Stability Of Biological Systems Research Articles

Inclusion complexes of novel formyl chromone Schiff bases with β-Cyclodextrin: Synthesis, characterization, DNA binding studies and in-vitro release study

The present study involved the synthesis of five novel Schiff bases (SB1-SB5) of formyl chromone and their inclusion complexes with β-cyclodextrin through kneading approach to enhance the solubility and stability of SBs. Characterization was conducted using FTIR, NMR, SEM, TEM, p-XRD, and Mass Spectrometry. UV fluorescence and pH stability studies confirmed the formation of the inclusion complex. Structural validation of complexes was conducted via molecular docking (PDB ID: 1BFN) and 50 ns MD simulation study. DFT studies were performed on SBs using B3LYP/6–31 + G(d,p) basis set. All SBs exhibited favorable ADME properties and high binding interactions were observed in molecular docking with ctDNA (PDB Id: 1BNA). Further, in-vitro UV absorption and fluorescence experiments demonstrated strong ctDNA interactions for all Schiff bases, with binding constants in the order of 105 M−1, indicating groove binding mode. Among the SBs, SB4 exhibited the highest affinity for DNA grooves, with a binding constant (Kb) of 1.7 × 106 M−1. However, the SB4/β-Cyd inclusion complex also interacted with DNA but with low binding constants compared to SB4. An in-vitro release study of SB4/β-Cyd, revealed 78.92 % dissolution of the inclusion complex, highlighting its potential for enhanced solubility and stability in biological systems.

Computation-Guided Discovery of Diazole Monosubstituted Tetrazines as Optimal Bioorthogonal Tools.

Monosubstituted tetrazines are important bioorthogonal reactive tools due to their rapid ligation with trans-cyclooctene. However, their application is limited by the reactivity-stability paradox in biological environments. In this study, we demonstrated that steric effects are crucial in resolving this paradox through theoretical methods and developed a simple synthetic route to validate our computational findings, leading to the discovery of 1,3-azole-4-yl and 1,2-azole-3-yl monosubstituted tetrazines as superior bioorthogonal tools. These new tetrazines surpass previous tetrazines in terms of high reactivities and elevated stabilities. The most stable tetrazine exhibits a reasonable stability (71% remaining after 24 h incubation in cell culture medium) and an exceptionally high reactivity (k2 > 104 M-1 s-1 toward trans-cyclooctene). Due to its good stability in biological systems, a noncanonical amino acid containing such a tetrazine side chain was genetically encoded into proteins site-specifically via an expanded genetic code. The encoded protein can be efficiently labeled using cyclopropane-fused trans-cyclooctene dyes in living mammalian cells with an ultrafast reaction rate exceeding 107 M-1 s-1, making it one of the fastest protein labeling reactions reported to date. Additionally, we showed its superiority through in vivo reactions in living mice, achieving an efficient local anchoring of proteins. These tetrazines are expected to be optimal bioorthogonal reactive tools within living systems.

Enantioselective Carbon Isotope Exchange.

The synthesis of isotopically labeled organic molecules is vital for drug and agrochemical discovery and development. Carbon isotope exchange is emerging as a leading method to generate carbon-labeled targets, which are sought over hydrogen-based labels due to their enhanced stability in biological systems. While many bioactive small molecules bear carbon-containing stereocenters, direct enantioselective carbon isotope exchange reactions have not been established. We describe the first example of an enantioselective carbon isotope exchange reaction, where (radio)labeled α-amino acids can be generated from their unlabeled precursors using a stoichiometric chiral aldehyde receptor with isotopically labeled CO2 followed by imine hydrolysis. Many proteinogenic and non-natural derivatives undergo enantioselective labeling, including the late-stage radiolabeling of complex drug targets.

