Mining Symbionts of a Spider‐Transmitted Fungus Illuminates Uncharted Biosynthetic Pathways to Cytotoxic Benzolactones

A spider‐transmitted fungus (Rhizopus microsporus) that was isolated from necrotic human tissue was found to harbor endofungal bacteria (Burkholderia sp.). Metabolic profiling of the symbionts revealed a complex of cytotoxic agents (necroximes). Their structures were characterized as oxime‐substituted benzolactone enamides with a peptidic side chain. The potently cytotoxic necroximes are also formed in symbiosis with the fungal host and could have contributed to the necrosis. Genome sequencing and computational analyses revealed a novel modular PKS/NRPS assembly line equipped with several non‐canonical domains. Based on gene‐deletion mutants, we propose a biosynthetic model for bacterial benzolactones. We identified specific traits that serve as genetic handles to find related salicylate macrolide pathways (lobatamide, oximidine, apicularen) in various other bacterial genera. Knowledge of the biosynthetic pathway enables biosynthetic engineering and genome‐mining approaches.     

Hybrid dibismuthines and distibines as ligands towards transition metal carbonyls

The hybrid dibismuthines O(CH(2)CH(2)BiPh(2))(2) and MeN(CH(2)-2-C(6)H(4)BiPh(2))(2) react with [M(CO)(5)(thf)] (M = Cr or W) to form [{M(CO)(5)}(2){O(CH(2)CH(2)BiPh(2))(2)}] and [{Cr(CO)(5)}(2){MeN(CH(2)-2-C(6)H(4)BiPh(2))(2)}] containing bridging bidentate (Bi(2)) coordination. The unsymmetrical tertiary bismuthine complexes [M(CO)(5){BiPh(2)(o-C(6)H(4)OMe)}] are also described. Depending upon the molar ratio, the hybrid distibines O(CH(2)CH(2)SbMe(2))(2) and MeN(CH(2)-2-C(6)H(4)SbMe(2))(2) react with [M(CO)(5)(thf)] to give the pentacarbonyl complexes [{M(CO)(5)}(2){O(CH(2)CH(2)SbMe(2))(2)}] and [{Cr(CO)(5)}(2){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}] or tetracarbonyls cis-[M(CO)(4){O(CH(2)CH(2)SbMe(2))(2)}] and cis-[M(CO)(4){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}]. The latter can also be obtained from [Cr(CO)(4)(nbd)] or [W(CO)(4)(pip)(2)], and contain chelating bidentates (Sb(2)-coordinated) as determined crystallographically. S(CH(2)-2-C(6)H(4)SbMe(2))(2) coordinates as a tridentate (SSb(2)) in fac-[M(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}] (M = Cr or Mo) and fac-[Mn(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}][CF(3)SO(3)]. Fac-[Mn(CO)(3){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}][CF(3)SO(3)] contains NSb(2)-coordinated ligand in the solid state, but in solution a second species, Sb(2)-coordinated and with a κ(1)-CF(3)SO(3) replacing the coordinated amine is also evident. X-ray crystal structures were also determined for fac-[Cr(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}], fac-[Mn(CO)(3){S(CH(2)-2-C(6)H(4)SbMe(2))(2)}][CF(3)SO(3)] and fac-[Mn(CO)(3){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}] [CF(3)SO(3)]. Hypervalent N···Sb interactions are present in cis-[M(CO)(4){MeN(CH(2)-2-C(6)H(4)SbMe(2))(2)}] (M = Mo or W), but absent for M = Cr.     

Ab initio determination of the flexibility of 2'-aminoribonucleosides and 2'-aminoarabinonucleosides inserted in duplexes

The sugar puckering of adenosine and uridine nucleosides with an amino group at 2' in the ribo or arabino orientations are determined using high-level quantum mechanical calculations Only the conformations that have dihedrals compatible with their insertion into a duplex are retained. The amino group has always been found to be pyramidal and its orientation governs the conformation of the sugar. The energetically most favorable conformation of the 2'-aminoribonucleosides has the south puckering but must be discarded. For another orientation of the 2'-amino group, the conformation is energetically less favorable but has the north puckering. Calculations performed in the presence of a water molecule give similar results but with a smaller energy gap. The model then explains why the insertion of a 2'-aminoribonucleotide destabilizes double-stranded RNAs and also double-stranded DNAs. In the arabino orientation, an NH(2) substituent at 2' favors north puckering. In contrast to 2'-aminoribonucleosides, deoxynucleosides inserted into a duplex remain in the most energetically favorable conformation compatible with the canonical values of the torsion angles. The whole relaxed potential map, in the amplitude/pseudorotation space, shows that for natural deoxyadenosine there is only one valley in the east running from south to north puckering.     

