Chemical Correlation Research Articles

Benzophenone and chromone derivatives and their dimers from the scale-insect pathogenic fungus Orbiocrella petchii BCC 51377

A benzophenone derivative, orbiophenone A, and its homodimer, orbiocrellone A, a chromone derivative, orbiochromone A, four benzophenone–chromone heterodimers, orbiocrellones B–E, and a benzophenone–tetrahydroxanthone dimer, ent-secalonic acid I, were isolated from cultures of the scale-insect pathogenic fungus Orbiocrella petchii BCC 51377. Their structures were elucidated by spectroscopic analyses and chemical correlations. Orbiochromone A was isolated for the first time as an optically active natural product, and its absolute configuration was determined by the ECD spectrum combined with TD-DFT calculations. Four of the dimeric compounds, orbiocrellones B–D and ent-secalonic acid I, exhibited antimalarial activity against Plasmodium falciparum K1 with IC50 values of 5.7, 5.6, 14, and 5.5 μM, respectively.

Induction of Planar Chirality Using Asymmetric Click Chemistry by a Novel Desymmetrisation of 1,3‐Bisalkynyl Ferrocenes

The new asymmetric click CuAAC reaction is used for the first time to induce asymmetry in planar chiral compounds. There are only three classes of stereogenicity (atom‐centred, axial and planar), and these results are therefore of fundamental importance as well as practical significance, providing access to chiral ferrocenes at near enantiopurity. Here, we report asymmetric induction (AI) and kinetic resolution (KR) studies on a novel library of prochiral 1,2,3‐trisubstituted bis‐alkynylferrocenes, obtained by diiodination, derivatisation (including reduction and etherification), double Sonogashira coupling and finally transesterification, azidation or silylation. Desymmetrisation using chiral ligands to modify the CuAAC reaction proceeds in up to 60 % yield and >99.5 % ee, yielding planar chiral ferrocenes. The absolute configuration of two of the preferred products was proved by chemical correlation and related to the entire series by circular dichroism spectroscopy (CD).

Annealing environment dependent electrical and chemical state correlation of Li-doped NiO

The effects of annealing environments and dopants on the structural, chemical, optical, and electrical properties of NiO are investigated. Pristine NiO exhibits electrically insulating behavior regardless of the annealing environments (e.g., vacuum and O2 environments). On the other hand, Li-doped NiO exhibits electrical resistivities of ∼350 Ω cm and ∼9 Ω cm for the ceramics annealed under vacuum and O2, respectively with reduced optical band-gap. The structural analysis revealed that all the samples exhibit a cubic structure (Fm-3m, SG 225) without any measurable secondary phases. However, Li-doped NiO samples showed a reduction in the unit cell volume as compared to the undoped NiO samples. X-ray photoelectron spectroscopy revealed different residual Li content depending on the annealing environments, and the presence of induced Ni3+ state in the Li-doped NiO. These induced Ni3+ states and doped Li are responsible for the observed change in the structural and electrical properties of the Li-doped NiO samples.

Propagation of the Allosteric Signal in Phosphofructokinase from Bacillus stearothermophilus Examined by Methyl-Transverse Relaxation-Optimized Spectroscopy Nuclear Magnetic Resonance.

Phosphofructokinase from Bacillus stearothermophilus (BsPFK) is a 136 kDa homotetromeric enzyme. Binding of the substrate, fructose 6-phosphate (Fru-6-P), is allosterically regulated by the K-type inhibitor phosphoenolpyruvate (PEP). The allosteric coupling between the substrate and inhibitor is quantified by a standard coupling free energy that defines an equilibrium with the Fru-6-P-bound and PEP-bound complexes on one side and the apo form and ternary complex on the other. Methyl-transverse relaxation-optimized spectroscopy (Me-TROSY) nuclear magnetic resonance was employed to gain structural information about BsPFK in all four states of ligation relevant to the allosteric coupling. BsPFK was uniformly labeled with 15N and 2H and specifically labeled with δ-[13CH3]-isoleucine utilizing an isotopically labeled α-keto acid isoleucine precursor. Me-TROSY experiments were conducted on all four ligation states, and all 30 isoleucines, which are well dispersed throughout each subunit of the enzyme, are well-resolved in chemical shift correlation maps of 13C and 1H. Assignments for 17 isoleucines were determined through three-dimensional HMQC-NOESY experiments with [U-15N,2H];Ileδ1-[13CH3]-BsPFK and complementary HNCA and HNCOCA experiments with [U-2H,15N,13C]-BsPFK. The assignments allowed for the mapping of resonances representing isoleucine residues to a previously determined X-ray crystallography structure. This analysis, performed for all four states of ligation, has allowed specific regions of the enzyme influenced by the binding of allosteric ligands and those involved in the propagation of the allosteric effect to be identified and distinguished from one another.

