Monthly Archives: September 2023

Functionalized Fluorescent Organic Nanoparticles Based AIE Enabling Effectively Targeting Cancer Cell Imaging

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Functionalized Fluorescent Organic Nanoparticles Based AIE Enabling Effectively Targeting Cancer Cell Imaging

The cRGD-functionalized nanoparticles obtained by chiral self-assembly with red emission and AIE characteristics could serve as efficient fluorescent probes for targeting cancer cells.


Abstract

We report a fluorescent dye TM by incorporating the tetraphenylethylene (TPE) and cholesterol components into perylene bisimides (PBI) derivative. Fluorescence emission spectrum shows that the dye has stable red emission and aggregation-induced emission (AIE) characteristics. The incorporation of cholesterol components triggers TM to show induced chirality through supramolecular self-assembly. The cRGD-functionalized nanoparticles were prepared by encapsulating fluorescent dyes with amphiphilic polymer matrix. The functionalized fluorescent organic nanoparticles exhibit excellent biocompatibility, large Stokes’ shift and good photostability, which make them effective fluorescent probes for targeting cancer cells with high fluorescence contrast.

Photonanozyme with Light Mediated Activity

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Photonanozyme with Light Mediated Activity

This work summarizes the advances of photo-responsive nanozyme, of which the catalytic activity can be induced or enhanced using different energy electromagnetic waves (infrared, visible light, ultraviolet and X-rays). It offers light-controlled functions and applications that cannot be achieved by pristine nanozyme.


Abstract

Since the discovery that Fe3O4 nanoparticle has intrinsic natural peroxidase-like activity by Yan et al in 2007, mimicking native enzymes via nano-engineering (named as nanozyme) pays a new avenue to bypass the fragility and recyclability of natural enzymes and thus expedites the biocatalysis in multidisciplinary applications. In addition, the high programmability and structural stability attributes of nanozyme afford the ease of coupling with electromagnetic waves of different energies, providing great opportunities to construct photo-responsive nanozyme under user-defined electromagnetic waves, which is known as photo-nanozyme. In this concept, we aim to providing a summary of how electromagnetic waves with varying wavelengths can serve as external stimuli to induce or enhance the biocatalytic performance of photo-nanozymes, thereby offering fascinating functions that cannot be achieved by pristine nanozyme.

Exploring the Translational Gap of a Novel Class of Escherichia coli IspE Inhibitors

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Exploring the Translational Gap of a Novel Class of Escherichia coli IspE Inhibitors

Challenges in the discovery of selective IspE inhibitors with antibacterial activity and no toxicity: This work sheds light on the molecular properties for balancing enzymatic target and bacterial activities simultaneously as well as new starting points for the development of IspE inhibitors with a predicted new mode of action.


Abstract

Discovery of novel antibiotics needs multidisciplinary approaches to gain target enzyme and bacterial activities while aiming for selectivity over mammalian cells. Here, we report a multiparameter optimisation of a fragment-like hit that was identified through a structure-based virtual-screening campaign on Escherichia coli IspE crystal structure. Subsequent medicinal-chemistry design resulted in a novel class of E. coli IspE inhibitors, exhibiting activity also against the more pathogenic bacteria Pseudomonas aeruginosa and Acinetobacter baumannii. While cytotoxicity remains a challenge for the series, it provides new insights on the molecular properties for balancing enzymatic target and bacterial activities simultaneously as well as new starting points for the development of IspE inhibitors with a predicted new mode of action.

Nucleic Acid Detection through RNA‐Guided Protease Activity in Type III‐E CRISPR‐Cas Systems

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Nucleic Acid Detection through RNA-Guided Protease Activity in Type III-E CRISPR-Cas Systems

Two for one: We have established an assay for nucleic acid detection by using the target ssRNA-activated protease from the type III-E CRISPR-Cas system. This assay would allow simultaneous detection of one or two target genes or viruses, which could be further expanded by incorporating more type III-E systems of various species. This assay provides an easily adaptable platform for biological and clinical diagnosis.


