High-resolution ESI-MS Research Articles

The influence of phosphine ligands on the redox properties of 1,4-divinylanthrylene-bridged diruthenium complexes and a derived macrocyclic analog

We report on a series of dinuclear 1,4-divinylanthrylene-bridged diruthenium complexes 1A-Ru-PR3 with different phosphine ligands (PiPr3, PiPr2Me, PPh3, and PMe3) and with coordination numbers of five or six. All compounds were characterized by NMR spectroscopy, high resolution ESI-MS and, in the case of 1A-Ru-PiPr3 and 1A-Ru-PMe3, single crystal X-ray diffraction. Cyclic voltammetry measurements reveal that the PR3 ligands, besides tuning the redox potentials, exert a strong influence on the stability of their one- and two-electron oxidized forms. Information on the charge- and spin-density distribution was obtained by IR, UV/Vis/NIR and EPR spectroscopy. Our results indicate full charge and spin delocalization in 1A-Ru-PiPr3•+, 1A-Ru-PMe3•+ and macrocyclic, isophthalate-bridged 2A-Ru-PiPr2Me••2+, whereas 1A-Ru-PiPr2Me•+ constitutes a peculiar case, where valence-delocalized and valence-localized structures seem to coexist.

Okeanic acid–A, a trihydroxy fatty acid from the Okinawan cyanobacterium Okeania hirsuta

Trihydroxy fatty acids are oxidative metabolites of polyunsaturated fatty acids isolated from plants, bacteria, fungi, and microalgae and have a variety of biological activities. In this study, a new trihydroxy fatty acid, okeanic acid–A (1), was isolated together with malyngic acid (2) and 15,16-dihydromalyngic acid (3) from the cyanobacterium Okeania hirsuta collected in Okinawa, Japan. The planar structure of 1 was elucidated by detailed analyses using high-resolution ESI-MS and 1D and 2D NMR spectroscopy. The absolute configurations of the hydroxy groups in 1 were determined unambiguously by chemical derivatisation and a modified Mosher’s method. These cyanobacterial trihydroxy fatty acids (1–3) have identical configurations at their respective trihydroxy parts. Okeanic acid–A (1) showed mild growth-inhibitory activity against the marine diatom Nitzschia amabilis.

Optical sensing of L-dihydroxy-phenylalanine in water by a high-affinity molecular receptor involving cooperative binding of a metal coordination bond and boronate-diol.

Selective recognition and sensing of catecholamine-based neurotransmitters by fluorescent synthetic receptors capable of operating in pure water is a central topic of modern supramolecular chemistry that impacts biological and analytical chemistry. Despite advances achieved in the recognition of some neurotransmitters such as dopamine, little effort has been invested in the optical recognition of other neurotransmitters of paramount importance in biochemistry and medicinal chemistry such as the drug L-dihydroxy-phenylalanine (levodopa). Herein, a cationic Cu(II)-terpyridine complex bearing an intramolecular fluorescent quinolinium ring covalently linked to phenylboronic acid (CuL1) was synthesized, structurally described by single-crystal X-ray diffraction and studied in-depth as a fluorescent receptor for neurotransmitters in water. The complex CuL1 was designed to act as a receptor for levodopa through two Lewis acids of different natures (Cu(II) and B atoms) as cooperative binding points. The receptor CuL1 was found to have a strongly acidified -B(OH)2 group (pKa = 6.2) and exceptionally high affinity for levodopa (K = 4.8 × 106 M-1) with selectivity over other related neurotransmitters such as dopamine, epinephrine, norepinephrine and nucleosides in the micromolar concentration range at physiological pH. Such levodopa affinity/selectivity for a boronic acid-based receptor in water is still rare. On the basis of spectroscopic tools (11B NMR, UV-vis, EPR, and fluorescence), high-resolution ESI-MS, crystal structure, and DFT calculations, the interaction mode of CuL1 with levodopa is proposed in a 1 : 1 model using two-point recognition involving a boronate-catechol esterification and a coordination bond Cu(II)-carboxylate. Furthermore, a visual sensing ensemble was constructed using CuL1 and the commercial fluorescent dye eosin Y. Levodopa is efficiently detected by the displacement of the eosin Y bound to the Cu(II)-receptor, monitoring its green emission. The use of Cu(II)-boronate complexes for fast and selective neurotransmitter sensing was unexplored until now.

