Synthetic Reagents Research Articles

Green Template-Mediated Synthesis of Biowaste Nano-Hydroxyapatite: A Systematic Literature Review.

Hydroxyapatite (HA) is a well-known calcium phosphate ingredient comparable to human bone tissue. HA has exciting applications in many fields, especially biomedical applications, such as drug delivery, osteogenesis, and dental implants. Unfortunately, hydroxyapatite-based nanomaterials are synthesized by conventional methods using reagents that are not environmentally friendly and are expensive. Therefore, extensive efforts have been made to establish a simple, efficient, and green method to form nano-hydroxyapatite (NHA) biofunctional materials with significant biocompatibility, bioactivity, and mechanical strength. Several types of biowaste have proven to be a source of calcium in forming HA, including using chicken eggshells, fish bones, and beef bones. This systematic literature review discusses the possibility of replacing synthetic chemical reagents, synthetic pathways, and toxic capping agents with a green template to synthesize NHA. This review also shed insight on the simple green manufacture of NHA with controlled shape and size.

Efficacy of sustainable polymers to mitigate the negative effects of anisotropic clay minerals in flotation and dewatering operations

The depletion of high-grade ore resources and ongoing demand for mineral products has led to an increase in the exploitation of low-grade and complex ores, which often contain colloid clay particles (e.g., kaolinite) that are detrimental to flotation and dewatering unit operations in mineral processing. During flotation, clay particles increase the pulp viscosity and produce a slime coating by adsorption on the surface of valuable minerals resulting in the reduction of the flotation grade and recovery. Clay particles are also suspended in mine tailings that can cause dewatering challenges in flocculation operations. The clay mitigation strategies employed during flotation (dilution and use of dispersants) and dewatering (addition of flocculants) involve reagents from non-renewable sources that can have deleterious consequences on the environment and aquatic biota. As part of an effort to find environmentally benign reagents, we evaluated the performance of six sustainable polymers (protein- and polysaccharide-based biopolymers) for their potential as dispersants and flocculants of kaolinite clay particles. Their effectiveness was assessed via chalcopyrite froth flotation, settling, and turbidity tests. Zeta potential, adsorption isotherm by total organic carbon, and X-ray scattering tests were also conducted to understand the interactions between biopolymers and kaolinite mineral surfaces. At pH 7 and 10, the anionic polysaccharide pectin showed promising dispersant efficiency in flotation and the cationic protein protamine significantly improved kaolinite flocculation in dewatering operation. Outcomes of this investigation demonstrate that commercially available sustainable polymers or “biopolymers” have a significant potential to use to mitigate the negative effects of clay particles in minerals processing to reduce environmental issues arising from inorganic and synthetic organic reagents from non-renewable sources.

IBX-Mediated Organic Transformations in Heterocyclic Chemistry-A Decade Update.

O-Iodoxybenzoic acid (IBX) is a very mild and efficient hypervalent iodine synthetic reagent useful to carry out several selective oxidations. The present review highlights research reports on IBX-assisted transformations in heterocyclic derivatives, particularly from 2010 onward.

Operando generated copper‐based catalyst enabling efficient electrosynthesis of 2,5‐bis(hydroxymethyl)furan

Electrocatalytic upgrading of biomass-derived platform molecules has emerged as a sustainable and environmentally benign route to produce high-value chemicals. The main challenge lies in developing efficient catalysts for the selective activation of designated chemical bonds in the presence of various reducible groups. This work demonstrated a high-efficiency electrochemical conversion of 5-hydroxymethylfurfural (HMF) to 2,5-bis(hydroxymethyl)furan (BHMF), an important industrial synthetic reagent. A highly porous Cu-based catalyst was developed that achieved nearly 100% BHMF selectivity and long-term stability. Through comprehensive operando and ex-situ structural characterizations, an electrochemically generated catalyst with abundant Cu/Cu2O interfaces was identified as a catalytically active phase for HMF conversion. Deuterated BHMF, with the potential to produce deuterated drugs, was also synthesized using D2O as the deuterium source. Density functional theory calculations show that the Cu/Cu2O interface structure exhibits relatively low energy barriers for the hydrogenation of HMF to BHMF. This work provides insights into the origin of electrocatalytic hydrogenation activity and highlights the promising potential of the electrocatalytic synthesis of high-value chemicals.

