Modification Of Small Molecules Research Articles

Gradient Hole Injection Inducing Efficient Exciton Recombination in Blue (475 nm) Perovskite QLEDs.

Perovskite quantum dots (QDs) are emerging as excellent light sources for light-emitting diodes (LEDs). However, the performance of blue perovskite QD-based LEDs (QLEDs) still lags behind that of red and green counterparts, which is hindered by blue perovskite QDs with broad bandgaps that tend to increase nonradiative recombination. Here, we designed a gradient energy for hole injection utilizing multiple hole injection layers (HTLs) combined with carbazole-based small-molecule modification to reduce the hole injection barrier between HTLs and QD layers and improve the hole injection efficiency, realizing efficient exciton recombination in blue perovskite QLEDs. Moreover, the QD film on the designed HTLs demonstrates a lower surface roughness and improved photoluminescence properties. The optimized blue CsPbCl3-xBrx QLEDs exhibit an impressive external quantum efficiency of 20.7% with an electroluminescence peak at 475 nm and a turn-on voltage of 2.6 V, representing the state-of-the-art for blue perovskite LEDs emitting in the range of 460-480 nm.

Modifications of Protein-Bound Substrates by Trans-Acting Enzymes in Natural Products Biosynthesis.

Enzymatic modifications of small molecules are a common phenomenon in natural product biosynthesis, leading to the production of diverse bioactive compounds. In polyketide biosynthesis, modifications commonly take place after the completion of the polyketide backbone assembly by the polyketide synthases and the mature products are released from the acyl-carrier protein (ACP). However, exceptions to this rule appear to be widespread, as on-line hydroxylation, methyl transfer, and cyclization during polyketide assembly process are common, particularly in trans-AT PKS systems. Many of these modifications are catalyzed by specific domains within the modular PKS systems. However, several of the on-line modifications are catalyzed by stand-alone proteins. Those include the on-line Baeyer-Villiger oxidation, α-hydroxylation, halogenation, epoxidation, and methyl esterification during polyketide assembly, dehydrogenation of ACP-bound short fatty acids by acyl-CoA dehydrogenase-like enzymes, and glycosylation of ACP-bound intermediates by discrete glycosyltransferase enzymes. This review article highlights some of these trans-acting proteins that catalyze enzymatic modifications of ACP-bound small molecules in natural product biosynthesis.

A novel biosensor based on antibody-controlled strand displacement amplification (SDA) and hybridization chain reaction (HCR) for tetracycline detection

The specificity of antibodies and efficient amplification of nucleic acid molecules play an important role in developing biosensors for monitoring human and environmental health. Herein, integrating their capabilities by site-selective modification of small molecules on DNA, a biosensor based on antibody-controlled strand displacement amplification (SDA) and hybridization chain reaction (HCR) was developed. The SDA–HCR reaction was activated by the competitive binding of antibodies to free small molecules and small molecule-conjugated DNA. As a proof-to-concept, we developed a biosensor capable of detecting tetracycline (TC) with high sensitivity and specificity. First, TC was labeled with azide group through chemical modification, and TC–DNA was prepared by copper-free click chemistry. Further, the antibody-controlled SDA–HCR reaction was developed through serial optimization. By this method, TC could be detected in a linear range of 0.01–100 µM with a detection limit of 0.006 µM, and the recovery of actual samples was 96.62–100.31 % with 1.70–4.00 % RSD, suggesting satisfactory performance by the biosensor. Using this method, TC or any other small molecules can be detected without washing, immobilization, and multiple additional steps, which would simplify detection to a great degree. Consequently, the distinctive strategy proposed in this work may find more applications in the detection of other small molecules.