Synthesis, Characterization and Photophysical Properties of Mixed Ligand (η3-Allyl)palladium(II) Complexes with N,N’Aromatic Diimines

Palladium(II) complexes of the general formula [Pd(η3-C3H5)(L)](PF6), where L is 4,7-diphenyl-1,10-phenanthroline (1), 2,9-dimethyl-1,10-phenanthroline (2), 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (3), 5-methyl-1,10-phenanthroline (4), 3,4,7,8-tetramethyl-1,10-phenanthroline (5), and 2-(2′-pyridyl) quinoxaline (6), were synthesized and characterized using high-resolution ESI-MS, NMR techniques and, in the case of (6), single-crystal X-ray diffraction methods. In addition, their photophysical properties were investigated. Complexes (1)–(6) were emitted in the greenish-blue region, with those containing methyl-substituted phenanthrolines having the higher quantum yield (≈14%) in the solid state.

Mechanism of boric acid extraction by trioctylamine and tartaric acid

The separation of boron isotopes poses significant challenges due to their similar chemical properties. Previous studies have demonstrated that boron isotope separation can be achieved by solvent extraction of boric acid (H3BO3) using trioctylamine (TOA) and tartaric acid (DL-TA), resulting in a remarkable separation factor of up to 1.04 through chemical exchange. However, the coordination mechanism among these three compounds remains elusive, impeding our understanding of the isotope exchange process. In this study, the species in the aqueous and organic phases were investigated using extraction experiments (maximum loading method), alongside various characterization techniques (FT-IR, 11B NMR, and high-resolution ESI-MS), followed by DFT computations. The results showed that H3BO3 and DL-TA formed anionic complexes in the aqueous phase with stoichiometric ratios of 1:1 and 1:2, respectively. However, the stoichiometric ratios became more intricate in the organic phase, encompassing 1:1, 1:2, 2:2, 2:3, and 3:3. The average stoichiometric ratio of H3BO3 to DL-TA calculated within the range of 1:1 to 1:1.5. Protonated TOA could form ion pairs with these anionic complexes, while unprotonated TOA might form hydrogen bonds with the carboxyl groups in DL-TA, contributing to the complexity of the stoichiometric ratios between H3BO3 and TOA. The DFT calculations indicated that all complexes containing B(4)–O bonds, including 1:1, 1:2, 2:2, 2:3, and 3:3, effectively facilitated the exchange of isotopes with H3BO3. These findings pave the way to process optimization of boron isotope separation by solvent extraction of boric acid.

Coupling of Thiazole-2-Amines with Isocyanide Ligands in bis-(Isocyanide) Platinum Complex: A New Type of Reactivity

The treatment of cis-[PtCl2(XylNC)2] with thiazol-2-amines in a 2:1 ratio leads to a regioisomeric mixture of two binuclear complexes. These regioisomers are products of kinetic and thermodynamic control capable of regioisomerization. When the same reaction is carried out with a 5-fold excess of thiazol-2-amine, the nucleophile is able to react with the in situ-formed binuclear platinum(II) complexes, yielding a new type of bis-carbene platinum species. All new isolated compounds were characterized by 1H, 13C{1H}, and 195Pt{1H} NMR spectroscopy, high-resolution ESI-MS, and single-crystal X-ray diffraction.

Light-driven interconversion of Pd2L4 cage and mononuclear PdL2 mediated by the isomerization of azobenzene ligand

The lantern-shaped cage Pd2L4 and tweezer-like PdL2 can be synthesized from the trans- and cis-isomer of an azobenzene-containing ligand, respectively, which were characterized by 1H, 13C, 1H-1H COSY, DOSY NMR spectroscopies, high-resolution ESI-MS and density function theory (DFT) calculations. The interconversion of Pd2L4 and PdL2 can be achieved via the cis-trans isomerization of the azobenzene unit on the ligand upon alternative irradiation of light 365 nm or 420 nm.

