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Mass spectrometry (MS) and nuclear magnetic resonance (NMR) have evolved as the most common techniques in metabolomics studies, and each brings its own advantages and limitations. Unlike MS spectrometry, NMR spectroscopy is quantitative and does not require extra steps for sample preparation, such as separation or derivatization. Although the sensitivity of NMR spectroscopy has increased enormously and improvements continue to emerge steadily, this remains a weak point for NMR compared with MS. MS-based metabolomics provides an excellent approach that can offer a combined sensitivity and selectivity platform for metabolomics research. Moreover, different MS approaches such as different ionization techniques and mass analyzer technology can be used in order to increase the number of metabolites that can be detected. In this chapter, the advantages, limitations, strengths, and weaknesses of NMR and MS as tools applicable to metabolomics research are highlighted.

The date palm has been cultivated in dry and hot areas of the planet for much of human history. In the Kingdom of Saudi Arabia, dates are the main crop used as a source of food. Among several species of date fruits, the Ajwa AL-Madinah date is unique, growing only in Al-Madinah geographical region. The Ajwa date is used in traditional medicine due to its abundant active components and therapeutic properties. This study investigates the structural properties and the antioxidant effects of water-soluble polysaccharides extracted from Ajwa flesh and seed. The polysaccharides were isolated by two techniques including hot water and ultrasonic extraction. After isolation and partial purification, the physicochemical properties of four samples of polysaccharides extracted from flesh and seed were studied by several techniques including FTIR, solid-state NMR, elemental analysis, and mass spectrometry. Several radical scavenging experiments were combined to study the antioxidant activity of the polysaccharide compounds. FTIR and NMR results showed a structure typical of heterogeneous polysaccharides. Mass spectrometry revealed that the polysaccharide samples were composed mainly of mannose, glucose, galactose, xylose, arabinose, galacturonic acid, and fucose. In addition, the physicochemical properties and composition of polysaccharides extracted from flesh and seed were compared. The extracted polysaccharides showed antioxidant activity, with 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging, Fe chelating ability, hydroxyl free radical scavenging ability, and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging. These results highlight their potential to be a useful nutritional element or supplemental medication. [ABSTRACT FROM AUTHOR]

A set of dinuclear copper(I) complexes with the general formula [Cu2(μ-dppm)2(N^N)2]2+ were synthesized and characterized by 1HNMR, 31PNMR, and elemental analysis. The high-resolution mass spectra clearly illustrated isotopic pattern for the proposed dinuclear systems. The binding of the complexes toward human serum albumin (HSA) were evaluated, highlighting good binding affinities influenced by the nature of the substituted-diimine. The complexes induce changes in both the α-helix and the microenvironment structures of HSA. The HSA-bindings were modelled by molecular docking; [Cu2(μ-dppm)2(dppz)2][ClO4]2 (3) displays the highest binding score toward HSA due to the ability of dppz in establishing π-interactions. The anticancer properties of 1, 2 and 3 were screened against COLO 205, RCC-PR, HepGII and LLC-MK2 cell lines and the results were discussed. Complex 3 has better IC50 against all the cancer cell lines than that observed for cisplatin, but still lower than the cytotoxicity of Sunitinib. Moreover, complex 3 has higher selectivity towards cancer cells over normal cells when compared to cisplatin and sunitinib. [ABSTRACT FROM AUTHOR]

The syntheses of [Cu(PPh3)2(L)]NO3 and [Cu(PPh3)2(L-SO3Na)]NO3 were achieved through the reaction of Cu(PPh3)2NO3 and equimolar amount of the ligands (L = 5,6-diphenyl-3-[2-pyridyl]-1,2,4-triazine; LSO3Na = 5,6-diphenyl-3-[2-pyridyl]-1,2,4-triazine-4,4′-disulfonic acid disodium salt). The complexes were characterized by NMR and IR spectroscopy and mass spectrometry. The compounds exhibit similar absorption and emission spectra, suggesting a similar electronic structure. Ct-DNA binding studies show the strong influence of the net charge as Cu-L (positively charged) is able to bind to ct-DNA while Cu-LSO3Na (negatively charged) is not. The net charge of the complexes affects the thermodynamic and kinetic binding parameters toward human serum albumin. HSA-binding of the complexes was further investigated by molecular docking, revealing different binding sites on the HSA protein as a function of the net charge. The different anticancer activities of the complexes towards ovcar-3 and hope-62 cancer cell lines are suggestive of a role for the overall charge of the complexes. Interaction with the DNA is not the major mechanism for this class of complexes. The overall net charge of the pharmacophore (anticancer agent) should be a key consideration in the design of anticancer metal complexes. [ABSTRACT FROM AUTHOR]

