High-resolution NMR Spectroscopy Research Articles

Post-acquisition correction of NMR spectra distorted by dynamic and static field inhomogeneity of cryogen-free magnets

Post-acquisition correction of NMR spectra is an important part of NMR spectroscopy that enables refined NMR spectra to be obtained, clean from undesirable out-phasing, broadening and noising. We describe analytical and numerical mathematical methods for post-acquisition correction of NMR spectra distorted by static and dynamic magnetic field inhomogeneity caused by imperfections of main superconducting coils and the cold head operation, typical for cryogen-free magnets. For the dynamic inhomogeneity, we apply a variant of the general reference deconvolution method, complemented with our mathematical analysis of spectral parameters. For the static inhomogeneity, we apply the method of a delayed Fourier transform, also supported with our analytical calculations. We verify our approach by correction processing of high-field experimental liquid-state 1H NMR spectra of water and ethanol as well as solid-state 13C MAS NMR spectra of adamantane and obtain good results for both static and dynamic field distortions. This work complements our previous work on instrumental suppression of dynamic distortions caused by the cold head operation. The results presented contribute well to the general field of processing NMR spectra and serve towards a more extensive use of cryogen-free magnets in high-resolution NMR spectroscopy.

PAP(248-286) Conformational Changes during the Lag Phase of Amyloid Fibril Formation.

The initial stage of fibril formation of C-terminal region PAP(248-286) of human seminal plasma protein prostatic acid phosphatase was considered. Amyloid fibrils from the peptide PAP(248-286) are termed as a semen-derived enhancer of viral infection (SEVI) found in abundant quantities in semen. The kinetics of the amyloid fibril formation process consists of two characteristic phases (lag phase/nucleation phase and growth phase/elongation phase). The lag phase can be caused by the presence of mature amyloid fibrils (seeds) in protein solution, so-called secondary nucleation. The secondary nucleation includes interaction of protein monomers with the mature fibril surface that leads to protein spatial structural changes for further amyloid fibril formation. In this work, changes of the PAP(248-286) spatial structure were obtained during the secondary nucleation phase. Pulsed-field gradient (PFG) NMR was used to characterize the behavior of monomeric PAP(248-286) in water solution after PAP(248-286) seed addition. The self-diffusion coefficient showed compactization of the peptide monomer due to fibril-monomer interactions. PAP(248-286) spatial structural changes were detected with the help of high-resolution NMR spectroscopy and molecular dynamics (MD) simulation. The folding of PAP(248-286) occurs due to backbone chain bending in the region of H270 and T275 amino acid residues. Obtained folded conformation of PAP(248-286) emerging in the secondary nucleation process is energetically favorable and retains after monomer-amyloid interaction. The structural changes are associated with localization of PAP(248-286) hydrophobic surface regions, which are probably responsible for peptide monomer-amyloid interactions.

Synthesis and Energetic Properties of N-Substituted 3,4- and 3,5-Dinitropyrazoles.

3,4- and 3,5-Dinitropyrazoles (DNPs) were substituted with acryl and allyl groups on the N1 nitrogen atom, resulting in three novel energetic materials. These compounds are all liquids at room temperature with melting points ranging from -60.2 to -38.6 °C and were fully characterized by high-resolution mass spectrometry, elemental analysis, proton and carbon nuclear magnetic resonance spectroscopy, and Fourier transform infrared spectroscopy. These materials were also tested for electrostatic discharge, friction, and impact sensitivities and then compared to DNP starting materials and to the explosive nitroglycerin (NG). These results indicate that the synthesized compounds are less sensitive to impact compared to NG and have higher thermal stabilities to decomposition.

In Situ Multinuclear Magic-Angle Spinning NMR: Monitoring Crystallization of Molecular Sieve AlPO4-11 in Real Time.