Metagenomic Insight Reveals the Microbial Structure and Function of the Full-Scale Coking Wastewater Treatment System: Gene-Based Nitrogen Removal

Microbial communities play crucial roles in pollutant removal and system stability in biological systems for coking wastewater (CWW) treatment, but a comprehensive understanding of their structure and functions is still lacking. A five month survey of four sequential bioreactors, anoxic 1/oxic 1/anoxic 2/oxic 2 (A1/O1/A2/O2), was carried out in a full-scale CWW treatment system in China to elucidate operational performance and microbial ecology. The results showed that A1/O1/A2/O2 had excellent and stable performance for nitrogen removal. Both total nitrogen (TN; (17.38 ± 6.89) mg·L−1) and ammonium–nitrogen (NH4+-N; (2.10 ± 1.34) mg·L−1) in the final biological effluent satisfied the Chinese national standards for CWW. Integrated analysis of 16S ribosome RNA (rRNA) sequencing and metagenomic sequencing showed that the bacterial communities and metagenomic function profiles of A1 and O1 shared similar functional structures, while those of A2 significantly varied from those of other bioreactors (p < 0.05). The results indicated that microbial activity was strongly connected with activated sludge function. Nitrosospira, Nitrosomonas, and SM1A02 were responsible for nitrification during the primary anoxic–oxic (AO) stage and Azoarcus and Thauera acted as important denitrifiers in A2. Nitrogen cycling-related enzymes and genes work in the A1/O1/A2/O2 system. Moreover, the hao genes catalyzing hydroxylamine dehydrogenase (EC 1.7.2.6) and the napA and napB genes catalyzing nitrate reductase (EC 1.9.6.1) played important roles in the nitrification and denitrification processes in the primary and secondary AO stages, respectively. The mixed liquor suspended solids (MLSS)/total solids (TS), TN removal rate (RR), total organic carbon (TOC) (RR), and NH4+-N (RR) were the most important environmental factors for regulating the structure of core bacterial genera and nitrogen-cycling genes. Proteobacteria were the potential main participants in nitrogen metabolism in the A1/O1/A2/O2 system for CWW treatment. This study provides an original and comprehensive understanding of the microbial community and functions at the gene level, which is crucial for the efficient and stable operation of the full-scale biological process for CWW treatment.

Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases.

Type II topoisomerases are essential enzymes that modulate the topological state of DNA supercoiling in all living organisms. These enzymes alter DNA topology by performing double-stranded passage reactions on over- or underwound DNA substrates. This strand passage reaction generates a transient covalent enzyme-cleaved DNA structure known as the cleavage complex. Al-though the cleavage complex is a requisite catalytic intermediate, it is also intrinsically dangerous to genomic stability in biological systems. The potential threat of type II topoisomerase function can also vary based on the nature of the supercoiled DNA substrate. During essential processes such as DNA replication and transcription, cleavage complex formation can be inherently more dangerous on overwound versus underwound DNA substrates. As such, it is important to understand the profound effects that DNA topology can have on the cellular functions of type II topoisomerases. This review will provide a broad assessment of how human and bacterial type II topoisomerases recognize and act on their substrates of various topological states.

Advances in Physicochemical and Biochemical Characterization of Archaeosomes from Polar Lipids of Aeropyrum pernix K1 and Stability in Biological Systems.

Archaeosomes are vesicles made from archaeal lipids. They are characterized by remarkable thermostability, resistance to enzymatic degradation, long-term stability, and immunomodulatory properties. In this review the current status of physicochemical properties of archaeal lipids and their stability in biological systems is presented, focusing on total polar lipids from Aeropyrum pernix K1. The isolated total polar lipids from Aeropyrum pernix K1 consist exclusively of glycerol ether lipids with isoprenoid groups attached to glycerol via ether linkages. More specifically, the two major polar lipids extracted from the membranes are C25,25-achaetidyl(glucosyl)inositol and C25,25-achaetidylinositol. An overview of the results of the effects of temperature and pH on the stability, structural organization, fluidity, and permeability of archaeosomes composed of pure C25,25 was examined by a combination of techniques, including fluorescence emission spectroscopy, electron paramagnetic resonance, differential scanning calorimetry, and confocal microscopy. We also compared the physicochemical properties of pure vesicles composed of either archaeal lipids or conventional lipids (e.g., 1,2-dipalmitoyl-sn-glycero-3-phosphocholine) with mixed vesicles composed of both lipid types. Archaeal lipids are discussed in terms of their potential use as a targeted drug delivery system based on the results of in vivo and cytotoxicity studies.

