Neurogenic and angiogenic poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloyl-glutamate) hydrogel: preconditioning effect under oxidative stress and use in neuroregeneration.

Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability (G', 2.3-2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases.

Progress in Treatment and Diagnostics of Infectious Disease with Polymers.

In this era of advanced technology and innovation, infectious diseases still cause significant morbidity and mortality, which need to be addressed. Despite overwhelming success in the development of vaccines, transmittable diseases such as tuberculosis and AIDS remain unprotected, and the treatment is challenging due to frequent mutations of the pathogens. Formulations of new or existing drugs with polymeric materials have been explored as a promising new approach. Variations in shape, size, surface charge, internal morphology, and functionalization position polymer particles as a revolutionary material in healthcare. Here, an overview is provided of major diseases along with statistics on infection and death rates, focusing on polymer-based treatments and modes of action. Key issues are discussed in this review pertaining to current challenges and future perspectives.

Polymeric Carbon Nitride with Chirality Inherited from Supramolecular Assemblies.

The facile synthesis of chiral materials is of paramount importance for various applications. Supramolecular preorganization of monomers for thermal polymerization has been proven as an effective tool to synthesize carbon and carbon nitride-based (CN) materials with ordered morphology and controlled properties. However, the transfer of an intrinsic chemical property, such as chirality from supramolecular assemblies to the final material after thermal condensation, was not shown. Here, we report the large-scale synthesis of chiral CN materials capable of enantioselective recognition. To achieve this, we designed supramolecular assemblies with a chiral center that remains intact at elevated temperatures. The optimized chiral CN demonstrates an enantiomeric preference of ca. 14 %; CN electrodes were also prepared and show stereoselective interactions with enantiomeric probes in electrochemical measurements. By adding chirality to the properties transferrable from monomers to the final product of a thermal polymerization, this study confirms the potential of using supramolecular precursors to produce carbon and CN materials and electrodes with designed chemical properties.

Controlled synthesis of multifunctional dome-shaped micro- and nano-structures via a robust physical route for biological applications.

Micro- and nano-particles are elemental for many current and developing technologies. Specifically, these particles are being used extensively in biological studies and applications, which include imaging, drug delivery and therapeutics. Recent advances have led to the development of multifunctional particles, which have the potential to further enhance their effectiveness, enabling novel applications. Therefore, many efforts have been devoted to producing well-defined particles for specific needs. However, the conventional fabrication methodologies used to develop particles are time consuming, making it extremely challenging to fine-tune the properties of the particles for multifunctional applications. Herein, we present a simple and facile method to fabricate dome-shaped micron- and nano-sized particles via a robust physical route. The presented method enables particles to be designed using a vast range of materials, with different sizes and compositions. The versatility of this method enables the engineering of multifunctional particles with pre-defined properties that can be adjusted to a specific biological application. We demonstrate the fabrication of dome-shaped particles using physical vapor deposition (PVD) and a polystyrene-bead-monolayer-based mechanical mask. We show domes from several materials and coatings; in particular, we demonstrate the development process for biocompatible magnetic iron oxide domes. We find that our magnetic domes exhibit an Fe3O4 structure with a high magnetization saturation. In addition, we examine the biocompatibility of the magnetic domes by performing viability tests and morphological analysis. The ability to design and fabricate micro- and nano-particles upon request in a simple and relatively high-throughput manner opens possibilities for the development of new smart multifunctional particles for both therapeutic and diagnostic applications.

Peptide Bond Formation in the Protonated Serine Dimer Following Vacuum UV Photon-Induced Excitation.

Possible routes for intra-cluster bond formation (ICBF) in protonated serine dimers have been studied. We found no evidence of ICBF following low energy collision-induced dissociation (in correspondence with previous works), however, we do observe clear evidence for ICBF following photon absorption in the 4.6-14 eV range. Moreover, the comparison of photon-induced dissociation measurements of the protonated serine dimer to those of a protonated serine dipeptide provides evidence that ICBF, in this case, involves peptide bond formation (PBF). The experimental results are supported by ab initio molecular dynamics and exploration of several excited state potential energy surfaces, unraveling a pathway for PBF following photon absorption. The combination of experiments and theory provides insight into the PBF mechanisms in clusters of amino acids, and reveals the importance of electronic excited states reached upon UV/VUV light excitation.

