Polyaromatic Group Embedded Cd(II)-Coordination Polymers for Microwave-Assisted Solvent-Free Strecker-Type Cyanation of Acetals.

In this work, two new 1D Cd(II) coordination polymers (CPs), [Cd(L1)(NMF)2]n (1) and [Cd(L2)(DMF)(H2O)2]n·n(H2O) (2), have been synthesized, characterized and employed as catalysts for the microwave-assisted solvent-free Strecker-type cyanation of different acetals. Solvothermal reaction between the pro-ligand, 5-{(pyren-1-ylmethyl)amino}isophthalic acid (H2L1) or 5-{(anthracen-9-ylmethyl)amino}isophthalic acid (H2L2), and Cd(NO3)2.6H2O in the presence of NMF or DMF:THF solvent, produces the coordination polymer 1 or 2, respectively. These frameworks were characterized by single-crystal and powder X-ray diffraction analyses, ATR-FTIR, elemental and thermogravimetry analysis. Their structural analysis revealed that both CPs show one-dimensional structures, but CP 1 has a 1D double chain type structure whereas CP 2 is a simple one-dimensional network. In CP 1, the dinuclear {Cd2(COO)4} unit acts as a secondary building unit (SBU) and the assembly of dinuclear SBUs with deprotonated ligand (L12-) led to the formation of a 1D double chain framework. In contrast, no SBU was observed in CP 2. To test the catalytic effectiveness of these 1D compounds, the solvent-free Strecker-type cyanation reactions of different acetals in presence of trimethylsilyl cyanide (TMSCN) was studied with CPs 1 and 2 as heterogenous catalysts. CP 1 displays a higher activity (yield 95%) compared to CP 2 (yield 84%) after the same reaction time. This is accounted for by the strong hydrogen bonding packing network in CP 2 that hampers the accessibility of the metal centers, and the presence of the dinuclear Cd(II) SBU in CP 1 which can promote the catalytic process in comparison with the mononuclear Cd(II) center in CP 2. Moreover, the recyclability and heterogeneity of both CPs were tested, demonstrating that they can be recyclable for at least for four cycles without losing their structural integrity and catalytic activity.

Putative Identification of New Phragmaline-Type Limonoids from the Leaves of Swietenia macrophylla King: A Case Study Using Mass Spectrometry-Based Molecular Networking.

Swietenia macrophylla King is a plant commonly known as Brazilian mahogany. The wood from its stem is highly prized for its exceptional quality, while its leaves are valued for their high content of phragmalin-type limonoids, a subclass of compounds known for their significant biological activities, including antimalarial, antitumor, antiviral, and anti-inflammatory properties. In this context, twelve isolated limonoids from S. macrophylla leaves were employed as standards in mass spectrometry-based molecular networking to unveil new potential mass spectrometry signatures for phragmalin-type limonoids. Consequently, ultra-performance liquid chromatography coupled with high-resolution mass spectrometry was utilized for data acquisition. Subsequently, the obtained data were analyzed using the Global Natural Products Social Molecular Networking platform based on spectral similarity. In summary, this study identified 24 new putative phragmalin-type limonoids for the first time in S. macrophylla. These compounds may prove valuable in guiding future drug development efforts, leveraging the already established biological activities associated with limonoids.

Electrocatalytic Behavior of an Amide Functionalized Mn(II) Coordination Polymer on ORR, OER and HER.

The new 3D coordination polymer (CP) [Mn(L)(HCOO)]n (Mn-CP) [L = 4-(pyridin-4-ylcarbamoyl)benzoate] was synthesised via a hydrothermal reaction using the pyridyl amide functionalized benzoic acid HL. It was characterized by elemental, FT-IR spectroscopy, single-crystal and powder X-ray diffraction (PXRD) analyses. Its structural features were disclosed by single-crystal X-ray diffraction analysis, which revealed a 3D structure with the monoclinic space group P21/c. Its performance as an electrocatalyst for oxygen reduction (ORR), oxygen evolution (OER), and hydrogen evolution (HER) reactions was tested in both acidic (0.5 M H2SO4) and alkaline (0.1 M KOH) media. A distinct reduction peak was observed at 0.53 V vs. RHE in 0.1 M KOH, which corresponds to the oxygen reduction, thus clearly demonstrating the material's activity for the ORR. Tafel analysis revealed a Tafel slope of 101 mV dec-1 with mixed kinetics of 2e- and 4e- pathways indicated by the Koutecky-Levich analysis. Conversely, the ORR peak was not present in 0.5 M H2SO4 indicating no activity of Mn-CP for this reaction in acidic media. In addition, Mn-CP demonstrated a noteworthy activity toward OER and HER in acidic media, in contrast to what was observed in 0.1 M KOH.

