In the current work, the reactions of [60]fullerene with alkynes promoted by OH− (base) are addressed. The treatment of C60 with alkynes in the presence of TBAOH produces alkynylation products (R-C60–H) with high selectivity in o-DCB at 100 °C. Plausible reaction mechanisms were proposed. This work provides a convenient and environmental friendly method for the functionalization of fullerenes.In the current work, the reactions of [60]fullerene with alkynes promoted by OH− (base) are addressed. The treatment of C60 with alkynes in the presence of TBAOH produces alkynylation products (R-C60–H) with high selectivity in o-DCB at 100 °C.Fullerenes functionalized with alkynyl groups are particularly valuable in materials science and organic chemistry due to their excellent electrochemical properties, among others. The combination of fullerene and acetylene units is not only a potential precursor for developing novel fullerene-based dimers or polymers,1,2 but also can promote the conjunction pathway with a supramolecular framework providing new properties. For example, it has been reported that fullerene covalently linked to acetylenic polythiophene produces unique photoelectronic properties.3,4 On the other hand, alkynes are considered as one of the most outstanding building blocks for unsaturated molecular scaffolds in organic synthesis, owing to their transformation potential into various functional groups.5–8Up to now, the easiest method to achieve acetylene deriva-tives of C60 is based on reactions of fullerene with alkynyllithium. Komatsu et al. reported the synthesis, characterization and properties of the first acetylene derivative of C60 containing a trimethylsilyl ethynyl group or a phenylethynyl group.9,10 Diedrish et al. prepared a series of alkynylfullerenes using the same method.1,11 However, the use of organolithium reagents led to complex experimental conditions, due to them being extremely sensitive to air and moisture.12 Hence, new methods for the preparation of alkynylfullerene compounds are necessary, reducing the steps involved in the synthesis, and responding to new regulations associated with sustainability. In this sense, these new procedures would not only be efficient, selective, high-yielding, but also easy to operate and environmentally friendly.In this work, our group deeply worked on the new functionalized chemistry of fullerenes with alkynes and found that the nucleophilic carbon functionalization of C60 with alkynes could be mediated by OH−. In this sense, TBAOH (tetra-n-butyl-ammoniumhydroxide) was used as a source of OH−, because it is cheap, environment friendly, and allows getting a high efficiency in the transformations. This new process allows getting highly functionalized alkynylfullerene derivatives through a one-step reaction. Furthermore, the protocol is simple, and works with a wide range of alkynes. Interestingly, different types of alkynes undergo diverse reaction pathways.A series of phenylacetylene compounds were chosen as model substrates to optimize the reaction. The experimental procedure for the new nucleophilic reaction is very simple: a mixture composed by C60 (36 mg) and a series of alkynes (20 equiv.) was stirred in o-DCB (o-dichlorobenzene) with a solution 1.0 mol L−1 of TBAOH/CH3OH (150 μL, 3 equiv.), as the OH− source, under argon gas for 1 h at 100 °C. The colour of the reaction gradually changed from purple to dark green after the addition of TBAOH/CH3OH. It was observed that the use of an excess TBAOH or longer reaction time did not improve the yield because of the formation of polar side products, like multiple addition compounds.13 Subsequently, a trifluoroacetic acid treatment, produced the different alkynylfullerenes 2a–2d with 1,2-addition and the yield is 35.2%, 29%, 21.1%, 31.5%, respectively (listed in
