Palladium nanoparticles immobilized on polyethylenimine-derivatized gold surfaces for catalysis of Suzuki reactions: development and application in a lab-on-a-chip context

Gold surface-bound hyperbranched polyethyleneimine (PEI) films decorated with palladium nanoparticles have been used as efficient catalysts for a series of Suzuki reactions. This thin film-format demonstrated good catalytic efficiency (TON up to 3.4 × 10³) and stability. Incorporation into a quartz crystal microbalance (QCM) instrument illustrated the potential for using this approach in lab-on-a-chip-based synthesis applications.

Gold surface-bound hyperbranched polyethyleneimine (PEI) films decorated with palladium nanoparticles have been used as efficient catalysts for a series of Suzuki reactions in a lab-on-a-chip format.

Metal and metal-oxide nanostructures and nanoparticles are often key features in materials used in separation technology, biomedical devices, and catalysis.^1,2 Poor mechanical strength and a tendency to aggregate, thus reducing the surface to volume ratio, both limit their use in real-time applications.^3,4 To overcome these shortcomings, nanoparticles are often dispersed in a matrix, such as sol–gel, biopolymers, and carbon-based materials without disturbing their innate properties at nano-scale level.^5,6 Functionalized polymers have been explored extensively in this regard due to their robustness, low cost, ease of handling, and their amenability for chemical modification.^7–9Recently, we have demonstrated the immobilization of hyperbranched polyethyleneimine (PEI) hydrogels on metallic surfaces for use as antifouling surfaces.¹⁰ Owing to their hydrogelation properties, polymers of this type have proven useful in therapeutic applications, for e.g. bio-mineralization, and the formation of nanostructures.^11,12 PEI is a hyperbranched polymer containing very high densities of primary, secondary and tertiary amines, in a 1 : 2 : 1 ratio, and are capable of coordination with transition metals to form nanostructures.^13,14 Recent reports on amine functionalized polymer-supported heterogeneous catalysts for C–C coupling reactions (Table 1-SI^†) prompted us to deploy PEI as a matrix for synthesizing surface-bound palladium nanoparticles for use as catalysts of C–C coupling reactions. For catalytic applications, a miniaturized microfluidic setup, such as a lab-on-a-chip device, can significantly reduce the consumption of chemicals, catalysts, process time and be beneficial for on-site analysis.^15,16In this study, we demonstrate the use of the PEI surface-supported nanoparticles for as a support for catalysis of the Suzuki reaction the possibility for using of these Pd-nanoparticle immobilized PEI-derivatized gold surfaces for performing Suzuki reactions in a microfluidics device. Catalytic surface fabrication (Scheme 1) was performed using gold sputtered quartz surfaces (Au/quartz) that were functionalized with 11-mercaptoundecanoic acid (MuDA), and then activated and derivatization with PEI. The polymer attachment was carried out at high ionic strength (150 mM NaCl), which has been found to enhance the thickness and growth of PEI brush-like structures.¹⁰ Optimization of the Pd nanoparticle synthesis procedure was performed by varying incubation times and Pd(OAc)₂ concentrations (Table 1-SI^†). A quartz crystal microbalance (QCM) was used to monitor the amount of Pd deposited on the PEI coated Au/quartz resonators.Open in a separate windowScheme 1Palladium immobilization on polyethyleneimine coated Au/quartz surfaces.The energy dispersive X-ray (EDX) spectrum confirmed the presence of Pd in the PEI film with a distinct band at 2.8 keV (Fig. 1A). XPS spectra of the Pd-bound PEI surfaces revealed the presence of the anticipated proleptic elements (C_1s, N_1s, O_1s, Pd_3d and Au_4f) (Fig. 1A-SI^†). Deconvoluted peaks differentiated the amine N of PEI (399.8 eV) from that of the amide N (–*N–C O–, 400.8 eV) (Fig. 1B-SI^†).^17,18 Bands around 335 and 340 eV in the survey spectra correspond to the 3d_5/2 and 3d_3/2 states of the surface bound Pd.¹⁹ The deconvoluted bands at 335.3 and 338.2 demonstrated the presence of Pd(0) and Pd(ii), respectively (Fig. 1B). Importantly, peak integration showed the immobilized Pd to be predominantly in the Pd(0) state, with less than 5% present as Pd(ii).¹⁹Open in a separate windowFig. 1(A) Energy dispersive X-ray (EDX) analysis and (B) X-ray photoelectron spectra (XPS) of the palladium nanoparticle immobilized PEI coated Au/quartz surface.RAIR spectra confirmed the presence of the PEI on the gold surface based on the discernible vibrational bands of the –N–H–, –CH– and –CN– bending modes of the adsorbed PEI film (Fig. 2). Subtle differences can be observed in the RAIR spectra of the PEI before and after Pd immobilization. The band corresponding to –N–H– bending mode has been significantly red shifted emphasizing the interaction of the Pd particles with the amine moieties of the PEI film (Fig. 2, inset). This, together with the XPS data, provides evidence for the reduction of Pd(ii) to Pd(0) and its incorporation as nanoparticles into the PEI brush layer.Open in a separate windowFig. 2RAIR spectra of PEI coated Au/quartz surface before and after Pd immobilization.SEM images (Fig. 3) showed uniform long-range coating of the palladium nanoparticles on the PEI immobilized surface (PEI/Pd). The crystallinity of the Pd coated PEI surface was evaluated with powder diffraction measurements which showed characteristic peaks for Pd(111), Pd(200) and Pd(220) with Miller indices of 40, 47.2 and 68.3° (JCPDS No. 98-004-7386), respectively, again confirming the presence of Pd nanoparticles in the (0) oxidation state (curve a, Fig. 2-SI^†).Open in a separate windowFig. 3Scanning electron micrographs of (A) gold surface, (B) polyethyleneimine (PEI) film and (C) PEI-supported palladium particles fabricated on Au/quartz surfaces.The possibility of using these surfaces for catalysis of the Suzuki reaction was explored using a series of phenylboronic acids and substituted aryl halides (†). The amount of catalytic nanopalladium loaded was determined by QCM. Au/quartz surfaces coated with PEI/Pd were immersed in the reaction mixtures at 55 °C for 12 h (Section 1.7-SI^†). Reactions of aryl halides with a series of arylboronic acids offered the corresponding products in good to excellent yield (†). This negligible effect on Pd catalyst poisoning confirms the nature of the catalytic Pd exists predominantly in the (0) oxidation state.²⁰ No biphenyl product has been observed when the Suzuki reaction was performed in presence of unmodified Au/quartz surface (without PEI and Pd).Suzuki cross-coupling reactions of aryl halides with arylboronic acids using PEI/Pd as catalysts^a