REVIEW ARTICLE: HCV IMPACTON THE PATTERN OF CIRC-RNAEXPRESSION IN HCV RELATED HCC

Circular RNAs (circRNAs) are a class of non-coding RNAs with a circular, covalent structure, which are highly conserved, stable unique molecules found in eukaryotic cells. The most notable character of circRNAs is their high stability in biological systems which is a key factor in their potential for use in a variety of RNA-focused medical applications. Despite the fact that circRNAs have a wide range of biological roles and regulatory functions, their circular structure and sequence overlap with their linear mRNA counterparts make it difficult to research them in depth. Furthermore, little is known about their function in viral infections and in immune responses.Since circRNAs have been found to be involved in a number of viral infections (including hepatitis B virus infection and human papilloma virus infection), their significance in viral infections is being more recognized in the last years.In this review, we aimed to provide a broad basis and overview on the biogenesis, significance and regulatory roles of circRNAs in the context of viral hepatitis C virus (HCV) infection, and HCV related hepatocellular carcinoma. Owing to the fact that the chronic HCV infection is the leading cause of HCC in the western countries especially Egypt. HCV can act directly on cell signaling pathways to promote HCC by inhibiting tumor suppressor genes or by causing activation of signaling pathways that up-regulate growth and division. Because viruses frequently manipulate cellular pathways to control viral gene expression, cellular and viral circRNA landscapes in virus-infected cells are altered. Studying the contribution of circRNAs in these pathways may give valuable information in the pathogenesis of HCC caused by HCV or in finding more reliable therapeutic approaches.

Development of Stable Liposomal Drug Delivery System of Thymoquinone and Its In Vitro Anticancer Studies Using Breast Cancer and Cervical Cancer Cell Lines

Thymoquinone, a well-known phytoconstituent derived from the seeds of Nigella sativa, exhibits unique pharmacological activities However, despite the various medicinal properties of thymoquinone, its administration in vivo remains challenging due to poor aqueous solubility, bioavailability, and stability. Therefore, an advanced drugdelivery system is required to improve the therapeutic outcome of thymoquinone by enhancing its solubility and stability in biological systems. Therefore, this study is mainly focused on preparing thymoquinone-loaded liposomes to improve its physicochemical stability in gastric media and its performance in different cancer cell line studies. Liposomes were prepared using phospholipid extracted from egg yolk. The liposomal nano preparations were evaluated in terms of hydrodynamic diameter, zeta potential, microscopic analysis, and entrapment efficiency. Cell-viability measurements were conducted using breast and cervical cancer cell lines. Optimized liposomal preparation exhibited polygonal, globule-like shape with a hydrodynamic diameter of less than 260 nm, PDI of 0.6, and zeta potential values of −23.0 mV. Solid-state characterizations performed using DSC and XRPD showed that the freeze-dried liposomal preparations were amorphous in nature. Gastric pH stability data showed no physical changes (precipitation, degradation) or significant growth in the average size of blank and thymoquinone-loaded liposomes after 24 h. Cell line studies exhibited better performance for thymoquinone-loaded liposomal drug delivery system compared with the thymoquinone-only solution; this finding can play a critical role in improving breast and cervical cancer treatment management.

Nanobiotechnology with Therapeutically Relevant Macromolecules from Animal Venoms: Venoms, Toxins, and Antimicrobial Peptides.

Some diseases of uncontrolled proliferation such as cancer, as well as infectious diseases, are the main cause of death in the world, and their causative agents have rapidly developed resistance to the various existing treatments, making them even more dangerous. Thereby, the discovery of new therapeutic agents is a challenge promoted by the World Health Organization (WHO). Biomacromolecules, isolated or synthesized from a natural template, have therapeutic properties which have not yet been fully studied, and represent an unexplored potential in the search for new drugs. These substances, starting from conglomerates of proteins and other substances such as animal venoms, or from minor substances such as bioactive peptides, help fight diseases or counteract harmful effects. The high effectiveness of these biomacromolecules makes them promising substances for obtaining new drugs; however, their low bioavailability or stability in biological systems is a challenge to be overcome in the coming years with the help of nanotechnology. The objective of this review article is to describe the relationship between the structure and function of biomacromolecules of animal origin that have applications already described using nanotechnology and targeted delivery.

A Simple Method of Synthesis of 3-Carboxy-2,2,5,5-Tetraethylpyrrolidine-1-oxyl and Preparation of Reduction-Resistant Spin Labels and Probes of Pyrrolidine Series.