Open in a separate windowaAll reactions were performed in o-DCB using an oil bath at 100 °C. Molar ratio of compound 1 : C60 = 20 : 1.bCF3COOH was used in the reaction of C60 with 1a–1c. While PhCH2Br was used in the case of C60 with 1d.cIsolated yield.The structures of 1,2-addition C60 compounds 2a–2d were fully characterized and elucidated by their HRMS, 1H NMR, 13C NMR, and UV-vis spectra. The products 2a–2c exhibited proper molecular weights in their mass spectra. The 13C NMR spectra for 2a–2c clearly exhibited no more than 29 peaks in the range of 134–152 ppm, associated with the sp2-carbons of the fullerene cage, which is consistent with the Cs symmetry of their molecule structure, and the peak placed at 54–55 ppm for the sp3-carbon of fullerene and alkyne. The UV-vis spectra for all products showed a peak at 434 nm, which is the characteristic peak of the 1,2-adducts of C60.The previous analysis allows proposing a reaction mechanism for the formation of 2a–2d as is shown in Scheme l. First, the reaction of terminal alkynes 1 with TBAOH/CH3OH generates an intermediate compound 3, which suffers a nucleophilic addition to produce 4 (RC60−). The protonation of the intermediate species 4 leads to the formation of the product 2.Open in a separate windowScheme 1Proposed mechanism for the formation of 2a–2c.The reactivity of other types of alkynes in the same conditions was also studied. The derivatives 2a (in general conditions), and 2d (when CF3COOH changed to PhCH2Br) were curiously obtained when the terminal alkynes were transformed into ethylphenylpropiolate. The structures composed by two different C60-with alkynes were studied and determined through their HRMS, 1H NMR, 13C NMR, and UV-vis spectra. The results indicated that the cleavage of ethylphenylpropiolate occurred at the C–C bond, specifically, between phenylpropynyl and ethoxycarbonyl. This fact is confirmed by the crystal structure of 2d (Fig. 1).Open in a separate windowFig. 1Single crystal structure of 2d with 30% ellipsoid probability (hydrogens are omitted). The CCDC number of the crystal structure is: 2082000.A plausible mechanism for the formation of 2a and 2d compounds is deduced in the Scheme 2. The substrate 5 undergoes hydrolysis (under base conditions) to produce a carboxylic anion, which decomposes to CO2. Because the conjugated phenylethynyl group can disperse the negative charge, it makes it possible to form the intermediate 6. The α,β-unsaturated carboxylic acid 6 undergo decarboxylation14 and generates a carbanion 3 in base condition to attack C60. The protonation or nucleophilic addition of benzyl bromide produces 2a and 2d, respectively.Open in a separate windowScheme 2Proposed mechanism for the formation of 2d.The reactivity of the ester group was deeply studied using ethyl propiolate as substrate, which has a weak acid proton and an electron-withdrawing ester group in its structure. It is interesting to observe that the reactions of C60 with 7 using TBAOH/CH3OH (1.0 mol L−1) and TBAOH/isopropanol (1.0 mol L−1) led to different products as the unprecedented product 7a and 7b with an isolated yield of 35.2% and 11.8% respectively. In addition, three CH3O− groups were incorporated in the adduct 7a, apparently, methanol participates in the reaction and two bonds of alkyne are broken. Nevertheless, the alkynylfullerene derivative 7c with an isolated yield of 27.5% was obtained at room temperature (Fig. 2). The reaction between C60 with 7 and TBAOH/CH3OH (1.0 mol L−1), suggests that methanol participates in the reaction. Obviously, the reactions follow different routes in the presence of methanol and isopropanol.Open in a separate windowFig. 2Reaction of C60 and 7 in the presence of OH−.The structure of derivatives 7a–7c were estimated through HRMS, 1H NMR, 13C NMR, HMBC, HSQC and UV-vis spectra. HRMS (+ESI) of 7a and HRMS (-ESI) of 7c show the protonated molecular ions ([M + H]+) and ([M–H]−), which are placed at 869.6473 and 817.0260, respectively (Fig. S23 and S29 in ESI†). These are in good agreement with the assigned structures (7a: C66H13O4+, calcd. 869.0814; 7c: C65H5O2−, calcd. 