New phenalenone derivatives from the Hawaiian volcanic soil-associated fungus Penicillium herquei FT729 and their inhibitory effects on indoleamine 2,3-dioxygenase 1 (IDO1).

Phenalenone derivatives sourced from fungi are polyketides that have attracted significant interest because of their diverse chemical structures and potential bioactivities. As part of our ongoing quest to discover novel natural products with biological properties from diverse natural resources, three unreported phenalenone derivatives (1-3), named ent-12-methoxyisoherqueinone (1), (-)-scleroamide (2), and (+)-scleroamide (3), together with four known phenalenone derivatives, ent-atrovenetinone (4), isoherqueinone (5), herqueinone (6), and ent-peniciherquinone (7) were isolated from the Hawaiian soil fungus Penicillium herquei FT729, collected on the Big Island, Hawaii. Compounds 2 and 3 were enantiomers, which were separated using a chiral-phase HPLC column, which provided optically pure compounds 2 and 3. The structures of the novel compounds were established by extensive spectroscopic analyses, including 1D and 2D NMR and high-resolution ESIMS. Their absolute configurations were determined using quantum chemical electronic circular dichroism (ECD) calculations. The inhibitory activity of the isolated compounds (1-7) against indoleamine 2,3-dioxygenase 1 (IDO1) was assessed. Compounds 1, 5-7 inhibited IDO1, with IC50 values of 32.59, 36.86, 19.05, and 24.18μM, respectively. These findings demonstrated that the phenalenone derivatives 1 and 5-7, as IDO1 inhibitors, are promising anticancer immunotherapeutic agents.

Synthesis and Characterization of 1,4-Benzodioxane-6-Carboxylic Acid Amide Analogs

A library of new 1,4-benzodioxane-6-carboxylic acid amide analogs was designed and synthesized. These analogs were obtained in six steps from gallic acid. Firstly, esterification of the commercially available gallic acid in methanol in the presence of sulfuric acid afforded methyl 3,4,5-trihydroxybenzoate (9) in satisfactory yield. The ester 9 was then reacted with an excess of 1,2-dibromoethane in the presence of K2CO3 in acetone to furnish the 6,8-disubstituted-1,4-benzodioxane (10) in 45% yield. The reaction of 10 with various mercaptans gave the sulfide derivative 11, 12, and 13 in moderate yield. Subsequent hydrolysis of the methyl ester in 13 followed by conversion to the acid chloride and reaction of the acid chloride intermediate with different commercially available primary and secondary amines gave the amide analogs 18 - 32 with an average yield of 43%. Conversion of the sulfide group in Compound 23 to Sulfoxide 33 or Sulfone 34 was accomplished by reaction with either 30% H2O2/TeO2 or 30% H2O2, respectively. The structures of the synthesized compounds were characterized using FTIR, 1H-NMR, 13C-NMR, and high-resolution ESI-MS.

Intermolecular (Isocyano group)···PtII interactions involving coordinated isocyanides in cyclometalated PtII complexes

A series of platinum(II) isocyanide complexes [Pt(ppy)Cl(CNR)] (ppy = 2-phenylpyridinato-C2,N; R = Mes 1, C6H2–2,6-Me2–4-Br 2, C6H2–2-F-3-Cl-4-Br 3, naphthalen-2-yl 4) were prepared and characterized by high resolution ESI-MS, 1D and 2D NMR, IR, UV–Vis absorption, and photoluminescence spectroscopies, as well as single-crystal X-ray diffraction. Analysis of X-ray diffraction data allowed us to identify (isocyano group)···PtII interactions where the nitrogen atom of the isocyano group acts as a π-hole donor toward a dz2-orbital of PtII. The presence of these noncovalent interactions was confirmed by DFT calculations followed by NCI analysis and topological analysis of the electron density distribution within the framework of Bader's theory (QTAIM method). Processing of CSD data allowed verification of the contacts between coordinated isocyano moieties and various d9 and d8- metal-centers (AuI, AuIII, AgI, PtII, PdII, NiII, RhI) to be performed.

