Search

To maintain sustainable broadacre farming in the future, a better understanding of soil microbiome functions and processes associated with adapting agronomic management practices will be key. This is primarily due to the irreplaceable roles of the soil microbiome in soil and plant interactions, human health and ecosystem functions and stability. We approached this challenge by reviewing how different land management practices influence soil microbial communities. The important role that the soil microbiome plays in cropping systems is analyzed in the context of an overview of changes in land management over the past two decades using southern Australian dryland farming as a case study. Many major changes in management have occurred in this system during this time, including (i) reduction in tillage, with a corresponding increase in direct drilling and stubble retention; (ii) inclusion of oilseeds and pulses in cereal-dominated rotation systems; (iii) decrease in the pasture-dominated grain production systems; (iv) increased use of agrochemicals; (v) different soil amelioration applications and (vi) development of innovative agricultural technology. We review the overarching role of climate extremes in impacting agronomic management practices in southern Australian farming systems. In all, we demonstrate the complex interplay between land management changes and the activity, diversity and functions of the soil microbiome, with reference to changes in agronomic management practices.

Inspired by a new biosynthetic hypothesis, we report a biomimetic total synthesis of atrachinenins A and B that explains their racemic nature. The synthesis exploits an intermolecular Diels–Alder reaction between a quinone meroterpenoid and E-β-ocimene, followed by intramolecular (3 + 2) cycloaddition and a late-stage aerobic oxidation. Divergent transformations of a simple model system gave several complex polycyclic scaffolds, while also suggesting a structure revision for atrachinenin C.

Transition-metal complexes bearing labile ligands can be difficult to isolate and study in solution because of unwanted dinucleation or ligand substitution reactions. Metal–organic frameworks (MOFs) provide a unique matrix that allows site isolation and stabilization of well-defined transition-metal complexes that may be of importance as moieties for gas adsorption or catalysis. Herein we report the development of an in situ anion metathesis strategy that facilitates the postsynthetic modification of Cu(I) complexes appended to a porous, crystalline MOF. By exchange of coordinated chloride for weakly coordinating anions in the presence of carbon monoxide (CO) or ethylene, a series of labile MOF-appended Cu(I) complexes featuring CO or ethylene ligands are prepared and structurally characterized using X-ray crystallography. These complexes have an uncommon trigonal planar geometry because of the absence of coordinating solvents. The porous host framework allows small and moderately sized molecules to access the isolated Cu(I) sites and displace the “place-holder” CO ligand, mirroring the ligand-exchange processes involved in Cu-centered catalysis.

The Buchwald–Hartwig cross-coupling reaction between 4-methylumbelliferone-derived nonaflates with amides, carbamates, and sulfonamides is described. A wide variety of N-substituted 7-amino coumarin analogues was prepared in good to excellent yields. The photophysical properties of aqueous-soluble derivatives were determined, and they displayed auxochrome-based variations. Gram-scale synthesis provided an acrylamide analogue, which was used to fabricate a fluorescent poly(2-hydroxylethyl methacrylate) (pHEMA) hydrogel that was resistant to leaching in ultrapure H2O. We envisage that our reported protocol to access 7-amino-4-methylcoumarin derivatives will find use toward the development of new fluorescent coumarin-based probes by researchers in the field.

Boronate ester bullvalenes are now accessible in two to four operationally simple steps. This unlocks late-stage diversification through Suzuki cross-coupling reactions to give mono-, di-, and trisubstituted bullvalenes. Moreover, a linchpin strategy enables preprogrammed installation of two different substituents. Analysis of solution phase isomer distributions and single-crystal X-ray structures reveals that isomer preference in the crystal lattice is due to general shape selectivity.

A biomimetic approach to total synthesis can offer several benefits, including the development of cascade reactions for the rapid generation of molecular complexity, and guidance in the structure revision of old natural products and the anticipation of new ones. Herein, we describe how a biomimetic synthesis of bruceol, a pentacyclic meroterpenoid, led to the anticipation, isolation, and synthesis of isobruceol. The key step in the synthesis of both bruceol and isobruceol was an intramolecular hetero-Diels–Alder reaction of an o-quinone methide that was formed by dearomatization of an electron-rich chromene. The synthesis of an elusive biosynthetic intermediate also allowed a concise synthesis of eriobrucinol via a photochemical [2 + 2] cycloaddition. Furthermore, some speculation on the biosynthesis of prenylated bruceol derivatives inspired the development of a Claisen/Cope/Diels–Alder cascade reaction. We also report the generation of halogenated bruceol derivatives and the synthesis of several protobruceol natural products using singlet oxygen ene reactions.

Eremophila sturtiiand E. mitchelliiare found in the arid and temperate regions of Australia and, because of their similar appearances, are often confused. Previous phytochemical investigations have described mitchellene sesquiterpenes (1–5) reported from E. mitchelliibut are here demonstrated to be from E. sturtii. A previous study that described serrulatic acids (16and 17) from a species reported as E. sturtiiactually used E. mitchellii. In addition, two new C-15 modified analogues, mitchellenes F (14) and G (15), were isolated from E. sturtii. The absolute configuration of 14was determined with the first X-ray structure of a compound with the mitchellene skeleton.