Spectrum of small-bowel mucosal abnormalities identified by capsule endoscopy in patients with portal hypertension of varied etiology

Background

Bleeding from small intestinal ectopic varices and persistent anemia caused by portal hypertensive enteropathy (PHE) can be very challenging. Capsule endoscopy (CE) is one of the best noninvasive modalities in identifying such lesions.

Aim

The aims of this study are to study the prevalence of small-bowel changes related to portal hypertension (PHT) and to correlate them with the observations related to the effects of portal hypertension in the esophagus, stomach, and colon.

Methods

Thirty-two patients with various etiologies of PHT with either anemia or gastrointestinal bleed were included along with age- and sex-matched controls without PHT. All patients underwent blood tests, gastroscopy, colonoscopy, and CE. The small-bowel findings by CE were categorized as inflammatory-like and vascular lesions. The small-bowel changes were analyzed to find out any association with various demographic, clinical, and endoscopic variables.

Results

Thirty-one out of 32 patients with PHT (96.8%) had PHE identified by CE. Of them, 31 (96.8%) had inflammatory-like appearance, 11 (34.4%) had vascular lesions, and 2 (6.2%) had small-bowel varices. Inflammatory-like appearance was noted in eight (25%) and angiodysplastic lesions in two (6.2%) controls. Findings compatible with PHE were detected in 96.8% of the patients and 25% of the controls (X ² =34.72, p=0.000).The presence of PHE was not associated with any of the above-mentioned variables.

Conclusions

Small-bowel mucosal changes were seen in significantly higher number of patients with PHT with anemia.

     

Influence of heavy metals in Parkinson’s disease: an overview

Journal of Neurology - Parkinson’s disease (PD) is an ageing disorder with deterioration of dopamine neurons which leads to motor complications like tremor, stiffness, slow movement and...     