Uncovering growth species of multivariate MOFs in liquid phase by mass spectrometry

The unveiling of MOF growth mechanism is hampered by the lack of fundamental knowledge about the very early stage of nucleation, especially the form and ratio of molecular species in the solution for crystal growth. Herein, we report the detection of growth species for a series of MOFs with mono-linker, Cu-MOF-2-BDC and Cu-MOF-2-NDC, and two linkers, MTV-MOF-2-(C4H4)x, by high resolution ESI-MS, where a large variety of Cu-containing species are identified unambiguously. The solvent molecules such as H2O, methanol and DMF participate in the formation of these species, other than ethanol. Furthermore, in the growth solution of MTV-MOF-2-(C4H4)x, growth species containing two different organic linkers are observed. The feeding ratio is not the only factor controlling the distribution of growth species for MTV-MOFs, but also the solvent involves in coordination, an aspect usually overlooked previously.

Azine Steric Hindrances Switch Halogen Bonding to N-Arylation upon Interplay with σ-Hole Donating Haloarenenitriles.

An interplay between 4-bromo- and 4-iodo-5-nitrophthalonitriles (XNPN, X=Br or I) and any one of the azines (pyridine 1, 4-dimethylaminopyridine 2, isoquinoline 3, 4-cyanopyridine 4, 2-methylpyridine 5, 2-aminopyridine 6, quinoline 7, 1-methylisoquinoline 8, and 2,2'-bipyridine 9) proceeds differently depending on steric and electronic effects of the heterocycles. Sterically unhindered azines 1-3 underwent N-arylation to give the corresponding azinium salts (characterized by 1 H and 13 C{H} NMR and high-resolution ESI-MS). In contrast, azines 4-9 with sterically hindered N atoms or bearing an electron-withdrawing substituent, form stable co-crystals with XNPN, where two interacting molecules are bound by halogen bonding. In all obtained co-crystals, X⋅⋅⋅N structure-directed halogen bonds were recognized and theoretically evaluated including DFT calculations (PBE0-D3/def2-TZVP level of theory), QTAIM analysis, molecular electrostatic potential surfaces, and noncovalent interaction plot index. Estimated energies of halogen bonding vary from -7.6 kcal/mol (for 6 ⋅ INPN) to -11.4 kcal/mol (5 ⋅ INPN).

Efficient Photogeneration of Hydrogen Boosted by Long-Lived Dye-Modified Ir(III) Photosensitizers and Polyoxometalate Catalyst

Efficient Photogeneration of Hydrogen Boosted by Long-Lived Dye-Modified Ir(III) Photosensitizers and Polyoxometalate Catalyst

2,5-Dibromothiophenes: Halogen Bond Involving Packing Patterns and Their Relevance to Solid-State Polymerization

A series of 2,5-dibromo-3-R-thiophenes (R = COONa 1, CN 2, CONH2 3, CON(H)Me 4, CON(H)Bn 5, CON(CH2CH2)2O 6, CON(H)NH2 7, CON(H)OH 8) were prepared and studied via high-resolution ESI-MS, 1H and 13...

Comparing the original and biosimilar biotherapeutics of the monoclonal antibody eculizumab by intact mass measurement and middle-up mass spectrometry analysis