Molecular sieves are crystalline three-dimensional frameworks with well-defined channels and cavities. They have been widely used in industry for many applications such as gas separation/purification, ion exchange, and catalysis. Obviously, understanding the formation mechanisms is fundamentally important. High-resolution solid-state NMR spectroscopy is a powerful method for the study of molecular sieves. However, due to technical challenges, the vast majority of the high-resolution solid-state NMR studies on molecular sieve crystallization are ex situ. In the present work, using a new commercially available NMR rotor that can withhold high pressure and high temperature, we examined the formation of molecular sieve AlPO4-11 under dry gel conversion conditions by in situ multinuclear (1H, 27Al, 31P, and 13C) magic-angle spinning (MAS) solid-state NMR. In situ high-resolution NMR spectra obtained as a function of heating time provide much insights underlying the crystallization mechanism of AlPO4-11. Specifically, in situ 27Al and 31P MAS NMR along with 1H → 31P cross-polarization (CP) MAS NMR were used to monitor the evolution of the local environments of framework Al and P, in situ 1H → 13C CP MAS NMR to follow the behavior of the organic structure directing agent, and in situ 1H MAS NMR to unveil the effect of water content on crystallization kinetics. The in situ MAS NMR results lead to a better understanding of the formation of AlPO4-11.

Early Stage UV‐B Induced Molecular Modifications of Human Eye Lens γD‐Crystallin

Inside Front Cover: The human crystalline lens is composed of densely packed biopolymers that are constantly exposed to UV light throughout life and whose dysfunction leads to cataract. High-resolution protein NMR spectroscopy identified the early onset of molecular UV-B damage of aromatic amino acids in γD crystallin as part of the photoprotective capacity of the lens. This is reported by Jochen Balbach and co-workers in article number 2200526.

Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine

ObjectiveThe transformations that occur in diterpenoid alkaloids during the process of sand frying for Chinese herbal medicine preparation have yet to be clarified. This study investigated the structural changes that take place in 3-acetylaconitine during a simulation of heat-processing and evaluated the toxicity and biological activity of the pyrolysis products. MethodsThe diterpenoid alkaloid 3-acetylaconitine was heated at 180 °C for 15 min to simulate the process of sand frying. The pyrolysis products were separated using column chromatography, and their structures were investigated using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. Further, in vivo cardiotoxicity and acute toxicity of 3-acetylaconitine and its pyrolysis products were compared, and the aconitine-induced arrhythmia model was employed to evaluate the antiarrhythmic effect of the pyrolysis products. ResultsTwo new diterpenoid alkaloids, pyroacetylaconitine and 16-epi-pyroacetylaconitine, a pair of epimers at C-16, were isolated. After comparing the structures of these compounds, possible transformation pathways were proposed. Compared with the prototype compound, 3-acetylaconitine, the cardiotoxicity and acute toxicity of the heat-transformed products were significantly decreased. In the biological activity assay, the two pyrolysis products exhibited an effective increase in ventricular premature beat latency, a reduction in the occurrence of ventricular tachycardia, as well as an increase in the rate of arrhythmia inhibition, implying strong antiarrhythmic activity. ConclusionCompared with 3-acetylaconitine, its pyrolysis products displayed lower toxicity and good antiarrhythmic effects; thus, they have potential for being developed into antiarrhythmic medicines.Please cite this article as: Wang YJ, Wang Y, Tao P. Structural characterization, in vivo toxicity and biological activity of two new pyro-type diterpenoid alkaloids derived from 3-acetylaconitine. J Integr Med. 2023; 21(3): 302–314.

Antihyperlipidemic effect of Vaccinium dunalianum buds based on biological activity screening and LC-MS.