Potential in vitro antioxidant and protective effects of Gymnema montanum H. on alloxan-induced oxidative damage in pancreatic β-cells, HIT-T15

The present study describes the antioxidant activities of ethanol extract from Gymnema montanum (GLEt) which is an endemic plant of India. Antioxidant activity of the GLEt was studied in vitro based on scavenging of hydroxyl radicals, superoxide anions, nitric oxide, hydrogen peroxide, peroxynitrite, reducing power and inhibition of lipid peroxidation estimated in terms of thiobarbituric acid reactive substances (TBARS). Further, we examined its protective effect against alloxan-induced oxidative stress in pancreatic β-cells, HIT-T15 by measuring the free radical generation, malonaldehyde formation and antioxidant levels such as CAT, GPx and GSH. Results showed that G. montanum leaves exhibited significant antioxidant activities measured by various in vitro model systems. The HIT-T15 cell line studies showed the tendency of GLEt to increase antioxidant levels meanwhile decrease the free radical formation and inhibit the lipid peroxidation. The antioxidant activity was found to be well correlated with the phenolic phytochemicals present in the extract. GC–MS analyses revealed the presence of few phenolic compounds in the extract. As this plant has already been demonstrated for a variety of medicinal properties from our laboratory, results of this study suggest that G. montanum is an interesting source for antioxidant compounds and useful for various therapeutic applications.     

Double-step invagination technique—A novel approach to retrieve embedded esophageal self-expanding metal stent

Self-expanding metal stenting is an established treatment modality in the management of esophageal growth and stricture. Reactive tissue ingrowth at the uncovered portion of the self-expanding metal stent (SEMS) anchors it in position, preventing its migration. When removal of such an embedded SEMS is clinically indicated, the procedure of endoscopic retrieval is fraught with serious complications. Temporary deployment of a larger fully covered “rescue” SEMS within the embedded SEMS has been reported to be useful in the extraction of the embedded SEMS. When the regression of embedding tissue, is only partially achieved by such “rescue” fully covered SEMS, further extraction of the embedded SEMS can prove to be technically challenging. Here we report two cases where a novel technique, namely the “double-step invagination technique,” was useful in retrieving such embedded esophageal SEMS.     

Enantioselective hyperporous molecularly imprinted thin film polymers

Significant enantioselective recognition has been achieved through the introduction of long range ordered and highly interconnected 300 nm diameter pores in molecularly imprinted polymer matrices.

Significant enantioselective recognition has been achieved through the introduction of long range ordered and highly interconnected 300 nm diameter pores in molecularly imprinted polymer matrices.

For applications such as heterogenous catalysis, separation and surface-based sensing, enhancing numbers of recognition sites and diffusion to and from these sites are factors critical for improving material performance.^1–6 Examples include the incorporation of reactive or ligand-selective functionality in porous inorganic matrices, e.g. zeolites,^7,8 super porous silica,^9,10 anodized alumina,^11,12 and synthetic polymers by chemical functionalization/grafting.^13,14Ligand-selective recognition sites can be generated in a polymer matrix by molecular imprinting.^15,16 The recognition properties of molecularly imprinted materials have led to them being used in a wide range of applications.^17,18 With our long-term objective to develop lab-on-a-chip mini-reactors incorporating catalytic molecularly imprinted polymers (MIPs), where the issues of active site density and mass transfer are critical, we endeavored to explore the possibility of enhancing MIP catalytic functionality through combining the imprinting technique with the use of a sacrificial scaffold. MIPs capable of facilitating chemical reactions have been prepared using a strategy akin to that used in the development of catalytic antibodies,^19,20 whereby a transition state analogue (TSA) is used as template during the MIP synthesis. MIPs have been developed for a wide range of chemical transformations,²¹ such as hydrolysis,²² oxidation,²³ [2 + 2] photodimerization,²⁴ cycloaddition²⁵ and asymmetric hydrogenation.²⁶ For many applications, including catalysis, numbers of high affinity sites and mass transfer are issues limiting performance.^27,28 The synthesis of imprinted polymers with structural features that facilitate ligand access to recognition sites has been explored using polymer synthesized with sacrificial scaffolds, e.g. silica,²⁹ anodized alumina,³⁰ micelles³¹ and monodisperse (latex) polystyrene (PS) beads.^32,33 These strategies have been successfully used to enhance the performance of surface-based sensing techniques, e.g. quartz crystal microbalance (QCM),³² and electrochemical methods.¹²For this study we selected a previously described MIP capable of catalyzing a transamination reaction,³⁴ the physiologically important synthesis of an α-amino acid from the corresponding α-ketocarboxylic acid, in this case the reaction of phenylpyruvic acid and pyridoxamine to yield phenylalanine and pyridoxal³⁴ (Scheme S1^†). The enantiomers of a TSA for this reaction were used as templates in the MIP synthesis, Fig. 1. Features of this polymer system include its enantioselectivity, whereby the choice of template chirality gave the resultant methacrylic acid (MAA)–ethylene glycol dimethacrylate (EGDMA) copolymer with the corresponding enantioselectivity, and catalytic functionality in aqueous media.Open in a separate windowFig. 1Structures of the (A) l- and (B) d-transition state analogues for the reaction of phenylpyruvic acid and pyridoxamine to yield phenylalanine and pyridoxal, as first proposed by Winkler et al.³⁵The regular highly porous structures previously prepared using sacrificial self-assembled monodisperse polystyrene beads were perceived to offer good potential for enhancing diffusion and thus template binding site accessibility.^32,33 However, the solubility of the polystyrene beads in the porogen previously used in the MIP synthesis, chloroform, necessitated an alternative solvent, that while not dissolving the polystyrene beads was still capable of solubilizing the polymerization reaction mixture components. The screening of solvents with dielectric constants below that of chloroform (4.8 at 293 K), led to the identification of n-heptane (1.9 at 293 K) as a solvent that could solubilize polymerization reaction components without increasing competition for electrostatic interactions between template and monomer and without dissolving the polystyrene beads, which are normally removed by dissolving in toluene (2.4 at 293 K).To ascertain the impact of the sacrificial scaffold on imprinted polymer recognition characteristics in a QCM microfluidics device, a series of polymer films was prepared on SiO₂@Au-coated quartz crystal resonators (≈0.12 cm² in area), Fig. 2. The investigated polymer systems were either prepared in the presence of n-heptane as solvent or without any solvent, with and without the presence of self-assembled monodisperse 300 nm PS beads, and either in the presence, or absence of the l-TSA template, † The self-assembled beads showed long-range order, as seen in scanning electron microscopy (SEM) studies, Fig. 3D and S1.^† Interestingly, our initial studies to establish the chemistry used microscope slides (≈15 cm² in area), highlighting the potential for producing these materials in larger formats.Open in a separate windowFig. 2Schematic representation of the strategy used for preparing hyperporous molecularly imprinted polymer films using sacrificial polystyrene (latex) beads on QCM resonators.Poly(MAA-co-EGDMA) systems synthesized and analyzed in this study