Objectives. In this biosimilar research, we compare the monoclonal antibody eculizumab obtained from different drugs [original Soliris® (Alexion Pharmaceuticals) and candidate Elizaria® (Generium)] by intact mass measurement and middle-up mass spectrometry analysis to enhance the role of mass spectrometry methods in biopharmaceutical development processes.Methods. The intact mass measurement is performed using a high-resolution ESI-MS. The middle-up analysis is performed by reversed-phase high-performance liquid chromatography with ESI-MS detection, subsequent IdeS treatment of antibodies, and disulfide bond reduction.Results. We have shown some small differences between the original and candidate drugs in the minor glycans level. Man5 glycan is only found in the original Soliris, and G0 is only found in the Elizaria. Glycation sites are also found in the light chain and Fd subunits of the original Soliris. The glycation level does not exceed 4.4%. The non-clipped C-end lysine level and G0F glycan levels are slightly lower in the original Soliris. All registered differences are not crucial for eculizumab’s quality and do not affect its effectiveness and preclinical safety. Generally, the results show a high level of similarity between the original and candidate drugs.Conclusions. The comparative mass spectrometry analysis of eculizumab in the original Soliris and Elizaria allows us to estimate their high degree of similarity by molecular masses and major modification profiles.

Bioactive metabolites from the desert plant-associated endophytic fungus Chaetomium globosum (Chaetomiaceae)

Globosumin, an undescribed chromene-4,7(4aH)-dione-tetramic acid PKS-PKS-NRPS hybrid, and globosumone, an undescribed azaphilone, together with ten known metabolites, were isolated from the desert plant-associated endophytic fungus Chaetomium globosum (Chaetomiaceae). The planar structures and relative configurations of globosumin and globosumone were determined by high-resolution ESI-MS and NMR data, and the absolute configurations of these two metabolites were determined by electronic circular dichroism (ECD) and circular dichroism (CD) combined with time-dependent density functional theory (TDDFT)-based quantum-chemical calculations. Chaetoglobosin A displayed biological effects against the seedling growth of Arabidopsis thaliana (Brassicaceae) in a dose-dependent manner, and this compound also exhibited biological activity against two cancer cell lines, A549 and HepG2, with IC50 values of 6.82 ± 2.34 and 38.62 ± 7.44 μM, respectively.

Coordination-Assembled Water-Soluble Anionic Lanthanide Organic Polyhedra for Luminescent Labeling and Magnetic Resonance Imaging.

Lanthanide-containing functional complexes have found a variety of applications in materials science and biomedicine because of their unique electroptical and magnetic properties. However, the poor stability and solubility in water of multicomponent lanthanide organic assemblies significantly limit their practical applications. We report here a series of water-stable anionic Ln2nL3n-type (n = 2, 3, 4, and 5) lanthanide organic polyhedra (LOPs) constructed by deprotonation self-assembly of three fully conjugated ligands (H4L1 and H4L2a/b) featuring a 2,6-pyridine bitetrazolate chelating moiety. The outcomes of the LOPs formation reactions were found to be very sensitive toward the reaction conditions including base, metal source, solvents, and concentrations as characterized by a combination of NMR, high-resolution ESI-MS and X-ray crystallography. Ligands H4L2a/b manifested an excellent sensitization toward lanthanide ions (Ln = EuIII and TbIII), with high luminescent quantum yields for Tb8L2a12 (Φ = 11.2% in water) and Eu8L2b12 (Φ = 76.8% in DMSO) measured in polar solvents. Furthermore, due to the giant molecular weight and rigidity of the polyhedral skeleton, Gd8L2b12 showed a very high longitudinal relaxivity (r1) of 400.53 mM-1S-1. The performance of Gd8L2b12 as potential magnetic resonance imaging contrast agents (CAs) in vivo was evaluated with much longer retention time in the tumor sites compared with the commercial GdIII-based CAs. Dual-modal imaging potential has also been demonstrated with the mixed Eu/Gd LOPs. Our results not only provide a new design route toward water-stable multinuclear lanthanide organic assemblies but also offer potential candidates of supramolecular-edifices for bioimaging and drug delivery.

