Non-aqueous Environment Research Articles

Supramolecular DNA-Based Catalysis in Organic Solvents

The distinct folding accompanied by its polymorphic character renders DNA G-quadruplexes promising biomolecular building blocks to construct novel DNA-based and supramolecular assemblies. However, the highly polar nature of DNA limits the use of G-quadruplexes to water as a solvent. In addition, the archetypical G-quadruplex fold needs to be stabilized by metal-cations, which is usually a potassium ion. Here, we show that a noncovalent PEGylation process enabled by electrostatic interactions allows the first metal-free G-quadruplexes in organic solvents. Strikingly, incorporation of an iron-containing porphyrin renders the self-assembled metal-free G-quadruplex catalytically active in organic solvents. Hence, these “supraGymes” enable DNA-based catalysis in organic media. The results will allow the broad utilization of DNA G-quadruplexes in nonaqueous environments.

Preparation and application of solvent-free liquid proteins with enhanced thermal and anhydrous stabilities

This perspective details a robust chemical modification strategy to protect proteins from temperature, aggregation, and non-aqueous environments.

Amperometric titration of palladium with diethylamino-4-methyl-hexine-2-ola-4 solutionsin nonaqueous environments

Amperometric titration of palladium with diethylamino-4-methyl-hexine-2-ola-4 solutionsin nonaqueous environments

Locomotion of micromotors in paper chips.

Locomotion of nano/micromotors in non-aqueous environments remains a challenging task. We assembled magnetic micromotors with different surface coatings and explored their locomotion in paper chips. Poly(L-lysine) deposition resulted in positively charged micromotors. Immobilized cellulase was used to increase the micromotors' paper penetration depth while a polyethylene glycol (PEG) coating was employed to limit the interaction between the micromotors and the cellulose fibers. All micromotors were able to move in the top layers of the paper chips with velocities dependent on the magnetic forces used to induce their locomotion, their sizes and the types of employed paper chips. Maximum speeds of up to ∼25 μm s-1 were observed for PEGylated micromotors in the fibrous cellulose environment. This type of micromotors has the potential to be considered in the area of paper microfluidics to facilitate distribution, or collection of moieties for biosensing or cell culture.

The intramolecular self-healing strategy applied to near infrared fluorescent aminotricarbocyanines

We present the synthesis and photophysical studies of three novel near-infrared (NIR) aminotricarbocyanine derivatives with self-contained antioxidant moieties, gallic acid and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). The aim of this work is to apply the intramolecular self-healing strategy to water soluble aminotricarbocyanines exploring the effect of the direct attachment of an antioxidant moiety to the fluorophore core. The synthesized dyes also include a functional group (-COOH) in their chemical structure for further (bio)conjugation of the fluorescent probe to biomolecules or surfaces. The photostability of the dyes was investigated spectroscopically in cuvette experiments as well as microscopically in dye embedded PMMA films. The rigid heptamethine modified dyes show enhanced photostability in aqueous and non-aqueous air-saturated environments by means of a self-healing process through redox quenching of reactive intermediates from excited states.

An organogel library for solution NMR analysis of nanoparticle suspensions in non-aqueous samples

Surface contrast solution NMR methods (scNMR) are emerging as powerful tools to investigate the adsorption of small molecule ligands to the surface of nanoparticles (NP), returning fundamental insight into the kinetics and thermodynamics of sorption, as well as structural information on the adsorbed species. A prerequisite for the acquisition of high quality solution NMR data is the preparation of homogeneous and stable samples that return consistent NMR spectra and allow extensive signal averaging. Unfortunately, this condition does not apply to NMR samples containing NPs that often show a tendency to sediment and accumulate at the bottom of the NMR tube over the course of the experiment. We have recently shown that preparing NMR samples in an agarose gel matrix inhibits sedimentation and allows the characterization of small molecule-NP interactions by scNMR. Unfortunately, as the agarose gel only forms in aqueous solution, this sample preparation method cannot be used to stabilize NP suspensions in a non-aqueous environment. Here, we introduce a library of 48 organogels, based on low molecular-mass organic gelators (LMOGs), to prepare NMR samples of small molecule/NP systems in a wide range of organic solvents. In addition, we present a simple method that takes advantage of 1H transverse relaxation (1H-R2) measurements to screen the library and identify the best gelator to characterize the small molecule-NP interaction of interest in the solvent of choice. We expect the results of this study will enable the preparation of homogeneous and stable samples of NPs in non-aqueous environments, therefore dramatically increasing the applicability of scNMR to the characterization of heterogeneous interactions and to the investigation of the role played by solvent molecules in regulating the kinetics and thermodynamics of sorption.

