scholarly journals Infrequent Metadynamics Study of Rare-event Electrostatic Channeling

2021 ◽  
Author(s):  
Yan Xie ◽  
Scott Calabrese Barton
Keyword(s):  
Rare Event ◽  
Cascade Reactions ◽  
Single Step ◽  
Chemical Transformations ◽  
Transport Efficiency ◽  
Multiple Chemical

The efficiency of cascade reactions, which consist of multiple chemical transformations that occur in a single step without purification steps, is limited by the transport efficiency of intermediates between adjacent...

scholarly journals The application of the CSB to the prediction of single step reactions and reaction pathways

2004 ◽  
Vol 2 (4) ◽  
pp. 598-616 ◽  
Author(s):  
Grażyna Nowak ◽  
Grzegorz Fic
Keyword(s):  
Combinatorial Chemistry ◽  
Common Sense ◽  
Cascade Reactions ◽  
Single Step ◽  
Model Reaction ◽  
Reaction Pathways ◽  
Chemical Transformations ◽  
Step Process ◽  
Step Procedure ◽  
Selective Generation

AbstractApplications of the CSB (Common-Sense Builder) system for the logic-oriented and knowledge-assisted simulation of chemical reaction courses are described. We present the possibility of using the CSB for two ways of reaction simulation, i.e., as a multi-step process or as single step procedure. Results of the first simulation type are given to predict the course, and to model reaction mechanism. The second one is capable of complex chemical transformations such as multi-component and cascade reactions to generate structurally diverse products for combinatorial chemistry. In several experiments performed, we analyze the capabilities and limitations of the CSB modules and controlling tools for the examination and selective generation of solutions.

scholarly journals A simple and versatile design concept for fluorophore derivatives with intramolecular photostabilization

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Jasper H. M. van der Velde ◽  
Jens Oelerich ◽  
Jingyi Huang ◽  
Jochem H. Smit ◽  
Atieh Aminian Jazi ◽  
...  
Keyword(s):  
Single Molecule ◽  
Unnatural Amino Acids ◽  
Photophysical Properties ◽  
Super Resolution ◽  
Single Step ◽  
General Strategy ◽  
Self Healing ◽  
Chemical Transformations ◽  
Scaffolding Strategy ◽  
Organic Fluorophore

Abstract Intramolecular photostabilization via triple-state quenching was recently revived as a tool to impart synthetic organic fluorophores with ‘self-healing’ properties. To date, utilization of such fluorophore derivatives is rare due to their elaborate multi-step synthesis. Here we present a general strategy to covalently link a synthetic organic fluorophore simultaneously to a photostabilizer and biomolecular target via unnatural amino acids. The modular approach uses commercially available starting materials and simple chemical transformations. The resulting photostabilizer–dye conjugates are based on rhodamines, carbopyronines and cyanines with excellent photophysical properties, that is, high photostability and minimal signal fluctuations. Their versatile use is demonstrated by single-step labelling of DNA, antibodies and proteins, as well as applications in single-molecule and super-resolution fluorescence microscopy. We are convinced that the presented scaffolding strategy and the improved characteristics of the conjugates in applications will trigger the broader use of intramolecular photostabilization and help to emerge this approach as a new gold standard.

Synthetic Approaches for Building Tricyclic Cage-like Motifs Found in Indoxamycins

2020 ◽  
Vol 24 ◽  
Author(s):  
Saqlain Haider ◽  
Ikhlas A. Khan ◽  
Hanfeng Ding ◽  
Amar G. Chittiboyina
Keyword(s):  
Natural Products ◽  
Michael Addition ◽  
Claisen Rearrangement ◽  
Biological Activities ◽  
Cascade Reactions ◽  
Biological Properties ◽  
Starting Material ◽  
Central Core ◽  
Chemical Transformations ◽  
One Pot