Organocatalytic chiral polymeric nanoparticles for asymmetric aldol reaction.

Chiral polymeric particles (CPPs) were studied extensively in recent years due to their importance in pharmaceutical applications. Here, nanosized CPPs were synthesized and applied as catalysts for direct asymmetric aldol reaction. The CPPs were prepared by miniemulsion or inverse miniemulsion based on various chiral amino acid derivatives and characterized by dynamic light scattering and scanning electron microscopy. The nanoparticles with spherical structure between 250 and 400 nm and high chiral surface area were used as catalysts in the aldol reaction at room temperature without additional solvent. l-tryptophan gave the highest enantiomeric excess, >86% with similar catalytic performance four times.

Chiral Porous Carbon Surfaces for Enantiospecific Synthesis.

Chiral surfaces, developed in the last decade, serve as media for enantioselective chemical reactions. Until today, they have been based mostly on developments in silica templating, and are made mainly from imprints of silicate materials developed a long time ago. Here, a chiral porous activated carbon surface was developed based on a chiral ionic liquid, and the surface chemistry and pore structure were studied to lay a new course of action in the field. The enantioselectivities of surfaces are examined by using variety of methods such as circular dichroism, linear sweep voltammetry and catalysis. These techniques revealed a 28.1% preference for the D enantiomer of the amino acid proline, and linear sweep voltammetry confirmed chirality recognition by another probe. An aldol surface chiral catalytic reaction was devised and allowed to determine the root of the enantiomeric excess. These results affirm the path toward a new type of chiral surface.

Photoacoustic measurement of localized optical dichroism in chiral crystals.

In this communication, we present a novel method to measure local optical dichroism (OD) in opaque crystal powder suspensions using photoacoustic (PA) effect. Our method is based upon the novel laser speckle contrast technique, in combination with a simple statistical approach, we were able to measure the OD of chiral crystals suspensions under completely random orientation.

Sonochemically Prepared BSA Microspheres as Adsorbents for the Removal of Organic Pollutants from Water.

This work investigates, for the first time, the application of sonochemically prepared bovine serum albumin (BSA) microspheres (BSAMS) as adsorbents of industrial organic pollutant dyes, such as rhodamine B (RhB), rhodamine 6G (Rh6G), and methylene blue (MB). These dyes also serve as model compounds for other organic pollutants such as bisphenol A and 2-nitrophenol. Adsorption kinetics of the dyes by the BSAMS was studied using pseudo-first-order (PFO) and pseudo-second-order (PSO) kinetic models. It was found that RhB follows PFO, with an adsorption capacity, qe,cal, of 7.9 mg/g, which was closer to the experimental adsorption capacity of qe,exp. of 7.6 mg/g. However, MB and Rh6G were controlled by PSO kinetics, with a qe,cal of 5.6 mg/g for MB and 6.6 mg/g for Rh6G, closer to the experimental adsorption capacity of 5.7 and 6.4 mg/g, respectively. The intraparticle diffusion (ID) model applied to the three dyes indicated multi-linearity with ID as the rate-limiting step in the adsorption process. Furthermore, the adsorption equilibria for each of the organic pollutants were studied through various isotherm models such as Langmuir, Freundlich, Temkin, and Halsey, which indicated physical interaction between the BSAMS and the dye pollutants, thus suggesting the applicability of the BSAMS as pollutant adsorbent materials. It was found that the BSAMS can effectively remove RhB, MB, and Rh6G from wastewater with efficiencies of 95.5, 83.3, and 97.9%, respectively.

Toward Efficient Synthesis of Porous All-Carbon-Based Nanocomposites for Enantiospecific Separation.