Amadori products (deoxyfructosyllysine derivatives) that can selectively interact with phenylboronic acids and borate ions were synthesized. The intramolecular interactions between the fructosyl moiety and phenylboronic acid incorporated into various positions of the peptide chain were investigated using high-resolution mass spectrometry (HR–MS), circular dichroism (CD), and nuclear magnetic resonance (NMR). [ABSTRACT FROM AUTHOR]

A high quantum yield (QY) of photoluminescence (PL) in nanomaterials is necessary for a wide range of applications. Unfortunately, the weak PL and moderate stability of atomically precise silver nanoclusters (NCs) suppress their utility. Herein, we accomplished a ≥26-fold PL QY enhancement of the Ag29(BDT)12(TPP)4 cluster (BDT: 1,3-benzenedithiol; TPP: triphenylphosphine) by doping with a discrete number of Au atoms, producing Ag29− xAu x(BDT)12(TPP)4, x=1-5. The Au-doped clusters exhibit an enhanced stability and an intense red emission around 660 nm. Single-crystal XRD, mass spectrometry, optical, and NMR spectroscopy shed light on the PL enhancement mechanism and the probable locations of the Au dopants within the cluster. [ABSTRACT FROM AUTHOR]

Suaeda vermiculata, an edible halophytic plant, used by desert nomads to treat jaundice, was investigated for its hepatoprotective bioactivity and safety profile on its mother liquor aqueous-ethanolic extract. Upon LC-MS (Liquid Chromatography-Mass Spectrometry) analysis, the presence of several constituents including three major flavonoids, namely quercetin, quercetin-3-O-rutinoside, and kaempferol-O-(acetyl)-hexoside-pentoside were confirmed. The aqueous-ethanolic extract, rich in antioxidants, quenched the DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals, and also showed noticeable levels of radical scavenging capacity in ABTS (2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid) assay. For the hepatoprotective activity confirmation, the male rat groups were fed daily, for 7 days (n = 8/group, p.o.), either carboxyl methylcellulose (CMC) 0.5%, silymarin 200 mg/kg, the aqueous-ethanolic extract of the plant Suaeda vermiculata (100, 250, and 500 mg/kg extract), or quercetin (100 mg/kg) alone, and on day 7 of the administrations, all the animal groups, excluding a naïve (250 mg/kg aqueous-ethanolic extract-fed), and an intact animal group were induced hepatotoxicity by intraperitoneally administering carbon tetrachloride (CCl4). All the animals were sacrificed after 24 h, and aspartate transaminase and alanine transaminase serum levels were observed, which were noted to be significantly decreased for the aqueous-ethanolic extract, silymarin, and quercetin-fed groups in comparison to the CMC-fed group (p < 0.0001). No noticeable adverse effects were observed on the liver, kidney, or heart's functions of the naïve (250 mg/kg) group. The aqueous-ethanolic extract was found to be safe in the acute toxicity (5 g/kg) test and showed hepatoprotection and safety at higher doses. Further upon, the cytotoxicity testings in HepG-2 and HepG-2/ADR (Adriamycin resistant) cell-lines were also investigated, and the IC50 values were recorded at 56.19 ± 2.55 µg/mL, and 78.40 ± 0.32 µg/mL (p < 0.001, Relative Resistance RR 1.39), respectively, while the doxorubicin (Adriamycin) IC50 values were found to be 1.3 ± 0.064, and 4.77 ± 1.05 µg/mL (p < 0.001, RR 3.67), respectively. The HepG-2/ADR cell-lines when tested in a combination of the aqueous-ethanolic extract with doxorubicin, a significant reversal in the doxorubicin's IC50 value by 2.77 folds (p < 0.001, CI = 0.56) was noted as compared to the cytotoxicity test where the extract was absent. The mode of action for the reversal was determined to be synergistic in nature indicating the role of the aqueous-ethanolic extract. [ABSTRACT FROM AUTHOR]

Over the past two decades, nuclear magnetic resonance (NMR) has emerged as one of the three principal analytical techniques used in metabolomics (the other two being gas chromatography coupled to mass spectrometry (GC-MS) and liquid chromatography coupled with single-stage mass spectrometry (LC-MS)). The relative ease of sample preparation, the ability to quantify metabolite levels, the high level of experimental reproducibility, and the inherently nondestructive nature of NMR spectroscopy have made it the preferred platform for long-term or large-scale clinical metabolomic studies. These advantages, however, are often outweighed by the fact that most other analytical techniques, including both LC-MS and GC-MS, are inherently more sensitive than NMR, with lower limits of detection typically being 10 to 100 times better. This review is intended to introduce readers to the field of NMR-based metabolomics and to highlight both the advantages and disadvantages of NMR spectroscopy for metabolomic studies. It will also explore some of the unique strengths of NMR-based metabolomics, particularly with regard to isotope selection/detection, mixture deconvolution via 2D spectroscopy, automation, and the ability to noninvasively analyze native tissue specimens. Finally, this review will highlight a number of emerging NMR techniques and technologies that are being used to strengthen its utility and overcome its inherent limitations in metabolomic applications. [ABSTRACT FROM AUTHOR]