Oral microbiome-systemic link studies: perspectives on current limitations and future artificial intelligence-based approaches

Abstract

In the past decade, there has been a tremendous increase in studies on the link between oral microbiome and systemic diseases. However, variations in study design and confounding variables across studies often lead to inconsistent observations. In this narrative review, we have discussed the potential influence of study design and confounding variables on the current sequencing-based oral microbiome-systemic disease link studies. The current limitations of oral microbiome-systemic link studies on type 2 diabetes mellitus, rheumatoid arthritis, pregnancy, atherosclerosis, and pancreatic cancer are discussed in this review, followed by our perspective on how artificial intelligence (AI), particularly machine learning and deep learning approaches, can be employed for predicting systemic disease and host metadata from the oral microbiome. The application of AI for predicting systemic disease as well as host metadata requires the establishment of a global database repository with microbiome sequences and annotated host metadata. However, this task requires collective efforts from researchers working in the field of oral microbiome to establish more comprehensive datasets with appropriate host metadata. Development of AI-based models by incorporating consistent host metadata will allow prediction of systemic diseases with higher accuracies, bringing considerable clinical benefits.     

Influence of self‐assembling peptide nanofibre scaffolds on retinal differentiation potential of stem/progenitor cells derived from ciliary pigment epithelial cells

Aim of the study was to investigate the influence of the self‐assembling peptide nanofibre scaffolds (SAPNs) on the growth, proliferation and retinal neuronal differentiation of the stem/progenitor cells (SCs) derived from the ciliary pigment epithelium (CPE) of human cadaveric eye. Here SAPNs (RADA16‐I, PM), which is well described in previous studies, commercially available and xeno‐free. The CPE cells isolated were cultured in DMEM/F12 supplemented with N2 and growth factors such as basic fibroblast growth factor and epidermal growth factor, encapsulated in the scaffolds. The entrapped SCs actively expanded and formed clone‐like clusters in the scaffolds. Many cells in the cluster were proliferating, as revealed by 5‐bromo‐2‐deoxyuridine uptake and could be maintained for up to 6 days and expressed neural progenitor markers such as β‐III tubulin, Nestin, Pax6 and Musashi1. Upon differentiation of these cells in conditioned medium, the cells exhibited retinal neuronal markers such as s‐Opsin, rhodopsin and Recoverin. The RT² profiler polymerase chain reaction array experiments showed selective gene expression, possibly involved in neural stem/progenitor cell adhesion and differentiation. These findings suggest the suitability of the three‐dimensional culture system for the proliferation and maintenance of CPE stem/progenitor cells (CPE‐NS) and for possible use in ex vivo studies of small molecules, drug deliveries for retinal diseases and for use in combination with directed stem/progenitor cell differentiation. and ultimately for tissue replacement therapies. Copyright © 2014 John Wiley & Sons, Ltd.