Abstract

RNA-guided protease activity was recently discovered in the type III-E CRISPR-Cas systems (Craspase), providing a novel platform for engineering a protein probe instead of the commonly used nucleic acid probe in nucleic acid detection assays. Here, by adapting a fluorescence readout technique using the affinity- and fluorescent protein dual-tagged Csx30 protein substrate, we have established an assay monitoring Csx30 cleavage by target ssRNA-activated Craspase. Four Craspase-based nucleic acid detection systems for genes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), norovirus, and the influenza virus (IFV) were reconstituted with demonstrated specificity. The assay could reliably detect target ssRNAs at concentrations down to 25 pM, which could be further improved approximately 15 000-fold (ca. 2 fM) by incorporating a recombinase polymerase isothermal preamplification step. Importantly, the species-specific substrate cleavage specificity of Craspase enabled multiplexed diagnosis, as demonstrated by the reconstituted composite systems for simultaneous detection of two genes from the same virus (SARS-CoV-2, spike and nsp12) or two types of viruses (SARS-CoV-2 and IFV). The assay could be further expanded by diversifying the fluorescent tags in the substrate and including Craspase systems from various species, thus potentially providing an easily adaptable platform for clinical diagnosis.

Synthesis of a N‐heterocyclic Olefin‐Ligated Pd Complex [(NHO)Pd{[2‐(CH3O)C6H4]3P}Cl2] as a Catalyst for Suzuki−Miyaura Coupling

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Synthesis of a N-heterocyclic Olefin-Ligated Pd Complex [(NHO)Pd{[2-(CH3O)C6H4]3P}Cl2] as a Catalyst for Suzuki−Miyaura Coupling

N-heterocyclic olefin (NHO) is known as a highly electron-donative ligand, but its application to metal catalysts has rarely been studied. In this study, a well-defined NHO ligated-Pd catalyst was developed. N-substituents on NHO ligand affected the catalytic performance, and the addition of a phosphine co-ligand, in particular [2-(MeO)C6H4]3P was effective to enhance the activity.


Abstract

N-heterocyclic olefin (NHO) is known as a highly electron-donative ligand, but its application to metal catalysts has rarely been studied. In this study, we synthesized 2-methyleneimidazolidine ligands equipped with a bicyclic frameworks with the goal of developing a NHO-ligated Pd catalyst. These synthesized [(NHO)PdCl(μ-Cl)]2 complexes had a phosphine co-ligand that proved effective as a catalyst for Suzuki-Miyaura coupling at ambient temperature. By optimizing the N-substituents of NHO ligands and a phosphine co-ligand, we developed a [(NHO)Pd{[2-(CH3O)C6H4]3P}Cl2] complex as a catalyst that shows good catalytic activity.

Design and Synthesis of Rigid‐Featured Tertiary Amine‐Derived C2‐Symmetric Chiral Furan‐N,N′‐dioxide Ligands

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Design and Synthesis of Rigid-Featured Tertiary Amine-Derived C2-Symmetric Chiral Furan-N,N′-dioxide Ligands

Newly developed rigid-featured chiral Fu-2NO ligands possesses two pyrroloimidazolone-based N-oxides as non-flat chiral walls, and afforded the opportunity for fine-tuning the ligand's electronic and conformational properties by judicious choice of the substituent in the nonligating nitrogen atom.


Abstract

To expand the chemical space of chiral N-oxides and chiral furan-containing ligands, herein we designed and synthesized a new class of rigid-featured tertiary amine-derived C2 -symmetric chiral furan-N,N′-dioxide (Fu-2NO) ligands from optically pure l-prolinamides/hydroxylprolinamides in operationally simple two steps and up to 57 % overall yield. The newly developed rigid-featured chiral Fu-2NO ligands possesses two pyrroloimidazolone-based N-oxides as non-flat chiral walls, and afforded the opportunity for fine-tuning the ligand electronic and conformational properties by judicious choice of the substituent in the nonligating nitrogen atom. More importantly, The Fu-2NO ligands can tolerate air and moisture such that no special handling is needed for their storage, and can be applied in the Ni(II)-catalyzed asymmetric Friedel-Crafts alkylation reaction of indole.

Enantiospecific Total Synthesis of (−)‐Hyacinthacine A1 and (+)‐Hyacinthacine A1 and Their Homologues Using Nitrogen Substituted Donor–Acceptor Cyclopropane

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Enantiospecific Total Synthesis of (−)-Hyacinthacine A1 and (+)-Hyacinthacine A1 and Their Homologues Using Nitrogen Substituted Donor–Acceptor Cyclopropane

Utilizing the nitrogen-substituted donor-acceptor cyclopropane, enantiospecific total syntheses of (−)-hyacinthacine A1⋅HCl and (+)-hyacinthacine A1⋅HCl were achieved. The key reactions were highly stereo- and regioselective intramolecular cyclopropanation with rhodium(II) acetate and regioselective ring opening of nitrogen-substituted D−A cyclopropanes.