Enzyme-induced carbonate precipitation utilizing fresh urine and calcium-rich zeolites

Enzyme-induced carbonate precipitation (EICP) is a biocementation technique that produces comparatively fewer carbon dioxide emissions than traditional cementation. However, the use of synthetic reagents for EICP is costly, and the process produces an ammonium byproduct that is a water pollutant. This study utilized fresh human urine as a source of urea and calcium-rich zeolites as an ammonium adsorbent and a source of calcium ions for the EICP cementation technique. Batch hydrolysis, adsorption, and biocementation experiments were conducted to determine the effects of zeolite type, zeolite form (i.e., exchangeable ion), ammonium adsorption, and calcium release. The results showed that calcium-rich chabazite adsorbed comparable ammonium ions and released 2.7-times more calcium ions on average than calcium-rich clinoptilolite; calcium-rich chabazite also released calcium ions in excess without the addition of calcium chloride in solution. Additionally, synthetic-fresh urine and real-fresh urine had comparable ammonium adsorption and calcium release trends. Finally, inclusion of a pre-hydrolysis step reduced the ammonium adsorption by 3.9-times; additionally, longer adsorption times led to CaCO3 precipitation outside of the sand column, which is an undesirable outcome for soil biocementation. Even with this limitation, the CaCO3 content of sand columns ranged from 0.48% to 0.92%, which signifies the potential of the proposed process for cementation, given a higher initial concentration of urea. The results from this work show the ability to use both a waste stream, human urine, and a naturally occurring material, zeolites, to greatly reduce the economic and environmental stressors of conventional soil binders for applications such as liquefaction mitigation (e.g., Portland cement) and dust suppression (e.g., synthetic polymers).

Cutting edge of diphenyl phosphorazidate (DPPA) as a synthetic reagent – A fifty-year odyssey

Recent developments of diphenyl phosphorazidate (DPPA, (C6H5O)2P(O)N3) has been reviewed.

Samarium(ii) iodide-mediated reactions applied to natural product total synthesis.

Natural product synthesis remains a field in which new synthetic methods and reagents are continually being evaluated. Due to the demanding structures and complex functionality of many natural products, only powerful and selective methods and reagents will be highlighted in this proceeding. Since its introduction by Henri Kagan, samarium(ii) iodide (SmI2, Kagan's reagent) has found increasing use in chemical synthesis. Over the years, many reviews have been published on the application of SmI2 in numerous reductive coupling procedures as well as in natural product total synthesis. This review highlights recent advances in SmI2-mediated synthetic strategies, as applied in the total synthesis of natural products since 2004.

Biocatalytic Alkylation Chemistry: Building Molecular Complexity with High Selectivity.

Biocatalysis has traditionally been viewed as a field that primarily enables access to chiral centers. This includes the synthesis of chiral alcohols, amines and carbonyl compounds, often through functional group interconversion via hydrolytic or oxidation-reduction reactions. This limitation is partly being overcome by the design and evolution of new enzymes. Here, we provide an overview of a recently thriving research field that we summarize as biocatalytic alkylation chemistry. In the past 3-4 years, numerous new enzymes have been developed that catalyze sp3 C-C/N/O/S bond formations. These enzymes utilize different mechanisms to generate molecular complexity by coupling simple fragments with high activity and selectivity. In many cases, the engineered enzymes perform reactions that are difficult or impossible to achieve with current small-molecule catalysts such as organocatalysts and transition-metal complexes. This review further highlights that the design of new enzyme function is particularly successful when off-the-shelf synthetic reagents are utilized to access non-natural reactive intermediates. This underscores how biocatalysis is gradually moving to a field that build molecules through selective bond forming reactions.