Anaerobic granular sludge is composed of multispecies microbial aggregates embedded in a matrix of extracellular polymeric substances (EPS). Here we characterized the chemical fingerprint of the polysaccharide fraction of EPS in anaerobic granules obtained from full-scale reactors treating different types of wastewater. Nuclear magnetic resonance (NMR) signals of the polysaccharide region from the granules were very complex, likely as a result of the diverse microbial population in the granules. Using nonmetric multidimensional scaling (NMDS), the 1H NMR signals of reference polysaccharides (gellan, xanthan, alginate) and those of the anaerobic granules revealed that there were similarities between the polysaccharides extracted from granules and the reference polysaccharide alginate. Further analysis of the exopolysaccharides from anaerobic granules, and reference polysaccharides using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) revealed that exopolysaccharides from two of the anaerobic granular sludges studied exhibited spectra similar to that of alginate. The presence of sequences related to the synthesis of alginate was confirmed in the metagenomes of the granules. Collectively these results suggest that alginate-like exopolysaccharides are constituents of the EPS matrix in anaerobic granular sludge treating different industrial wastewater. This finding expands the engineered environments where alginate has been found as EPS constituent of microbial aggregates. [ABSTRACT FROM AUTHOR]

A set of dinuclear copper(I) complexes with the general formula [Cu2(μ-dppm)2(N^N)2]2+ were synthesized and characterized by 1HNMR, 31PNMR, and elemental analysis. The high-resolution mass spectra clearly illustrated isotopic pattern for the proposed dinuclear systems. The binding of the complexes toward human serum albumin (HSA) were evaluated, highlighting good binding affinities influenced by the nature of the substituted-diimine. The complexes induce changes in both the α-helix and the microenvironment structures of HSA. The HSA-bindings were modelled by molecular docking; [Cu2(μ-dppm)2(dppz)2][ClO4]2 (3) displays the highest binding score toward HSA due to the ability of dppz in establishing π-interactions. The anticancer properties of 1, 2 and 3 were screened against COLO 205, RCC-PR, HepGII and LLC-MK2 cell lines and the results were discussed. Complex 3 has better IC50 against all the cancer cell lines than that observed for cisplatin, but still lower than the cytotoxicity of Sunitinib. Moreover, complex 3 has higher selectivity towards cancer cells over normal cells when compared to cisplatin and sunitinib. [ABSTRACT FROM AUTHOR]

• A tridentate schiff base ligand containing naphtyl moiety with general formula (N^N^OH) was synthesized. • Pt-L2 was obtained from the ligand with the formula [PtCl(N^N^O)]. • Changes in the relative viscosity of ct-DNA indicated an intercalation mode of binding for Pt-L2. • Pt-L2 indicated the spontaneous formation of an adduct with BSA with good binding affinity. • Pt-L2 possesses better IC 50 values compared to cisplatin against two cancer cell lines. A tridentate Schiff base ligand was synthesized via the reaction of 2-hydroxynpthaldehyd with N -phenyl-o-phenylenediamine. The obtained ligand was utilized in synthesizing Pt-L2 [PtCl(N^N^O)]. The ligand and Pt-L2 were characterized by IR, NMR and mass spectroscopies as well as elemental analysis. The DNA-binding of Pt-L2 was examined by fluorescence quenching using the EB-DNA adduct method. The apparent affinity for the compound toward ct-DNA was nearly twice the affinity of ethidium bromide. Changes in the relative viscosity induced by platinum complexes of ct-DNA indicated an intercalation mode of binding for Pt-L2 and covalent binding for the second platinum compound, Pt-L1, synthesized from 3-ethoxysalicyaldehyde and N -phenyl-o-phenylenediamine. BSA-binding by Pt-L2 indicated the spontaneous formation of an adduct with the protein with good binding affinity (7.7 × 104). The anticancer activities of Pt-L2 were evaluated against two cancer cell lines and compared to that of Pt-L1 and cisplatin. Pt-L2 has better IC 50 values, possibly because of its highly π-delocalized planar system. Moreover, selectivity index for Pt-L2 is high (SI = 168) which is one of the criteria for potential chemotherapeutic agents (higher than that observed for cisplatin (SI = 37)). [Display omitted] [ABSTRACT FROM AUTHOR]

