One-pot synthesis of heteroaryl diketoalkynyl C-glycoside and dialkynyl di-C-glycoside analogues by three-component successive coupling reaction.

The synthesis of heteroaryl diketoalkynyl C-glycoside and dialkynyl di-C-glycoside analogues has been accomplished by successive coupling of heteroaromatics, oxalyl chloride and terminal sugar alkynes in one pot. The three-component coupling reaction catalyzed by CuI gives heteroaryl diketoalkynyl C-glycosides. The same three-component coupling in the presence of n-BuLi produces dialkynyl di-C-glycosides, and the 1:1 of molar ratio of heteroaromatics to terminal sugar alkynes affords the corresponding esters of dialkynyl di-C-glycosides. The desired products have been obtained in good to excellent yields. This sequential one-pot method is mild and efficient, suitable for different heteroaromatics and terminal sugar alkynes. The sugar alkynes include furanosides, pyranosides, and acyclic sugars. Twenty-seven examples have been given. The mechanism for the formation of the desired products has been elucidated.

Water Plays Multifunctional Roles in the Intervening Formation of Secondary Organic Aerosols in Ozonolysis of Limonene: A Valence Photoelectron Spectroscopy and Density Functional Theory Study.

Although water may affect aqueous aerosol chemistry, how it intervenes in the formation of secondary organic aerosols (SOAs) at the molecular level remains elusive. Ozonolysis of limonene is one of the most important sources of indoor SOAs. Here, we report the valence electronic properties of limonene aerosols and SOAs derived from limonene ozonolysis (Lim-SOAs) via aerosol vacuum ultraviolet photoelectron spectroscopy, with a focus on the effects of water on Lim-SOAs. The first vertical ionization energy of limonene aerosols is measured to be 8.79 ± 0.07 eV. While water significantly increases the total photoelectron yield of Lim-SOAs, three photoelectron features attributable to Lim-SOAs each exhibit distinct dependence on the fraction of water in aerosols, implying that different formation pathways and molecular origins are involved in the formation of Lim-SOAs. Combined with density functional theory calculation and mass spectrometry measurements, this study reveals that water, particularly the water dimer, enhances the formation of Lim-SOAs by altering the ozonolysis energetics and pathways by intervening in its Criegee chemistry, acting as both a catalyst and a reactant. The atmospheric implication is discussed.

Effects of Different End Functional Groups Hyperbranched Polymers-Modified Carbon Nanotubes on the Crystallization and Mechanical Properties of Poly(l-lactic acid) (PLLA).

Poly-l-lactic acid (PLLA) is a biodegradable polymer with great mechanical properties and good transparency, but its low crystallization rate greatly limits its application. Hyperbranched polyesters (HBPs) modified carbon nanotubes (CNTs) are an ideal nucleating agent to prove the crystallization of PLLA. To compare different terminal group HBPs' effect on the modification of CNTs and the crystallization of PLLA, through the condensation reaction and amidation reaction, CNTs-H202 and CNTs-N102 were prepared, respectively. The modification was confirmed by Fourier-transform infrared (FTIR) spectroscopy, X-ray electron spectroscopy (XPS), and thermogravimetric analysis (TGA). Using transmission electron microscopy (TEM), we observed the changes on the surface of modified CNTs. PLLA/CNT composites were prepared, and differential scanning calorimetry (DSC) was used to investigate the crystallization behavior of the composites. The mechanical properties of PLLA/CNT composites were investigated as well. The results showed that the modified CNTs had a better promotion on PLLA crystallization and mechanical properties than the unmodified CNTs. CNTs-N102 had a slight advantage on the promotion on PLLA crystallization, which was caused by the lower grafting rate of HBP N102, and CNTs-H202 had a better promotion on the mechanical properties of PLLA, which was caused by the better compatibility with PLLA. In conclusion, hydroxy-terminated HBP is a better CNT modified material than amino-terminated HBP.

Effects of Amino Hyperbranched Polymer-Modified Carbon Nanotubes on the Crystallization Behavior of Poly (L-Lactic Acid) (PLLA).