MALDI-TOF Mass Spectrometry for the Diagnosis of Citrus Canker Caused by Xanthomonas citri subsp. citri.

Citrus canker, caused by the bacterium Xanthomonas citri subsp. citri (Xcc), is a disease that causes serious problems to the global citrus industry. Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry (MS) has been used in human medicine to diagnose various diseases caused by both fungi and bacteria. In agriculture, this technique has potential for the diagnosis of diseases due to the low cost of large-scale analysis and quickness. This study showed that MALDI-TOF MS combined with chemometric analysis was effective for differentiating the macromolecule profile of orange leaves with canker lesions, healthy leaves, and leaves with phytotoxicity symptoms, proving that this technique may be used for the rapid diagnosis of citrus canker.

Chemophenetic Significance of Anomalocalyx uleanus Metabolites are Revealed by Dereplication Using Molecular Networking Tools.

Anomalocalyx uleanus (Pax & K. Hoffm.) Ducke (Euphorbiaceae) is a singular species in the genus and is restricted and exclusive to the Brazilian Amazon. A phytochemical study of A. uleanus leaves was performed, yielding the isolation of five major compounds: catechin/epicatechin, afzelin, quercetin 3-O-α-L-rhamnopyranoside, and astilbin. The phytochemical compositions of the methanolic extracts of leaves, roots, bark, and stem bark were determined using a dereplication approach. Forty-six compounds were annotated from the liquid chromatography-mass spectrometry (LC-MS/MS) data, while four lipids were identified using gas chromatography-mass spectrometry (GC-MS). In total, fifty compounds were detected, and they belonged to the primary metabolism and several classes of natural products such as flavonoids, flavonoids O-glycosides, flavonoids C-glycosides, biflavonoids, procyanidin, triterpene, triterpenes esterified with phenylpropanoids, phenylpropanoid derivatives, flavonolignans, coumarins, quinic acid derivatives, and benzoic acid derivatives. This is the first report on the phytochemical data of the genus Anomalocalyx, and the results of this study will contribute to the chemosystematic knowledge of the Euphorbiaceae family and justify the need for investigation of the pharmacological potential of the species A. uleanus.

Rapid differentiation of graft Citrus sinensis with and without Xylella fastidiosa infection by mass spectrometry.

RATIONALE: Xylella fastidiosa causes citrus variegated chlorosis (CVC) in sweet orange trees. A diagnostic method for detecting CVC before the symptoms appear, which would inform citrus producers in advance about when the plant should be removed from the orchard, is essential for reducing pesticide application costs. METHODS: Chemometrics was applied to high-performance liquid chromatography diode array detector (HPLC-DAD) data to evaluate the similarities and differences between the chromatographic profiles. A liquid chromatography/atmospheric pressure chemical ionization mass spectrometry selected reaction monitoring (LC/APCI-MS-SRM) method was developed to identify the major compounds and to determine their amounts in all samples. RESULTS: We evaluated the effect of this bacterium on the variation in the chemical profile in citrus plants. The organs of C. sinensis grafted on C. limonia were analyzed. Chemometrics was applied to the obtained data, and two major groups were differentiated. Flavonoids were observed in one group (leaves) and coumarins in the second (roots), both at higher concentrations in the plants with CVC symptoms than in those without the symptoms and those in the negative control. The rootstocks also interfered in the metabolism of the scion. CONCLUSIONS: The developed LC/APCI-MS-SRM method for detecting CVC before the symptoms appear is simple and accurate. It is inexpensive, and many samples can be screened per hour using 1 mg of leaves. Knowledge of the influence of the rootstock on the chemical profile of the graft is limited. This study demonstrates the effect of the rootstock in synthesizing flavonoids and increasing its content in all parts of the graft.