Protection of biological assemblies is critical to applications in biotechnology, increasing the durability of enzymes in biocatalysis or potentially stabilizing biotherapeutics during transport and use. Here we show that a porous hydrogen-bonded organic framework (HOF) constructed from water-soluble tetra-amidinium (1·Cl4) and tetracarboxylate (2) building blocks can encapsulate and stabilize biomolecules to elevated temperature, proteolytic and denaturing agents, and extend the operable pH range for catalase activity. The HOF, which readily retains water within its framework structure, can also protect and retain the activity of enzymes such as alcohol oxidase, that are inactive when encapsulated within zeolitic imidazolate framework (ZIF) materials. Such HOF coatings could provide valid alternative materials to ZIFs: they are metal free, possess larger pore apertures, and are stable over a wider, more biologically relevant pH range.

Reaction of diamide ligand, namely N,N’-2,6-bis (4-pyridylmethyl) pyridine dicarboxamide (L) with cadmium nitrate and cadmium perchlorate has given rise to the formation of two types coordination polymers. Compound (CP1-Cd) with formula molecule {[Cd (L)2(H2O)2](NO3)2·6H2O}n is a one-dimensional coordination polymer while compound (CP2-Cd), with formula molecule {[Cd (L)2(H2O)2](ClO4)2·31⁄2H2O.CH3OH}n, is a two dimensional coordination polymer. These coordination polymers were prepared via slow evaporation methods and completely characterized by combination of solid state techniques such as Fourier Transform Infrared (FTIR) spectroscopy, elemental analysis and X-ray crystallography. This study revealed that coordination polymers derived from N,N’-2,6-bis (4-pyridylmethyl) pyridine dicarboxamide can accommodate anions with different sizes, showing good potential as anion receptor.

We previously reported potent ligands and inhibitors of Mycobacterium tuberculosisdethiobiotin synthetase (MtDTBS), a promising target for antituberculosis drug development (Schumann et al., ACS Chem Biol. 2021, 16, 2339–2347); here, the unconventional origin of the fragment compound they were derived from is described for the first time. Compound 1(9b-hydroxy-6b,7,8,9,9a,9b-hexahydrocyclopenta[3,4]cyclobuta[1,2-c]chromen-6(6aH)-one), identified by an in silicofragment screen, was subsequently shown by surface plasmon resonance to have dose-responsive binding (KD= 0.6 mM). Clear electron density was revealed in the DAPA substrate binding pocket when 1was soaked into MtDTBS crystals, but the density was inconsistent with the structure of 1. Here, we show that the lactone of 1hydrolyzes to a carboxylic acid (2) under basic conditions, including those of the crystallography soak, with a subsequent ring opening of the component cyclobutane ring forming a cyclopentylacetic acid (3). Crystals soaked directly with authentic 3produced an electron density that matched that of crystals soaked with presumed 1, confirming the identity of the bound ligand. The synthetic utility of fortuitously formed 3enabled the subsequent compound development of nanomolar inhibitors. Our findings represent an example of chemical modification within drug discovery assays and demonstrate the value of high-resolution structural data in the fragment hit validation process.

Porous molecular solids are garnering increasing attention with examples of high surface areas and applications in molecular separations. Recently, amorphous networks of molecular cages have shown increased porosity with respect to their crystalline counterparts. However, the structures of amorphous materials cannot be precisely elucidated by X-ray diffraction techniques, thus molecular simulations are vital to understanding their pore structures and the origin of porosity. Here, we use GPU-accelerated molecular dynamics simulations as an efficient methodology to construct representative amorphous network structures. We employ Voronoi network analysis of amorphous networks of seven previously reported cage molecules to provide insight into structure–property relationships. Accordingly, we apply this understanding to delineate synthetic design features that give rise to highly porous analogues of chemically robust cages constructed from carbon–carbon bonds.

ABSTRACTTwo-component gene regulatory systems (TCSs) are a major mechanism by which bacteria respond to environmental stimuli and thus are critical to infectivity. For example, the control of virulence regulator/sensor kinase (CovRS) TCS is central to the virulence of the major human pathogen group A Streptococcus(GAS). Here, we used a combination of quantitative in vivophosphorylation assays, isoallelic strains that varied by only a single amino acid in CovS, and transcriptome analyses to characterize the impact of CovS on CovR phosphorylation and GAS global gene expression. We discovered that CovS primarily serves to phosphorylate CovR, thereby resulting in the repression of virulence factor-encoding genes. However, a GAS strain selectively deficient in CovS phosphatase activity had a distinct transcriptome relative to that of its parental strain, indicating that both CovS kinase and phosphatase activities influence the CovR phosphorylation status. Surprisingly, compared to a serotype M3 strain, serotype M1 GAS strains had high levels of phosphorylated CovR, low transcript levels of CovR-repressed genes, and strikingly different responses to environmental cues. Moreover, the inactivation of CovS in the serotype M1 background resulted in a greater decrease in phosphorylated CovR levels and a greater increase in the transcript levels of CovR-repressed genes than did CovS inactivation in a serotype M3 strain. These data clarify the influence of CovS on the CovR phosphorylation status and provide insight into why serotype M1 GAS strains have high rates of spontaneous mutations in covSduring invasive GAS infection, thus providing a link between TCS molecular function and the epidemiology of deadly bacterial infections.