Poly-L-lactic acid (PLLA) is an environmentally friendly and renewable polymer material with excellent prospects, but its low crystallization rate greatly limits its application. Through the amidation reaction between amino hyperbranched polymer (HBP N103) and carboxylated carbon nanotubes (CNTs), CNTs-N103 was obtained. The modification was confirmed by Fourier-transform infrared (FTIR) spectroscopy, X-ray electron spectroscopy (XPS) and thermogravimetric analysis (TGA). Using transmission electron microscopy (TEM), we observed the changes on the surface of modified CNTs. PLLA/CNT composites were prepared, and differential scanning calorimetry (DSC) was used to investigate the crystallization behavior of the composites. The results showed that the addition of CNTs could greatly improve the crystallization properties of PLLA; at the same concentration, the modified CNTs had better regulation ability in PLLA crystallization than the unmodified CNTs. Moreover, in the concentration range of 0.1-1%, with the increase in HBP concentration, the ability of CNTs-N103 to regulate the crystallization of PLLA increased as well. Wide-angle X-ray diffraction (WAXD) once again proved the improvement of the crystallization ability. The results of polarized optical microscopy (PLOM) showed that the number of nucleation points increased and the crystal became smaller.

Optimized Multiscale Entropy Model Based on Resting-State fMRI for Appraising Cognitive Performance in Healthy Elderly.

Many studies have indicated that an entropy model can capture the dynamic characteristics of resting-state functional magnetic resonance imaging (rfMRI) signals. However, there are problems of subjectivity and lack of uniform standards in the selection of model parameters relying on experience when using the entropy model to analyze rfMRI. To address this issue, an optimized multiscale entropy (MSE) model was proposed to confirm the parameters objectively. All healthy elderly volunteers were divided into two groups, namely, excellent and poor, by the scores estimated through traditional scale tests before the rfMRI scan. The parameters of the MSE model were optimized with the help of sensitivity parameters such as receiver operating characteristic (ROC) and area under the ROC curve (AUC) in a comparison study between the two groups. The brain regions with significant differences in entropy values were considered biomarkers. Their entropy values were regarded as feature vectors to use as input for the probabilistic neural network in the classification of cognitive scores. Classification accuracy of 80.05% was obtained using machine learning. These results show that the optimized MSE model can accurately select the brain regions sensitive to cognitive performance and objectively select fixed parameters for MSE. This work was expected to provide the basis for entropy to test the cognitive scores of the healthy elderly.

Tuber Brain Proportion Determines Epilepsy Onset in Children With Tuberous Sclerosis Complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder characterized by epilepsy and structural abnormalities of the brain. Little research has been done to explore the relationship between the tuber brain proportion (TBP) and epilepsy. We investigated several quantitative cerebral lesions including TBP on magnetic resonance imaging (MRI) and their impact on the onset age, seizure mode, and antiseizure treatment effectiveness of epilepsy in children with TSC. METHODS: We reviewed the clinical characteristics and MRI information of 44 children with TSC who had experienced epileptic seizures. Supratentorial tubers were quantitatively manually measured to calculate the TBP. The numbers of cortical/subcortical cyst-like tubers, diffuse lesions, subependymal nodules, and subependymal giant cell astrocytomas were also evaluated. RESULTS: Twelve children (27.3%) had experienced infantile spasms, thirteen children (29.5%) had early-onset epilepsy, and twenty-seven patients (64.3%) had a significant reduction in the frequency of seizures after antiseizure treatments. The median TBP was 9.2%, and diffuse lesions (range: 0-2) and cortical cyst-like lesions (range: 0-17) were seen in seven and seventeen children, respectively. The values of TBP (P < 0.001), diffuse lesions (P < 0.001), and cortical cyst-like tubers (P < 0.001) were all associated with early-onset epilepsy. The values of TBP (P = 0.004) and cortical cyst-like tuber (P < 0.001) were associated with the occurrence of infantile spasms. The values of TBP (P = 0.01), diffuse lesions (P = 0.04), and cortical cyst-like tubers (P = 0.004) were negatively associated with the effectiveness of antiseizure treatments. There was no significant correlation between subcortical cyst-like tuber, subependymal nodule, subependymal giant cell astrocytoma, and epilepsy severity. CONCLUSIONS: Increasing abnormality of the cerebral hemispheres, as shown by quantitative MRI analysis including TBP, cortical cyst-like tubers, and diffuse lesions, is associated with measures of more severe epilepsy due to TSC. The values of TBP demonstrate strong significance for early-onset epilepsy.