817.0290). The 1,2-addition pattern of 7a and 7c was further confirmed through UV-vis spectra which shown a characteristic sharp peak placed at 435 nm. Fig. 3 displays the 1H NMR spectrum of 7a, where the methoxy protons are characterized by the three singlets situated at 3.48, 3.51, and 3.65 ppm, respectively.13,15 The C60–H proton was observed at 6.97 ppm. The ratio defined by peak area of the methoxy protons and the C60–H proton is 3 : 1, consist with the addends added to C60 is methoxy groups, and indicated that the methanol from TBAOH solution took part in the reaction. Two methoxy protons (3.51 and 3.65 ppm) show 3JCH correlations with the carbon of the methenyl group respectively (Fig. S26 in ESI†), which indicates that these two methoxyl groups were linked to the same carbon of methenyl. HSQC NMR (Fig. S27 in ESI†) confirmed the structure of 7a. It should be noted that there is another peak with a retention time at 6.8 min associated with a HPLC trace of the reaction of C60 with TBAOH/CH3OH (1.0 mol L−1) (Fig. S5 in ESI†). Data extracted from HRMS, 1H NMR, 13C NMR, HMBC, HSQC and UV-vis spectra, lead us to inferred that the peak placed before 7a belongs to product 7b (Fig. S29–S33 in ESI†).Open in a separate windowFig. 3Expanded 1H NMR spectrum of 7a recorded using CS2/(DMSO-d6 as the external lock) measured in a 600 MHz instrument.A reaction mechanism is proposed and shown in the Scheme 3. The key is that the alcoholic solution (in the TBAOH) could affect the structure of the final products. Ethyl propiolate 7 is an α,β-unsaturated carbonyl compound in the reaction. Methanol attacks to β-carbon (basic conditions), and produces the intermediate 8. To verify the alcohol exchange reaction, a control experiment between 7 and TBAOH/CH3OH (1.0 mol L−1, 150 μL, 3 equiv.) in o-DCB was carried out for 1 h at 100 °C. As expected, 1H NMR spectra of the reaction shows peaks at 4.26 ppm (q, 2H) and 1.32 ppm (t, 3H), which are associated with methylene and methyl protons of compound 7, respectively. In addition, the peak around 3.80 ppm is associated with methyl proton of methyl propiolate (Fig. S42 in ESI†), and it reveals that the crude contains both ethyl propiolate 7 and methyl propiolate, confirming the alcohol exchange reaction. Therefore, 7a and 7b products are both detected. However, similar reactions do not take place in the case of phenylacetylene and ethylphenylpropiolate are used as substrates, probably due to the steric hindrance of the phenyl ring in the molecule. The produced intermediate 8 generates 9via Michael addition.15,16 A part of 9 produces 11 through alcohol exchange reaction. The Michael addition, and subsequent protonation, would afford the generation of 7a and 7b. However, the Michael addition reaction was restricted when methanol was changed to isopropanol. This fact was ascribed to two reasons: (1) the steric effect of isopropanol; (2) the lower reactivity of isopropanol.17–19 Thus, a deprotonation reaction of 7 happens when isopropanol is present. The generated intermediate 13 undergoes through nucleophilic addition and protonation to produce 7c.Open in a separate windowScheme 3Proposed mechanism for the formation of 7a–7c. 相似文献
Decay-accelerating factor (DAF), a complement regulatory protein, also serves as a receptor for Dr adhesin-bearing Escherichia coli. The repeat three of DAF was shown to be important in Dr adhesin binding and complement regulation. However, Dr adhesins do not bind to red blood cells with the rare polymorphism of DAF, designated Dr(a(-)); these cells contain a point mutation (Ser165-Leu) in DAF repeat three. In addition, monoclonal antibody IH4 specific against repeat three was shown to block both Dr adhesin binding and complement regulatory functions of DAF. Therefore, to identify residues important in binding of Dr adhesin and IH4 and in regulating complement, we mutated 11 amino acids-predominantly those in close proximity to Ser165 to alanine-and expressed these mutations in Chinese hamster ovary cells. To map the mutations, we built a homology model of repeat three based on the poxvirus complement inhibitory protein, using the EXDIS, DIAMOD, and FANTOM programs. We show that perhaps Ser155, and not Ser165, is the key amino acid that interacts with the Dr adhesin and amino acids Gly159, Tyr160, and Leu162 and also aids in binding Dr adhesin. The IH4 binding epitope contains residues Phe148, Ser155, and L171. Residues Phe123 and Phe148 at the interface of repeat 2-3, and also Phe154 in the repeat three cavity, were important for complement regulation. Our results show that residues affecting the tested functions are located on the same loop (148 to 171), at the same surface of repeat three, and that the Dr adhesin-binding and complement regulatory epitopes of DAF appear to be distinct and are approximately 20 A apart. 相似文献