4-Deoxyraputindole C induces cell death and cell cycle arrest in tumor cell lines.

Several molecules extracted from natural products exhibit different biological activities, such as ion channel modulation, activation of signaling pathways, and anti-inflammatory or antitumor activity. In this study, we tested the antitumor ability of natural compounds extracted from the Raputia praetermissa plant. Among the compounds tested, an alkaloid, here called compound S4 (4-Deoxyraputindole C), showed antitumor effects against human tumor lineages. Compound S4 was the most active against Raji, a lymphoma lineage, promoting cell death with characteristics that including membrane permeabilization, dissipation of the mitochondrial potential, increased superoxide production, and lysosomal membrane permeabilization. The use of cell death inhibitors such as Z-VAD-FMK (caspase inhibitor), necrostatin-1 (receptor-interacting serine/threonine-protein kinase 1 inhibitor), E-64 (cysteine peptidases inhibitor), and N-acetyl- L-cysteine (antioxidant) did not decrease compound S4-dependent cell death. Additionally, we tested the effect of cellular activity on adherent human tumor cells. The highest reduction of cellular activity was observed in A549 cells, a lung carcinoma lineage. In this lineage, the effect on the reduction of the cellular activity was due to cell cycle arrest, without plasma membrane permeabilization, loss of the mitochondrial potential or lysosomal membrane permeabilization. Compound S4 was able to inhibit cathepsin B and L by a nonlinear competitive (negative co-operativity) and simple-linear competitive inhibitions, respectively. The potency of inhibition was higher against cathepsin L. Compound S4 promoted cell cycle arrest at G 0 and G 2 phase, and increase the expression of p16 and p21 proteins. In conclusion, compound S4 is an interesting molecule against cancer, promoting cell death in the human lymphoma lineage Raji and cell cycle arrest in the human lung carcinoma lineage A549.

Integrated Analytical Tools for Accessing Acridones and Unrelated Phenylacrylamides from Swinglea glutinosa.

In natural product studies, the purification of metabolites is an important challenge. To accelerate this step, alternatives such as integrated analytical tools should be employed. Based on this, the chemical study of Swinglea glutinosa (Rutaceae) was performed using two rapid dereplication strategies: Target Analysis (Bruker Daltonics®, Bremen, Germany) MS data analysis combined with MS/MS data obtained from the GNPS platform. Through UHPLC-HRMS data, the first approach allowed, from crude fractions, a quick and visual identification of compounds already reported in the Swinglea genus. Aside from this, by grouping compounds according to their fragmentation patterns, the second approach enabled the detection of eight molecular families, which presented matches for acridonic alkaloids, phenylacrylamides, and flavonoids. Unrelated compounds for S. glutinosa have been isolated and characterized by NMR experiments, Lansamide I, Lansiumamide B, Lansiumamide C, and N-(2-phenylethyl)cinnamamide.

Radial asymmetries in population receptive field size and cortical magnification factor in early visual cortex.

Human visual cortex does not represent the whole visual field with the same detail. Changes in receptive field size, population receptive field (pRF) size and cortical magnification factor (CMF) with eccentricity are well established, and associated with changes in visual acuity with eccentricity. Visual acuity also changes across polar angle. However, it remains unclear how RF size, pRF size and CMF change across polar angle. Here, we examine differences in pRF size and CMF across polar angle in V1, V2 and V3 using pRF modeling of human fMRI data. In these visual field maps, we find smaller pRFs and larger CMFs in horizontal (left and right) than vertical (upper and lower) visual field quadrants. Differences increase with eccentricity, approximately in proportion to average pRF size and CMF. Similarly, we find larger CMFs in the lower than upper quadrant, and again differences increase with eccentricity. However, pRF size differences between lower and upper quadrants change direction with eccentricity. Finally, we find slightly smaller pRFs in the left than right quadrants of V2 and V3, though this difference is very small, and we find no differences in V1 and no differences in CMF. Moreover, differences in pRF size and CMF vary gradually with polar angle and are not limited to the meridians or visual field map discontinuities. PRF size and CMF differences do not consistently follow patterns of cortical curvature, despite the link between cortical curvature and polar angle in V1. Thus, the early human visual cortex has a radially asymmetric representation of the visual field. These asymmetries may underlie consistent reports of asymmetries in perceptual abilities.