[Optimized multi-scale entropy to localize epileptogenic hemisphere of temporal lobe epilepsy based on resting-state functional magnetic resonance imaging].

Entropy model is widely used in epileptic electroencephalogram (EEG) analysis, but there are few reports on how to objectively select the parameters to compute the entropy model in the analysis of resting-state functional magnetic resonance imaging (rfMRI). Therefore, an optimization algorithm to confirm the parameters in multi-scale entropy (MSE) model was proposed, and the location of epileptogenic hemisphere was taken as an example to test the optimization effect by supervised machine learning. The rfMRI data of 20 temporal lobe epilepsy (TLE) patients with hippocampal sclerosis, positive on structural magnetic resonance imaging, were divided into left and right groups. Then, the parameters in MSE model were optimized by the receiver operating characteristic curves (ROC) and area under ROC curve (AUC) values in sensitivity analysis, and the entropy value of the brain regions with statistically significant difference between the groups were taken as sensitive features to epileptogenic hemisphere lateral. The optimized entropy values of these bio-marker brain areas were considered as feature vectors input into the support vector machine (SVM). Finally, combining optimized MSE model with SVM could accurately distinguish epileptogenic hemisphere in TLE at an average accuracy rate of 95%, which was higher than the current level. The results show that the MSE model parameter optimization algorithm can accurately extract the functional imaging markers sensitive to the epileptogenic hemisphere, and achieve the purpose of objectively selecting the parameters for MSE in rfMRI, which provides the basis for the application of entropy in advanced technology detection.

Effects of Hyperbranched Polyester-Modified Carbon Nanotubes on the Crystallization Kinetics of Polylactic Acid.

Poly-l-lactic acid (PLLA) is a prospective renewable and degradable material, but slow crystallization limits its processing and application. By dehydration condensation of hydroxyl-terminated hyperbranched resin (H202) and carboxylated carbon nanotubes (CNTs), a modified CNT, CNTs-H202, was obtained. Grafting was confirmed by Fourier transform infrared (FTIR) spectroscopy, and the grafting content was assessed by thermogravimetric analysis (TGA). Changes in surface atom content were explored by X-ray electron spectroscopy (XPS). Transmission electron microscopy (TEM) observed the increase of black dots on the surface of carbon nanotubes. PLLA/CNTs and PLLA/CNTs-H202 composites were prepared, and differential scanning calorimetry (DSC) was used to investigate the crystallization behavior of the composites. The results showed that during the cooling process, PLLA/CNTs-H202 had a larger crystalline full width at half-maximum (FWHM) compared with PLLA/CNTs and exhibited the ability to hinder chain segment movement during the subsequent reheating process. The crystallization activation energy was calculated by the Kissinger method, and it was found that the activation energy of the carbon tube increased slightly after grafting. Wide-angle X-ray diffraction (WAXD) once again proved the improvement of the crystallization ability. The results of polarized optical microscopy (PLOM) showed that the number of crystal nuclei increased and the crystal became smaller.

Efficient synthesis of novel indolizine C-nucleoside analogues via coupling of sugar alkynes, pyridines and α-bromo carbonyl compounds in one pot.

The synthesis of novel indolizine C-nucleoside analogues has been achieved by the three-component coupling reaction of sugar alkynes, pyridines and α-bromo carbonyl compounds in one pot. The corresponding products are obtained in good to excellent yields. 49 examples have been given. The synthetic method is convenient, practical and efficient. It is suitable for various substrates including structurally diversified sugar alkynes with sensitive groups. The sugar alkynes include pyranosides, furanosides, and acyclic sugars. A plausible mechanism for the formation of indolizine C-nucleoside analogues has been elucidated.

Concise synthesis of thiophene C-nucleoside analogues bearing sugar residues and aromatic residues through dimerization and sulfur heterocyclization of sugar alkynes and substituted iodoethynylbenzene.