Abstract:: Indoxamycins A-F, a novel class of polyketides, were isolated from the saline culture of marine-derived actinomyces by Sato et al. in 2009. Intriguing stereochemical complexity involving tricyclic [5.5.6] cage-like structures with six consecutive chiral centers challenged many organic chemists. Chemical ingenuity, implementation of pioneered reactions along with fine chemical transformations allowed not only the rapid construction of the central core but also allowed minor structural revision and paved the information to delineate the absolute stereostructures of these complex polyketide marine natural products. To achieve the central core structure in indoxamycins A-F, reactions like the Ireland- Claisen rearrangement, an enantioselective 1,6-enyne reductive cyclization, and one-pot cascade reactions of 1,2- addition/oxa-Michael/methylenation were employed. Using the chiral pool approach, the readily available R-carvone was employed as a cost-effective starting material to achieve the concise total syntheses of (-)-indoxamycins A and B, in which Pauson-Khand, Cu-catalyzed Michael addition and tandem retro-oxa-Michael addition/1,2-addition/oxa-Michael addition reactions were employed. The antipodes, (+)-indoxamycins can be easily accessed by simply switching to S-carvone as the starting material. Synthetically prepared indoxamycins A-F are devoid of antiproliferative properties which disagrees with the work reported by Sato and co-workers for (-)-indoxamycins A and F. Nevertheless, ready access to such complex natural products allows probing the untapped potential biological activities of these polyketides including cytotoxicity. A concise overview of interesting, key chemical transformations including named reactions in establishing the architecture of indoxamycins was compiled to inspire organic chemists and help reinvigorate the development of novel strategies for the asymmetric synthesis as well as the development of novel derivatives of indoxamycins with unique physicochemical and biological properties.

scholarly journals Human Cytomegalovirus Labeled with Green Fluorescent Protein for Live Analysis of Intracellular Particle Movements

2005 ◽  
Vol 79 (5) ◽  
pp. 2754-2767 ◽  
Author(s):  
Kerstin Laib Sampaio ◽  
Yolaine Cavignac ◽  
York-Dieter Stierhof ◽  
Christian Sinzger
Keyword(s):  
Green Fluorescent Protein ◽  
Human Cytomegalovirus ◽  
Fluorescent Protein ◽  
Rare Event ◽  
Single Step ◽  
Wild Type Virus ◽  
Cell Cortex ◽  
Long Distance ◽  
Infected Cells ◽  
Green Fluorescent

ABSTRACT Human cytomegalovirus (HCMV) replicates in the nuclei of infected cells. Successful replication therefore depends on particle movements between the cell cortex and nucleus during entry and egress. To visualize HCMV particles in living cells, we have generated a recombinant HCMV expressing enhanced green fluorescent protein (EGFP) fused to the C terminus of the capsid-associated tegument protein pUL32 (pp150). The resulting UL32-EGFP-HCMV was analyzed by immunofluorescence, electron microscopy, immunoblotting, confocal microscopy, and time-lapse microscopy to evaluate the growth properties of this virus and the dynamics of particle movements. UL32-EGFP-HCMV replicated similarly to wild-type virus in fibroblast cultures. Green fluorescent virus particles were released from infected cells. The fluorescence stayed associated with particles during viral entry, and fluorescent progeny particles appeared in the nucleus at 44 h after infection. Surprisingly, strict colocalization of pUL32 and the major capsid protein pUL86 within nuclear inclusions indicated that incorporation of pUL32 into nascent HCMV particles occurred simultaneously with or immediately after assembly of the capsid. A slow transport of nuclear particles towards the nuclear margin was demonstrated. Within the cytoplasm, most particles performed irregular short-distance movements, while a smaller fraction of particles performed centripetal and centrifugal long-distance movements. Although numerous particles accumulated in the cytoplasm, release of particles from infected cells was a rare event, consistent with a release rate of about 1 infectious unit per h per cell in HCMV-infected fibroblasts as calculated from single-step growth curves. UL32-EGFP-HCMV will be useful for further investigations into the entry, maturation, and release of this virus.

scholarly journals Current state of and need for enzyme engineering of 2-deoxy-D-ribose 5-phosphate aldolases and its impact