The buds of Vaccinium dunalianum Wight are used as folk medicine in the Yi settlement of the Yunnan Province, China. It has long been used as herbal tea in the local area owing to its effects of lowering blood lipids and body weight. However, there are only a few studies on its antihyperlipidemic effects, effective substances and mechanisms, especially its effectiveness in diet-induced hyperlipidemia. This study aimed to elucidate the therapeutic effects, pharmacodynamic material bases, and mechanisms of V. dunalianum buds on diet-induced hyperlipidemia. A high-fat diet-induced hyperlipidemic Sprague-Dawley (SD) rat model was established. Rats were gavaged with different doses of aqueous extract of V. dunalianum(VDW) for 8 weeks and their sera and organ samples were collected. The antihyperlipidemic effect of VDW on SD rats was evaluated based on the biochemical indices and histopathological outcomes. Liquid chromatography-mass spectrometry(LC-MS) was used to determine the main components in VDW, which were separated and purified using sequential chromatographic methods. Their chemical structures were determined using high-resolution electrospray ionization mass spectroscopy and nuclear magnetic resonance spectroscopy. 6'-O-caffeoyl-arbutin, as the principal component of VDW, was also evaluated for its antihyperlipidemic activity using an approach similar to that used for VDW. Lastly, the potential targets of VDW and 6'-O-caffeoyl-arbutin in lowering blood lipids were screened out using network pharmacology, and the selected targets were docked with arbutin derivatives. The expression of target proteins was determined using western blotting to illustrate the antihyperlipidemic mechanisms of VDW and 6'-O-caffeoyl-arbutin. VDW reduced triglyceride, total cholesterol, low-density lipoprotein, alanine transaminase, and aspartate transaminase levels in the serum of modeled rats, and increased high-density lipoprotein levels. There was an improvement in steatoses, and lipid droplet accumulation decreased in vivo after VDW intervention. LC-MS revealed that VDW mainly contained arbutin and chlorogenic acid derivatives. Sixteen compounds were isolated and identified. 6'-O-caffeoyl-arbutin was the main compound of VDW (>21.67%) that showed obvious antihyperlipidemic effect with low hepatic damage at different doses. PTGS2, ADH1C, and MAOB were screened out using network pharmacology and they showed strong correlations with arbutin derivative through molecular docking. Results from WB showed that VDW and 6'-O-caffeoyl-arbutin could reduce blood lipid levels by reducing the protein expression of PTGS2, ADH1C, and MAOB. 6'-O-caffeoyl-arbutin was the main component of V. dunalianum buds. VDW and 6'-O-caffeoyl-arbutin could regulate blood lipid levels in the high-fat diet-induced rat model of hyperlipidemia without damaging their vital organs. Furthermore, they could regulate the expression of PTGS2, ADH1C, and MAOB proteins and play a role in lowering blood lipids. The findings of this study lay a foundation for the further development of V. dunalianum and 6'-O-caffeoyl-arbutin as health supplements or drugs for the management of hyperlipidemia.

High-Resolution NMR Spectroscopy at Large Fields with Nitrogen Vacancy Centers.

Ensembles of nitrogen-vacancy (NV) centers are used as sensors to detect nuclear magnetic resonance signals from micron-sized samples at room temperature. In this scenario, the regime of large magnetic fields is especially interesting as it leads to a large nuclear thermal polarization-thus, to a strong sensor response even in low concentration samples-while chemical shifts and J couplings become more accessible. Nevertheless, this regime remains largely unexplored owing to the difficulties of coupling NV-based sensors with high-frequency nuclear signals. In this Letter, we circumvent this problem with a method that maps the relevant energy shifts in the amplitude of an induced nuclear spin signal that is subsequently transferred to the sensor. This stage is interspersed with free-precession periods of the sample nuclear spins where the sensor does not participate. Thus, our method leads to high spectral resolutions ultimately limited by the coherence of the nuclear spin signal.