Smart machine learning or discovering meaningful physical and chemical contributions through dimensional stacking

Despite remarkable advances in characterization techniques of functional materials yielding an ever growing amount of data, the interplay between the physical and chemical phenomena underpinning materials’ functionalities is still often poorly understood. Dimensional reduction techniques have been used to tackle the challenge of understanding materials’ behavior, leveraging the very large amount of data available. Here, we present a method for applying physical and chemical constraints to dimensional reduction analysis, through dimensional stacking. Compared to traditional, uncorrelated techniques, this approach enables a direct and simultaneous assessment of behaviors across all measurement parameters, through stacking of data along specific dimensions as required by physical or chemical correlations. The proposed method is applied to the nanoscale electromechanical relaxation response in (1 − x)PMN-xPT solid solutions, enabling a direct comparison of electric field- and chemical composition-dependent contributors. A poling-like, and a relaxation-like behavior with a domain glass state are identified, and their evolution is tracked across the phase diagram. The proposed dimensional stacking technique, guided by the knowledge of the underlying physics of correlated systems, is valid for the analysis of any multidimensional dataset, opening a spectrum of possibilities for multidisciplinary use.

Interface-Sensitive Raman Microspectroscopy of Water via Confinement with a Multimodal Miniature Surface Forces Apparatus

Modern interfacial science is increasingly multidisciplinary. Unique insight into interfacial interactions requires new multimodal techniques for interrogating surfaces with simultaneous complementary physical and chemical measurements. Here, we describe the design and testing of a microscope that incorporates a miniature surface forces apparatus (μSFA) in sphere vs flat geometry for force-distance measurements, while simultaneously acquiring Raman spectra of the confined zone. The simple optical setup isolates independent optical paths for (i) the illumination and imaging of Newton's rings and (ii) Raman scattering excitation and efficient signal collection. We benchmark the methodology by examining Teflon thin films in asymmetric (Teflon-water-glass) and symmetric (Teflon-water-Teflon) configurations. Water is observed near the Teflon-glass interface with nanometer-scale sensitivity in both the distance and Raman signals. We perform chemically resolved, label-free imaging of confined contact regions between Teflon and glass surfaces immersed in water. Remarkably, we estimate that the combined approach enables vibrational spectroscopy with single water monolayer sensitivity within minutes. Altogether, the Raman-μSFA allows exploration of molecular confinement between surfaces with chemical selectivity and correlation with interaction forces.

Correlation study on chemical constitutes of cardiac glycosides in Taxillus chinensis and its Nerium indicum host by UPLC-Q-TOF-MS/MS

To build up an identification method on cardiac glycosides in Taxillus chinensis and its Nerium indicum host, and evaluate the influence on medicine quality from host to T. chinensis, ultra-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass-mass spectrometry(UPLC-Q-TOF-MS/MS)was applied. The samples of T. chinensis(harvested from N. indicum)and its N. indicum host were collected in field. The samples of T. chinensis(harvested from Morus alba)and its M. alba host was taken as control substance. All samples were extracted by ultrasonic extraction in 70% ethanol. Chromatographic separation was performed on an ACQUITY UPLC HSS T3 C_(18)(2.1 mm×100 mm,1.8 μm)column at 40 ℃. Gradient elution was applied, and the mobile phase was consisted of 0.1% formic acid water and acetonitrile. The 0.5 μL of sample solution was injected and the flow rate of the mobile phase was kept at 0.6 mL·min~(-1) in each run. It was done to identify cardiac glycosides and explore the chemical composition correlation in T. chinensis and its N. indicum host by analyzing positive and negative ion mode mass spectrometry data, elemental composition, cardiac glycoside reference substance and searching related literatures. A total of 29 cardiac glycosides were identified, 28 of it belonged to N. indicum host, 5 belonged to T. chinensis(harvested from N. indicum host), none of cardiac glycoside was identified in T. chinensis(harvested from M. alba host). The result could provide a reference in evaluating the influence in T. chinensis medicine quality from host. It was rapid, accurate, and comprehensive to identify cardiac glycosides in T. chinensis and its N. indicum host by UPLC-Q-TOF-MS/MS.