Abstract

A concise and efficient enantiospecific total synthesis of (−)-hyacinthacine A1 and (+)-hyacinthacine A1 was achieved from commercially available starting material L-pyroglutamic acid and D-glutamic acid, respectively. For the synthesis of this trihydroxylated pyrrolizidine ring, we employed the nitrogen-substituted donor-acceptor cyclopropane as a key intermediate. The synthetic approach relies on two crucial steps, highly stereo- and regioselective intramolecular cyclopropanation with Rh2(OAc)4 and regioselective ring opening of a nitrogen-substituted donor-acceptor cyclopropane.

Air‐Induced Hydroxyphosphorylation of α‐Trifluoromethyl Styrenes with H‐Phosphonates and H‐Phosphine Oxides

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Air-Induced Hydroxyphosphorylation of α-Trifluoromethyl Styrenes with H-Phosphonates and H-Phosphine Oxides

Mn-mediated hydroxyphosphonylation of α-CF3-styrenes with H-phosphonates and transition-metal-free hydroxyphosphinylation of α-CF3-styrenes with H-phosphine oxides with the assistance of air were developed. A variety of β-hydroxy-β-CF3-phosphonates and β-hydroxy-β-CF3-phosphine oxides were synthesized in moderate to good yields.


Abstract

Efficient synthesis of β-hydroxy-β-CF3-phosphonates and β-hydroxy-β-CF3-phosphine oxides by Mn-mediated or transition-metal-free hydroxyphosphorylation of α-trifluoromethy)styrenes with H-phosphonates or H-phosphine oxides with the assistance of air, respectively, was described.

Trends in the Diversification of the Detergentome

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Trends in the Diversification of the Detergentome

Growing detergentome. Recent synthesis concepts and detergent building blocks, i. e., head, linker, tail, are reviewed regarding their availability and role in the expansion of the detergentome (entirety of all detergents). The development of detergents for membrane protein studies turns out to be a key driver for detergent diversity. Metric-assisted optimization strategies will facilitate the development of tailor-made and safe-to-use detergents.


Abstract

Detergents are amphiphilic molecules that serve as enabling steps for today's world applications. The increasing diversity of the detergentome is key to applications enabled by detergent science. Regardless of the application, the optimal design of detergents is determined empirically, which leads to failed preparations, and raising costs. To facilitate project planning, here we review synthesis strategies that drive the diversification of the detergentome. Synthesis strategies relevant for industrial and academic applications include linear, modular, combinatorial, bio-based, and metric-assisted detergent synthesis. Scopes and limitations of individual synthesis strategies in context with industrial product development and academic research are discussed. Furthermore, when designing detergents, the selection of molecular building blocks, i. e., head, linker, tail, is as important as the employed synthesis strategy. To facilitate the design of safe-to-use and tailor-made detergents, we provide an overview of established head, linker, and tail groups and highlight selected scopes and limitations for applications. It becomes apparent that most recent contributions to the increasing chemical diversity of detergent building blocks originate from the development of detergents for membrane protein studies. The overview of synthesis strategies and molecular blocks will bring us closer to the ability to predictably design and synthesize optimal detergents for challenging future applications.

Theoretical Understanding on the Facilitated Photoisomerization of a Carbonyl Supported Borane System

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Theoretical Understanding on the Facilitated Photoisomerization of a Carbonyl Supported Borane System

MS-CASPT2//CASSCF calculations reveal detailed mechanisms for the photoisomerization of boron compounds, showing that the steric hindrance influences their photoisomerization activity.


Abstract

Boron compound BOMes2 containing an internal B−O bond undergoes highly efficient photoisomerization, followed by sequential structural transformations, resulting in a rare eight-membered B, O-heterocycle (S. Wang, et al. Org. Lett. 2019, 21, 5285–5289). In this work, the detailed reaction mechanisms of such a unique carbonyl-supported tetracoordinate boron system in the first excited singlet (S1) state and the ground (S0) state were investigated by using the complete active space self-consistent field and its second-order perturbation (MS-CASPT2//CASSCF) method combined with time-dependent density functional theory (TD-DFT). Moreover, an imine-substituted tetracoordinated organic boron system (BNMes2) was selected for comparative study to explore the intrinsic reasons for the difference in reactivity between the two types of compounds. Steric factor was found to influence the photoisomerization activity of BNMes2 and BOMes2. These results rationalize the experimental observations and can provide helpful insights into understanding the excited-state dynamics of heteroatom-doped tetracoordinate organoboron compounds, which facilitates the rational design of boron-based materials with superior photoresponsive performances.