Evaluation of Alkaloids Isolated from Ruta graveolens as Photosynthesis Inhibitors.

Eight alkaloids (1⁻8) were isolated from Ruta graveolens, and their herbicide activities were evaluated through in vitro, semivivo, and in vivo assays. The most relevant results were observed for Compounds 5 and 6⁻8 at 150 µM, which decreased dry biomass by 20% and 23%, respectively. These are significant results since they presented similar values with the positive control, commercial herbicide 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). Based on the performed assays, Compound 5 (graveoline) is classified as an electron-transport inhibitor during the light phase of photosynthesis, as well as a plant-growth regulator. On the other hand, Compounds 6⁻8 inhibited electron and energy transfers, and are also plant-growth inhibitors. These phytotoxic behaviors based on acridone and quinolone alkaloids may serve as a valuable tool in the further development of a new class of herbicides since natural products represent an interesting alternative to replace commercial herbicides, potentially due their low toxicity.

Isolation of Chavibetol and Methyleugenol from Essential Oil of Pimenta pseudocaryophyllus by High Performance Liquid Chromatography.

A high performance liquid chromatography (HPLC) method was developed for the simultaneous isolation, on a semi-preparative scale, of chavibetol and methyleugenol from the crude essential oil of P. pseudocaryophyllus leaves. The purity of the isolated compounds and their quantifications were developed using GC/FID. Chavibetol was isolated with high purity (98.7%) and mass recovery (94.6%). The mass recovery (86.4%) and purity (85.3%) of methyleugenol were lower than those of chavibetol. Both compounds were identified on the basis of spectral analysis. The results suggest that the method can provide chavibetol with high purity, mass recovery, and productivity from crude essential, which will be used in bioassays against stored insect pests.

Identification of Meliatoxins in Melia azedarach Extracts Using Mass Spectrometry for Quality Control.

Indiscriminate use of synthetic pesticides can be hazardous to both humans and the environment, but the use of natural products as a source of bio-based products, such as Melia azedarach extracts, is an interesting approach to overcome these hazards. Unfortunately, the limonoids found in M. azedarach with desired insecticidal properties (e.g. azadirachtin) may also be present with limonoids toxic to mammals. The goal of this report was to develop a fast and reliable MS-based experiment to characterize meliatoxins in crude extracts of M. azedarach, in order to provide unequivocal assessment of the safety for extracts for application in the field. MS and MS/MS experiments using MALDI ionization were evaluated as tools for the assignment of characteristic ions produced by each meliatoxin in crude extracts.The use of different experiments in combination, such as the analysis of fragment m/z 557 and [M + Na]+ (adducts ions m/z 681 and m/z 667), MALDI-MS can be used for detection of meliatoxins A1/B1 or A2/B2 in a crude extract and may be used to discriminate meliatoxins A from B, respectively. Subsequent MS/MS experiments can distinguish between the presence of group 1 and/or 2 in each class of meliatoxins classifying the proposed approach as a quick and efficient quality control method of meliatoxins in real M. azedarach samples.

A Simple Defined Medium for the Production of True Diketopiperazines in Xylella fastidiosa and Their Identification by Ultra-Fast Liquid Chromatography-Electrospray Ionization Ion Trap Mass Spectrometry.

Diketopiperazines can be generated by non-enzymatic cyclization of linear dipeptides at extreme temperature or pH, and the complex medium used to culture bacteria and fungi including phytone peptone and trypticase peptone, can also produce cyclic peptides by heat sterilization. As a result, it is not always clear if many diketopiperazines reported in the literature are artifacts formed by the different complex media used in microorganism growth. An ideal method for analysis of these compounds should identify whether they are either synthesized de novo from the products of primary metabolism and deliver true diketopiperazines. A simple defined medium (X. fastidiosa medium or XFM) containing a single carbon source and no preformed amino acids has emerged as a method with a particularly high potential for the grown of X. fastidiosa and to produce genuine natural products. In this work, we identified a range of diketopiperazines from X. fastidiosa 9a5c growth in XFM, using Ultra-Fast Liquid Chromatography coupled with mass spectrometry. Diketopiperazines are reported for the first time from X. fastidiosa, which is responsible for citrus variegated chlorosis. We also report here fatty acids from X. fastidiosa, which were not biologically active as diffusible signals, and the role of diketopiperazines in signal transduction still remains unknown.