Design of Synthetic Polymer Nanoparticles That Capture and Neutralize Target Molecules

Protein affinity reagents that specifically and strongly bind to target molecules are widely used in disease detection, diagnosis, and therapy. Although antibodies and their fragments are the gold standard in protein-protein inhibitors (PPIs), synthetic polymers such as linear polymers, dendrimers, and nanoparticles as cost-effective PPIs have attracted great attention as alternatives to antibodies. These polymers exhibit high affinity to the target by imitating natural protein-protein interactions. However, only a few in vivo applications have been reported. Here, our recent advances in the development of synthetic polymers for in vivo application are reviewed. Poly(N-isopropylacrylamide) (pNIPAm) was used as a model of synthetic affinity reagents. Incorporation of both sulfated carbohydrate and hydrophobic monomers into lightly crosslinked pNIPAm nanoparticles (NPs) captured and neutralized vascular endothelial growth factor (VEGF) and inhibited tumor growth upon intravenous injection into tumor-bearing mice. Modification of a liposome with the pNIPAm-based linear polymer increased the polymer circulation time after intravenous injection and improved the affinity for the target. The pNIPAm-based NPs delivered by oral administration captured the target small molecules and inhibited their absorption from the intestine. Our recent findings provide useful information for the design of synthetic polymers that capture target molecules in vivo.

Photodegradation of Biohazardous Dye Brilliant Blue R Using Organometallic Silver Nanoparticles Synthesized through a Green Chemistry Method.

Simple SummaryIn the paper, we utilize silver nanoparticles as a catalyst in the degradation of a hazardous dye. The nanoparticles are formed from the simple silver salt by using only a plant extract from a commonly occurring herb. The plant extract contains compounds that can both reduce the silver salt and subsequently cap the surface of the as-prepared particles. There are many environmental advantages to using such an approach—nanoparticles are prepared by using simple green chemistry and the catalytic degradation of dye is carried out by sunlight energy. Such a method can be used as a very cheap, green method to neutralize hazardous substances in-house.Nowadays, nanostructures having tremendous chemical and physical properties are gaining attention in the biomedical industry. However, when they are prepared through classical methods (physical and chemical), they are often non-biocompatible and toxic. Considering the mentioned factors, in this research, organometallic silver nanostructures (OMAgNs) have been prepared by the green chemistry method using the acetone, methanol, and methanol-hexane-based extracts of the medicinally important plant Cichorium intybus. Secondary metabolites from C. intybus can be used as an alternative to synthetic reagents at an industrial scale to manufacture biosafe and economical nanostructures with enhanced physicochemical parameters. Prepared nanostructures were characterized using SEM, XRD, FTIR, TGA, UV, and zeta potential measurement. SEM analysis revealed different shapes of OMAgNs, prepared with various extracts. XRD analysis showed the crystallinity of the nanostructures. FTIR spectroscopy helped to identify groups of compounds present in the extracts and used for the OMAgNs synthesis. Out of the three tested OMAgNs, those prepared with methanol extract were selected due to the highest obtained yield and stability (highest negative zeta potential) and were tested as a cost-efficient and active agent to photodegrade organic pollutant, Brilliant Blue R, using energy from sunlight. A decrease in UV-VIS absorbance confirmed the rapid degradation of the dye.

Bifacial PNAs Destabilize MALAT1 by 3' A-Tail Displacement from the U-Rich Internal Loop.