Interaction of Metamitron and Fenhexamid with Ca2+-Montmorillonite Clay Surfaces: A Density Functional Theory Molecular Dynamics Study

Metamitron (Meta), an herbicide, and fenhexamid (Fen), a fungicide, are authorized by the European Union to be used in agriculture. This article reports theoretical calculations about Meta and Fen in interaction with a clay surface: a Ca-montmorillonite (Mont). Conformational searches have been performed thanks to Car–Parrinello molecular dynamics simulations from which geometries have been extracted. Interaction and adsorption energies have been calculated for isomers of Meta or Fen in interaction with Mont to understand the relative stability of various kinds of complexation. Substantial adsorption energies are comparable for Meta and Fen: around −40 kcal/mol. For Fen-Mont, the CO monodentate family is surprisingly the lowest in energy. Moreover, the 10 lowest-energy isomers involve complexation on Fen carbonyl oxygens. The Meta-Mont lowest-energy family, N-N, does not involve π delocalization breaking within Meta. At the same time, the stronger the interaction energy is, the larger the structural modifications within Mont are, particularly concerning the interacting cation distance to the surface. The non-negligible charge transfer and the magnitude of the adsorption energy speak in favor of the chemisorption of the pesticide on the surface. © 2019 Wiley Periodicals, Inc.     

Friction and nanowear of polystyrene against hydrophobic and hydrophilic substrates

The ambition of this study is to analyze the role of interfacial interactions in friction and nanowear of polystyrene, by comparing friction against hydrophobic wafers (methyl‐terminated) and hydrophilic wafers (hydroxyl‐terminated) as a function of sliding velocity and normal force. Friction experiments are performed with a translation tribometer and nanowear investigation is achieved by using atomic force microscopy (AFM) analysis of the wafer surfaces after friction. Experimental results show that the friction coefficients measured on hydrophilic surfaces are always larger than those obtained with hydrophobic surfaces, indicating a relationship between friction and interfacial interactions. Elsewhere, AFM analysis shows that polystyrene transfer appears for a higher normal force in the case of hydrophobic substrates compared to hydrophilic one. However, the corresponding tangential (or friction) force necessary to detect transfer is quite similar for both types of substrates, indicating that the initial wear of polystyrene occurs for a similar threshold interfacial shear. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 2449–2454, 2006     

Silver‐Free Two‐Component Approach in Gold Catalysis: Activation of [LAuCl] Complexes with Derivatives of Copper,Zinc, Indium,Bismuth, and Other Lewis Acids

Complexes of type [LAuCl] (L=phosphine, phosphite, NHC and others) are widely employed in homogeneous catalysis, however, they are usually inactive as such and must be used jointly with a halide scavenger. To date, this role has mostly been entrusted to silver salts (AgSbF₆, AgPF₆, AgBF₄, AgOTf, etc.). However, silver salts can be the source of deactivation processes or side reactions, so it is sometimes advisable to use silver‐free cationic gold complexes, which can be difficult to synthesize and to handle compared with the more robust chloride. We show in this study that various Lewis acids of the transition and main group metal families are expedient substitutes to silver salts. We have tested Cu^I, Cu^II, Zn^II, In^III, Si^IV, Bi^III, and other salts in a variety of typical Au^I‐catalyzed transformations, and the results have revealed that [LAuCl] can form active species in their presence.     

Unexpected Self‐Assembly of a Homochiral Metallosupramolecular M4L4 Catenane

Two enantiomerically pure 9,9′‐spirobifluorene‐based bis(pyridine) ligands 1 and 2 were prepared to study their self‐assembly behavior upon coordination to cis‐protected palladium(II) ions. Whereas the sterically more demanding ligand, 2 , gave rise to the expected dinuclear metallosupramolecular M₂L₂ rhombi, the sterically less demanding ligand, 1 , acts as a template to give rise to a homochiral metallosupramolecular M₄L₄ catenane.     

PMLABe Diol Synthesized by Ring‐Opening Polymerization of Racemic Benzyl β‐Malolactonate Initiated by Rare‐Earth Trisborohydride Complexes: An Experimental and DFT Study

Polymer diols are a class of polymeric building blocks of high interest for the synthesis of complex macromolecular edifices. Rare‐earth borohydride complexes are known as efficient initiators for the ring‐opening polymerization (ROP) of cyclic esters, directly affording α,ω‐dihydroxy‐telechelic polyesters. Here, were report the direct synthesis of poly(benzyl β‐malolactonate) (PMLABe) diols, from the ROP of racemic (benzyl β‐malolactonate) (rac‐MLABe), a valuable and renewable monomer, initiated by the homoleptic [Ln(BH₄)₃(thf)₃] (Ln=La, Nd, and Sm) complexes. These initiators enabled the controlled ROP of this β‐lactone, affording well‐defined syndiotactic‐enriched (P_r≈0.83) PMLABes (M_n up to 21 300 g mol^?1, Ð_M≈1.5) as evidenced by size exclusion chromatography, ¹H and ¹³C NMR spectroscopy, and MALDI‐ToF mass spectrometry analyses. The first and second insertions of rac‐MLABe, as assessed by DFT calculations, revealed more favorable stationary front‐side than migratory back‐side insertions, the thermodynamically and kinetically competitive ROP on two distinct arms with that on a one arm‐only, and the thermodynamically slightly favored formation of syndiotactic‐enriched PMLABes.