A new strategy to improve the dielectric properties of cellulose nanocrystals (CNCs): Surface modification of small molecules

Nanocellulose finds various applications in advanced electrical devices due to its impressive mechanical properties, thermal stability, and degradability. Cellulose nanocrystals (CNCs) with excellent dielectric properties may act as a fresh dielectric plastic. In this study, a new strategy of small molecule modification was used to improve the dielectric constant, breakdown strength, and band gap of the CNCs. The dipole moments, dipole density, and the anisotropic impact of surface groups on the dielectric constant were studied. The number of sulfates in the CNCs showed a gradient due to alkali treatment and sulfonation, which allowed for a controlled range of the dielectric constant of nanocellulose between 4.9 and 11.9. TEMPO oxidation (2,2,6,6-tetramethylpiperidine-1-oxyl) and cyanoethylation of the CNCs further increased the dielectric constant to 11.1 and 13.2, respectively, and the dielectric loss 10−1. By understanding and innovating organic polymer dielectrics, we can provide significant benefits to the electronics and device industries.

Enzymatic Synthesis of l-Methionine Analogues and Application in a Methyltransferase Catalysed Alkylation Cascade.

Chemical modification of small molecules is a key step for the development of pharmaceuticals. S-adenosyl-l-methionine (SAM) analogues are used by methyltransferases (MTs) to transfer alkyl, allyl and benzyl moieties chemo-, stereo- and regioselectively onto nucleophilic substrates, enabling an enzymatic way for specific derivatisation of a wide range of molecules. l-Methionine analogues are required for the synthesis of SAM analogues. Most of these are not commercially available. In nature, O-acetyl-l-homoserine sulfhydrolases (OAHS) catalyse the synthesis of l-methionine from O-acetyl-l-homoserine or l-homocysteine, and methyl mercaptan. Here, we investigated the substrate scope of ScOAHS from Saccharomyces cerevisiae for the production of l-methionine analogues from l-homocysteine and organic thiols. The promiscuous enzyme was used to synthesise nine different l-methionine analogues with modifications on the thioether residue up to a conversion of 75 %. ScOAHS was combined with an established MT dependent three-enzyme alkylation cascade, allowing transfer of in total seven moieties onto two MT substrates. For ethylation, conversion was nearly doubled with the new four-enzyme cascade, indicating a beneficial effect of the in situ production of l-methionine analogues with ScOAHS.

Alkaline hydrogen production promoted by small-molecule modification on flowerlike Co2(OH)2CO3

Developing a low-cost and high-efficiency nonprecious metal-based catalyst for hydrogen evolution reaction (HER) is of great significance for the utilization of hydrogen energy. In this work, we report a molecular-modification strategy to fabricate a self-supported hydrogen evolution electrode, specially by grafting the macrocyclic molecules (HHTP = 2,3,6,7,10,11-hexahydroxytriphenylene) on the surface of a cobaltous dihydroxycarbonate (COC) seed layer. The HHTP-COC electrode is endowed with a rod-like structure, which provides favorable access for charge transportation and mass exchange. The macrocyclic molecule structure in HHTP can be grafted on COC and improve the electrical conductivity, while the interaction between HHTP and COC induces the rearrangement of charge configuration on the surface. Due to the combination effects of several aspects, the HHTP-COC electrode achieves astonishing HER activity, with a low overpotential of 61.0 mV (η10, at the current density of 10 mA cm−2) and excellent stability in alkaline condition. This kind of interface engineering based on the organic molecules can be applied to the design and manufacture of electrocatalysts in the field of energy conversion and storage.

BAHD Company: The Ever-Expanding Roles of the BAHD Acyltransferase Gene Family in Plants.

Plants' ability to chemically modify core structures of specialized metabolites is the main reason why the plant kingdom contains such a wide and rich array of diverse compounds. One of the most important types of chemical modifications of small molecules is the addition of an acyl moiety to produce esters and amides. Large-scale phylogenomics analyses have shown that the enzymes that perform acyl transfer reactions on the myriad small molecules synthesized by plants belong to only a few gene families. This review is focused on describing the biochemistry, evolutionary origins, and chemical ecology implications of one of these families-the BAHD acyltransferases. The growth of advanced metabolomic studies coupled with next-generation sequencing of diverse plant species has confirmed that the BAHD family plays critical roles in modifying nearly all known classes of specialized metabolites. The current and future outlook for research on BAHDs includes expanding their roles in synthetic biology and metabolic engineering.