We report herein a new class of synthetic reagents for targeting the element for nuclear expression (ENE) in MALAT1, a long noncoding RNA upregulated in many cancers. The cis-acting ENE contains a U-rich internal loop (URIL) that forms an 11 base UAU-rich triplex stem with the truncated 3' oligo-A tail of MALAT1, protecting the terminus from exonuclease digestion and greatly extending transcript lifetime. Bifacial peptide nucleic acids (bPNAs) similarly bind URILs via base triple formation between two uracil bases and a synthetic base, melamine. We synthesized a set of low molecular weight bPNAs composed of α-linked peptide, isodipeptide, and diketopiperazine backbones and evaluated their ENE binding efficacy in vitro via oligo-A strand displacement and consequent exonuclease sensitivity. Degradation was greatly enhanced by bPNA treatment in the presence of exonucleases, with ENE half-life plunging to 6 min from >24 h. RNA digestion kinetics could clearly distinguish between bPNAs with similar URIL affinities, highlighting the utility of functional assays for evaluating synthetic RNA binders. In vitro activity was mirrored by a 50% knockdown of MALAT1 expression in pancreatic cancer (PANC-1) cells upon treatment with bPNAs, consistent with intracellular digestion triggered by a similar ENE A-tail displacement mechanism. Pulldown from PANC-1 total RNA with biotinylated bPNA enriched MALAT1 > 4000× , supportive of bPNA-URIL selectivity. Together, these experiments establish the feasibility of native transcript targeting by bPNA in both in vitro and intracellular contexts. Reagents such as bPNAs may be useful tools for the investigation of transcripts stabilized by cis-acting poly(A) binding RNA elements.

Nitroacetonitrile and Its Synthetic Equivalents.

Nitroacetonitrile (NAN) serves as a cyano(nitro)methylating agent facilitating the construction of polyfunctionalized compounds; however, its explosive property is a significant drawback in terms of practical handling. Alkali metal salts of NAN are thermally stable, but their insolubility in organic solvents restricts their use as a synthetic reagents. On the contrary, dipyrrolidinium cyano-aci-nitroacetate is soluble in common organic solvents and thermally stable, allowing for its use as an alternative synthetic equivalent of nitroacetonitrile for the construction of polyfunctionalized frameworks via cyano(nitro)methylation.

Feasibility study of oxidized hyaluronic acid cross-linking acellular bovine pericardium with potential application for abdominal wall repair

Bovine pericardium(BP)is one of the biological membranes with extensive application in tissue engineering. To fully investigate the potential clinical applications of this natural biological material, a suitable cross-linking reagent is hopefully adopted for modification. Glutaraldehyde (GA) is a clinically most common synthetic cross-linking reagent. In the study, oxidized hyaluronic acid (AHA) was developed to substitute GA to fix acellular bovine pericardium (ABP) for lower cytotoxicity, aiming to evaluate the feasibility of AHA as a cross-linking reagent and develop AHA-fixed ABP as a biological patch for abdominal wall repair. The AHA with the feeding ratio (1.8:1.0) has an appropriate molecular weight and oxidation degree, almost no cytotoxicity and good cross-linking effect. The critical cross-linking characteristics and cytocompatibility of AHA-fixed ABP were also investigated. The results demonstrated that 2.0% AHA-fixed ABP had the most suitable mechanical properties, thermal stability, resistance to enzymatic degradation and hydrophilicity. Moreover, 2.0% AHA-fixed samples exhibited an excellent cytocompatibility with human peritoneal mesothelial cells (HPMC) and low antigenicity. It also showed a prominent anti-calcification ability required for abdominal wall repair. Our data provided experimental basis for future research on AHA as a new cross-linking reagent and AHA-fixed ABP for abdominal wall repair.