Two new sarpagine-type indole alkaloids and antimalarial activity of 16-demethoxycarbonylvoacamine from Tabernaemontana macrocarpa Jack.

Two new sarpagine-type indole alkaloids (1 and 2), together with five known alkaloids; 12-methoxy-4-methylvoachalotine (3), 16-demethoxycarbonylvoacamine (4), isositsirikine (5), affinisine (6), affinine (7), were isolated from the bark of Tabernaemontana macrocarpa Jack. The structures of these alkaloids were determined based on spectroscopic data, chemical correlation, and comparison with the literature. 16-Demethoxycarbonylvoacamine (4) showed antiplasmodial activities against Plasmodium falciparum 3D7 and cytotoxic activities against human cell line, HepG2 cells.

G-SERF Editing in Two-Dimensional Pure-Shift Total Correlation Spectroscopy: Scalar Coupling Measurements for a Group of Spins in Organic Molecules.

A novel G-SERF-PSYCHE-TOCSY (gradient encoded selective refocusing in pure shift yielded by chirp excitation version of total correlation spectroscopy) NMR pulse scheme has been proposed, which produces TOCSY chemical shift correlations, on one hand, and scalar coupling values for the spins scalarly coupled to irradiated resonances, by showing them as doublets along the indirect dimension, on the other. Therefore, recording such an experiment, for a group of spins with overlapping chemical shifts, in organic molecules can adequately provide scalar coupling information in a G-SERF manner along the indirect dimensions, and they can be assigned to particular spin pairs. Such COSY chemical shift correlations (which appear as doublets for the scalarly coupled spins) can be readily discriminated from the TOCSY peaks (which do not show such splitting) in the G-SERF-PSYCHE-TOCSY spectrum.

Altercrasins A⁻E, Decalin Derivatives, from a Sea-Urchin-Derived Alternaria sp.: Isolation and Structural Analysis Including Stereochemistry.

In order to find out the seeds of antitumor agents, we focused on potential bioactive materials from marine-derived microorganisms. Marine products include a number of compounds with unique structures, some of which may exhibit unusual bioactivities. As a part of this study, we studied metabolites of a strain of Alternaria sp. OUPS-117D-1 originally derived from the sea urchin Anthocidaris crassispina, and isolated five new decalin derivatives, altercrasins A–E (1–5). The absolute stereostructure of altercrasins A (1) had been decided by chemical transformation and the modified Mosher’s method. In this study, four decalin derivatives, altercrasins B–E (2–5) were purified by silica gel chromatography, and reversed phase high-performance liquid chromatography (RP HPLC), and their structures were elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) spectroscopic analyses. The absolute configuration of them were deduced by the comparison with 1 in the NMR chemical shifts, NOESY correlations, and electronic circular dichroism (ECD) spectral analyses. As a result, we found out that compound pairs of 1/2 and 4/5 were respective stereoisomers. In addition, their cytotoxic activities using murine P388 leukemia, human HL-60 leukemia, and murine L1210 leukemia cell lines showed that 4 and 5 exhibit potent cytotoxicity, in especially, the activity of 4 was equal to that of 5-fluorouracil.