Strategies for Structural Modification of Small Molecules to Improve Blood–Brain Barrier Penetration: A Recent Perspective

In the development of central nervous system (CNS) drugs, the blood-brain barrier (BBB) restricts many drugs from entering the brain to exert therapeutic effects. Although many novel delivery methods of large molecule drugs have been designed to assist transport, small molecule drugs account for the vast majority of the CNS drugs used clinically. From this perspective, we review studies from the past five years that have sought to modify small molecules to increase brain exposure. Medicinal chemists make it easier for small molecules to cross the BBB by improving diffusion, reducing efflux, and activating carrier transporters. On the basis of their excellent work, we summarize strategies for structural modification of small molecules to improve BBB penetration. These strategies are expected to provide a reference for the future development of small molecule CNS drugs.

Preserving the work function of Ultra-Violet-ozone treated indium tin oxide by triarylamine-based small molecule modification for solution-processed organic light-emitting diodes with increased external quantum efficiency

UV-ozone treatment is one of the most common ways to increase the work function of indium tin oxide (ITO), which is used as the transparent conducting anode in organic light-emitting diodes (OLEDs). However, the work function increase is time sensitive when the samples are left or processed in air, often returning to a similar value to that measured before UV-ozone treatment. We found that for OLEDs formed by solution processing and containing a poly(ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hole injection layer that there was no advantage in terms of device efficiency of using UV-ozone treated ITO. However, if a triarylamine-based small molecule [N1,N3,N5-tris(4-n-butylphenyl)-N1,N3,N5-triphenylbenzene-1,3,5-triamine, 4-n-BTDAB] was introduced onto the UV-ozone treated ITO then the work function was stabilised. When 4-n-BTDAB was introduced between UV-ozone treated ITO and PEDOT:PSS, the resultant solution processed OLEDs were found to have a maximum external quantum efficiency ≈20% higher (corresponding to an absolute increase of ≈2% to around 12%) compared to devices with the same structure but without the triarylamine layer.

Computational design of small molecular modulators of protein-protein interactions with a novel thermodynamic cycle: Allosteric inhibitors of HIV-1 integrase.

Targeting protein-protein interactions for therapeutic development involves designing small molecules to either disrupt or enhance a known PPI. For this purpose, it is necessary to compute reliably the effect of chemical modifications of small molecules on the protein-protein association free energy. Here we present results obtained using a novel thermodynamic free energy cycle, for the rational design of allosteric inhibitors of HIV-1 integrase (ALLINI) that act specifically in the early stage of the infection cycle. The new compounds can serve as molecular probes to dissect the multifunctional mechanisms of ALLINIs to inform the discovery of new allosteric inhibitors. The free energy protocol developed here can be more broadly applied to study quantitatively the effects of small molecules on modulating the strengths of protein-protein interactions.

Anti-COVID drugs: repurposing existing drugs or search for new complex entities, strategies and perspectives.

At the end of 2019, a novel virus causing severe acute respiratory syndrome spread globally. There are currently no effective drugs targeting SARS-CoV-2. In this study, based on the analysis of numerous references and selected methods of computational chemistry, the strategy of integrative structural modification of small-molecules with antiviral activity into potential active complex molecules has been presented. Proposed molecules have been designed based on the structure of triterpene oleanolic acid and complemented by structures characteristic of selected anti-COVID therapy assisted drugs. Their pharmaceutical molecular parameters and the preliminary bioactivity were calculated and predicted. The results of the above analyses show that among the designed complex substances there are potential antiviral agents directed mainly on SARS-CoV-2.

Controlling gene expression with light: a multidisciplinary endeavour.

The expression of a gene to a protein is one of the most vital biological processes. The use of light to control biology offers unparalleled spatiotemporal resolution from an external, orthogonal signal. A variety of methods have been developed that use light to control the steps of transcription and translation of specific genes into proteins, for cell-free to in vivo biotechnology applications. These methods employ techniques ranging from the modification of small molecules, nucleic acids and proteins with photocages, to the engineering of proteins involved in gene expression using naturally light-sensitive proteins. Although the majority of currently available technologies employ ultraviolet light, there has been a recent increase in the use of functionalities that work at longer wavelengths of light, to minimise cellular damage and increase tissue penetration. Here, we discuss the different chemical and biological methods employed to control gene expression, while also highlighting the central themes and the most exciting applications within this diverse field.