Resynthesis of NMC111 Cathodic Material from Real Waste Lithium Ion Batteries

In this work, the role of the experimental conditions during the synthesis of LiNi1/3Mn1/3Co1/3O2 cathodic material (NMC) precursor was evaluated. Precursor synthesis was carried out starting from the electrodic powder obtained from the mechanical treatment of spent lithium ion batteries. Metals were extracted by acid-reducing leaching of the electrodic powder with an extraction yield higher than 90%. Cobalt was the most concentrated metals followed by manganese and nickel. Iron, copper and aluminium, coming from battery cases and current collectors, were present as impurities in the leachate. Selective precipitation of the impurities was performed prior to precipitate the mixed hydroxide. Ni1/3Mn1/3Co1/3(OH)2 precipitations were carried out using two concentrations of NH4OH and under nitrogen or air atmosphere. The effect of these parameters was evaluated on the NMCs structure by XRD analysis and on the electrochemical performance by the galvanostatic cycling of the NMCs when assembled in half lithium cells. XRD analysis of the NMCs have showed the obtainment of the typical layered structure of LiNi1/3Mn1/3Co1/3O2 for any synthesized NMC and no other phases related to single oxides were found. The evaluation of the electrochemical performance has showed a significant role of the precipitation atmosphere and an improvement of the specific capacity was attained using the lowest concentration of NH4OH. Remarkably, specific capacity values of recovered NMCs were comparable to NMCs synthesized under the same experimental conditions but using synthetic reagents.

Almond-shell biomass ash (ABA): A greener alternative to the use of commercial alkaline reagents in alkali-activated cement

The use of almond-shell biomass ash (ABA) as an alternative component to the commercial reagents used in the activation of blast furnace slag (BFS) systems is investigated. The presence in its chemical composition of a high content of K2O indicates that it can alkalinize the medium. 100% waste-based mixtures ABA/BFS were studied by micro- and macrostructural tests. A compressive strength of 44 MPa was achieved by the mortar with 25% ABA addition cured for 7 days at 65 °C. The microstructural analysis showed the formation of slightly different C(K)-A-S-H gels to those formed when using KOH. The use of ABA in BFS mortars is shown as a greener alternative for construction materials because the replacement of synthetic chemical reagents that produced around a 75–80% of reduction in the values of kgCO2eq/m3 material.

Poly(2‐ethyl‐2‐oxazoline) grafted gellan gum for potential application in transmucosal drug delivery

Gellan gum (GG) has been used to prepare polymeric carriers with prolonged retention on the eye surface for topical ocular drug delivery. In this work, GG was chemically modified with short poly(2‐ethyl‐2‐oxazoline) (PEtOx) chains that were expected to have minimal adhesion to mucosal tissues (mucoadhesion). The choice of synthetic procedure, solvents, and reagents has been dictated by biocompatibility of the materials and possible application in drug delivery. The grafts were synthesized via cationic ring‐opening polymerization and their living chains were attached onto deprotonated gellan backbone. The derivatives with three degrees of grafting were prepared by varying the in‐feed mass ratio of PEtOx grafts over GG. NMR and FT‐IR spectroscopies, thermogravimetric analysis, and SEC evidenced that the grafting had actually taken place. However, a greater diffusion coefficient determined for the copolymer, using diffusion‐ordered spectroscopy (NMR), in relation to the diffusion of the unmodified GG, suggested either partial degradation of the backbone or a more compact structure of the copolymer. GG and its graft copolymers (GG‐g‐PEtOx) were found to be highly biocompatible with cells cultured under their induction at concentration of 1, 0.1 and 0.01 mg/mL demonstrated a physiological morphology, as well as an increase in viability and proliferation.

A simple and convenient synthesis of novel 9-arylidene-9,11-dihydro-8H-benzo[h]pyrano[3,4 -b]quinolin-8-ones

In this work, a simple and convenient synthesis of a new series of benzo[h]quinoline-based α-arylidene cycloketone derivatives, namely 9-arylidene-9,11-dihydro-8H-benzo[h]pyrano[3,4-b]quinolin-8-ones, has been achieved for the first time in good yields through Claisen–Schmidt condensation reaction of readily synthesized benzo[h]pyrano[3,4-b]quinolin-8-one with aromatic aldehydes under eco-friendly solvent-free condition. Our synthetic strategy features experimental simplicity, inexpensive reagents and satisfactory yields, which would contribute to the usefulness of this method.

Optimization of Mesoporous Silica Nanoparticles through Statistical Design of Experiment and the Application for the Anticancer Drug.