Polypyrrole-coated tape electrode for flexible supercapacitor applications

A non-conductive tape was covered with graphite by the attachment of tape on bulk graphite and subsequently peeled off from the surface. Flexible tape with thin graphite coating was designed as the current collector. Polypyrrole film was synthesized potentiostatically on the flexible tape electrode surface from pyrrole monomer in sulfuric acid medium. Topographical, morphological, compositional and electrochemical properties of polypyrrole films were investigated by AFM, SEM, FTIR and potentiostatic/galvanostatic techniques, respectively. Polypyrrole flexible electrodes, electroplated in acidic medium, were cycled in aqueous and non-aqueous electrolyte environments, specifically, acetonitrile and ionic liquid. The capacitance retention rate of the polypyrrole-based electrode cycled in deep eutectic solvent increased by 11% after 3000 scans. The highest specific capacitance of the electropolymerized polypyrrole-based electrode was 545 F g−1 in aqueous electrolyte, that is, water containing 1 M LiClO4, at scan rate 100 mV s−1. Polypyrrole-based electrodes can be synthesized on flexible tapes as a cheap and easy method for supercapacitor applications.

Synthesis and Crystallographic Characterization of X-Substituted 2,4-Dinitrophenyl-4′-phenylbenzenesulfonates

Treatment of 2,4-dinitrophenol with sulfonyl chlorides in the presence of pyridine results in the formation of undesired pyridinium salts. In non-aqueous environments, the formation of the insoluble pyridinium salt greatly affects the formation of the desired product. A facile method of producing the desired sulfonate involves the use of an aqueous base with a water-miscible solvent. Herein, we present the optimization of methods for the formation of sulfonates and its application in the production of desired x-substituted 2,4-dinitrophenyl-4′-phenylbenzenesulfonates. This strategy is environmentally benign and supports a wide range of starting materials. Additionally, the intermolecular interactions of these sulfonate compounds were investigated using single-crystal x-ray diffraction data.

Parallel Interconnected Kinetic Asymmetric Transformation (PIKAT) with an Immobilized ω-Transaminase in Neat Organic Solvent.

Comprising approximately 40% of the commercially available optically active drugs, α-chiral amines are pivotal for pharmaceutical manufacture. In this context, the enzymatic asymmetric amination of ketones represents a more sustainable alternative than traditional chemical procedures for chiral amine synthesis. Notable advantages are higher atom-economy and selectivity, shorter synthesis routes, milder reaction conditions and the elimination of toxic catalysts. A parallel interconnected kinetic asymmetric transformation (PIKAT) is a cascade in which one or two enzymes use the same cofactor to convert two reagents into more useful products. Herein, we describe a PIKAT catalyzed by an immobilized ω-transaminase (ωTA) in neat toluene, which concurrently combines an asymmetric transamination of a ketone with an anti-parallel kinetic resolution of an amine racemate. The applicability of the PIKAT was tested on a set of prochiral ketones and racemic α-chiral amines in a 1:2 molar ratio, which yielded elevated conversions (up to >99%) and enantiomeric excess (ee, up to >99%) for the desired products. The progress of the conversion and ee was also monitored in a selected case. This is the first report of a PIKAT using an immobilized ωTA in a non-aqueous environment.

LC-MS/MS determination of plasma catecholamines after selective extraction by borated zirconia.

For the first time, boronate affinity chromatography and metal oxide affinity chromatography mechanisms for cis-diol-compounds extraction are simultaneously realized on a single material, termed borated zirconia. This material was prepared by hydrolyzing zirconium butoxide with boric acid under non-aqueous environment. The diameter of formed particles is around 200nm. By extracting catechol under different pH conditions or with phosphate ion competition, the dual affinity mechanisms of borated zirconia are confirmed. Benefiting from such unique feature, borated zirconia can function well under neutral condition. By using borated zirconia for dispersive solid phase extraction, specific capture of cis-diol-containing catecholamines, including epinephrine (E), norepinephrine (NE) and dopamine (DA), was achieved. A reliable LC-MS/MS method was established and validated for quantification of these target analytes in plasma samples after derivatisation with benzoyl chloride. The linear ranges are 0.010-0.200ng·mL-1 for E and DA, and 0.050-1.000ng·mL-1 for NE. The limits of quantification are 0.008, 0.020 and 0.004ng·mL-1 for E, NE and DA respectively. By analyzing samples from healthy volunteers and schizophrenia patients, the plasma concentrations of E, NE and DA were found to behigher for the latter. Graphical AbstractSchematic representation of boronate combined metal oxide affinity chromatography (BMOAC) extraction of cis-diol catecholamines from human plasma by borated zirconia following with benzoyl chloride derivatization and LC-MS determination.