Theoretical and structural studies of a stable dinuclear sodium complex of dicoumarol - 3,3′-(pyridin-3-ylmethanediyl)bis(4‑hydroxy-2H-chromen-2-one)

The synthesis of a dicoumarol derivative (C24H15NO6) is reported via fusing 4-hydroxycoumarin with 3-pyridinecarboxaldehyde. The sodium derivative [Na2(C24H14NO6)2(MeOH)2(H2O)2] was synthesized by treating sodium methoxide with the dicoumarol ligand (C24H15NO6). The resulting dinuclear sodium complex was structurally characterized using various spectroscopic and analytical techniques including 1H, 13C{1H}-NMR, high resolution ESI-MS(+), infrared spectroscopy, elemental and single crystal diffraction analyses. The molecular structure of [Na2(C24H14NO6)2(MeOH)2(H2O)2] exhibits coordination of methanol, water and dicoumarol. B3LYP calculations were carried out to optimize the theoretical structural parameters and theoretical 1H and 13C NMR spectra for comparison with the respective experimental data which are well correlated.

Two new secondary metabolites isolated from Avena sativa L. (Oat) seedlings and their effects on osteoblast differentiation

Seedlings of natural crops are valuable sources of pharmacologically active phytochemicals. In this study, we aimed to identify new active secondary metabolites in Avena sativa L. (oat) seedlings. Two new compounds, avenafuranol (1) and diosgenoside (2), along with eight known compounds (3–10) were isolated from the A. sativa L. seedlings. Their chemical structures were elucidated via 1D and 2D NMR spectroscopy, high-resolution ESIMS, IR spectroscopy, optical rotation analysis, and comparisons with the reported literature. The effect of each isolated compound on alkaline phosphatase (ALP) activity for osteoblast differentiation induced by bone morphogenetic protein-2 (BMP-2) was investigated using the C2C12 immortal mouse myoblast cell line. Compounds 1, 4, 6, 8, and 9 induced dose-dependent increases in ALP expression relative to ALP expression in cells treated with only BMP-2, and no cytotoxicity was observed. These results suggest that A. sativa L. seedlings are a natural source of compounds that may be useful for preventing bone disorders.

Manganese Telluride Carbonyl Complexes: Facile Syntheses and Exotic Properties-Reversible Transformations, Hydrogen Generation, Paramagnetic, and Semiconducting Properties.

A novel family of five Mn-Te-CO complexes was prepared via facile syntheses: mono spirocyclic [Mn4Te(CO)16]2- (1), four-membered Mn2Te2 ring-type [Mn2Te2(CO)8]2- (2), hydride-containing square pyramidal [HMn3Te2(CO)9]2- (3), and dumbbell-shaped [Mn6Te6(CO)18]4- (4) and [Mn6Te10(CO)18]4- (5). Electron-precise complexes 4 and 5 exhibit unusual paramagnetism arising from two types of Mn atoms in different oxidation states, as determined by X-ray photoelectron spectroscopy, electron paramagnetic resonance, and density functional theory (DFT) calculations. The structural transformations from small-sized Mn4Te 1 and Mn2Te2 2 to the largest Mn6Te10 5 were controllable, the off/on magnetic-switched transformation between HMn3Te2 3 and 5 was reversible, and the magnetic transformation between Mn6Te6 4 and 5 was observed. Interestingly, the reversible dehydridation and hydridation between the HMn3Te2-based cluster 3 and [Mn3Te2(CO)9]- were successfully accomplished, in which the release of a high yield of H2 was detected by gas chromatography. In addition, upon the addition of CO, cluster 3 first forms a carbonyl-inserted intermediate [HMn3Te2(CO)10]2- (3'), detected by the high resolution ESI-MS, which is readily transformed to a dimeric dihydrido cluster [{HMn3Te2(CO)10}2]2- (6) with the introduction of O2. These low- to high-nuclearity complexes exhibit rich redox properties with semiconducting behavior in solids, possessing low but tunable energy gaps (1.06-1.62 eV) due to efficient electron transport via nonclassical C-H···O(carbonyl) interactions. The structural nature, reversible structural transformations, controllable on/off magnetic switches, electron communication networks, and associated chemical properties for hydrogen generation are discussed in detail and supported by DFT calculations, density of states, band structures, and noncovalent interaction analyses.