Insektizide für die Landwirtschaft: Chemische Schädlingsbekämpfung

This article presents an overview over chemical pest control in agriculture. A general introduction is given to pests, active ingredients, biochemical modes of action and activity profiles.     

DOIT: a program to calculate thermal rate constants and mode‐specific tunneling splittings directly from quantum‐chemical calculations

In this contribution we discuss computational aspects of a recently introduced method for the calculation of proton tunneling rate constants, and tunneling splittings, which has been applied to molecules and complexes, and should apply equally well to bulk materials. The method is based on instanton theory, adapted so as to permit a direct link to the output of quantum‐chemical codes. It is implemented in the DOIT (dynamics of instanton tunneling) code, which calculates temperature‐dependent tunneling rate constants and mode‐specific tunneling splittings. As input, it uses the structure, energy, and vibrational force field of the stationary configurations along the reaction coordinate, computed by conventional quantum‐chemical programs. The method avoids the difficult problem of calculating the exact least‐action trajectory, known as the instanton path, and instead focusses on the corresponding instanton action, because it governs the dynamic properties. To approximate this action for a multidimensional system, the program starts from the one‐dimensional instanton action along the reaction coordinate, which can be obtained without difficulty. It then applies correction terms for the coupling to the other vibrational degrees of freedom, which are treated as harmonic oscillators (transverse normal modes). The couplings are assumed linear in these modes. Depending on the frequency and the character of the transverse modes, they may either decrease or increase the action, i.e., help or hinder the transfer. A number of tests have shown that the program is at least as accurate as alternative programs based on transition‐state theory with tunneling corrections, and is also much less demanding in computer time, thus allowing application to much larger systems. An outline of the instanton formalism is presented, some new developments are introduced, and special attention is paid to the connection with quantum‐chemical codes. Possible sources of error are investigated. To show the program in action, calculations are presented of tunneling rates and splittings associated with triple proton transfer in the chiral water trimer. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 787–801, 2001     

Mechanistic Insights into the Mode of Action of Bifunctional Pyrrolidine‐Squaramide‐Derived Organocatalysts

The catalytic modes of action of three squaramide‐derived bifunctional organocatalysts have been investigated using DFT methods. The [5+2] cycloaddition between oxidopyrylium ylides and enals was used as the model reaction. Two primary modes were possible for the different catalysts studied. The preference for one mode over the other was due to the possibility of additional favorable π–π interactions between the hydrogen‐bond activated pyrylium ylide and an electron‐deficient aromatic ring bonded to the squaramide NH group. The model can be extended to other reactions catalyzed by the same catalysts, such as formal [2+2] cycloadditions between nitroalkenes and α,β‐unsaturated aldehydes. The computational results were in excellent concurrence with the available experimental reports on the observed total enantioselectivity and differences in diastereoselectivity depending on the substrate and the reaction.     

Moderne Flammschutzmittelfür Kunststoffe

Flame retardants are incorporated into a large number of plastics to reduce the flammability. They are applied to make our life more secure and to protect our belongings from burning down. In this article different classes of flame retardants are introduced and their modes of action within the polymers are illustrated. An overview concerning the requirements for modern flame retardants is given.     

Determination of the action modes of cellulases from hydrolytic profiles over a time course using fluorescence‐assisted carbohydrate electrophoresis

Fluorescence‐assisted carbohydrate electrophoresis (FACE) is a sensitive and simple method for the separation of oligosaccharides. It relies on labeling the reducing ends of oligosaccharides with a fluorophore, followed by PAGE. Concentration changes of oligosaccharides following hydrolysis of a carbohydrate polymer could be quantitatively measured continuously over time using the FACE method. Based on the quantitative analysis, we suggested that FACE was a relatively high‐throughput, repeatable, and suitable method for the analysis of the action modes of cellulases. On account of the time courses of their hydrolytic profiles, the apparent processivity was used to show the different action modes of cellulases. Cellulases could be easily differentiated as exoglucanases, β‐glucosidases, or endoglucanases. Moreover, endoglucanases from the same glycoside hydrolases family had a variety of apparent processivity, indicating the different modes of action. Endoglucanases with the same binding capacities and hydrolytic activities had similar oligosaccharide profiles, which aided in their classification. The hydrolytic profile of Trichoderma reesei Cel12A, an endoglucanases from T. reesei, contained glucose, cellobiose, and cellotriose, which revealed that it may have a new glucosidase activity, corresponding to that of EC 3.2.1.74. A hydrolysate study of a T. reesei Cel12A‐N20A mutant demonstrated that the FACE method was sufficiently sensitive to detect the influence of a single‐site mutation on enzymatic activity.     