Chiral separation and asymmetric synthesis and catalysis are crucial processes for obtaining enantiopure compounds, which are especially important in the pharmaceutical industry. The efficiency of the separation processes is readily increased by using porous materials as the active material can interact with a larger surface area. Silica, metal-organic frameworks, or chiral polymers are versatile porous materials that are established in chiral applications, but their instability under certain conditions in some cases requires the use of more stable porous materials such as carbons. In addition to their stability, porous carbon materials can be tailored for their ability to adsorb and catalytically activate different chemical compounds from the liquid and the gas phase. The difficulties imposed by the functionalization of carbons with chiral species were tackled in the past by carbonizing chiral ionic liquids (CILs) together with a template to create pores, which results in the entire body of a material that is built up from the precursor. To increase the atomic efficiency of ionic liquids for better economic utilization of CILs, the approach presented here is based on the formation of a composite between CIL-derived chiral carbon and a pristine carbon material obtained from carbohydrate precursors. Two novel enantioselective carbon composite materials are applied for the chiral recognition of molecules in the gas phase, as well as in solution. The enantiomeric ratio of the l-composite for phenylalanine from the solution was (L/D) = 8.4, and for 2-butanol from the gas phase, it was (S/R) = 1.3. The d-composite showed an opposite behavior, where the enantiomeric ratio for phenylalanine was (D/L) = 2.7, and for 2-butanol from the gas phase, it was (R/S) = 1.3.

Solvent-Free Mechanochemical Synthesis of ZnO Nanoparticles by High-Energy Ball Milling of ε-Zn(OH)2 Crystals.

A detailed investigation is presented for the solvent-free mechanochemical synthesis of zinc oxide nanoparticles from ε-Zn(OH)2 crystals by high-energy ball milling. Only a few works have ever explored the dry synthetic route from ε-Zn(OH)2 to ZnO. The milling process of ε-Zn(OH)2 was done in ambient conditions with a 1:100 powder/ball mass ratio, and it produced uniform ZnO nanoparticles with sizes of 10-30 nm, based on the milling duration. The process was carefully monitored and the effect of the milling duration on the powder composition, nanoparticle size and strain, optical properties, aggregate size, and material activity was examined using XRD, TEM, DLS, UV-Vis, and FTIR. The mechanism for the transformation of ε-Zn(OH)2 to ZnO was studied by TGA and XPS analysis. The study gave proof for a reaction mechanism starting with a phase transition of crystalline ε-Zn(OH)2 to amorphous Zn(OH)2, followed by decomposition to ZnO and water. To the best of our knowledge, this mechanochemical approach for synthesizing ZnO from ε-Zn(OH)2 is completely novel. ε-Zn(OH)2 crystals are very easy to obtain, and the milling process is done in ambient conditions; therefore, this work provides a simple, cheap, and solvent-free way to produce ZnO nanoparticles in dry conditions. We believe that this study could help to shed some light on the solvent-free transition from ε-Zn(OH)2 to ZnO and that it could offer a new synthetic route for synthesizing ZnO nanoparticles.

Gas Phase Bond Formation in Dipeptide Clusters.

Protein bonds between amino acids are one of the most important biological linkages that create life. The detection of amino acids in the interstellar environments and in meteorites may lead to the suggestion that amino acids came from outer space and that peptides bonds may have been created in the gas phase. Here we show experimentally the creation of covalent bonds, most likely peptide bonds, between serine dipeptides in the gas phase. More specifically, we show that spraying a solution of Ser-Ser dipeptides results, in addition to dipeptide clusters, in a peak with the same mass as the serine tetrapeptide, which also has the same fragmentation pattern. Moreover, we show that this mass is formed upon collision induced dissociation of clusters containing four serine dipeptides. Thence, if the dipeptide can be generated abiotically the polymerization process may occur spontaneously.

Enantioselective Crystallization of Chiral Inorganic Crystals of ϵ-Zn(OH)2 with Amino Acids.

Many inorganic materials can form crystals, but little is known about their enantioselective crystallization. Herein, we report on the enantioselective crystallization of ϵ-Zn(OH)2 (Wulfingite) chiral crystals by using amino acids. Crystals of ϵ-Zn(OH)2 were crystallized from supersaturated sodium hydroxide and zinc nitrate aqueous solutions in the presence of l- or d-arginine. All of the chiral measurements, such as selective chiral adsorption by circular dichroism (CD), chiral chromatography, and polarimetry measurements, clearly show chiral discrimination during the crystallization of ϵ-Zn(OH)2 . In addition, a new method has been developed for identifying chirality in crystals by using electron paramagnetic resonance (EPR). Although the values of chiral induction of the ϵ-Zn(OH)2 crystals obtained are somewhat low, these values are still significant because they demonstrate that enantioselectivity during the crystallization of chiral inorganic crystals with chiral additives can be achieved. The method can be applied to many chiral inorganic systems. Understanding and controlling the crystallization of chiral inorganic crystals is important for gaining knowledge on the interaction of chiral molecules with inorganic surfaces. This knowledge can lead to an understanding of basic scientific questions such as the evolution of homochirality in biomolecules and the development of chiral inorganic crystals for a variety of purposes such as asymmetric catalysis and optical applications.