Tectonochemistry andp‐tConditions of Ramgarh and Almora Gneisses from Askot Klippe, Kumaun Lesser Himalaya

The chemical and petrological correlation of metamorphic nappes and klippes overlying the Proterozoic sedimentary units in the Kumaun Himalaya is still debated. The Ramgarh and Almora gneisses, not previously distinguished in the Askot Klippe, show distinct field, petrological and chemical signatures markedly similar to the tectonostratigraphic disposition of the Almora Nappe. A negative Eu anomaly in the Ramgarh granitic gneisses indicates lesser plagioclase fractionation while the Eu anomaly in the Almora pelitic gneisses is likely to have been controlled by feldspar crystallization in restites. During the anatexis at > 776°C temperature and >6.6 kbar pressure, the melt moved slightly away to its crystallization sites. The Rb/Sr ratio ∼0.54 and Nb ∼10 ppm is consistent with the granodioritic composition. The negative Sr anomaly in the underlying Ramgarh granitic gneisses indicates a distinct mantle derived source/plagioclase fractionation with a notable correspondence to other late orogenic granites, particularly the basement Ulleri gneisses from the Nepal Himalaya. Ramgarh gneisses plot in the late‐ and post‐COLG field. The Askot ensemble is likely to be the tectonometamorphically reworked basement, viz. the Ramgarh Group along with its metapelitic cover of the Almora Group, together comprising southward thrust remnants of the leading edge of the Indian Plate that collided with Tibet during the Tertiary Himalayan orogeny.

Structure of TeO2 glass: Results from 2D 125Te NMR spectroscopy

Despite its chemical simplicity, a definitive description of the structure of TeO2 glass has remained elusive due to the complexity of the Te-O coordination environment. In this work we probe the Te-O coordination environment in glassy TeO2 using 2D 125Te isotropic-anisotropic chemical shift correlation nuclear magnetic resonance (NMR) spectroscopy. The NMR results are consistent with the presence of two Te-O environments in this glass, characterized by their distinct set of 125Te chemical shift parameters. The dominant environment (~89%) is a distorted trigonal bipyramidal TeO4 unit, reminiscent of that observed in crystalline γ-TeO2. A second, minor (~11%) component can be assigned, on the basis of its chemical shift parameters, to a TeO3 unit. The resulting average coordination number, nTeO, measured by 125Te NMR (nTeO ≈ 3.9) is higher than its previously reported value obtained using neutron diffraction (nTeO ≈ 3.7).

12α-hydroxy-N-demethyl-sauroxine, a lycodane type alkaloid from Phlegmariurus saururus

12α-hydroxy-N-demethyl-sauroxine (1), another new Lycopodium alkaloid from the Lycodane group, was isolated from Phlegmariurus saururus (Lam.) B. Øllg. (Lycopodiaceae). Elucidation of the chemical structure and relative stereochemistry were stated by spectroscopic data and chemical correlation. In addition, the inhibitory activity on acetylcholinesterase for 1 was determined as well as for N-methyllycodine (2), a derivative with the same nucleus, previously identified in P. saururus (IC50 = 33.8 ± 0.8 μM and 547.5 ± 0.5 μM, respectively) and N-demethylsauroxine (3) whose inhibition in the actual conditions was better than the previously informed.

Hybridization of TEDOR and NCX MAS solid-state NMR experiments for simultaneous acquisition of heteronuclear correlation spectra and distance measurements.

Magic angle spinning (MAS) solid-state NMR (ssNMR) spectroscopy is a major technique for the characterization of the structural dynamics of biopolymers at atomic resolution. However, the intrinsic low sensitivity of this technique poses significant limitations to its routine application in structural biology. Here we achieve substantial savings in experimental time using a new subclass of Polarization Optimized Experiments (POEs) that concatenate TEDOR and SPECIFIC-CP transfers into a single pulse sequence. Specifically, we designed new 2D and 3D experiments (2D TEDOR-NCX, 3D TEDOR-NCOCX, and 3D TEDOR-NCACX) to obtain distance measurements and heteronuclear chemical shift correlations for resonance assignments using only one experiment. We successfully tested these experiments on N-Acetyl-Val-Leu dipeptide, microcrystalline U-13C,15N ubiquitin, and single- and multi-span membrane proteins reconstituted in lipid membranes. These pulse sequences can be implemented on any ssNMR spectrometer equipped with standard solid-state hardware using only one receiver. Since these new POEs speed up data acquisition considerably, we anticipate their broad application to fibrillar, microcrystalline, and membrane-bound proteins.