Asphaltenes are n-alkane insoluble compounds found in crude oils and heavy fuels (high and non-boiling petroleum fractions). Asphaltene molecular structure has not been fully elucidated, and their presence in fuels is a source of concern. They reduce combustion efficiency and are responsible for particulate matter emissions. Removing the asphaltenes, or deasphalting, is a way of upgrading the fuel to improve its quality. This study reports the removal of asphaltenes from heavy fuel oil (HFO) using a solvent extraction method, and the detailed molecular characterization of the deasphalted oil (DAO) using positive ion atmospheric pressure photo ionization Fourier transform-ion cyclotron resonance mass spectrometry (APPI (+) FT-ICR/MS) and 1H and 13C Nuclear magnetic resonance (NMR) spectroscopy. Approximately 8.2 mass % of asphaltenes were removed from HFO using n-heptane as solvent. This resulted in significant improvements in the HFO's physical properties. The resulting DAO was five times less viscous and contained significantly less heavy metals (e.g., Ni and V). There was also a slight reduction in the sulfur content from 3.3 to 3.1 mass %. 52,753 and 46,315 ions with a mass to charge ratio (m / z) ranging from 154 to 1200 were detected in HFO and DAO samples, respectively, using APPI FT-ICR/MS. Amongst them, 6729 (HFO) and 6030 (DAO) ions were resolved into their underlying elemental compositions (C, H, O, N and S) and a unique chemical formula was assigned to each mass. The resolved masses were then further classified based on their molecular class and were analyzed as a function of double bond equivalent (DBE) vs carbon number. 1H and 13C NMR analyses of HFO and DAO were performed and the results indicate the total aromatic groups in HFO (1H 7.7 mol %, 13C 37.6 mol %) are more compared to DAO (1H 4.7 mol %, 13C 32.6 mol %). The average molecular parameters (AMPs) of HFO and DAO were also calculated from the 1H and 13C NMR spectra and compared. A surrogate molecule that visualizes the average molecular structure of the entire fuel was developed for both HFO and DAO using the data from the above analytical techniques. Understanding the molecular chemistry of these fuels provides valuable data to develop better desulfurization techniques for these sulfur laden fuels and help predict fuel properties using structure-property relationships. [ABSTRACT FROM AUTHOR]

• 64% of the ionized aromatic species have one or more S atoms. • ESI data indicates polar species have higher aromaticity than non-polar species. • A single molecule surrogate was designed for the vacuum residue. Vacuum residues (VR) are the bottom of the barrel products left after vacuum distillation of crude oils. VR are primarily used as feedstock for production of syn -gas and hydrogen via gasification; and heavy fuel oil (HFO) for use as fuel in power generation and shipping. However, VR contain relatively large amounts of sulfur (upto 8% by mass) and require the removal of varying amounts depending on the emission norms (eg. International Maritime Organization 2020 sulfur regulations). Understanding the fuel molecular structure and, in particular, the structure of sulfur species enables the adoption and optimization of suitable desulfurization strategies. In the present work, detailed molecular characterization of the sulfur species in VR was performed using positive ion atmospheric pressure photoionization (APPI) and electrospray ionization (ESI) coupled to Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry (MS). Ions possessing mass to charge (m / z) in the range of 100 to 1200 were detected using the ultra-high resolution instrument and were resolved into unique chemical formulas (C c H h S s N n O o). The assigned masses were then divided into molecular classes based on the presence of heteroatoms, and plots of carbon number versus double bond equivalency (DBE) were made for each molecular class. The molecular classes were further sub-divided based on the presence of sulfur families like sulfides (Su), thiophenes (Th), benzothiophenes (BT), dibenzothiophenes (DBT) and benzonaphthothiophene (BNT) and their derivatives. A single surrogate molecule that represents the average structure of the VR sample was then designed based on the average molecular parameters (AMP) obtained from APPI and ESI FT-ICR MS. Plausible core skeletal structures of VR were drawn from the average DBE value, and then a symmetrical, alkylated, polyaromatic sulfur heterocycles (PASH) molecule was formulated as the VR surrogate. A number of physical and thermo-chemical properties of the VR surrogate were then predicted using quantitative structure property relationships (QSPR). The VR surrogate proposed here will enable high-fidelity computational studies, including chemical kinetic modeling, property estimation, and emissions modeling. [ABSTRACT FROM AUTHOR]