Growth of Hybrid Inorganic/Organic Chiral Thin Films by Sequenced Vapor Deposition.

One of the many challenges in the study of chiral nanosurfaces and nanofilms is the design of accurate and controlled nanoscale films with enantioselective activity. Controlled design of chiral nanofilms creates the opportunity to develop chiral materials with nanostructured architecture. Molecular layer deposition (MLD) is an advanced surface-engineering strategy for the preparation of hybrid inorganic-organic thin films, with a desired embedded property; in our study this is chirality. Previous attempts to grow enantioselective thin films were mostly focused on self-assembled monolayers or template-assisted synthesis, followed by removal of the chiral template. Here, we report a method to prepare chiral hybrid inorganic-organic nanoscale thin films with controlled thickness and impressive enantioselective properties. We present the use of an MLD reactor for sequenced vapor deposition to produce enantioselective thin films, by embedding the chirality of chiral building blocks into thin films. The prepared thin films demonstrate enantioselectivity of ∼20% and enantiomeric excess of up to 50%. We show that our controlled synthesis of chiral thin films generates opportunities for enantioselective coatings over various templates and 3D membranes.

Amino acid-based ionic liquids as precursors for the synthesis of chiral nanoporous carbons.

The synthesis of chiral nanoporous carbons based on chiral ionic liquids (CILs) of amino acids as precursors is described. Such unique precursors for the carbonization of CILs yield chiral carbonaceous materials with high surface area (≈620 m2 g-1). The enantioselectivities of the porous carbons are examined by advanced techniques such as selective adsorption of enantiomers using cyclic voltammetry, isothermal titration calorimetry, and mass spectrometry. These techniques demonstrate the chiral nature and high enantioselectivity of the chiral carbon materials. Overall, we believe that the novel approach presented here can contribute significantly to the development of new chiral carbon materials that will find important applications in chiral chemistry, such as in chiral catalysis and separation and in chiral sensors. From a scientific point of view, the approach and results reported here can significantly deepen our understanding of chirality at the nanoscale and of the structure and nature of chiral nonporous materials and surfaces.

Environmental impact and potential use of coal fly ash and sub-economical quarry fine aggregates in concrete.

The Israeli quarry industry produces 57 Mt of raw material and ∼4-6Mt of associated sub-economical by-products annually. These sub-economical quarry fines are not used because production and transportation costs considerably exceed their retail value. Therefore these by-products, are stored in large piles of fine grain size particles, create environmental risks to their surrondings. This paper evaluates the possibility of mixing the sub-economical quarry by-products of two Israeli quarries with sub-economical Class F coal fly ash (<20wt.% CaO) to form an economical aggregate sand substitute to be used as a concrete filler product. To study the feasibility of the aggregate as partial substitute to sand in concrete several analyses, including leaching experiements (EN12457-2), analytical techinques (SEM-EDX, ICP-MS, ICP-AES, and XRD), as well as an analysis of the mechanical and chemical properties of the concrete aggregate (strength, workability, and penetration) were performed. Scrubbing quarry waste with coal fly ash was found to be very effective for reducing the leaching rate of potentially harmful trace elements. In addition, adding fly ash with quarry fines as partial substitute to sand enhanced the performance of the concrete mixture and the properties of the fresh and harden concrete.

Chiral Purity of Crystals Using Low-Frequency Raman Spectroscopy.