The synthesis process or composition of mesoporous silica nanoparticles (MSNs) affects the physicochemical properties. Using these properties, MSNs were synthesized through the Box–Behnken design (BBD) among statistical experimental methods. The effect of the amounts of synthetic reagents, hexadecyl triethyl ammonium bromide (CTAB), tetraethyl orthosilicate (TEOS), and 2 N sodium hydroxide (NaOH), was studied using the reaction surface design. Surface area, particle size, and zeta potential were set as response values. The physicochemical properties of the optimized MSNs were evaluated, and the effect as a drug delivery system was evaluated by loading doxorubicin hydrochloride (DOX). Nano-sized MSNs were successfully prepared with 0.617 g of CTAB, 8.417 mL of TEOS, and 2.726 mL of 2 N NaOH and showed excellent physicochemical properties. The optimized MSNs showed negligible toxicity in MCF-7 cells. The drug release profile from DOX-loaded MSNs (MSN@DOX) showed an increased rate of release with decreasing pH of the medium, with the release profile sustained for 48 h. In the cytotoxicity test, the sustained drug release mechanism of MSN@DOX was confirmed. This study proposed a new statistical approach to the synthesis of MSNs.

Detection of Viruses and Virus-Neutralizing Antibodies Using Synthetic Erythrocytes: Toward a Tuneable Tool for Virus Surveillance.

The hemagglutination inhibition assay (HAI) is a classical method used worldwide in many analytical applications, including pathogen identification, vaccine production monitoring, and detection and characterization of pathogen-neutralizing antibodies (n-Ab). This is also a World Health Organization (WHO) reference method for the global surveillance of influenza viruses, which provides the information needed for the annual reformulation of the flu vaccine. HAI is a simple and inexpensive method that is performed without sophisticated equipment. However, it has to be carried out with fresh red blood cells (RBCs), a highly variable, unstable, and hard to mass-produce reagent, which impairs assay reproducibility. Here, we used the tests employed for influenza surveillance as a model to develop synthrocytes©, a synthetic reagent that could substitute animal erythrocytes in HAI. Contrary to previous examples exploiting sophisticated production paths to generate therapeutic synthetic RBCs, we founded production on the identification of microparticles able to generate different sedimentation patterns when agglutinated or not, which is the main requirement for HAI testing. Upon incorporation of influenza-binding receptors and optimization of production and assay conditions, synthrocytes succeeded in binding influenza A(H1N1) and B viruses as erythrocytes do, but were faster and more stable. Synthrocytes were finally employed in an HAI-like assay to detect the WHO reference reagents for influenza surveillance. Our results show that it is possible to substitute erythrocytes in classical HAI by a highly tuneable and potentially mass-produced synthetic reagent, which should facilitate worldwide HAI standardization with minimal equipment or training requirements.

Derivatization Design of Synthetically Accessible Space for Optimization: In Silico Synthesis vs Deep Generative Design.

Molecular design is of utmost importance in lead optimization programs ultimately determining the fate of the project and the speed to reach preclinical stage. Newly designed lead analogues or new chemotypes must successfully address the challenges in the multidimensional optimization process throughout several optimization cycles. The speed, quality, and creativity of the designs can have a major impact on the cycle time, the number of required cycles, and the number of compounds needed to be synthesized and evaluated that in combination affect the overall timeline and cost of the lead optimization phase. Recently, a new concept, generative design with deep learning, has become popular for de novo design of project relevant analogue sets. We have developed a de novo design technology called "derivatization design" that applies artificial-intelligence-assisted forward in silico synthesis for the generation of near neighbor lead analogues as well as scaffold variations. The several attractive features of the methodology include synthetic feasibility, reagent availability and cost data associated with each new molecule; thus, detailed synthetic assessment is automatically generated during the design. As a result, these practically important data types can become an early part of the ranking and selection process for cycle time reduction. The power of derivatization design is demonstrated in a simple design study of DDR1 inhibitors and comparison of the produced molecules to a recently published data set obtained with deep generative design.