Stable free radicals are widely used as molecular probes and labels in various biophysical and biomedical research applications of magnetic resonance spectroscopy and imaging. Among these radicals, sterically shielded nitroxides of pyrrolidine series demonstrate the highest stability in biological systems. Here, we suggest new convenient procedure for preparation of 3-carboxy-2,2,5,5-tetraethylpyrrolidine-1-oxyl, a reduction-resistant analog of widely used carboxy-Proxyl, from cheap commercially available reagents with the yield exceeding the most optimistic literature data. Several new spin labels and probes of 2,2,5,5-tetraethylpyrrolidine-1-oxyl series were prepared and reduction of these radicals in ascorbate solutions, mice blood and tissue homogenates was studied.

Assessment of the Biodiversity Status: Study of Developmental Stability

This paper considers the importance of monitoring the state of biological diversity as a priority area of research in the context of increasing anthropogenic impact and global climate change, modern requirements for indicators that can be used to solve this issue, and approaches for characterizing the background state and its possible deviations based on studies of homeostatic mechanisms to ensure the stability of biological systems.

HPTLC: A Tool for Determination of Curcumin in Mammalian Samples

Curcumin, an important phytoconstituent obtained from Curcuma longa L. (turmeric) is used traditionally in the treatment of various inflammatory diseases like arthritis, stroke and bowel diseases, etc. Despite its many health benefits, instability of curcumin in plasma is a major issue. The retention of curcumin in plasma must be properly evaluated in order to establish its stability in biological systems. The current study presents an HPTLC method undertaken for detection of curcumin and determination of its stability in plasma and different tissues of rats. The plasma and tissue samples were appropriately processed to render them suitable for HPTLC analysis. The method employed HPTLC glass plates precoated with silica gel 60F254 as the stationary phase. The mobile phase developed consisted of chloroform, methanol and glacial acetic acid which successfully gave distinct bands for curcumin with a Rf value of 0.95. This newly developed HPTLC method was found to be reproducible and accurate in quantifying curcumin in mammalian samples. This method was further utilized to efficiently estimate the time for which curcumin is retained in its native form in mammalian tissues and plasma alike.

Antimicrobial activity and stability of protonectin with D-amino acid substitutions.

The misuse and overuse of antibiotics result in the emergence of resistant bacteria and fungi, which make an urgent need of the new antimicrobial agents. Nowadays, antimicrobial peptides have attracted great attention of researchers. However, the low physiological stability in biological system limits the application of naturally occurring antimicrobial peptides as novel therapeutics. In the present study, we synthesized derivatives of protonectin by substituting all the amino acid residues or the cationic lysine residue with the corresponding D-amino acids. Both the D-enantiomer of protonectin (D-prt) and D-Lys-protonectin (D-Lys-prt) exhibited strong antimicrobial activity against bacteria and fungi. Moreover, D-prt showed strong stability against trypsin, chymotrypsin and the human serum, while D-Lys-prt only showed strong stability against trypsin. Circular dichroism analysis revealed that D-Lys-prt still kept typical α-helical structure in the membrane mimicking environment, while D-prt showed left hand α-helical structure. In addition, propidium iodide uptake assay and bacteria and fungi killing experiments indicated that all D-amino acid substitution or partially D-amino acid substitution analogs could disrupt the integrity of membrane and lead the cell death. In summary, these findings suggested that D-prt and D-Lys-prt might be promising candidate antibiotic agents for therapeutic application against resistant bacteria and fungi infection. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Novel Aqueous Fabrication and Characterization of Gold Coated Cobalt Nanoparticles

Background: Biological applications such as imaging and targeted drug delivery and many others require non-toxic, stable, inert and biocompatible nanoparticles. Coating the nanoparticles with inert materials is one of the ways that is used to enhance the stability and biocompatibility of nanoparticles. In particular, gold coating is very attractive as it reduces the toxicity of the magnetic nanoparticles, enhances their stability in biological systems and provides stable and inert platforms for further functionalization. However, current methods for the fabrication of gold-coated magnetic nanoparticles are carried out in non-aqueous media with toxic organic solvents at very high temperatures. In this article, we demonstrate a novel procedure for the fabrication of gold-coated cobalt nanoparticles. Unlike previous procedures that are performed in nonaqueous conditions at elevated temperatures, this method can be carried out exclusively in aqueous media at ambient conditions. Methods: Cobalt nanoparticles were prepared by the reduction of a cobalt precursor and subsequently coated with gold by an electroless plating procedure. The Co NPs and the gold-coated Co NPs were characterized by ultraviolet-visible (UVVis) spectroscopy, X-ray diffraction (XRD), superconducting quantum interference device (SQUID) magnetometry, scanning electron (SEM) and transmission electron (TEM) microscopy. Results: Results from SEM and TEM imaging indicated that the resulting gold-coated Co NPs had a Co core and an Au shell, were well dispersed and within the nanoscale range in terms of size (45 ± 8 nm in diameter). EDX confirmed the presence of both Co and Au in the coated sample. XRD data demonstrated a pattern with diffraction peaks indicating presence of gold and cobalt. SQUID results indicated that the magnetic properties of the nanoparticles were maintained even after coating with gold. Conclusion: All these results confirmed the fabrication of stable, well dispersed magnetic gold-coated Co NPs in aqueous media making them potentially ideal for downstream applications such as in vivo imaging, therapeutics and biological applications. Keywords: Nanoparticles, magnetic nanoparticles, cobalt nanoparticles, characterization, gold-coated, shell, core.