Moderne Fungizide: Pilzbekämpfung in der Landwirtschaft

Many new fungicides were introduced into agriculture during in the last years. Due to their broad spectrum, the strobilurines have become one of the most important classes of fungicides. This account presents new active ingredients which were introduced since 1995, describes the various modes of action and the main target‐crops.     

Image‐Based Morphological Profiling Identifies a Lysosomotropic,Iron‐Sequestering Autophagy Inhibitor

Chemical proteomics is widely applied in small‐molecule target identification. However, in general it does not identify non‐protein small‐molecule targets, and thus, alternative methods for target identification are in high demand. We report the discovery of the autophagy inhibitor autoquin and the identification of its molecular mode of action using image‐based morphological profiling in the cell painting assay. A compound‐induced fingerprint representing changes in 579 cellular parameters revealed that autoquin accumulates in lysosomes and inhibits their fusion with autophagosomes. In addition, autoquin sequesters Fe²⁺ in lysosomes, resulting in an increase of lysosomal reactive oxygen species and ultimately cell death. Such a mechanism of action would have been challenging to unravel by current methods. This work demonstrates the potential of the cell painting assay to deconvolute modes of action of small molecules, warranting wider application in chemical biology.     

CH Activation Generates Period‐Shortening Molecules That Target Cryptochrome in the Mammalian Circadian Clock

The synthesis and functional analysis of KL001 derivatives, which are modulators of the mammalian circadian clock, are described. By using cutting‐edge C? H activation chemistry, a focused library of KL001 derivatives was rapidly constructed, which enabled the identification of the critical sites on KL001 derivatives that induce a rhythm‐changing activity along with the components that trigger opposite modes of action. The first period‐shortening molecules that target the cryptochrome (CRY) were thus discovered. Detailed studies on the effects of these compounds on CRY stability implicate the existence of an as yet undiscovered regulatory mechanism.     

Mathematical modeling of the action of biosensor possessing variable parameters

Electrochemical biosensor containing flat semi-permeable membrane covering enzyme-containing layer has been investigated. Mathematical modeling of the action modes of electrochemical biosensors with outer diffusion membrane was performed. Operation of the biosensor under the conditions when the permeability of the membrane and the activity of the biocatalytic layer depend on the parameters of the probe has been examined. The pH and temperature were selected as the main parameters which often affect the action of biosensors. A set of parameters was selected when the biosensor operates in kinetic and diffusion modes of action. The response time of the biosensor was shown to be sensitive to the mode of the biosensor action especially in the boundary region of the biosensor action. The linearity of the biosensor (the linear dependence of the biosensor response on the substrate concentration) in the deep diffusion mode can be increased by several magnitudes, whereas the response time increases only several times.     

Asymmetric Total Synthesis of Heronamides A–C: Stereochemical Confirmation and Impact of Long‐Range Stereochemical Communication on the Biological Activity

Heronamides are biosynthetically related metabolites isolated from marine‐derived actinomycetes. Heronamide C shows potent antifungal activity by targeting membrane phospholipids possessing saturated hydrocarbon chains with as‐yet‐unrevealed modes of action. In spite of their curious hypothesized biosynthesis and fascinating biological activities, there have been conflicts in regard to the reported stereochemistries of heronamides. Here, we describe the asymmetric total synthesis of the originally proposed and revised structures of heronamide C, which unambiguously confirmed the chemical structure of this molecule. We also demonstrated nonenzymatic synthesis of heronamides A and B from heronamide C, which not only proved the postulated biosynthesis, but also confirmed the correct structures of heronamides A and B. Investigation of the structure–activity relationship of synthetic and natural heronamides revealed the importance of both long‐range stereochemical communication and the 20‐membered macrolactam ring for the biological activity of these compounds.     

