Dual roles of 3-aminopropyltriethoxysilane in preparing molecularly imprinted silica particles for specific recognition of target molecules

3-Aminopropyltriethoxysilane (APTES) is a silane widely used to supply amino groups for further modifications on various materials, but it is less studied as a catalyst to catalyze sol–gel silica polymerization. Here, by using APTES as the catalyst instead of the conventional basic catalysts, a novel strategy was developed to prepare silica-based molecularly imprinted polymers (MIPs). Meanwhile, APTES was employed as the functional monomer to create imprinted nanocavities for specific recognition of target molecules. The as-synthesized MIP exhibited ultra-high recognition capability due to the elimination of the detrimental effect on the imprinting performance caused by the additional catalysts. The preparation process, specificity, pH effect, binding capacity and affinity of the MIP were studied in detail. The MIP microparticles could be packed into a solid phase extraction column for removing the target molecule in water efficiently, and the molecule could easily be enriched by 40 times. The interaction of the functional monomer and template was studied by the calculation method, giving a more clear understanding of the recognition behaviours of the imprinted polymers. The strategy could be extended not only to prepare highly specific MIPs for other small phosphoric molecules, but also for biomolecules e.g. phosphorylated peptides or proteins.

A novel strategy was developed for preparing highly selective molecularly imprinted polymers using 3-aminopropyltriethoxysilane as both a functional monomer and catalyst.     

Novel synthesis of divergent aryl imidazoles from ketones involving copper-catalyzed α-amination and oxidative C–C bond cleavage

A one-pot synthesis, initiated by a copper salt with inorganic (NH₄)₂CO₃ as the nitrogen source, forms divergent aryl imidazole derivatives from ketones via α-amination and oxidative C–C bond cleavage reactions. The approach provides a simple and rapid synthesis of imidazole derivatives and has certain versatility.

A one-pot synthesis, initiated by a copper salt with (NH₄)₂CO₃ as the nitrogen source, forms divergent aryl imidazole derivatives from ketones via C–H activation, α-amination and oxidative C–C bond cleavage and condensation cascade reaction.