Irrigation deficit turns almond by-products into a valuable source of antimicrobial (poly)phenols

Almond (Prunus dulcis (Mill.) D. A. Webb) production keeps an increasing trend worldwide, leading to augment in generation of harmful by-products that should be valorized as a source of bioactive phytochemicals with application in the development of new added-value products. The assessment of almond hulls and skins on their (poly)phenolic composition was developed upon two seasons, under five irrigation regimes, regarding total phenolics, flavonoids, and ortho-diphenols, as well as individual phenolic compounds analyzed by High-Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD). As functional tests, extracts were assessed on their radical scavenging activity in vitro and reducing power, and screened on their antimicrobial activity against multidrug resistant bacterial pathogens. The phenolic profile and antioxidant activities were evaluated in blanching water as well. Naringenin-7-O-glucoside and isorhamnetin-3-O-rutinoside were the most abundant phenolics in almond hulls and skins. Influence of irrigation treatments and season on phenolic content differed among by-products; hulls being more influenced by irrigation and skins by the agro-climatic conditions. The synthesis of individual phenolics was more influenced by season than treatment. According to the chemical and biological correlations, the presence of (poly)phenols seems to be responsible for the antioxidant and antimicrobial properties revealed. The knowledge generated upon the present work contributes to understand the variability of almond by-products composition attributable to seasonal and irrigation conditions, and to envisage valorization alternatives for these under explored residues and blanching water.

Ligand biological activity predicted by cleaning positive and negative chemical correlations

Predicting ligand biological activity is a key challenge in drug discovery. Ligand-based statistical approaches are often hampered by noise due to undersampling: The number of molecules known to be active or inactive is vastly less than the number of possible chemical features that might determine binding. We derive a statistical framework inspired by random matrix theory and combine the framework with high-quality negative data to discover important chemical differences between active and inactive molecules by disentangling undersampling noise. Our model outperforms standard benchmarks when tested against a set of challenging retrospective tests. We prospectively apply our model to the human muscarinic acetylcholine receptor M1, finding four experimentally confirmed agonists that are chemically dissimilar to all known ligands. The hit rate of our model is significantly higher than the state of the art. Our model can be interpreted and visualized to offer chemical insights about the molecular motifs that are synergistic or antagonistic to M1 agonism, which we have prospectively experimentally verified.

Polyoxygenated Cyclohexenes and Their Chlorinated Derivatives from the Leaves of Uvaria cherrevensis.

The chemical study of leaf extracts from Uvaria cherrevensis resulted in the identification of 11 new polyoxygenated cyclohexenes, cherrevenols A-K (1-11), and a new seco-cyclohexene derivative, cherrevenol L (12). Nine known compounds (13-21) were also isolated. Three of the isolated compounds are chlorinated polyoxygenated cyclohexenes. The structures of these compounds were determined using spectroscopic methods and, in some cases (compounds 2, 6, 8, and 10), single-crystal X-ray crystallographic structural analysis or chemical correlation (compounds 6 and 7). Compounds 6 and 7 were both isolated as scalemic mixtures (ee 23-24%).

Structure Elucidation, Conformation, and Configuration of Cytotoxic 6-Heptyl-5,6-dihydro-2 H-pyran-2-ones from Hyptis Species and Their Molecular Docking to α-Tubulin.

Cytotoxic 6-heptyl-5,6-dihydro-2 H-pyran-2-ones are chemical markers of Hyptis (Lamiaceae) and are responsible for some of the therapeutic properties of species with relevance to traditional medicine. The present investigation describes the isolation of known pectinolides A-C (1-3), in addition to the new pectinolides I-M (4-8), from two Mexican collections of H. pectinata by HPLC. The novel biosynthetically related monticolides A (9) and B (10) were also isolated by high-speed countercurrent chromatography from H. monticola, an endemic species of the Brazilian southeastern high-altitude regions. A combination of chemical correlations, chiroptical measurements, and Mosher ester NMR analysis was used to confirm their absolute configuration. The utility of DFT-NMR chemical shifts and JH-H calculations was assessed for epimer differentiation. Molecular docking studies indicated that 6-heptyl-5,6-dihydro-2 H-pyran-2-ones have a high affinity for the pironetin-binding site of α-tubulin, which may be a possible mechanism contributing to the cytotoxic potential of these small and flexible molecules.