Morphology Tuning of Self-Assembled Perylene Monoimide from Nanoparticles to Colloidosomes with Enhanced Excimeric NIR Emission for Bioimaging

Organic near-infrared (NIR) fluorescent probes have been recognized as an emerging class of materials exhibiting a great potential in advanced bioanalytical applications. However, synthesizing such organic probes that could simultaneously work in the NIR spectral range and have large Stokes shift, high stability in biological systems, and high photostability have been proven challenging. In this work, aggregation induced excimeric NIR emission in aqueous media was observed from a suitably substituted perylene monoimide (PeIm) dye. Controlled entrapment of the dye into pluronic F127 micellar system to preserve its monomeric green emission in aqueous media was also established. The aggregation process of the PeIm dye to form organic nanoparticles (NPs) was evaluated experimentally by the means of transmission electron microscope imaging as well as theoretically by the molecular dynamics simulation studies. Tuning the morphology along with the formation of colloidosomes by the controlled self-aggregation of PeIm NPs in aqueous suspension was demonstrated successfully. Finally, both excimeric and monomeric emissive PeIm NPs as well as PeIm colloidosomes were employed for the bioimaging in vitro.

Analysis of all time-delay stability for biological systems using symbolic computation methods

All time-delay stability for biological systems shows that the time-delay system possess good reliability,so this issue has always been the highlight of the scholars research. However,researchers usually adopt the traditional mathematical methods or numerical calculation methods. Based on Hurwitz criterion and polynomial complete discriminant system,a sufficient and necessary algebraic criterion of all time-delay stability for nonlinear biological systems with parameters was introduced. By using symbolic computation methods,such as the methods of Grbner basis,triangular decomposition and real solution classification,a systematic and algorithmic approach for automatically analyzing all time-delay stability of biological systems with parameters was proposed. All the computations in our approach are all exact,which may help biologists and engineers to perform algebraic analysis for certain biological models. The successful experiments on the all time-delay stability analysis of several biological models,such as time delayed Lotka-Volterra systems and SIR epidemic models with time delay,showed the feasibility of our algebraic approach and also the superiority of symbolic computation methods compared with traditional mathematic methods.

Evolution of availability of curcumin inside poly-lactic-co-glycolic acid nanoparticles: impact on antioxidant and antinitrosant properties.

PurposeCurcumin exhibits antioxidant properties potentially beneficial for human health; however, its use in clinical applications is limited by its poor solubility and relative instability. Nanoparticles exhibit interesting features for the efficient distribution and delivery of curcumin into cells, and could also increase curcumin stability in biological systems. There is a paucity of information regarding the evolution of the antioxidant properties of nanoparticle-encapsulated curcumin.MethodWe described a simple method of curcumin encapsulation in poly-lactic-co-glycolic acid (PLGA) nanoparticles without the use of detergent. We assessed, in epithelial cells and in an acellular model, the evolution of direct antioxidant and antinitrosant properties of free versus PLGA-encapsulated curcumin after storage under different conditions (light vs darkness, 4°C vs 25°C vs 37°C).ResultsIn epithelial cells, endocytosis and efflux pump inhibitors showed that the increased antioxidant activity of PLGA-encapsulated curcumin relied on bypassing the efflux pump system. Acellular assays showed that the antioxidant effect of curcumin was greater when loaded in PLGA nanoparticles. Furthermore, we observed that light decreased, though heat restored, antioxidant activity of PLGA-encapsulated curcumin, probably by modulating the accessibility of curcumin to reactive oxygen species, an observation supported by results from quenching experiments. Moreover, we demonstrated a direct antinitrosant activity of curcumin, enhanced by PLGA encapsulation, which was increased by light exposure.ConclusionThese results suggest that the antioxidant and antinitrosant activities of encapsulated curcumin are light sensitive and that nanoparticle modifications over time and with temperature may facilitate curcumin contact with reactive oxygen species. These results highlight the importance of understanding effects of nanoparticle maturation on an encapsulated drug’s activity.