A different approach to the quantification of human seminal plasma metabolites using high-resolution NMR spectroscopy

In this study, a reliable method was established for the absolute quantification of metabolite concentrations in human seminal plasma using ERETIC2, a quantification tool developed by Bruker based on the PULCON principle. The performance of the ERETIC2 was examined using an AVANCE III HD NMR spectrometer (600 MHz) equipped with a triple inverse 1.7 mm TXI probe in terms of some experimental parameters that may affect the accuracy and precision of the quantitative results. Then, the accuracy, precision, and repeatibility of ERETIC2 were determined using L-asparagine solutions at different concentrations. And it was evaluated by comparing it with the classical internal standard (IS) quantification method. The relative standard deviation (RSD) values for ERETIC2 were calculated in the range of 0.55–1.90% and the minimum recovery value was 99.9%, while the RSD values for the IS method were calculated in the range of 0.88–5.83% and recovery value was minimum 91.0%. Besides, the RSD values of the inter-day precisions for the ERETIC2 and IS methods were obtained to be in the range of 1.25 − 3.03% and 0.97 − 3.46%, respectively. Finally, the concentration values of seminal plasma metabolites were determined using different pulse programs with both methods for samples obtained from normozoospermic control and azoospermic patient groups. The results proved that this quantification method developed using NMR spectroscopy is easy to use in complex sample systems such as biological fluids and is a good alternative to the classical internal standard method in terms of accuracy and sensitivity. In addition, the improvement of the spectral resolution and sensitivity with the microcoil probe technology and the possibility of analyzing with minimum sample quantities has contributed positively to the results of this method.

Elucidating dynamic anaerobe metabolism with HRMAS 13C NMR and genome-scale modeling

Anaerobic microbial metabolism drives critical functions within global ecosystems, host–microbiota interactions, and industrial applications, yet remains ill-defined. Here we advance a versatile approach to elaborate cellular metabolism in obligate anaerobes using the pathogen Clostridioides difficile, an amino acid and carbohydrate-fermenting Clostridia. High-resolution magic angle spinning nuclear magnetic resonance (NMR) spectroscopy of C. difficile, grown with fermentable 13C substrates, informed dynamic flux balance analysis (dFBA) of the pathogen’s genome-scale metabolism. Analyses identified dynamic recruitment of oxidative and supporting reductive pathways, with integration of high-flux amino acid and glycolytic metabolism at alanine’s biosynthesis to support efficient energy generation, nitrogen handling and biomass generation. Model predictions informed an approach leveraging the sensitivity of 13C NMR spectroscopy to simultaneously track cellular carbon and nitrogen flow from [U-13C]glucose and [15N]leucine, confirming the formation of [13C,15N]alanine. Findings identify metabolic strategies used by C. difficile to support its rapid colonization and expansion in gut ecosystems.

Expanding the Role of Dimeric Species: On-Cycle Involvement, Improved Stability, and Control of Stereo-Specificity. A Case Study of Atom-Economic Catalytic Hydrothiolation

A common assumption that dimeric metal complexes in many catalytic systems represent a resting state and are not directly involved in catalytic processes was revised in a combined experimental and theoretical study. On-cycle participation of dimeric metal complexes, rather than typically assumed off-cycle involvement, was revealed, and advantageous performance in terms of improved selectivity was observed. The conceptual rationalization for the participation of dimeric species in the catalytic cycle was developed. The Pd-catalyzed hydrothiolation process (where strong Pd–S binding is well established and a persistent opinion for the inactive/poisoning role of dimeric species is presumed) was evaluated as a challenging system to test the concept. Activation of an (NHC)Pd(Cl)(acac) precatalyst (NHC─N-heterocyclic carbene and acac─acetylacetonate) under the reaction conditions produced monomeric (NHC)Pd(SPh)2 or dimeric (NHC)2Pd2(SPh)4 species depending on the steric bulkiness of the NHC ligand. Dimeric complexes possessed higher selectivity and tolerated disulfide impurities in contrast to monomeric complexes. Quantum chemical modeling suggested that dimeric catalysis proceeds through the opening of only one (μ-SPh)–Pd bridging bond with retention of the dimeric structure. The second bridging bond is maintained, which prevents the monomerization of the complex. Catalytically active species were detected in a hydrothiolation reaction by high-resolution mass spectrometry and NMR spectroscopy. Proving the opportunity for productive homogeneous catalysis via strongly coordinated dimeric metal species opens new opportunities for catalyst design in the increased nuclearity dimension.