Correlating weathered, microphenocryst-rich, intermediate tephra: An approach combining bulk and single shard analyses from the Lepué Tephra, Chile and Argentina

Chemical correlation of intermediate tephra deposits using microanalytical data is problematic because (i) the phenocryst content of their component glass shards affects major and trace element analyses (ii) bulk chemistry can be affected by variations in mineral/lithic components across the fall-out, and (iii) weathering readily alters their composition. All of these problems affect the Lepué Tephra, a prominent marker horizon extensively distributed across the Los Lagos Region of Chile and the Chile-Argentina frontier in north-western Patagonia, which was erupted from Volcán Michinmahuida at c. 11000 cal a BP. Weathering of terrestrial cover-bed deposits in this hyper-humid depositional environment leaves only a few occurrences of the tephra which contain fresh glass shards for microbeam analysis, but their highly phenocrystic nature makes data interpretation difficult. Equally, leaching of mobile elements during weathering causes considerable compositional changes across the fall-out region and is evident in bulk sample analyses. Elements such as the REE and Y, generally regarded as immobile, show marked mobility. Within the REE, the development of “M-type” tetrad effects and positive Ce-anomalies result from a combination of dissolution/leaching of the REE from the bulk sample and retention by co-precipitation of Ce4+ on Fe-oxyhydroxides in this high-rainfall, hyper-humid, oxic environment. Chemical correlation of the Lepué Tephra is thus not straightforward. However, by careful consideration of the data for a limited range of elements, chemical correlation can be achieved using elements which (i) are incompatible in magmatic systems (and thus their ratios are unaffected by the presence of phenocrysts in single glass shard microbeam analysis) and (ii) are not mobilised in these weathering conditions. These elements are Zr, Hf, Nb, Ta and Th. Their ratios (i) allow for the comparison of single grain and bulk sample analyses, extending the geographic range over which data can be compared for the Lepué Tephra, (ii) provide a robust chemical correlation of this weathered, intermediate tephra deposit, enabling correlation even where elements traditionally considered immobile (REE, Y, and U) have been significantly mobilised, and (iii) allow the Lepué Tephra to be distinguished from other local tephra deposits. This combined analytical approach enables tephras that have been variably weathered to become useful marker beds over much wider geographical areas than previously feasible, thereby enhancing their tephrochronological application in Quaternary research.

Boosting Quantum Machine Learning Models with a Multilevel Combination Technique: Pople Diagrams Revisited.

Inspired by Pople diagrams popular in quantum chemistry, we introduce a hierarchical scheme, based on the multilevel combination (C) technique, to combine various levels of approximations made when molecular energies are calculated. When combined with quantum machine learning (QML) models, the resulting CQML model is a generalized unified recursive kernel ridge regression that exploits correlations implicitly encoded in training data composed of multiple levels in multiple dimensions. Here, we have investigated up to three dimensions: chemical space, basis set, and electron correlation treatment. Numerical results have been obtained for atomization energies of a set of ∼7000 organic molecules with up to 7 atoms (not counting hydrogens) containing CHONFClS, as well as for ∼6000 constitutional isomers of C7H10O2. CQML learning curves for atomization energies suggest a dramatic reduction in necessary training samples calculated with the most accurate and costly method. In order to generate millisecond estimates of CCSD(T)/cc-pvdz atomization energies with prediction errors reaching chemical accuracy (∼1 kcal/mol), the CQML model requires only ∼100 training instances at CCSD(T)/cc-pvdz level, rather than thousands within conventional QML, while more training molecules are required at lower levels. Our results suggest a possibly favorable trade-off between various hierarchical approximations whose computational cost scales differently with electron number.