The synthesis of thiophene C-nucleoside analogues bearing sugar residues (mono- and disaccharides) and aromatic residues has been achieved by symmetric dimerization of terminal sugar alkynes or unsymmetric dimerization of terminal sugar alkynes and substituted iodoethynylbenzene followed by sulfur heterocyclization in one pot. Homocoupling of terminal sugar alkynes and subsequent sulfur heterocyclization produce thiophene C-nucleoside analogues bearing disaccharides. Unsymmetric dimerization of terminal sugar alkynes and substituted iodoethynylbenzene followed by sulfur heterocyclization give thiophene C-nucleoside analogues bearing monosaccharide and aromatic residues. This approach is concise, general and mild, and is suitable for structurally diverse pyranosides, furanosides, and acyclic sugars. Thirty-two examples have been given and the corresponding products are obtained in moderate to excellent yields.

Synthesis of het(aryl) imidazole C-nucleoside analogues by CoFe2O4 NPs catalyzed muti-component coupling reaction.

A general synthesis of hetaryl and aryl C-4(5) linked imidazole C-nucleoside analogues has been developed by the reaction of sugar alkynes with het(aryl) iodides, KMnO4/TBAB oxidation and CoFe2O4 NPs catalyzed muti-component coupling of the corresponding diketones, NH4OAc and aromatic aldehydes in one-pot. The sugar alkynes include pyranosides and furanosides with acid sensitive protecting groups. The het(aryl) iodides comprise iodoaromatics, iodoheterocycles, and sterically hindered iodoheteroaromatics.

Simultaneous determination of seven endogenous aldehydes in human blood by headspace gas chromatography-mass spectrometry.

Endogenous aldehydes (EAs) formed by the free-radical-mediated reaction are regarded as potential biological markers of several diseases. In this work, an automated and solvent-free analytical method was developed for quantitative analysis of seven EAs (C1-C7) in human blood by using gas chromatography-mass spectrometry coupled with a headspace generator sampler (HS-GC-MS). A 1:4 (blood:water) dilution and the 1,2­dibromopropane internal standard were introduced to reduce the influence of the matrix effect from complex biological fluids. The sample preparation steps were simplified. Various experimental parameters for derivatization and extraction conditions were studied such as HS extraction temperature and time, the amount of derivatization reagent, pH and the salt effect. Under these optimum conditions, seven low-mass aldehydes were separated and analyzed within 10 min. Additionally, this method achieved limits of detection in the range of 0.0692-0.864 µg/L, an excellent linearity with correlation coefficients higher than 0.9996 and appropriate repeatability and reproducibility values (RSD < 12% at low, middle and high levels). The HS-GC-MS method was applied to measure the concentrations of the seven aldehydes in blood from bladder cancer patients (n = 15) and control subjects (n = 15). Compared with the control subjects, the levels of butanal (p < 0.01), formaldehyde, acetaldehyde, propanal, pentanal, hexanal and heptanal (all p < 0.001) were increased significantly, indicating that EAs may be useful as biomarkers in the early diagnosis of bladder cancer.

General and efficient one-pot synthesis of novel sugar/heterocyclic(aryl) 1,2-diketones from sugar terminal alkynes by Sonogashira/tetra-n- butylammonium permanganate oxidation.

A new approach for one-pot synthesis of novel sugar/heterocyclic(aryl) 1,2-diketones has been achieved by the reaction of various sugar terminal alkynes with heterocyclic(aryl) iodides at room temperature. This one-pot protocol includes Sonogashira coupling and mild n-Bu4NMnO4 oxidation reaction. This method is mild, general and efficient. Fifty-six examples have been given and the sugar/heterocyclic(aryl) 1,2-diketones were obtained in 71-94% yields. The sugar terminal alkynes include 9 structurally different sugars in pyranose, furanose, and acyclic form which have various protecting groups, sensitive groups, and sterically bulky substituents. The heterocyclic(aryl) iodides include sterically bulky heterocyclic compounds and iodobenzenes with electron-donating, electron-neutral, and electron-withdrawing substituents.

Synthesis of substituted mono- and diindole C-nucleoside analogues from sugar terminal alkynes by sequential sonogashira/heteroannulation reaction.

The synthesis of substituted mono- and diindole C-nucleoside analogues has been achieved in good to excellent yields by sequential Sonogashira coupling/NaAuCl4-catalyzed heteroannulation reactions of substituted 2-iodoanilines with various sugar terminal alkynes in one pot. The method is general, mild, and efficient and suitable for a wide range of sugar substrates, and 42 examples are given. The amino group of the substituted 2-iodoanilines is unprotected. The sugar terminal alkynes include furanosides, pyranosides, and acyclic glycosides with free hydroxyl groups, sensitive functional subtituents, and various protecting groups having different steric hindrance.