2021 ◽  
Author(s):  
Juha Rouvinen ◽  
Martina Andberg ◽  
Johan Pääkkönen ◽  
Nina Hakulinen ◽  
Anu Koivula
Keyword(s):  
Protein Engineering ◽  
Catalytic Mechanism ◽  
Cascade Reactions ◽  
Single Step ◽  
Enzyme Engineering ◽  
Enzymatic Reactions ◽  
Tim Barrel ◽  
The Stability

Abstract Deoxyribose-5-phosphate aldolases (DERAs, EC 4.1.2.4) are acetaldehyde-dependent, Class I aldolases catalyzing in nature a reversible aldol reaction between an acetaldehyde donor (C2 compound) and glyceraldehyde-3-phosphate acceptor (C3 compound, C3P) to generate deoxyribose-5-phosphate (C5 compound, DR5P). DERA enzymes have been found to accept also other types of aldehydes as their donor, and in particular as acceptor molecules. Consequently, DERA enzymes can be applied in C–C bond formation reactions to produce novel compounds, thus offering a versatile biocatalytic alternative for synthesis. DERA enzymes, found in all kingdoms of life, share a common TIM barrel fold despite the low overall sequence identity. The catalytic mechanism is well-studied and involves formation of a covalent enzyme-substrate intermediate. A number of protein engineering studies to optimize substrate specificity, enzyme efficiency, and stability of DERA aldolases have been published. These have employed various engineering strategies including structure-based design, directed evolution, and recently also machine learning–guided protein engineering. For application purposes, enzyme immobilization and usage of whole cell catalysis are preferred methods as they improve the overall performance of the biocatalytic processes, including often also the stability of the enzyme. Besides single-step enzymatic reactions, DERA aldolases have also been applied in multi-enzyme cascade reactions both in vitro and in vivo. The DERA-based applications range from synthesis of commodity chemicals and flavours to more complicated and high-value pharmaceutical compounds. Key points • DERA aldolases are versatile biocatalysts able to make new C–C bonds. • Synthetic utility of DERAs has been improved by protein engineering approaches. • Computational methods are expected to speed up the future DERA engineering efforts. Graphical abstract

Doubleisomerization / cycloisomerization / aromatization of 1-(allyloxy)-2-(cyclopropylmethyl)benzenes to give 2-ethyl-3-isopropylbenzofurans using multitasking single rhodium catalyst

2021 ◽  
Author(s):  
Yuta Sato ◽  
Tsuyoshi Matsuzaki ◽  
Tsunayoshi Takehara ◽  
Makoto Sako ◽  
Takeyuki Suzuki ◽  
...  
Keyword(s):  
Rhodium Catalyst ◽  
Reaction Vessel ◽  
Chemical Transformations ◽  
Catalyst Systems ◽  
Multiple Chemical ◽  
Single Reaction

Multitasking single-catalyst systems that allow multiple chemical transformations within a single reaction vessel are important for the development of eco-compatible chemistry. Here, we have developed a rhodium-catalyzed system that transforms...

scholarly journals Light-Driven Biocatalysis in Liposomes and Polymersomes: Where Are We Now?

Catalysts ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 12 ◽  
Author(s):  
Guoshu Wang ◽  
Kathrin Castiglione
Keyword(s):  
Carbon Fixation ◽  
Research Effort ◽  
Proton Translocation ◽  
Cascade Reactions ◽  
Organic Chemical ◽  
Proton Pumps ◽  
Chemical Transformations ◽  
Energy Cycle ◽  
Artificial Photosynthetic ◽  
Energy Dependent

The utilization of light energy to power organic-chemical transformations is a fundamental strategy of the terrestrial energy cycle. Inspired by the elegance of natural photosynthesis, much interdisciplinary research effort has been devoted to the construction of simplified cell mimics based on artificial vesicles to provide a novel tool for biocatalytic cascade reactions with energy-demanding steps. By inserting natural or even artificial photosynthetic systems into liposomes or polymersomes, the light-driven proton translocation and the resulting formation of electrochemical gradients have become possible. This is the basis for the conversion of photonic into chemical energy in form of energy-rich molecules such as adenosine triphosphate (ATP), which can be further utilized by energy-dependent biocatalytic reactions, e.g. carbon fixation. This review compares liposomes and polymersomes as artificial compartments and summarizes the types of light-driven proton pumps that have been employed in artificial photosynthesis so far. We give an overview over the methods affecting the orientation of the photosystems within the membranes to ensure a unidirectional transport of molecules and highlight recent examples of light-driven biocatalysis in artificial vesicles. Finally, we summarize the current achievements and discuss the next steps needed for the transition of this technology from the proof-of-concept status to preparative applications.