Evaluation of antidesmone alkaloid as a photosynthesis inhibitor.

Antidesmone, isolated from Waltheria brachypetala Turcz., owns special structural features as two α,ß-unsaturated carbonyl groups and a side alkyl chain that can compete with the quinones involved in the pool of plastoquinones at photosystem II (PSII). In this work, we showed that the alkaloid is an inhibitor of Hill reaction and its target was located at the acceptor side of PSII. Studies of chlorophyll (Chl) a fluorescence showed a J-band that indicates direct action of antidesmone in accumulation of QA- (reduced plastoquinone A) due to the electron transport blocked at the QB (plastoquinone B) level similar to DCMU. In vivo assays indicated that antidesmone is a selective post-emergent herbicide probe at 300µM by reducing the biomass production of Physalis ixacarpa plants. Furthermore, antidesmone also behaves as pre-emergent herbicide due to inhibit Physalis ixacarpa plant growth about 60%. Antidesmone, a natural product containing a 4(1H)-pyridones scaffold, will serve as a valuable tool in further development of a new class of herbicides.

Acridone Alkaloids from Swinglea glutinosa (Rutaceae) and Their Effects on Photosynthesis.

Continuing our search for herbicide models based on natural products, we investigated the action mechanisms of five alkaloids isolated from Swinglea glutinosa (Rutaceae): Citrusinine-I (1), glycocitrine-IV (2), 1,3,5-trihydroxy-10-methyl- 2,8-bis(3-methylbut-2-en-1-yl)-9(10H)-acridinone (3), (2R)-2-tert-butyl-3,10-dihydro-4,9-dihydroxy-11-methoxy-10-methylfuro[3,2-b]acridin-5(2H)-one (4), and (3R)-2,3,4,7-tetrahydro-3,5,8-trihydroxy-6-methoxy-2,2,7-trimethyl-12H-pyrano[2,3-a]acridin-12-one (5) on several photosynthetic activities in an attempt to find new compounds that affect photosynthesis. Through polarographic techniques, the compounds inhibited the non-cyclic electron transport in the basal, phosphorylating, and uncoupled conditions from H2 O to methylviologen (=MV). Therefore, they act as Hill reaction inhibitors. This approach still suggested that the compounds 4 and 5 had their interaction site located at photosystem I. Studies on fluorescence of chlorophyll a suggested that acridones (1-3) have different modes of interaction and inhibition sites on the photosystem II electron transport chain.

Essential Oil Variation from Twenty Two Genotypes of Citrus in Brazil-Chemometric Approach and Repellency Against Diaphorina citri Kuwayama.

The chemical composition of volatile oils from 22 genotypes of Citrus and related genera was poorly differentiated, but chemometric techniques have clarified the relationships between the 22 genotypes, and allowed us to understand their resistance to D. citri. The most convincing similarities include the synthesis of (Z)-ß-ocimene and (E)-caryophyllene for all 11 genotypes of group A. Genotypes of group B are not uniformly characterized by essential oil compounds. When stimulated with odor sources of 22 genotypes in a Y-tube olfactometer D. citri preferentially entered the arm containing the volatile oils of Murraya paniculata, confirming orange jasmine as its best host. C. reticulata × C. sinensis was the least preferred genotype, and is characterized by the presence of phytol, (Z)-ß-ocimene, and ß-elemene, which were not found in the most preferred genotype. We speculate that these three compounds may act as a repellent, making these oils less attractive to D. citri.

Flavonoids as noncompetitive inhibitors of Dengue virus NS2B-NS3 protease: inhibition kinetics and docking studies.

