Stereochemical rearrangements in tricarbonylrhenium(I) halide complexes of the non-racemic chiral ligand 2-[(4R),(5R)-dimethyl-1,3-dioxan-2-yl]pyridine (L): a dynamic NMR study

Tricarbonylrhenium(I) halide complexes of the non-racemic chiral ligand 2-[(4R),(5R)-dimethyl-1,3-dioxan-2-yl]pyridine (L), namely fac-[ReX(CO)3L] (X = Cl, Br or I), have been prepared and their latent fluxionality studied by dynamic NMR techniques in the slow and intermediate exchange regimes. In solution, these complexes give rise to four diastereoisomers, depending on the configuration at the metal and at the acetal-carbon atom, respectively; the relative populations are in the order SR > RR >> RS > SS. At moderate temperatures, a reversible ‘acetal ring flip’ leads to formal inversion of configuration at the acetal-carbon atom; the free energies of activation are in the range 84 - 88 kJ mol-1 at 298 K. Above ca. 370 K, reversible ligand dissociation also occurs, leading to an exchange of all four diastereoisomers on the NMR chemical shift time-scale

A detailed NMR study of the solution stereodynamics in tricarbonylrhenium(I) halide complexes of the non-racemic chiral ligand 2,6-bis[(4R,5R)-4,5-dimethyl-1,3-dioxolan-2-yl]pyridine (L¹) and the molecular structure of fac-[ReBr(CO)₃(L¹)]

1 Tricarbonylrhenium(I) halide complexes of the non-racemic chiral ligand 2,6-bis[(4R, 5R)-dimethyl-1,3-dioxan-2-yl]pyridine (L¹), namely fac-[ReX(CO)₃(L¹)] (X = Cl, Br or I), have been prepared. In these complexes the ligand is bound in a bidentate fashion, with the N atom of the pyridine ring and an O atom of one of the acetal rings co-ordinated to the octahedral metal centre. The bidentate mode is confirmed by the X-ray structure of fac-[ReBr(CO)₃(L¹)]. There are four possible diastereoisomers, depending on the configuration at the metal centre and at the acetal-carbon atom of the co-ordinated ring; the X-ray structure of fac-[ReBr(CO)₃(L¹)] shows that the SR diastereoisomer is present in the solid state. In solution, three of the four possible diastereoisomers are observed, namely SR, RR and RS; their relative populations are in the order SR > RR > SS. Above ambient temperature the complexes are stereochemically non-rigid. The fluxional kinetics have been measured by a combination of standard band shape analysis and selective inversion experiments. Two distinct processes are present: an acetal ring flip and exchange of the pendant and co-ordinated acetal rings. The latter process occurs via two independent mechanisms, namely tick-tock and rotation pathways. The activation energies for the stereodynamics are in the ranges 72 – 73 kJ mol⁻¹ (tick-tock), 77 – 78 kJ mol⁻¹ (acetal ring flip) and 83 – 90 kJ mol⁻¹ (rotation) at 298 K

Solvent and water mediated structural variations in deoxynivalenol and their potential implications on the disruption of ribosomal function

Sherpa Romeo green journal: open accessFusarium head blight (FHB) is a disease of cereal crops caused by trichothecene producing Fusarium species. Trichothecenes, macrocylicic fungal metabolites composed of three fused rings (A–C) with one epoxidef unctionality, area class of mycotoxins known to inhibit protein synthesis in eukaryotic ribosomes. These toxins accumulate in the kernels of infected plants rendering them unsuitable for human and animal consumption. Among the four classes of trichothecenes (A–D) A and B are associated with FHB, where the type B trichothecene deoxynivalenol (DON) is most relevant. While it is known that these toxins inhibit protein synthesis by disrupting peptidyl transferase activity, the exact mechanism of this inhibition is poorly understood. The three-dimensional structures and H-bonding behavior of DON were evaluated using one-and two-dimensional nuclear magnetic resonance (NMR) spectroscopy techniques. Comparisons of the NMR structure presented here with the recently reported crystal structure of DON bound in the yeast ribosome reveal insights into the possible toxicity mechanism of this compound. The work described herein identifies a waterbinding pocket in the core structure of DON, where the 3OH plays an important role in this interaction. These results provide preliminary insights into how substitution at C3 reduces trichothecene toxicity. Further investigations along these lines will provide opportunities to develop trichothecene remediation strategies based on the disruption of water binding interactions with 3OH.Ye

Hydrogen-bonding interactions in T-2 toxin studies using solution and solid-state NMR