scholarly journals A Multi-Enzyme Cascade Reaction for the Production of 2’3’‑cGAMP

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 590
Author(s):  
Martin Becker ◽  
Patrick Nikel ◽  
Jennifer N. Andexer ◽  
Stephan Lütz ◽  
Katrin Rosenthal
Keyword(s):  
Cyclic Gmp ◽  
Reaction Rate ◽  
Atp Synthesis ◽  
Cascade Reactions ◽  
Single Step ◽  
One Pot ◽  
Complex Molecules ◽  
Complex Products ◽  
Enzyme Cascade ◽  
Enzyme Cascades

Multi-enzyme cascade reactions for the synthesis of complex products have gained importance in recent decades. Their advantages compared to single biotransformations include the possibility to synthesize complex molecules without purification of reaction intermediates, easier handling of unstable intermediates, and dealing with unfavorable thermodynamics by coupled equilibria. In this study, a four-enzyme cascade consisting of ScADK, AjPPK2, and SmPPK2 for ATP synthesis from adenosine coupled to the cyclic GMP-AMP synthase (cGAS) catalyzing cyclic GMP-AMP (2’3’-cGAMP) formation was successfully developed. The 2’3’‑cGAMP synthesis rates were comparable to the maximal reaction rate achieved in single-step reactions. An iterative optimization of substrate, cofactor, and enzyme concentrations led to an overall yield of 0.08 mole 2’3’-cGAMP per mole adenosine, which is comparable to chemical synthesis. The established enzyme cascade enabled the synthesis of 2’3’-cGAMP from GTP and inexpensive adenosine as well as polyphosphate in a biocatalytic one-pot reaction, demonstrating the performance capabilities of multi-enzyme cascades for the synthesis of pharmaceutically relevant products.

Palladium-Catalyzed Cascade Reactions for Annulative π -Extension of Indoles to Carbazoles through C–H Bond Activation

2020 ◽  
Vol 24 (22) ◽  
pp. 2612-2633
Author(s):  
Enakshi Dinda ◽  
Samir Kumar Bhunia ◽  
Ranjan Jana
Keyword(s):  
Bond Activation ◽  
Photophysical Properties ◽  
Underlying Mechanism ◽  
Direct Conversion ◽  
Cascade Reactions ◽  
Research Area ◽  
Single Step ◽  
Palladium Catalyzed ◽  
Pharmaceutical Industries ◽  
Active Research

The annulative π-extension (APEX) reactions through C-H bond activation has tremendous potential to access fused aromatic systems from relatively simple aromatic compounds in a single step. This state-of-the-art technique has the ability to streamline the synthesis of functionalized materials useful in material science, biomedical research, agroand pharmaceutical industries. Furthermore, C-H activation strategy does not require prefunctionalization steps, which allows for the late-stage modification of the functional molecule with requisite molecular properties. Owing to their unique photophysical properties, carbazoles are widely used in photovoltaic cells, biomedical imaging, fluorescent polymer, etc. It is also ubiquitously found in many natural products, agrochemicals and privileged medicinal scaffolds. Hence, direct conversion of easily accessible indole to carbazole remains an active research area. In the last decades, significant advancement has been made to access carbazole moiety directly from indole through cascade C-H activation. The underlying mechanism behind this cascade π-extension strategy is the facile electrophilic metalation at the C-3 position of the indole moiety, 1,2- migration and electro cyclization. In this review, we will discuss recent literature reports for the palladium-catalyzed π-extension of indole to carbazole moiety through C-H bond activation.

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