Profiling of Taxoid Compounds in Plant Cell Cultures of Different Species of Yew (Taxus spp.)

Plant cell cultures of various yew species are a profitable source of taxoids (taxane diterpenoids) with antitumor activity. So far, despite intensive studies, the principles of the formation of different groups of taxoids in cultured in vitro plant cells have not been fully revealed. In this study, the qualitative composition of taxoids of different structural groups was assessed in callus and suspension cell cultures of three yew species (Taxus baccata, T. canadensis, and T. wallichiana) and two T. × media hybrids. For the first time, 14-hydroxylated taxoids were isolated from the biomass of the suspension culture of T. baccata cells, and their structures were identified by high-resolution mass spectrometry and NMR spectroscopy as 7β-hydroxy-taxuyunnanin C, sinenxane C, taxuyunnanine C, 2α,5α,9α,10β,14β-pentaacetoxy-4(20), 11-taxadiene, and yunnanxane. UPLC-ESI-MS screening of taxoids was performed in more than 20 callus and suspension cell lines originating from different explants and grown in over 20 formulations of nutrient media. Regardless of the species, cell line origin, and conditions, most of the investigated cell cultures retained the ability to form taxane diterpenoids. Nonpolar 14-hydroxylated taxoids (in the form of polyesters) were predominant under in vitro culture conditions in all cell lines. These results, together with the literature data, suggest that dedifferentiated cell cultures of various yew species retain the ability to synthesize taxoids, but predominantly of the 14-OH taxoid group compared to the 13-OH taxoids found in plants.

Glycolipids as a promising ingredient in food and pharmaceutical technologies

The relevance of the analysis of scientific publications devoted to the study of the composition, properties, methods of preparation, areas of application, as well as the qualitative and quantitative identification of glycolipids is determined by the prospects for their use as alternative natural surfactants. Glycolipids possessing comparable surfactant properties with widely used surfactants of a petrochemical nature, and distinguished by the absence of toxicity and environmental friendliness, exhibit pronounced physiological and functional properties.Currently, there are no systematic data covering various aspects of the composition, physicochemical properties of glycolipids.The purpose of this research is to clarify the classification of glycolipids, to summarize data on the advantages and disadvantages of various industrial methods for obtaining glycolipids; systematization of data on the properties of glycolipids by application; identification of the most effective methods for the qualitative and quantitative identification of glycolipids.Particular attention is paid to the analysis of data on the possibility of isolating glycolipids from plant materials, including secondary resources of the oil and fat industry.The data presented in the review indicate that glycolipids, including those isolated from plant materials, are characterized by a high biotechnological potential for their use in the creation of pharmaceuticals, cosmetics, and functional foods.Of the known methods for the industrial production of glycolipids, currently the most common and cost-effective methods are those based on microbiological and enzymatic synthesis.Promising raw materials for the production of glycolipids are secondary products of processing of oilseeds – phosphatide emulsions and phosphatide concentrates containing up to 5% glycolipids in their composition. There are currently no methods for obtaining glycolipids from this type of raw material.Of the known methods for the qualitative and quantitative identification of glycolipids (TLC, HPTLC, HPLC, NMR), the most promising method is high-resolution NMR spectroscopy, as it is the most informative, rapid and accurate.

Ionic Liquids as Working Fluids for Heat Storage Applications: Decomposition Behavior of N-Butyl-N-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate.