Novel syntheses of aryl quinoxaline C-nucleoside analogs by mild and efficient three-component sequential reactions.

Novel syntheses of C-nucleoside analogs with aryl quinoxalines as nucleobase surrogates have been accomplished by mild and efficient three-component sequential reactions in high yields with a wide scope of substrates. The mechanism was clarified by isolation of novel sugar 1,2-diketone derived from oxidation of the corresponding alkyne.

Novel regio- and stereoselective phosphonyl radical addition to glycals promoted by Mn(II)-air: syntheses of 1,2-dideoxy 2-C-diphenylphosphinylglycopyranosides.

1,2-Dideoxy-2-C-diphenylphosphinylglycopyranosides were first synthesized by the novel Mn(II)-air promoted reaction of diphenylphosphine oxide with various glycals in high yields with excellent regio- and stereoselectivities, which was clarified as a radical addition reaction controlled by the oxygen of vinyl ether.

Novel synthesis of methyl 4,6-O-benzylidenespiro[2-deoxy-alpha-D-arabino-hexopyranoside-2,2'-imidazolidine] and its homologue and sugar-gamma-butyrolactam derivatives from methyl 4,6-O-benzylidene-alpha-D-arabino-hexopyranosid-2-ulose.

Novel methyl 4,6-O-benzylidenespiro[2-deoxy-alpha-D-arabino-hexopyranoside-2,2'-imidazolidine] and its homologue methyl 4,6-O-benzylidene-3',4',5',6'-tetrahydro-1'H-spiro[2-deoxy-alpha-D-arabino-hexopyranoside-2,2'-pyrimidine] have been synthesized in good yields by reaction of methyl 4,6-O-benzylidene-alpha-D-arabino-hexopyranosid-2-ulose with 1,2-diaminoethane and 1,3-diaminopropane. The results are completely different from the reaction with arylamines or alkylamines. One-pot synthesis of novel (E)-methyl 4-[hydroxy (methoxy)methylene]-5-oxo-1-alkyl-(4,6-O-benzylidene-2-deoxy-alpha-D-glucopyranosido)[3,2-b]pyrrolidines has been achieved by the reaction of alkylamines with the butenolide-containing sugar, derived from the aldol condensation of methyl 4,6-O-benzylidene-alpha-D-arabino-hexopyranosid-2-ulose with diethyl malonate. These sugar-gamma-butyrolactam derivatives are potential GABA receptor ligands.

A water-soluble ruthenium glycosylated porphyrin catalyst for carbenoid transfer reactions in aqueous media with applications in bioconjugation reactions.

Water-soluble [Ru(II)(4-Glc-TPP)(CO)] (1, 4-Glc-TPP = meso-tetrakis(4-(beta-D-glucosyl)phenyl)porphyrinato dianion) is an active catalyst for the following carbenoid transfer reactions in aqueous media with good selectivities and up to 100% conversions: intermolecular cyclopropanation of styrenes (up to 76% yield), intramolecular cyclopropanation of an allylic diazoacetate (68% yield), intramolecular ammonium/sulfonium ylide formation/[2,3]-sigmatroptic rearrangement reactions (up to 91% yield), and intermolecular carbenoid insertion into N-H bonds of primary arylamines (up to 83% yield). This ruthenium glycosylated porphyrin complex can selectively catalyze alkylation of the N-terminus of peptides (8 examples) and mediate N-terminal modification of proteins (four examples) using a fluorescent-tethered diazo compound (15). A fluorescent group was conjugated to ubiquitin via 1-catalyzed alkene cyclopropanation with 15 in aqueous solution in two steps: (1) incorporation of an alkenic group by the reaction of N-hydroxysuccinimide ester 19 with ubiquitin and (2) cyclopropanation of the alkene-tethered Lys(6) ubiquitin (23) with the fluorescent-labeled diazoacetate 15 in the presence of a catalytic amount of 1. The corresponding cyclopropanation product (24) was obtained with approximately 55% conversion based on MALDI-TOF mass spectrometry. The products 23, 24, and the N-terminal modified peptides and proteins were characterized by LC-MS/MS and/or SDS-PAGE analyses.