Complexity and Stability in Biological Systems

The hypothesis that a positive correlation exists between the complexity of a biological system, as described by its connectance, and its stability, as measured by its ability to recover from disturbance, derives from the investigations of the physiologists, Bernard and Cannon, and the ecologist Elton. Studies based on the ergodic theory of dynamical systems and the theory of large deviations have furnished an analytic support for this hypothesis. Complexity in this context is described by the mathematical object evolutionary entropy, stability is characterized by the rate at which the system returns to its stable conditions (steady state or periodic attractor) after a random perturbation of its robustness. This article reviews the analytical basis of the entropy — robustness theorem — and invokes studies of genetic regulatory networks to provide empirical support for the correlation between complexity and stability. Earlier investigations based on numerical studies of random matrix models and the notion of local stability have led to the claim that complex ecosystems tend to be more dynamically fragile. This article elucidates the basis for this claim which is largely inconsistent with the empirical observations of Bernard, Cannon and Elton. Our analysis thus resolves a long standing controversy regarding the relation between complex biological systems and their capacity to recover from perturbations. The entropy-robustness principle is a mathematical proposition with implications for understanding the basis for the large variations in stability observed in biological systems having evolved under different environmental conditions.

Selective tracking of lysosomal Cu2+ ions using simultaneous target- and location-activated fluorescent nanoprobes.

Levels of lysosomal copper are tightly regulated in the human body. However, few methods for monitoring dynamic changes in copper pools are available, thus limiting the ability to diagnostically assess the influence of copper accumulation on health status. We herein report the development of a dual target and location-activated rhodamine-spiropyran probe, termed Rhod-SP, activated by the presence of lysosomal Cu(2+). Rhod-SP contains a proton recognition unit of spiropyran, which provides molecular switching capability, and a latent rhodamine fluorophore for signal transduction. Upon activation by lysosomal acidic pH, Rhod-SP binds with Cu(2+) by spiropyran-based proton activation, promoting, in turn, rhodamine ring opening, which shows a "switched on" fluorescence signal. However, to protect Rhod-SP from degradation and interference by the physiological environment, it is engineered on mesoporous silica nanoparticles (MSNs), and the surface of Rhod-SP@MSNs is further anchored with β-cyclodextrin (β-CD) to enhance the solubility and bioavailability of Rhod-SP@MSN-CD. Next, to enhance cell specificity, a guiding unit of c(RGDyK) peptide conjugated adamantane (Ad-RGD) as prototypical system, is incorporated on the surface of Rhod-SP@MSN-CD to target integrin αvβ3 and αvβ5 overexpressed on cancer cells. Fluorescence imaging showed that both Rhod-SP@MSN-CD and Rhod-SP@MSN-CD-RGD were suitable for visualizing exogenous and endogenous Cu(2+) in lysosomes of living cells. This strategy addresses some common challenges of chemical probes in biosensing, such as spatial resolution in cell imaging, the solubility and stability in biological system, and the interference from intracellular species. The newly designed nanoprobe, which allows one to track, on a location-specific basis, and visualize lysosomal Cu(2+), offers a potentially rich opportunity to examine copper physiology in both healthy and diseased states.

ChemInform Abstract: Highly Enantioselective Preparation of Fluorinated Phosphonates by Michael Addition of α‐Fluoro‐β‐ketophosphonates to Nitroalkenes.

Fluorinated phosphonates are excellent surrogates of phosphates, outperforming the latter in terms of hydrolytic stability in biological systems while retaining similar activities. However, methods for preparing chiral fluorinated phosphonates are very limited. In this report, racemic α-fluoro-β-ketophosphonates were used in stereoselective Michael addition to nitroalkenes promoted by trifunctional thiourea organocatalyst. Highly functionalised α-fluoro-β-keto-γ-nitrophosphonates were obtained in high yields of 84–99% with excellent stereochemical control (96–99% ee and 3:1–34:1 d.r.).