Ionic liquids (ILs) represent promising working fluids to be used in thermal energy storage (TES) technologies thanks to their peculiar properties, such as low volatility, high chemical stability, and high heat capacity. Here, we studied the thermal stability of the IL N-butyl-N-methylpyrrolidinium tris(pentafluoroethyl)trifluorophosphate ([BmPyrr]FAP), a potential working fluid for TES applications. The IL was heated at 200 °C for up to 168 h either in the absence or in contact with steel, copper, and brass plates to simulate the conditions used in TES plants. High-resolution magic angle spinning nuclear magnetic resonance spectroscopy was found to be useful for the identification of the degradation products of both the cation and the anion, thanks to the acquisition of 1H, 13C, 31P, and 19F-based experiments. In addition, elemental analysis was performed on the thermally degraded samples by inductively coupled plasma optical emission spectroscopy and energy dispersive X-ray spectroscopy. Our analysis shows a significant degradation of the FAP anion upon heating for more than 4 h, even in the absence of the metal/alloy plates; on the other hand, the [BmPyrr] cation displays a remarkable stability also when heated in contact with steel and brass.

Coordination Changes in Densified Aluminate Glass upon Compression up to 65 GPa: A View from Solid-State Nuclear Magnetic Resonance.

Deciphering the structural evolution in irreversibly densified oxide glasses is crucial for fabricating functional glasses with tunable properties and elucidating the nature of pressure-induced anomalous plastic deformation in glasses. High-resolution NMR spectroscopy quantifies atomic-level structural information on densified glasses; however, its application is limited to the low-pressure range due to technical challenges. Here, we report the first high-resolution NMR spectra of oxide glass compressed by diamond anvil cells at room temperature, extending the pressure record of such studies from 24 to 65 GPa. The results constrain the densification path through coordination transformation of Al cations. Based on a statistical thermodynamic model, the stepwise changes in the Al fractions of oxide glasses and the effects of network polymerization on the densification paths are quantified. These results extend the knowledge on densification of the previously unattainable pressure conditions and contribute to understanding the origin of mechanical strengthening of the glasses.

Energetically preferred Li+ ion jump processes in crystalline solids: Site-specific hopping in β-Li3VF6 as revealed by high-resolution 6Li 2D EXSY NMR

The visualization of atomic or ionic jump processes on the Ångström length scale is important to identify the preferred diffusion pathways in solid electrolytes for energy storage devices. Two-dimensional high-resolution 6Li nuclear magnetic resonance (NMR) spectroscopy is highly suited to yield unprecedented site-specific insights into local Li+ exchange processes within a single measurement. Here, the beta-modification of Li3VF6 is used as a model system for such an investigation as it provides a range of important Li+ geometric environments in one and the same crystal structure useful to elucidate qualitatively a ranking of energetic preferences of the Li+ exchange processes. In Li3VF6 the Li+ ions are subject to diffusive exchange processes among five crystallographically and magnetically inequivalent Li sites: LiFn (n = 6, 4). By using a sample with a natural concentration of the 6Li isotope, we suppressed unwanted spin-diffusion processes and visualized the various exchange processes on the ms time scale. We were able to verify the following ranking experimentally: Li+ ion jumps between face-shared polyhedra are preferred, followed by Li+ exchange between edge-shared configurations for which interstitial sites are needed to jump from site to site. Surprisingly, Li+ exchange between corner-shared polyhedra and Li+ hopping involving almost isolated LiF4 polyhedra do contribute to overall Li+ self-diffusion as well. In this sense, the current study experimentally verifies current predictions by theory but also extends our understanding of ion dynamics between corner-shared Li-bearing polyhedra.

Diversity of Structural, Dynamic, and Environmental Effects Explain a Distinctive Functional Role of Transmembrane Domains in the Insulin Receptor Subfamily.