Pseudilins: Halogenated,Allosteric Inhibitors of the Non‐Mevalonate Pathway Enzyme IspD

The enzymes of the non‐mevalonate pathway for isoprenoid biosynthesis have been identified as attractive targets with novel modes of action for the development of herbicides for crop protection and agents against infectious diseases. This pathway is present in many pathogenic organisms and plants, but absent in mammals. By using high‐throughput screening, we identified highly halogenated marine natural products, the pseudilins, to be inhibitors of the third enzyme, IspD, in the pathway. Their activity against the IspD enzymes from Arabidopsis thaliana and Plasmodium vivax was determined in photometric and NMR‐based assays. Cocrystal structures revealed that pseudilins bind to an allosteric pocket by using both divalent metal ion coordination and halogen bonding. The allosteric mode of action for preventing cosubstrate (CTP) binding at the active site was elucidated. Pseudilins show herbicidal activity in plant assays and antiplasmodial activity in cell‐based assays.     

Rücktitelbild: C?H Activation Generates Period‐Shortening Molecules That Target Cryptochrome in the Mammalian Circadian Clock (Angew. Chem. 24/2015)

The synthesis and functional analysis of KL001 derivatives, which are modulators of the mammalian circadian clock, are described. By using cutting‐edge C H activation chemistry, a focused library of KL001 derivatives was rapidly constructed, which enabled the identification of the critical sites on KL001 derivatives that induce a rhythm‐changing activity along with the components that trigger opposite modes of action. The first period‐shortening molecules that target the cryptochrome (CRY) were thus discovered. Detailed studies on the effects of these compounds on CRY stability implicate the existence of an as yet undiscovered regulatory mechanism.     

Biocide Use in the Antimicrobial Era: A Review

Biocides are widely used in healthcare and industry to control infections and microbial contamination. Ineffectual disinfection of surfaces and inappropriate use of biocides can result in the survival of microorganisms such as bacteria and viruses on inanimate surfaces, often contributing to the transmission of infectious agents. Biocidal disinfectants employ varying modes of action to kill microorganisms, ranging from oxidization to solubilizing lipids. This review considers the main biocides used within healthcare and industry environments and highlights their modes of action, efficacy and relevance to disinfection of pathogenic bacteria. This information is vital for rational use and development of biocides in an era where microorganisms are becoming resistant to chemical antimicrobial agents.     

Heterologous Expression and Characterization of an Acidic GH11 Family Xylanase from <Emphasis Type="Italic">Hypocrea orientalis</Emphasis>

A gene encoding glycoside hydrolase family 11 xylanase (HoXyn11B) from Hypocrea orientalis EU7–22 was expressed in Pichia pastoris with a high activity (413 IU/ml). HoXyn11B was partly N-glycosylated and appeared two protein bands (19–29 kDa) on SDS-PAGE. The recombinant enzyme exhibited optimal activity at pH 4.5 and 55 °C, and retained more than 90% of the original activity after incubation at 50 °C for 60 min. The determined apparent K _m and V _max values using beechwood xylan were 10.43 mg/ml and 3246.75 IU/mg, respectively. The modes of action of recombinant HoXyn11B on xylo-oligosaccharides (XOSs) and beechwood xylan were investigated by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), which indicated that the modes of action of HoXyn11B are different from HoXyn11A since it is able to release a significant amount of xylose from various substrates. This study provides an opportunity to better understand the hydrolysis mechanisms of xylan by xylanases from Trichoderma.     