Open accessThe structure of T-2 toxin in the solid-state is limited to X-ray crystallographic studies, which lack sufficient resolution to provide direct evidence for hydrogen-bonding interactions. Furthermore, its solution-structure, despite extensive Nuclear Magnetic Resonance (NMR) studies, has provided little insight into its hydrogen-bonding behavior, thus far. Hydrogen-bonding interactions are often an important part of biological activity. In order to study these interactions, the structure of T-2 toxin was compared in both the solution- and solid-state using NMR Spectroscopy. It was determined that the solution- and solid-state structure differ dramatically, as indicated by differences in their carbon chemical shifts, these observations are further supported by solution proton spectral parameters and exchange behavior. The slow chemical exchange process and cross-relaxation dynamics with water observed between the hydroxyl hydrogen on C-3 and water supports the existence of a preferential hydrogen bonding interaction on the opposite side of the molecule from the epoxide ring, which is known to be essential for trichothecene toxicity. This result implies that these hydrogen-bonding interactions could play an important role in the biological function of T-2 toxin and posits towards a possible interaction for the trichothecene class of toxins and the ribosome. These findings clearly illustrate the importance of utilizing solid-state NMR for the study of biological compounds, and suggest that a more detailed study of this whole class of toxins, namely trichothecenes, should be pursued using this methodology.Ye

Current and Future Experimental Strategies for Structural Analysis of Trichothecene Mycotoxins-A Prospectus

Fungal toxins, such as those produced by members of the order Hypocreales, have widespread effects on cereal crops, resulting in yield losses and the potential for severe disease and mortality in humans and livestock. Among the most toxic are the trichothecenes. Trichothecenes have various detrimental effects on eukaryotic cells including an interference with protein production and the disruption of nucleic acid synthesis. However, these toxins can have a wide range of toxicity depending on the system. Major differences in the phytotoxicity and cytotoxicity of these mycotoxins are observed for individual members of the class, and variations in toxicity are observed among different species for each individual compound. Furthermore, while diverse toxicological effects are observed throughout the whole cellular system upon trichothecene exposure, the mechanism of toxicity is not well understood. In order to comprehend how these toxins interact with the cell, we must first have an advanced understanding of their structure and dynamics. The structural analysis of trichothecenes was a subject of major interest in the 1980s, and primarily focused on crystallographic and solution-state Nuclear Magnetic Resonance (NMR) spectroscopic studies. Recent advances in structural determination through solution- and solid-state NMR, as well as computation based molecular modeling is leading to a resurgent interest in the structure of these and other mycotoxins, with the focus shifting in the direction of structural dynamics. The purpose of this work is to first provide a brief overview of the structural data available on trichothecenes and a characterization of the methods commonly employed to obtain such information. A summary of the current understanding of the relationship between structure and known function of these compounds is also presented. Finally, a prospectus on the application of new emerging structural methods on these and other related systems is discussed

Stabilisation of [WF5]+ and WF5 by pyridine: facile access to [WF5(NC5H5)3]+ and WF5(NC5H5)2

Accepted author manuscriptThe enhanced reactivity of [WF5]+ over WF6 has been exploited to access a neutral derivative of elusive WF5. The reaction of WF6(NC5H5)2 with [(CH3)3Si(NC5H5)][O3SCF3] in CH2Cl2 results in quantitative formation of trigonal-dodecahedral [WF5(NC5H5)3]+, which has been characterised as its [O3SCF3]− salt by Raman spectroscopy in the solid state and variable-temperature NMR spectroscopy in solution. The salt is susceptible to slow decomposition in solution at ambient temperature via dissociation of a pyridyl ligand, and the resultant [WF5(NC5H5)2]+ is reduced to WF5(NC5H5)2 in the presence of excess C5H5N, as determined by 19F NMR spectroscopy. Pentagonal-bipyramidal WF5(NC5H5)2 was isolated and characterised by X-ray crystallography and Raman spectroscopy in the solid state, representing the first unambiguously characterised WF5 adduct, as well as the first heptacoordinate adduct of a transition-metal pentafluoride. DFT-B3LYP methods have been used to investigate the reduction of [WF5(NC5H5)2]+ to WF5(NC5H5)2, supporting a two-electron reduction of WVI to WIV by nucleophilic attack and diprotonation of a pyridyl ligand in the presence of free C5H5N, followed by comproportionation to WV.Ye

31 P MAS NMR Spectroscopy of Hexachlorocyclotriphosphazene at Different Stages During Thermal Ring-Opening Polymerization

Abstract Thermal ring-opening polymerization of hexachlorocyclotriphosphazene was probed using 31 P magic-angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy. The spectrum of unreacted hexachlorocyclotriphosphazene was compared with the spectra of a reaction mixture at 3, 8 and 17.5 h of polymerization. Signals from trimer, oligomer, polymer and hydrolysis products were identified in the spectra and used to observe changes in the mixture during polymerization. The signal of poly(dichlorophosphazene) exhibits a complex behavior where ten individual components were observed and analyzed by deconvolution. These lines were preliminarily assigned to species with differing chain lengths based on their chemical shifts and relative intensities. This work shows that 31 P MAS NMR has the potential to provide quantitative information about the rates of chain propagation and cross-linking during thermal ring-opening polymerization