D-π-A azine based AIEgen with solvent dependent response towards a nerve agent.

We developed a D–π–A based unsymmetrical azine molecule 4-((E)-((E)-(4-(dipropylamino)benzylidene)hydrazono)methyl)benzonitrile [DPBN] and studied its optical and aggregation induced emission properties. The DPBN molecule shows good aggregation induced emission (AIE) behaviour with 1157-fold fluorescence enhancement in the aggregated state. In addition to that, both colorimetric as well as fluorometric sensing studies revealed that DPBN selectively detects diethylchlorophosphate (DCP), a potent nerve agent. Interestingly, DPBN shows solvent dependent optical output in the presence of DCPvia two different mechanisms. In the monomer state, it shows red shifted fluorescence enhancement along with color change from colorless to orange color via the formation of a new intramolecular charge transfer state in pure tetrahydrofuran (THF). In the aggregated state, DPBN shows blue shifted emission with fluorescence enhancement in THF–water mixture by protonation at the amine nitrogen centre. Thus, DPBN can be used as a diagnostic measure to selectively detect nerve agents like DCP. This study also paves the way for further development of molecular probes for nerve agents that would represent immense implications in various fields of chemistry and biology.

De novo protein design, a retrospective.

Proteins are molecular machines whose function depends on their ability to achieve complex folds with precisely defined structural and dynamic properties. The rational design of proteins from first-principles, or de novo, was once considered to be impossible, but today proteins with a variety of folds and functions have been realized. We review the evolution of the field from its earliest days, placing particular emphasis on how this endeavor has illuminated our understanding of the principles underlying the folding and function of natural proteins, and is informing the design of macromolecules with unprecedented structures and properties. An initial set of milestones in de novo protein design focused on the construction of sequences that folded in water and membranes to adopt folded conformations. The first proteins were designed from first-principles using very simple physical models. As computers became more powerful, the use of the rotamer approximation allowed one to discover amino acid sequences that stabilize the desired fold. As the crystallographic database of protein structures expanded in subsequent years, it became possible to construct proteins by assembling short backbone fragments that frequently recur in Nature. The second set of milestones in de novo design involves the discovery of complex functions. Proteins have been designed to bind a variety of metals, porphyrins, and other cofactors. The design of proteins that catalyze hydrolysis and oxygen-dependent reactions has progressed significantly. However, de novo design of catalysts for energetically demanding reactions, or even proteins that bind with high affinity and specificity to highly functionalized complex polar molecules remains an importnant challenge that is now being achieved. Finally, the protein design contributed significantly to our understanding of membrane protein folding and transport of ions across membranes. The area of membrane protein design, or more generally of biomimetic polymers that function in mixed or non-aqueous environments, is now becoming increasingly possible.

Spectroscopic Kinetic Monitoring and Molecular Dynamics Simulations of Biocatalytic Ester Hydrolysis in Non-Aqueous Solvent

The use of enzymes as catalysts is becoming an increasingly important tool in chemical synthesis, given the mild conditions and high chemoselectivity that can be achieved through enzyme-catalyzed reactions. However, a major limitation in the use of enzymatic biocatalysis is the degradation of enzyme structure and activity in non-aqueous media. Lipases are a subclass of esterases found in most, if not all, living organisms that break ester bonds in lipids. In this study, we explored the effects of various concentrations of non-aqueous organic solvents on pancreatic lipase activity and analyzed the relationships between different properties of solvents and the kinetics of enzymatic hydrolysis through spectroscopic monitoring of a synthetic colorimetric substrate, 4-nitrophenyl acetate. The influence of non-aqueous solvent environments on protein stability was further explored with molecular dynamics (MD) simulations on a 1 nanosecond timescale. Our results suggest a general trend of decreasing enzymatic activity with increasing concentrations of non-aqueous solvent; however, lipase activity in low concentrations of methanol, specifically 5% methanol, was 28% higher than lipase activity in water. Lipase activity in methanol also displayed the greatest rate of hydrolysis of the substrate compared to all other non-aqueous solvents. Interestingly, our MD simulations showed that the conformational state and stability of lipase in methanol is similar to that of the enzyme in water. Lipase activity works the best in 5% methanol which can be used in industry for chemical synthesis and enzyme-catalyzed reactions.

Valuable Fatty Acids in Bryophytes-Production, Biosynthesis, Analysis and Applications.