The aryl imidazole is a core skeleton for chiral ligands widely used in asymmetric synthesis,¹ as well as many drug molecules and natural products that possess anti-cancer, anti-infection, anti-histamine, anti-ulcer, antihypertensive, and anti-malarial activities (Fig. 1).² Therefore, how to construct an aryl imidazole core is of great significance and has been extensively studied for the development of different synthetic methods.Open in a separate windowFig. 1Bioactive molecules containing aryl imidazole.As early as 1858, imidazoles were first synthesized by Heinrich Debus'' research group,³ and many other synthetic methods have been reported since then. These include the Bredereck synthetic method,⁴ the Leusen reaction,⁵ the Debus-Radziszewski reaction,³ the Claisen rearrangement reaction,⁶ the Phillips method,⁷ the isonitrile synthesis,⁸ and the ketones method (Scheme 1a).⁹ These methods mostly involved the traditional amination process which typically employs indirect synthesis from halogenated hydrocarbons, unsaturated bonds, and/or acyl chlorides. This leads to an increase in the number of reaction steps and limits the diversity of the substrates.Open in a separate windowScheme 1Formation of imidazole derivatives and C–C single-bond cleavage.In the past decade, metal-catalyzed C–H bond activation and amination and the activation of C–C bond cleavage have been favored.^10–13 The activation energy of C–H and C–C bonds cleavage can be reduced by directly metal-catalyzed activation of the C–H and C–C bonds, which makes the reaction easier and simplifies the synthetic process. This resulted in the development of synthetic methods for imidazole skeletons involving metal-catalyzed amination.¹⁴ However, a common problem with these syntheses is that the starting substrates are not readily available so that these solutions are economically unreliable. Recently, a few of the tandem new bond formations after C–C bond cleavage draw our attention. These examples offer the reutilization of the molecule fragments, which can be utilized to synthesize various nitrogen-containing heterocyclic rings with the atomic economy. However, these methods also have some drawbacks and limitations that do not have universal application, such as need of ring tension for C–C bond breaking (Scheme 1b),¹¹ the participation of adjacent groups for C–C bond breaking (Scheme 1c), and C–C bond breaking in α-hydroxyketones and ketones (Scheme 1d and e).¹⁵Following our interest in tandem metal-catalyzed transformation for the heterocyclic synthesis,¹⁶ especially the α-amination catalyzed by transition metal complexes,¹⁷ which is an attractive reaction for the synthesis of amine derivatives and amino-functionalized heterocycles, we explored the metal-catalyzed α-amination reaction of ketones using ammonia released from ammonium carbonate. In transition metal-catalyzed amination, the simple inorganic ammonium salts as the nitrogen source is a change from the conventional nitrogen sources including iodoimines, chloramines T, organic azides, hydroxylamines, NFSI, aromatic nitroso derivatives, and other organic nitrogen-containing compounds. Furthermore, it is surprising that the catalytic α-amination of the ketone results in the tandem reactions for the synthesis of imidazole while producing a small amount of amide. Herein, we report a novel approach of imidazole formation involving α-amination and C–C bond cleavage reaction with an excellent substrate scope.Firstly, using propiophenone as the substrate, we investigated the effect of different reaction conditions on the reaction. As shown in ESI Table 1.^† The use of inexpensive ammonium carbonate as a nitrogen source and copper iodide as a catalyst and readily available starting materials makes this protocol economically visible.Under the optimal reaction conditions, we explored the substrate scope of the reaction (Scheme 2). In this investigation, the corresponding imidazole derivatives (2a–2p) were obtained from the reaction of a series of aromatic ketones. The results show that the substrates with electron-withdrawing groups on the aromatic ring have higher reactivity than the substrates with electron-donating substituents on the aromatic ring with the exception of 2k. The substrates containing electron-withdrawing groups on the aromatic ring afforded moderate to high yield of the imidazole products (2b–2g). In addition, the alkyl chain length of the aryl alkyl ketones also affected the yields of the reaction, and the longer the chain length, the lower the reactivity (2n, 2o). The α-aryl substituted aromatic ketones also can afford the corresponding imidazole product (2p).Open in a separate windowScheme 2Reactivity of the aryl alkyl ketones^[a]. [a] Reactions conditions: CuI (10 mol%), 1 (0.37 mmol), (NH₄)₂CO₃ (7.4 mmol), air, H₂O (0.37 mmol), MeOH (2 mL), and 100 °C for 6 h in a sealed tube.To understand the reaction for novel imidazole synthesis well, we designed a series of experiments to observe the special effects of some conditions on the imidazole synthesis (see ESI^†). The effect of the nitrogen source on the reaction was first investigated. No reaction occurred in the absence of (NH₄)₂CO₃. This result indicates that (NH₄)₂CO₃ is really a nitrogen source for the reaction and it may decompose into ammonia to form a complex with copper and participates in the catalytic cycle. To confirm this point, ammonia-saturated methanol was used as the reaction solvent. The reaction occurred, but the yield of the corresponding product was only 46%. This