The pharmaceutical industry is in need of new techniques to identify the chirality of solids due to regulatory and safety concerns regarding the biological activity of enantiomers. In this study, we present for the first time the application of low-frequency Raman spectroscopy as a new and sensitive method for analyzing the chiral purity of crystals. Using this method, we were able to identify small amounts, as low as 1 % w/w, of an enantiomer in racemic crystals. To demonstrate the capabilities of the method, we used a model system based on chiral crystals of enantiopure, racemic crystals and their mixtures in various ratios. We found that the low-frequency Raman spectra of racemic and enantiopure crystals are significantly different, reflecting the different hydrogen bond networks. Moreover, a comparison of the sensitivity of enantiomeric excess in chiral crystals to that of circular dichroism and X-ray diffraction measurements showed that low-frequency Raman attains high sensitivity comparable to chiral optical methods used for solutions. Overall, our proposed approach of using Raman spectroscopy for determining enantiomeric excess in crystals is simple, fast, and offers a high degree of chiral sensitivity.

Isothermal titration calorimetry for chiral chemistry.

One of the most powerful techniques that are currently available to measure thermodynamic parameters such as enthalpy (ΔH), Gibbs free energy (ΔG), entropy changes (ΔS), and binding affinity in chemical reactions is isothermal titration calorimetry (ITC). Recent advances in instrumentation have facilitated the development of ITC as a very essential analytical tool in biology and chemistry. In this article, we will focus on a review of the literature on the application of ITC for the study of chiral systems and chiral interactions. We present studies in which the ITC technique is used to study chiral interactions, for instance in chiral solutions, chiral organometallic complexes, guest-host chiral binding interactions, and biological macromolecules. Finally, we put strong emphasis on the most recent application of ITC for the study of chirality in nanosystems and at the nanoscale.

Bio-inspired synthesis of a hierarchical self-assembled zinc phosphate nanostructure in the presence of cowpea mosaic virus: in vitro cell cycle, proliferation and prospects for tissue regeneration.

Self-assembly is an important auto-organization process used in designing structural biomaterials which have the potential capability to heal tissues after traumatic injury. Although various materials having the ability to heal after injury are available, there is still a substantial need to develop new improved materials. To address this issue, we have developed hierarchical three-dimensional (3D) self-assembled zinc phosphate (Zn3(PO4)2) in the presence of cowpea mosaic virus (CPMV). Zn3(PO4)2 nanoparticles are self-assembled into nanosheets with a high degree of isotropy and then self-organized into a 3D structure that can enhance surface interactions with biological entities. The self-assembled structure is formed through the auto-organization of nanoparticles of size ∼50 nm under the influence of CPMV. The cellular response of self-assembled Zn3(PO4)2 and cell-particle adhesion behavior have been investigated through in vitro studies using modeled osteoblast-like MG63 cells. Self-assembled Zn3(PO4)2 resulted in proliferation of MG63 cells of up to 310% within 7 days of incubation. A 15% higher proliferation was obtained than with commercially available hydroxyapatite (HAp). Immunofluorescent analysis of MG63 cells after co-culturing with self-assembled Zn3(PO4)2 confirmed the healthy cytoskeletal organization and dense proliferation of MG63 cells. Further, Zn3(PO4)2 exhibited ∼28% cell-cycle progression in S phase, which is higher than obtained with commercially available HAp. Overall, these results demonstrate the multiple functions of hierarchical self-assembled Zn3(PO4)2 in the regeneration of bone tissue without defects and increasing the formation of cellular networks, and suggest its use in bone tissue engineering.

Characterization of Crystal Chirality in Amino Acids Using Low-Frequency Raman Spectroscopy.

We present a new method for differentiating racemic crystals from enantiopure crystals. Recently, developments in optical filters have enabled the facile use of Raman spectroscopy to detect low-frequency vibrational (LFV) modes. Here, for the first time, we use Raman spectroscopy to characterize the LFV modes for crystalline organic materials composed of chiral molecules. The LF-Raman spectra of racemic and enantiopure crystals exhibit a significant variation, which we attribute to different hydrogen-bond networks in the chiral crystal structures. Across a representative set of amino acids, we observed that when comparing racemic versus enantiopure crystals, the available LFV modes and their relative scattering intensity are strong functions of side chain polarity. Thus, LF-Raman can be used as a method that is complementary to the currently used methods for characterizing crystal chirality due to simpler, faster, and more sensitive measurements, along with the small sample size required, which is limited by the laser-beam diameter in the focus.