Bryophytes (mosses, liverworts and hornworts) often produce high amounts of very long-chain polyunsaturated fatty acids (vl-PUFAs) including arachidonic acid (AA, 20:4 Δ5,8,11,14) and eicosapentaenoic acid (EPA, 20:5 Δ5,8,11,14,17). The presence of vl-PUFAs is common for marine organisms such as algae, but rarely found in higher plants. This could indicate that bryophytes did not lose their marine origin completely when they landed into the non-aqueous environment. Vl-PUFA, especially the omega-3 fatty acid EPA, is essential in human diet for its benefits on healthy brain development and inflammation modulation. Recent studies are committed to finding new sources of vl-PUFAs instead of fish and algae oil. In this review, we summarize the fatty acid compositions and contents in the previous studies, as well as the approaches for qualification and quantification. We also conclude different approaches to enhance AA and EPA productions including biotic and abiotic stresses.

A novel turn-on red light emitting chromofluorogenic hydrazone based fluoride sensor: Spectroscopy and DFT studies

A new simple, small molecule hydrazone was synthesized from 1:1 condensation reaction of anthrone and 2-hydrazinobenzoic acid. It was characterized by absorption, emission spectrometry, FTIR, NMR, mass studies and investigated as a ratiometric, turn-on, luminescent chemosensor of fluoride ion (F−) in the red region (550−700 nm). The sensor is highly selective for fluoride ion in the DMSO medium in presence of other anions (Cl−, Br−, I−, PO43−, CN−, AcO−) with the limit of detection of ∼10−5 M. Upon addition of fluoride this chromofluorogenic sensor showed an instant color change from pale orange to red which was observed in naked eye and emitted red fluorescence under the UV light. A huge red shift of the ligand was observed in presence of F− which is of great interest. The energy optimized structure, electronic transitions involved in absorption and emission spectroscopy were supported by DFT and TDDFT studies. This color change was captured in RGB grabber application, installed in a smart phone which might be applicable for monitoring fluoride ion concentration in non-aqueous environment. In addition the sensor was used for the detection and estimation of F− in real samples using UV–vis spectroscopy. The results obtained were close to values obtained from the fluoride meter. Thus the above sensor might be used for the analysis of fluoride for real applications.

Platform for Screening Abiotic/Biotic Interactions Using Indicator Displacement Assays.

This paper describes novel adaptations of optically sectioned planar format assays to screen compounds for their affinities to materials surfaces. The novel platform, which we name optically sectioned indicator displacement assays (O-IDA), makes use of displaceable dyes in a format adaptable to high-throughput multiwell plate technologies. We describe two approaches: the first being where the dye exhibits fluorescence in both the surface bound and unbound state and the second, where fluorescence is lost upon displacement of the dye from the surface. Half maximal inhibitory concentration (IC50), binding affinity (Ki), and binding free energy (ΔGads) values can be extracted from the raw data. Representative biomolecules were tested for interactions with silica in an aqueous environment and ZnO(0001)-Zn and (10-10) facets in a nonaqueous environment. We provide the first experimental values for both the binding of small molecules to silica and the facet-dependent ZnO binding affinity of key amino acids associated with ZnO-specific oligopeptides. The specific data will be invaluable to those studying interactions at interfaces both experimentally and computationally. O-IDA provides a general framework for the high-throughput screening of molecule binding to materials surfaces, which has important applications in drug delivery, (bio-) catalysis, biosensing, and biomaterial engineering.

Minor Cannabinoids of Cannabis sativa L.

Cannabinoids from Cannabis sativa L. play an important role as natural products in clinics. The major cannabinoids compromise tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA) and its decarboxylated analogs. In this review, we focus on often neglected minor cannabinoids and discuss biosynthetic and chemical degradation routes to other neglected cannabinoids in Cannabis sativa starting from THCA, CBDA and cannabichromenic acid (CBCA). Based on the literature, patents and scientific reports, essential routes for the chemical modification of cannabinoids are discussed to explain chemical diversity chemical conversion and degradation by UV light, as well as temperature and pH leading to the formation of structurally unusual cannabinoids in planta called as minor cannabinoids. Based on known bioorganic reaction schemes and organic chemistry, principles for minor cannabinoid formation like [2+2] cycloaddition, Markonov condensation, radical introduction, or aromatization are discussed. Finally, the non-aqueous environment in Cannabis sativa trichomes is analyzed to clarify their role of a miniaturized bioreactors the light-induced conversion in a non-aqueous enviroment. The overall objective is to bridge from metabolic profiling via cannabinomics to structural and chemical diversity that allows the definition of patterns with consequences also to pharmacology and plant breeding.