Goals of work Although many patients with ovarian cancer achieve favorable responses to primary chemotherapy, the majority of women will experience recurrence of their cancer. Selection of second- or third-line chemotherapy ultimately depends on patient preferences for different side effects. To better understand this process, we evaluated preferences and symptom distress in patients with ovarian cancer.Patients and methods A total of 70 women with ovarian cancer who had previously received at least three cycles of platinum-based chemotherapy and currently undergoing chemotherapy for newly diagnosed or recurrent disease were interviewed in an outpatient chemotherapy clinic. The patients were asked to rank order 27 health states using a modified visual analog scale and to complete the Memorial Symptom Assessment Scale (MSAS).Main results Most favorable health states included perfect health, clinical remission and complete control of chemotherapy-induced nausea and vomiting (CINV). Least favorable health states included more severe CINV health states and death. Patients on first-line chemotherapy had less symptom distress, and rated sexual dysfunction, fatigue and memory loss more favorably than patients on second- or third-line chemotherapy (P<0.05). Married patients generally had less symptom distress compared to patients who were not married, but married patients indicated more distress with sexual dysfunction (P=0.04). Married patients rated alopecia less favorably than unmarried patients (P=0.03), but married patients viewed certain CINV health states more favorably (P=0.02–0.04).Conclusions CINV remains one of the most dreaded side effects of chemotherapy. Separate preference profiles exist for patients with newly diagnosed and recurrent disease, as well as for married versus unmarried patients. While MSAS scores and VAS rankings showed consistency across some health states, this was not true for CINV, suggesting that current symptom status may only influence patient preferences for selected side effects. 相似文献
Objective To evaluate the clinical course in patients with Duchenne muscular dystrophy admitted to our department who received corticosteroid treatment and to compare their course with that in patients who did not receive corticosteroid treatment.Patients and methodsWe performed a retrospective study of 20 pediatric patients with a diagnosis of Duchenne muscular dystrophy who were offered corticosteroid treatment: 10 patients received deflazacort and 10 refused the treatment. The MRC muscular strength scale and Vignos' functional scale were used to evaluate clinical course, which was compared in both groups.ResultsUntreated patients showed progressive worsening. Corticosteroid-treated patients showed disease stabilization both in muscular strength and functional performance. In addition, muscular balance improved in 70 % of these patients, but only 2 % showed functional improvement. The positive effect of steroid treatment had a mean duration of 12 months. Loss of independent gait occurred at similar ages in both groups (10.3 vs. 10.5 years). The results of Achilles' tendon surgery were poor.ConclusionsCorticosteroids produced clinical stabilization and improved muscular strength. Functional improvement was not significant, including loss of gait, probably because this loss also depends on an increase in joint contracture. Good coordination among multiprofessional teams is essential to achieve optimal results. 相似文献