lower yield may be due to the fact that only a limited amount of ammonia dissolved in methanol. Subsequently, the copper–ammonia complex (Cu[NH₃]₄SO₄) was prepared by the reaction of the copper salt with excess ammonia water and was used in the reaction. The result shows that the product was obtained in 72% yield, which confirmed that the copper–ammonia complex was not only the catalyst of the reaction, but also the nitrogen source. In addition, the effects of air and water on the reaction were also investigated. In the absence of water (anhydrous methanol) or air, no target product was obtained, indicating that water and air play an important role in the cleavage of C–C bond of propiophenone. Further, to confirm the α-C–H activation and α-amination in the imidazole formation, α-perdeuterated propiophenone was used as the substrate using deuterated methanol as a solvent in the presence of dry air and D₂O, the product was obtained in only 11% yield. The results show that C–H activation is a prerequisite for the reaction process.In addition, referring to the C–C bond cleavage reaction,^11,15 during the formation of imidazoles, we speculated that a portion of propiophenone may undergo cleavage of the C–C bond to produce an aldehyde. In order to confirm this, benzaldehyde was added to the reaction system, and only trace amount of original product 2a was found. In contrast, the corresponding aldehyde condensation products was obtained in yields of 66%, respectively. If 4 equivalents of benzaldehyde are added, the formation of 2a can also be completely inhibited. The results indicate that a competitive reaction occurs when an excess of other aldehyde is present, and the root cause is related to more rapidly α-amination than the cleavage of the C–C bond of propiophenone during the reaction. The experimental results make us to use other aldehydes and ketones in the synthesis of divergent aryl imidazoles. As shown in Scheme 3, divergent imidazoles were obtained in excellent yield by adding four equivalents of the aldehyde to the reaction system. Both aliphatic and aromatic aldehydes yield the ideal results, but ketones failed to afford pure corresponding products, the reaction is messy and complicated. It is interesting that when 1,2-diarylethan-1-one replaces propiophenone 1a, the addition of ketones resulted in the formation of corresponding 2H-imidazoles (Scheme 4). Meanwhile, the formation of 4j further indicates that the reaction rate of α-amination is faster than that of C–C bond cleavage. The structures of 2d and 3m, 4a were further confirmed by the X-ray single crystal analysis (the detailed crystal data are provided in the ESI^†).Open in a separate windowScheme 3The formation of divergent imidazoles from propiophenone and aldehydes^[a]. [a] Reactions conditions: CuI (10 mol%), 1a (0.37 mmol), aldehyde (1.48 mmol), (NH₄)₂CO₃ (7.4 mmol), air, MeOH (2 mL), 24 h, 100 °C, in a sealed tube.Open in a separate windowScheme 4The formation of divergent imidazoles from 1,α-biarylethanone.At the same time, ethylamine was used as a nitrogen source and phenylacetone as a substrate to react under the same reaction conditions. The intermediates α-ethylpheny-lacetone, (E)-ethylacetone-1-(ethylimino)-1-phenyl-propan-2-amine and N-ethylbenzamide and their products 1,3-diethyl-4-methyl-ene-5-phenyl-2,3-dihydro-1-himidazole were found by LC-MS (see ESI^†).On the basis of experimental results and the previously proposed mechanisms,¹⁸ a reaction pathway for aryl imidazole synthesis was proposed (Scheme 5). First, Cu(i) is oxidized to Cu(ii) under an oxygen atmosphere. The Cu(ii) species then forms a complex with ammonia (released from ammonium carbonate). Subsequently, the copper–ammonia complex reacts with the substrate to give intermediate A. A is converted into intermediate B after loss of a proton. B then undergoes a disproportionation reaction with NH₂ insertion to afford intermediate C. Intermediate D occurs via cleavage of C–Cu bond. Intermediate E forms via ammonia 1, 2-addition to species D. The intermediate E is then dehydrated to form compound F. Simultaneously, O₂ insertion into the C–Cu bond of intermediate A results in intermediate G. Addition of water then forms intermediate H. An aldehyde is then formed by electron transfer and cleavage of the C–C bond. Finally, the nucleophilic addition reaction of the aldehyde with intermediate F occurs to obtain the imidazole product by further dehydration and loss of a proton.Open in a separate windowScheme 5A proposed reaction pathway for aryl imidazole synthesis.In conclusion, under copper catalysis, the aryl alkyl ketones were reacted with an inorganic salt (NH₄)₂CO₃ in one-pot to form the imidazole derivatives by C–H activated amination and C–C oxidative cleavage. We speculate that in the imidazole synthesis, a portion of aryl alkyl ketones underwent the C–C bond cleavage, and the cleavage fragment is further subjected to a multicomponent cascade reaction with other reaction intermediates to form imidazole derivatives. The approach provides a simple and rapid synthesis for imidazole derivatives and has certain versatility. When the applicability of the reaction was further explored, it was found that the addition of other aldehydes in the reaction of the arylalkyl ketone inhibited the formation of the original product, but produced a new imidazole derivative formed by condensation with the aldehydes. In the aryl alkyl ketone reaction, the addition of other aldehydes and ketones can produce more diverse imidazole derivatives.     