Preparation of glycine mediated graphene oxide/g-C3N4 lamellar membranes for nanofiltration

In this work, we fabricated a series of composite membranes for nanofiltration by filtration-assisted assembly of graphene oxide (GO, with a thickness of ca. 2 nm) and graphitic carbon nitride (g-C3N4, with a thickness of ca. 5.2 nm) nanosheets with the assistance of glycine as a molecular linker to enhance their interactions. The effects of g-C3N4 and glycine concentrations on the lamellar spacing of GO and membrane performance were subsequently investigated. Interestingly, experimental and characterization results showed that both g-C3N4 and glycine could increase the interlayer spacing of pristine GO membranes, but the former reduced the dimensions of nanochannels while the latter led to enlarged channels. As compared with pristine GO membranes, the composite membranes resulted in faster water transportation without sacrificing solute retention. With further functionalization by introducing hyperbranched polyethyleneimine (HPEI) coating, we demonstrated that an integrated Gly-GO/g-C3N4 membrane (ca. 116 nm in thickness) exhibited excellent separation performance for various organic dye solutions under different operational conditions (feed concentration, pH, etc.). Long-term stability experiments showed that this membrane yielded 90%–93% dye rejection with only a slight decline in permeance over a 40 h testing period, indicating acceptable stability. The pure water permeance of the Gly-GO/g-C3N4 membrane reached as high as 207 L h−1 m−2 bar−1. These results indicate that the covalent modification of small molecules can improve the packing of GO nanosheets and lead to outstanding nanofiltration performance which has great potential applications in the field of water purification and separation.

Rational Modification of Small Molecules with High Device Reproducibility Induced by Improved Interfacial Contact through Intermolecular Hydrogen Bonds.

The interfacial contact between the semiconductor and the electrode can effectively affect the device performance through the penetration of metal atoms in semiconductors from the grain boundaries. Thus, how to design a novel molecule with few grain boundaries, namely, large grain size, in solid state is an important task to achieve excellent memory device with high reproducibility. Intermolecular hydrogen-bonding interaction has been proved to be a powerful driving force for molecules assembling into large crystalline aggregates. In this work, the molecular terminals with different numbers of electron-deficient imine (C═N) nitrogen atoms are designed to investigate the effect of hydrogen-bonding interaction on molecular crystalline grains and interfacial contact. X-ray diffraction and grazing-incidence small-angle X-ray scattering measurements verified the superior molecular aggregates and grain boundaries of the molecule with two hydrogen-bonding sites in solid state, donating the corresponding devices showing optimized ternary data-storage performance with lower threshold voltages and higher device reproducibility.

Current approaches for RNA-labelling to identify RNA-binding proteins.

RNA is involved in all domains of life, playing critical roles in a host of gene expression processes, host-defense mechanisms, cell proliferation, and diseases. A critical component in many of these events is the ability for RNA to interact with proteins. Over the past few decades, our understanding of such RNA-protein interactions and their importance has driven the search and development of new techniques for the identification of RNA-binding proteins. In determining which proteins bind to the RNA of interest, it is often useful to use the approach where the RNA molecule is the "bait" and allow it to capture proteins from a lysate or other relevant solution. Here, we review a collection of methods for modifying RNA to capture RNA-binding proteins. These include small-molecule modification, the addition of aptamers, DNA-anchoring, and nucleotide substitution. With each, we provide examples of their application, as well as highlight their advantages and potential challenges.

Identification of Protein Targets of Bioactive Small Molecules Using Randomly Photomodified Probes.

Identifying protein targets of bioactive small molecules often requires complex, lengthy development of affinity probes. We present a method for stochastic modification of small molecules of interest with a photoactivatable phenyldiazirine linker. The resulting isomeric mixture is conjugated to a hydrophilic copolymer decorated with biotin and a fluorophore. We validated this approach using known inhibitors of several medicinally relevant enzymes. At least a portion of the stochastic derivatives retained their binding to the target, enabling target visualization, isolation, and identification. Moreover, the mix of stochastic probes could be separated into fractions and tested for binding affinity. The structure of the active probe could be determined and the probe resynthesized to improve binding efficiency. Our approach can thus enable rapid target isolation, identification, and visualization, while providing information required for subsequent synthesis of an optimized probe.

