not only with the hydrogen bond in the complex of NCH···NCCH3···CH3, but also with the conventional tetrel bond in NCCH3···NCCH3···CH3.

[Risk factors for death in children with severe hand, foot and mouth disease].

OBJECTIVE: To study the death risk factors in children with severe hand, foot and mouth disease (HFMD). METHODS: A total of 164 children with severe HFMD between May 2010 and September 2012 were recruited and classified into death and survival groups according to their prognosis. The differences in general information, clinical signs and symptoms and laboratory examinations were compared between the two groups. The multivariate logistic regression analysis was used to identify death risk factors in children with severe HFMD. RESULTS: There were significant differences in the incidences of atypical rash, persistent fever, dyspnea, pulmonary hemorrhage, heart rate increase, blood pressure abnormalities, cold sweat, capillary refill time>3 seconds and frequent seizures, and blood glucose, serum creatine kinase and serum lactate levels between the death and the survival groups (P<0.05). The multivariate logistic regression analysis showed three independent death risk factors for children with severe HFMD: pulmonary hemorrhage (OR=9.466, 95%CI: 1.786-21.256), abnormal blood pressure (OR=5.224, 95%CI: 1.012-28.985) and elevated serum lactate level (OR=2.154, 95%CI: 1.020-8.253). CONCLUSIONS: Pulmonary hemorrhage, abnormal blood pressure and elevated serum lactate are major death risk factors for children with severe HFMD.

Simulated Gastric Acid Promotes the Horizontal Transfer of Multidrug Resistance Genes across Bacteria in the Gastrointestinal Tract at Elevated pH Levels.

The assessment of factors that can promote the transmission of antibiotic resistance genes (ARGs) across bacteria in the gastrointestinal tract is in great demand to understand the occurrence of infections related to antibiotic-resistant bacteria (ARB) in humans. However, whether acid-resistant enteric bacteria can promote ARG transmission in gastric fluid under high-pH conditions remains unknown. This study assessed the effects of simulated gastric fluid (SGF) at different pH levels on the RP4 plasmid-mediated conjugative transfer of ARGs. Moreover, transcriptomic analysis, measurement of reactive oxygen species (ROS) levels, assessment of cell membrane permeability, and real-time quantitative assessment of the expression of key genes were performed to identify the underlying mechanisms. The frequency of conjugative transfer was the highest in SGF at pH 4.5. Antidepressant consumption and certain dietary factors further negatively impacted this situation, with 5.66-fold and 4.26-fold increases in the conjugative transfer frequency being noted upon the addition of sertraline and 10% glucose, respectively, compared with that in the control group without any additives. The induction of ROS generation, the activation of cellular antioxidant systems, increases in cell membrane permeability, and the promotion of adhesive pilus formation were factors potentially contributing to the increased transfer frequency. These findings indicate that conjugative transfer could be enhanced under certain circumstances in SGF at elevated pH levels, thereby facilitating ARG transmission in the gastrointestinal tract. IMPORTANCE The low pH of gastric acid kills unwanted microorganisms, in turn affecting their inhabitation in the intestine. Hence, studies on the factors that influence antibiotic resistance gene (ARG) propagation in the gastrointestinal tract and on the underlying mechanisms are limited. In this study, we constructed a conjugative transfer model in the presence of simulated gastric fluid (SGF) and found that SGF could promote the dissemination of ARGs under high-pH conditions. Furthermore, antidepressant consumption and certain dietary factors could negatively impact this situation. Transcriptomic analysis and a reactive oxygen species assay revealed the overproduction of reactive oxygen species as a potential mechanism by which SGF could promote conjugative transfer. This finding can help provide a comprehensive understanding of the bloom of antibiotic-resistant bacteria in the body and create awareness regarding the risk of ARG transmission due to certain diseases or an improper diet and the subsequent decrease in gastric acid levels.

Single-walled carbon nanotube growth from chiral carbon nanorings: prediction of chirality and diameter influence on growth rates.

Catalyst-free, chirality-controlled growth of chiral and zigzag single-walled carbon nanotubes (SWCNTs) from organic precursors is demonstrated using quantum chemical simulations. Growth of (4,3), (6,5), (6,1), (10,1) and (8,0) SWCNTs was induced by ethynyl radical (C(2)H) addition to organic precursors. These simulations show a strong dependence of the SWCNT growth rate on the chiral angle, θ. The SWCNT diameter however does not influence the SWCNT growth rate under these conditions. This agreement with a previously proposed screw-dislocation-like model of transition metal-catalyzed SWCNT growth rates [Ding, F.; Proc. Natl. Acad. Sci. 2009, 106, 2506] indicates that the SWCNT growth rate is an intrinsic property of the SWCNT edge itself. Conversely, we predict that the rate of SWCNT growth via Diels-Alder cycloaddition of C(2)H(2) is strongly influenced by the diameter of the SWCNT. We therefore predict the existence of a maximum growth rate for an optimum diameter/chirality combination at a given C(2)H/C(2)H(2) ratio. We also find that the ability of a SWCNT to avoid defect formation during growth is an intrinsic quality of the SWCNT edge.