NS2B-NS3 is a serine protease of the Dengue virus considered a key target in the search for new antiviral drugs. In this study flavonoids were found to be inhibitors of NS2B-NS3 proteases of the Dengue virus serotypes 2 and 3 with IC50 values ranging from 15 to 44 µM. Agathisflavone (1) and myricetin (4) turned out to be noncompetitive inhibitors of dengue virus serotype 2 NS2B-NS3 protease with Ki values of 11 and 4.7 µM, respectively. Docking studies propose a binding mode of the flavonoids in a specific allosteric binding site of the enzyme. Analysis of biomolecular interactions of quercetin (5) with NT647-NHS-labeled Dengue virus serotype 3 NS2B-NS3 protease by microscale thermophoresis experiments, yielded a dissociation constant KD of 20 µM. Our results help to understand the mechanism of inhibition of the Dengue virus serine protease by flavonoids, which is essential for the development of improved inhibitors.

Isolation of arginase inhibitors from the bioactivity-guided fractionation of Byrsonima coccolobifolia leaves and stems.

Byrsonima coccolobifolia leaf and stem extracts were studied in the search for possible leishmanicidal compounds using arginase (ARG) from Leishmania amazonensis as a molecular target. Flavonoids 1b, 1e-1g, 2a, 2b, and 2d-2f showed significant inhibitory activity, with IC50 values ranging from 0.9 to 4.8 µM. The kinetics of the most active compounds were determined. Flavonoids 1e, 1f, 2a, 2b, and 2e were characterized as noncompetitive inhibitors of ARG with dissociation constants (Ki) ranging from 0.24 to 3.8 µM, demonstrating strong affinity. Structure-activity relationship studies revealed some similarities in the structural features of flavonoids related to ARG activity.

Development and aging of visual hemifield asymmetries in contrast sensitivity.

The relation of development and aging with models of visual anisotropies and their influence on low-level visual processing remain to be established. Our main goal was to explore visual performance asymmetries in development and normal aging using low-level contrast sensitivity behavioral tasks [probing two distinct spatiotemporal frequency channels, (a) intermediate spatial and null temporal frequency (3.5 cycles per degree (cpd) and 0 Hz); and (b) low spatial and high temporal frequency (0.25 cpd undergoing 25 Hz counterphase flicker)]. Different patterns of functional asymmetries were investigated within four (two neurodevelopmental and two adult) age groups (N = 258 participants; 8-65 years). We found a left visual hemifield/right hemisphere advantage for only the intermediate spatial frequency channel that was present early in life and remained stable throughout adulthood. In contrast, inferior/superior visual hemifield asymmetries, with a direct ecological meaning, were found for both spatiotemporal frequency channels. This inferior visual hemifield advantage emerged early in life and persisted throughout aging. These findings show that both right hemispheric and dorsal retinotopic patterns of dominance in low-level vision emerge early in childhood, maintaining during aging.

Antioxidant activity of an Mg(II) compound containing ferulic acid as a chelator: potential application for active packaging and riboflavin stabilisation.

Foods rich in riboflavin (Rf) are susceptible to degradation due to oxidative processes with the formation of radicals. Herein, we describe the features and stability of an Mg(II) complex containing ferulic acid (fer) and 1,10-phenanthroline (phen) as chelators: henceforth called Mg(phen)(fer). The electrochemical behavior of Mg(phen)(fer) is pH dependent and results from the stabilisation of the corresponding phenoxyl radical via complexation with Mg(II). This stabilisation enhances the antioxidant activity of Mg(phen)(fer) with respect to free fer and commercial antioxidants. Mg(phen)(fer) scavenges and neutralizes DPPH˙ (IC50 = 15.6 µmol L-1), ABTS˙+ (IC50 = 5.65 µmol L-1), peroxyl radical (IC50 = 5.64 µg L-1) and 1O2 (IC50 = 0.7 µg m-1). Mg(phen)(fer) effectively protects riboflavin (Rf) against photodegradation by quenching the singlet excited states of Rf regardless of the conditions. Also, the complex Mg(phen)(fer) was effectively incorporated into starch films, broadening its applications, as shown by microbiological studies. Thus, Mg(phen)(fer) has high potential for use in Rf-rich foods and to become a new alternative to the synthetic antioxidants currently used.