Mass spectrometric evidence for the modification of small molecules in a cobalt-60-irradiated rodent diet.

Following publication of Prasain et al.1 in Volume 52, Issue 8 of Journal of Mass Spectrometry, Figures 1 and 2 were found to be interchanged. The correct images and captions for Figures 1 and 2 are given below.

Mass spectrometric evidence for the modification of small molecules in a cobalt-60-irradiated rodent diet.

The purpose of this study was to investigate the effect of radiation on the content of animal diet constituents using global metabolomics. Aqueous methanolic extracts of control and cobalt-60-irradiated Teklad 7001 diets were comprehensively analyzed using nano-liquid chromatography-MS/MS. Among the over 2000 ions revealed by XCMS followed by data preprocessing, 94 positive and 143 negative metabolite ions had greater than 1.5-fold changes and p-values <0.01. Use of MetaboAnalyst statistical software demonstrated complete separation of the irradiated and non-radiated diets in unsupervised principal components analysis and supervised partial least squares discriminant analysis. Irradiation led to an increase in the content of phytochemicals such as glucosinolates and oxidized lipids in the diet. Twenty-eight metabolites that were significantly changed in the irradiated samples were putatively identified at the level of molecular formulae by MS/MS. MS/MSALL analysis of chloroform-methanol extracts of the irradiated diet showed increased levels of a number of unique linoleic acid-derived branched fatty acid esters of hydroxy fatty acids. These data imply that gamma irradiation of animal diets causes chemical changes to dietary components, which in turn may influence the risk of mammary cancer. Copyright © 2017 John Wiley & Sons, Ltd.

The Arabidopsis UGT87A2, a stress-inducible family 1 glycosyltransferase, is involved in the plant adaptation to abiotic stresses.

Glycosyltransferase (GT) family-1, the biggest GT family in plants, typically participates in modification of small molecules and affects many aspects during plant development. In Arabidopsis thaliana, although some UDP glycosyltransferases (UGTs) of family-1 have been functionally characterized, functions of most the UGTs remain unknown or fragmentary. Here, we report data for the Arabidopsis UGT87A2, a stress-regulated GT. We found that UGT87A2 could be dramatically induced by salinity, osmotic stress, drought and ABA. Overexpression of UGT87A2 (87A2OE) leads to accelerated germination and greening, higher survival rate as well as increased root length against abiotic stresses compared with those of wild-type (WT) plants. In addition, we observed lower water loss rate in the 87A2OE plants due to smaller stomatal apertures. The transgenic plants also showed reduced levels of H2 O2 and superoxide under low water status compared with those of WT plants. Consistently, function loss of UGT87A2 in ugt87a2 knockout lines resulted in opposite performances under these conditions. A transcriptome profiling revealed that 121 genes were differentially regulated upon UGT87A2 overexpression, and a large number of stress-induced genes were upregulated in UGT87A2 overexpression plants. Expression of seven genes among them were assessed by quantitative real-time polymerase chain reaction (qRT-PCR), including CPK32, CYP81F2, MYB96, DREB2A, FBS1, PUB23 and RAV2 under both control and stress treatments, and the results greatly validated our transcriptome data. Taken together, our findings support an explicit role of UGT87A2 in adaptation to abiotic stresses.

Improved efficiency in organic/inorganic hybrid solar cells by interfacial modification of ZnO nanowires with small molecules

We demonstrate improved photovoltaic performance of ZnO nanowire/poly(3-hexylthiophene) (P3HT) nanofiber hybrid devices using an interfacial modification of ZnO nanowires. Formation of cascade energy levels between the ZnO nanowire and P3HT nanofiber was achieved by interfacial modification of ZnO nanowires using small molecules tetraphenyldibenzoperiflanthene (DBP) and 3,4,9,10-perylenetetracarboxylic bisbenzimidazole (PTCBI). The successful demonstration of improved device performance owing to the cascade energy levels by small molecule modification is a promising approach toward highly efficient organic/inorganic hybrid solar cells.