Bubble-propelled micromotors based on hierarchical MnO2 wrapped carbon nanotube aggregates for dynamic removal of pollutants

Water pollution is currently an urgent public health and environmental issue. Bubble-propelled micromotors might offer an effective approach for dealing with environmental contamination. Herein, we present the synthesis of multi-walled carbon nanotube (MWCNT)/manganese dioxide (MnO₂) micromotors based on MWCNT aggregates as microscale templates by a simple one-step hydrothermal procedure. The morphology, composition, and structure of the obtained MWCNT/MnO₂ micromotors were characterized in detail. The MnO₂ nanoflakes formed a catalytic layer on the MWCNT backbone, which promoted effective bubble evolution and propulsion at remarkable speeds of 359.31 μm s⁻¹. The bubble velocity could be modulated based on the loading of MnO₂ nanoflakes. The rapid movement of these MWCNT/MnO₂ catalytic micromotors resulted in a highly efficient moving adsorption platform, which considerably enhanced the effectiveness of water purification. Dynamic adsorption of organic dyes by the micromotors increased the degradation rate to approximately 4.8 times as high as that of their corresponding static counterparts. The adsorption isotherms and adsorption kinetics were also explored. The adsorption mechanism was well fitted by the Langmuir model, following pseudo-second-order kinetics. Thus, chemisorption of Congo red at the heterogeneous MnO₂ wrapped microimotor surface was the rate determining step. The high propulsion speed and remarkable decontamination efficiency of the MWCNT/MnO₂ micromotors indicate potential for environmental contamination applications.

Water pollution is currently an urgent public health and environmental issue.     

Healing of osteotomy sites applying either piezosurgery or two conventional saw blades: a pilot study in rabbits

Purpose

The purpose of this study was to compare bone healing of experimental osteotomies applying either piezosurgery or two different oscillating saw blades in a rabbit model.

Methods

The 16 rabbits were randomly assigned into four groups to comply with observation periods of one, two, three and five weeks. In all animals, four osteotomy lines were performed on the left and right nasal bone using a conventional saw blade, a novel saw blade and piezosurgery.

Results

All three osteotomy techniques revealed an advanced gap healing starting after one week. The most pronounced new bone formation took place between two and three weeks, whereby piezoelectric surgery revealed a tendency to faster bone formation and remodelling. Yet, there were no significant differences between the three modalities.

Conclusions

The use of a novel as well as the piezoelectric bone-cutting instrument revealed advanced bone healing with a favourable surgical performance compared to a traditional saw.     

Femoral bone transport by a monolateral external fixator with or without the use of intramedullary nail: a single-department retrospective study

Backgrounds

Treatment for bone defect remains a challenge for orthopedists. Bone transport gives an effective alternative, which can be performed with an external fixator alone or combined with an intramedullary nail. Each has its advantages and disadvantages. We present a retrospective study to find out the optimal choice by evaluating the outcomes of treatment for femoral bone defect with two methods.

Methods

Two groups of patients, the monolateral external fixator alone (group A, n = 13) and the monolateral external fixator combined with intramedullary nail (group B, n = 15), were compared. Duration of the external fixator, external fixator index, radiographic consolidation index, complication, and total cost for treatment was also recorded. A modified classification of the Association for the Study and Application of the Method of Ilizarov (ASAMI) was used to assess results in two groups of patients; another SF-36 health survey questionnaire was used to assess the life qualities patients of two groups.

Results

Healing was achieved in 13/13 and 13/15 of the two groups, respectively. The rates of complications were significantly higher in the group A. Two patients performed amputations because of persistent deep infections in group B. Statistically significant difference was found when comparing ASAMI scores and categories of the SF-36 health survey.

Conclusions

Bone transport by monolateral external fixator with the use of intramedullary nail reduces the incidence of complication and the duration of external fixator time that give patients a better life quality in both physical and emotional. However, if chronic osteitis exists, bone transport should be treated with monolateral external fixator alone due to a lower rate of amputations.     

Effects of Music on Immunity and Physiological Responses in Healthcare Workers: A Randomized Controlled Trial

Research‐based evidence supports the effectiveness of soothing music in improving stress‐related psycho‐physiological indices in a clinical setting. However, there is currently insufficient scientific knowledge of the effects of music on immune markers of stress in humans. Therefore, the aims of the study were to compare the effects of music and quiet rest on the levels of interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α), interleukin‐10 (IL‐10), heart rate and mean arterial pressure among healthcare workers. By using a randomized controlled trial design, 60 nurses were randomly assigned to the stimulating or sedating music or rest groups for 30 min. Participants' psychoneuroimmunological parameters were measured using enzyme‐linked immunosorbent assays. General estimating equation was used to analyse data. Results revealed that IL‐6, TNF‐α and IL‐10 were not detectable in this population. No significance differences in heart rate were found among the three groups. However, the stimulating music group had significantly higher mean arterial pressure levels than the sedating music group but no differences between the quiet rest group and the sedating music group. Music with different tempi had little effect on mean arterial pressure. Any effect of music on immune markers of stress requires further research. Copyright © 2012 John Wiley & Sons, Ltd.     