A High-Energy-Density and Long-Life Chalcogenide-Iodide Redox Flow Battery

Redox flow batteries (RFBs) are promising technologies for application in both grid-scale power station and electric vehicles owing to their flexible architecture decoupling power and energy1, 2. The development of aqueous RFBs has been strongly hindered by low energy density, limited cell voltage and rapid capacity fading, which largely can be attributed to the poor solubility of electroactive species, small voltage window of water and limited ion selectivity capability of membrane1. Chalcogenide has been reported to have high solubility in nonaqueous environment with high charge/discharge reversibility, which makes it a promising anolyte candidate for aqueous RFBs3-5. However, it is found that these sulfur-based RFBs have been challenged by their poor cycle life and rate capability, owing to the strong shuttle phenomenon and slow kinetics of polysulfide reaction3, 5. It is critical to manipulate the competition between diffusion/crossover and the rate of electrochemical reaction of soluble active species in order to improve cycle life of RFBs. In this work, we exploited a composite-based ion-exchange membrane for chalcogenide-iodide RFBs. We evaluated the effectiveness of various membrane compositions and will discuss the role of each component in the membrane toward long-life operation. We applied UV-vis spectroscopy to probe the active reaction species involved in the RFB operation. In addition, we will discuss the use of complexing agent for polysulfide species to increase the energy density (molar electron number per molecule) and energy efficiency (higher reaction kinetics) of the chalcogenide-iodide RFBs. Acknowledgement: This work was fully supported by a grant from the Research Grant Council of the Hong Kong Special Administrative Region, China under NSFC/RGC Joint Research Scheme 2018/19 Project No. N_CUHK435/18. Reference: W. Wang, Q. Luo, B. Li, X. Wei, L. Li and Z. Yang, Adv. Funct. Mater., 23, 970-986 (2013).F. Pan and Q. Wang, Molecules, 20, 20499-20517 (2015).S. Yun, S. H. Park, J. S. Yeon, J. Park, M. Jana, J. Suk and H. S. Park, Adv. Funct. Mater., 1707593 (2018).N. Li, Z. Weng, Y. Wang, F. Li, H.-M. Cheng and H. Zhou, Energy Environ. Sci., 7, 3307-3312 (2014).Z. Li, G. Weng, Q. Zou, G. Cong and Y.-C. Lu, Nano energy, 30, 283-292 (2016).

Tuning the Selectivity and Activity of Electrochemical Interfaces with Defective Graphene Oxide and Reduced Graphene Oxide.

Engineered solid–liquid interfaces will play an important role in the development of future energy storage and conversion (ESC) devices. In the present study, defective graphene oxide (GO) and reduced graphene oxide (rGO) structures were used as engineered interfaces to tune the selectivity and activity of Pt disk electrodes. GO was deposited on Pt electrodes via the Langmuir–Blodgett technique, which provided compact and uniform GO films, and these films were subsequently converted to rGO by thermal reduction. Electrochemical measurements revealed that both GO and rGO interfaces on Pt electrodes exhibit selectivity toward the oxygen reduction reaction (ORR), but they do not have an impact on the activity of the hydrogen oxidation reaction in acidic environments. Scanning transmission electron microscopy at atomic resolution, along with Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), and scanning electron microscopy (SEM), revealed possible diffusion sites for H2 and O2 gas molecules and functional groups relevant to the selectivity and activity of these surfaces. Based on these insights, rGO interfaces are further demonstrated to exhibit enhanced activity for the ORR in nonaqueous environments and demonstrate the power of our ex situ engineering approach for the development of next-generation ESC devices.

A low temperature-rise and facile manipulation method for single micro objects at the air-substrate interface

Controlled pickup and release of micro objects in non-aqueous environment has large potential applications in lab-on-chip systems, biotechnology, biomedicine, and micro device fabrication, but this kind of manipulation has been scarcely reported. In this paper, a low temperature-rise and facile strategy is proposed to pick up and release single micro objects in air on a substrate. Chlorella cells, pollens, glass fibers, micro copper wires and graphene sheets at the air-substrate interface can be successfully picked up by the Van der Waals force between a stationary micro manipulation probe (MMP) and captured sample, and transported through an arbitrary 3D path in air to a desired position on the substrate by moving the device. The captured sample can be controllably released by ultrasonically exciting the MMP. The effects of working parameters such as the distance between the MMP’s tip and substrate, and cross-sectional shape and size of the vibration transmission rod and MMP on the release position deviation, are investigated and design guidelines for the manipulation device are proposed. Measured temperature rise at the MMP’s tip in contact with the captured sample, is lower than 0.4 °C, which makes it competitive in the manipulation of heat sensitive samples such as biological cells.