Synthetic aminopyrrolic receptors have apoptosis inducing activity

We report two synthetic aminopyrrolic compounds that induce apoptotic cell death. These compounds have been previously shown to act as receptors for mannosides. The extent of receptor-induced cell death is greater in cells expressing a high level of high-mannose oligosaccharides than in cells producing lower levels of high-mannose glycans. The ability of synthetic receptors to induce cell death is attenuated in the presence of external mannosides. The present results provide support for the suggestion that the observed cell death reflects an ability of the receptors to bind mannose displayed on the cell surface. Signaling pathway studies indicate that the synthetic receptors of the present study promote JNK activation, induce Bax translocation to the mitochondria, and cause cytochrome c release from the mitochondria into the cytosol, thus promoting caspase-dependent apoptosis. Such effects are also observed in cells treated with mannose-binding ConA. The present results thus serve to highlight what may be an attractive new approach to triggering apoptosis via modes of action that differ from those normally used to promote apoptosis.     

Light-Activated Rhenium Complexes with Dual Mode of Action against Bacteria

New antibiotics and innovative approaches to kill drug-resistant bacteria are urgently needed. Metal complexes offer access to alternative modes of action but have only sparingly been investigated in antibacterial drug discovery. We have developed a light-activated rhenium complex with activity against drug-resistant S. aureus and E. coli. The activity profile against mutant strains combined with assessments of cellular uptake and synergy suggest two distinct modes of action.     

Phenanthroline‐Catalyzed Stereoretentive Glycosylations

Carbohydrates are essential moieties of many bioactive molecules in nature. However, efforts to elucidate their modes of action are often impeded by limitations in synthetic access to well‐defined oligosaccharides. Most of the current methods rely on the design of specialized coupling partners to control selectivity during the formation of glycosidic bonds. Reported herein is the use of a commercially available phenanthroline to catalyze stereoretentive glycosylation with glycosyl bromides. The method provides efficient access to α‐1,2‐cis glycosides. This protocol has been performed for the large‐scale synthesis of an octasaccharide adjuvant. Density‐functional theory calculations, together with kinetic studies, suggest that the reaction proceeds by a double S_N2 mechanism.     

THE EFFECT OF NORFLURAZON ON PHOTOTROPIC REACTION IN Phaseolus aureus Roxb. SEEDLINGS

Abstract. The phototropic response of norflurazon-treated mung bean seedlings has been studied to evaluate the possible role of carotenoids, carotenoid-derived growth substances, or other factors in the perception/reaction system. Phototropism was slowed significantly in plants grown in white and blue light in the presence of norflurazon. This effect was evident in norflurazon-bleached seedlings, as well as in those whose pigment system was not affected, due to a shorter period of herbicide action. The possible modes of norflurazon action are discussed.     

Molecular Firefighting—How Modern Phosphorus Chemistry Can Help Solve the Challenge of Flame Retardancy

The ubiquity of polymeric materials in daily life comes with an increased fire risk, and sustained research into efficient flame retardants is key to ensuring the safety of the populace and material goods from accidental fires. Phosphorus, a versatile and effective element for use in flame retardants, has the potential to supersede the halogenated variants that are still widely used today: current formulations employ a variety of modes of action and methods of implementation, as additives or as reactants, to solve the task of developing flame‐retarding polymeric materials. Phosphorus‐based flame retardants can act in both the gas and condensed phase during a fire. This Review investigates how current phosphorus chemistry helps in reducing the flammability of polymers, and addresses the future of sustainable, efficient, and safe phosphorus‐based flame‐retardants from renewable sources.     

Two polymorphic forms of N‐(4‐chloro­phenyl)‐5‐[(4‐chlorophenyl)aminomethyl]‐6‐methyl‐2‐phenyl­pyrimidin‐4‐amine

Two polymorphic forms of the title compound, C₂₄H₂₀Cl₂N₄, were obtained and characterized using X‐ray crystal structure analysis. Colourless crystals of polymorph (Ia) were obtained from the oily mother residue. Recrystallization of polymorph (Ia) from an acetone–methanol mixture resulted in pale‐yellow crystals of polymorph (Ib). The major feature distinguishing the two polymorphic forms is their inter­action modes, and hence their packing arrangements. In the crystal structure of polymorph (Ia), there are N—H⋯N hydrogen bonds and also aromatic π–π stacking inter­actions between mol­ecules. The mol­ecules of polymorph (Ib) are linked by N—H⋯Cl hydrogen bonds only.