Women are often underrepresented in randomized clinical trials (RCT) of HIV-1 drugs. As a result, determining whether women have different virologic outcomes compared to men is not always possible because the gender-related analyses usually lack statistical power. To address this important public health concern, the Food and Drug Administration's (FDA) Division of Antiviral Products (DAVP) created a database including 20,328 HIV-positive subjects from 40 RCTs in 18 New Drug Applications (NDAs) submitted to the FDA between 2000 and 2008. These RCTs were conducted for at least 48 weeks in duration and were used to support approval of new molecular entity, new formulation, or major label change. To delineate potential gender differences in antiretroviral treatment (ART), we evaluated the percentage of subjects with HIV RNA less than 50 copies per milliliter at 48 weeks. Analyses of the database represent the most systematic review of gender-related ART efficacy data to date. Overall, the meta-analyses did not demonstrate statistically or clinically significant gender differences in virologic outcome at week 48. However, the corresponding subgroup analyses appear to show several statistically significant gender differences favoring males. 相似文献
OBJECTIVE Management of diabetic foot infection (DFI) has been hampered by limited means of accurately classifying disease severity. New hybrid nuclear/computed tomography (CT) imaging techniques elucidate a combination of wound infection parameters not previously evaluated as outcome prognosticators. Our aim is to determine if a novel standardized hybrid image-based scoring system, Composite Severity Index (CSI), has prognostic value in DFI. RESEARCH DESIGN AND METHODS Masked retrospective (99m)Tc-white blood cell (WBC) single photon emission CT (SPECT)/CT image interpretation and independent chart review of 77 patients (101 feet) suspected of DFI-associated osteomyelitis at a large municipal hospital between January 2007 and July 2009. CSI scores were correlated with probability of favorable outcome (no subsequent amputation/readmission after therapeutic intervention) during median 342-day follow-up. RESULTS CSI ranged from 0-13. Receiver operating characteristic accuracy for predicting favorable outcome was 0.79 (optimal cutoff CSI, ≤2; odds ratio of therapeutic failure for CSI >2, 15.1 [95% CI 4.4-51.5]). CSI of 0 had a 92% chance of favorable outcome, which fell progressively to 25% as indices rose to ≥7. Image-based osteomyelitis versus no osteomyelitis assessment was less accurate than CSI at predicting outcome (P = 0.016). In patients with intermediate severity (CSI 3-6), treatment failure decreased from 68 to 36% when antibiotic duration was extended to ≥42 days (P = 0.026). CONCLUSIONS (99m)Tc-WBC SPECT/CT hybrid image-derived wound infection parameters incorporated into a standardized scoring system, CSI, has prognostic value in DFI. 相似文献
In patients with acute upper gastrointestinal hemorrhage, standard practice is to transfuse packed red blood cells, often to an arbitrary level of hemoglobin or hematocrit (typically 10 g/dL and 30%, respectively) before endoscopy. Therefore, we aimed to determine first whether performing endoscopy in patients with upper gastrointestinal hemorrhage and a low hematocrit is safe and whether it predicts outcomes.
Methods
This cohort study included patients with carefully defined upper gastrointestinal hemorrhage captured in our gastrointestinal Healthcare Registry who underwent esophagogastroduodenoscopy. Patients were placed into 2 groups: low hematocrit (<30%) or high hematocrit (>30%). Clinical variables and outcomes, including cardiovascular events, intensive care unit transfer, and death, were measured.
Results
A total of 920 patients meeting entry criteria were identified. Baseline features among those with a low and high hematocrit were identical. Eight cardiovascular events occurred during or after esophagogastroduodenoscopy, including 5 of 587 (1%) in the less than 30% hematocrit group and 3 of 333 (1%) in the greater than 30% hematocrit group (P = .29). Blood transfusions were more common in the low hematocrit group (74% vs 24%, P <.001). However, correlation between the amount of blood transfused and hematocrit level was poor, and the number units of blood transfused was highly variable. There was no significant mortality difference in the 2 hematocrit groups.
Conclusion
Most patients with upper gastrointestinal hemorrhage presented with a hematocrit less than 30%. Performing endoscopy in patients with a low hematocrit was clearly safe; these data strongly imply that waiting for the hematocrit to reach a certain level before endoscopy is not necessary. 相似文献