Human InsR, IGF1R, and IRR receptor tyrosine kinases (RTK) of the insulin receptor subfamily play an important role in signaling pathways for a wide range of physiological processes and are directly associated with many pathologies, including neurodegenerative diseases. The disulfide-linked dimeric structure of these receptors is unique among RTKs. Sharing high sequence and structure homology, the receptors differ dramatically in their localization, expression, and functions. In this work, using high-resolution NMR spectroscopy supported by atomistic computer modeling, conformational variability of the transmembrane domains and their interactions with surrounding lipids were found to differ significantly between representatives of the subfamily. Therefore, we suggest that the heterogeneous and highly dynamic membrane environment should be taken into account in the observed diversity of the structural/dynamic organization and mechanisms of activation of InsR, IGF1R, and IRR receptors. This membrane-mediated control of receptor signaling offers an attractive prospect for the development of new targeted therapies for diseases associated with dysfunction of insulin subfamily receptors.

An S-Shaped Aβ42 Cross-β Hexamer Embedded into a Lipid Bilayer Reveals Membrane Disruption and Permeability.

The interactions of amyloid oligomers with membranes are known to contribute to cellular toxicity. Numerous in vitro experimental studies reported on the insertion of oligomers of different sizes that can induce cell membrane disruption, extract lipids, and form ion-permeable transmembrane pores. The current repertoire of amyloid-beta (Aβ) membrane-inserted folds that was subject to high-resolution structure NMR spectroscopy and computer simulations is devoid of any cross-β fibrillar structure. In this study, we explored the dynamics of an S-shaped Aβ42 cross-β hexamer model inserted into a lipid bilayer membrane by two atomistic molecular dynamics simulations. The initial model is characterized by the hydrophobic residues at the central hydrophobic core (residues 17-21, CHC) and the C-terminus (residues 30-42) embedded into the membrane. We observed major structural secondary, tertiary, and quaternary rearrangements leading to two distinct species, hexamer and two trimers, accompanied by membrane disruption and water permeation. The simulations show that some configurations, but not the majority, have the CHC and C-terminus hydrophobic residues exposed to the solvent. Overall, our computational results offer new perspectives to understand the relationship between Aβ42 assemblies and membrane permeability.

Eumitrins I-K: three new xanthone dimers from the lichen Usnea baileyi.

In the continuing discovery and structure elucidation of natural xanthone dimers, which are still rarely reported in absolute configuration, three new xanthone dimers, eumitrins I-K (1-3) were isolated from the lichen Usnea baileyi, a rich source of natural xanthone dimers. Their structures were elucidated unambiguously by spectroscopic analyses, including high-resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D nuclear magnetic resonance spectroscopy (1D and 2D NMR). The absolute configuration of all three compounds was established through DP4 probability and ECD calculation. All compounds revealed weak activity for their enzymatic inhibition against α-glucosidase and tyrosinase, as well as antibacterial activity.

Antiparasitic Meroterpenoids Isolated from Memnoniella dichroa CF-080171.

Memnoniella is a fungal genus from which a wide range of diverse biologically active compounds have been isolated. A Memnoniella dichroa CF-080171 extract was identified to exhibit potent activity against Plasmodium falciparum 3D7 and Trypanosoma cruzi Tulahuen whole parasites in a high-throughput screening (HTS) campaign of microbial extracts from the Fundación MEDINA's collection. Bioassay-guided isolation of the active metabolites from this extract afforded eight new meroterpenoids of varying potencies, namely, memnobotrins C-E (1-3), a glycosylated isobenzofuranone (4), a tricyclic isobenzofuranone (5), a tetracyclic benzopyrane (6), a tetracyclic isobenzofuranone (7), and a pentacyclic isobenzofuranone (8). The structures of the isolated compounds were established by (+)-ESI-TOF high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Compounds 1, 2, and 4 exhibited potent antiparasitic activity against P. falciparum 3D7 (EC50 0.04-0.243 μM) and T. cruzi Tulahuen (EC50 0.266-1.37 μM) parasites, as well as cytotoxic activity against HepG2 tumoral liver cells (EC50 1.20-4.84 μM). The remaining compounds (3, 5-8) showed moderate or no activity against the above-mentioned parasites and cells.