Effects of varied ionic calcium and phosphate on the proliferation, osteogenic differentiation and mineralization of human periodontal ligament cells in vitro

An S, Ling J, Gao Y, Xiao Y. Effects of varied ionic calcium and phosphate on the proliferation, osteogenic differentiation and mineralization of human periodontal ligament cells in vitro. J Periodont Res 2012; 47: 374–382. ©2011 John Wiley & Sons A/S Background and Objective: A number of bone‐filling materials containing calcium (Ca²⁺) and phosphate (P) ions have been used in the repair of periodontal bone defects; however, the effects that local release of Ca²⁺ and P ions has on biological reactions are not fully understood. In this study, we investigated the effects of various levels of Ca²⁺ and P ions on the proliferation, osteogenic differentiation and mineralization of human periodontal ligament cells (hPDLCs). Material and Methods: The hPDLCs were obtained using an explant culture method. Defined concentrations and ratios of ionic Ca²⁺ to inorganic P were added to standard culture and osteogenic induction media. The ability of hPDLCs to proliferate in these growth media was assayed using the Cell Counting Kit‐8. Cell apoptosis was evaluated by the fluorescein isothiocyanate–annexin V/propidium iodide double‐staining method. Osteogenic differentiation and mineralization were investigated by morphological observations, alkaline phosphatase activity and Alizarin Red S/von Kossa staining. The mRNA expression of osteogenic related markers was analysed using RT‐PCR. Results: Within the ranges of Ca²⁺ and P ion concentrations tested, we observed that increased concentrations of Ca²⁺ and P ions enhanced cell proliferation and formation of mineralized matrix nodules, whereas alkaline phosphatase activity was reduced. The RT‐PCR results showed that elevated concentrations of Ca²⁺ and P ions led to a general increase of Runx2 mRNA expression and decreased alkaline phosphatase mRNA expression, but gave no clear trend on osteocalcin mRNA levels. Conclusion: The concentrations and ratios of Ca²⁺ and P ions could significantly influence proliferation, differentiation and mineralization of hPDLCs. Within the range of concentrations tested, we found that the combination of 9.0 mm Ca²⁺ ions and 4.5 mm P ions were the optimal concentrations for proliferation, differentiation and mineralization in hPDLCs.     

Glutamate neurons in the substantia nigra compacta and retrorubral field

Dopaminergic neurons of the substantia nigra compacta (SNC), ventral tegmental area (VTA) and retrorubral field (RRF) play a role in reward, motivation, learning, memory, and movement. These neurons are intermingled with GABAergic neurons. Recent evidence shows that the VTA contains glutamatergic neurons expressing vesicular glutamate transporter type 2 (VGluT2); some of them co‐express tyrosine hydroxylase (TH). Here, we used a combination of radioactive in situ hybridisation and immunohistochemistry to explore whether any of the vesicular glutamate transporters [vesicular glutamate transporter type 1 (VGluT1), VGluT2, or vesicular glutamate transporter type 3 (VGluT3)] were encoded by neurons in the SNC or RRF. We found expression of VGluT2 mRNA, but not of VGluT1 or VGluT3, in the SNC and RRF. These VGluT2 neurons rarely showed TH immunoreactivity. Within the SNC, the VGluT2 neurons were infrequently found at the rostral level, but were often seen at the medial and caudal levels intercalated in the mediolateral portion of the dorsal tier, at a ratio of one VGluT2 neuron per 4.4 TH neurons. At this level, VGluT2 neurons were also found in the adjacent substantia nigra reticulata and substantia nigra pars lateralis. Within the RRF, the VGluT2 neurons showed an increasing rostrocaudal gradient of distribution. The RRF proportion of VGluT2 neurons in relation to TH neurons was constant throughout the rostrocaudal levels, showing an average ratio of one VGluT2 neuron per 1.7 TH neurons. In summary, we provide evidence indicating that the SNC and RRF, which are traditionally considered to be dopaminergic areas, have neurons with the ability to participate in glutamate signaling.