15N NMR Research Articles

Hydrogen Atom Abstraction from an OsII(NH3)2 Complex Generates an OsIV(NH2)2 Complex: Experimental and Computational Analysis of the N-H Bond Dissociation Free Energies and Reactivity.

Double hydrogen atom abstraction from (TMP)OsII(NH3)2 (TMP = tetramesitylporphyrin) with phenoxyl or nitroxyl radicals leads to (TMP)OsIV(NH2)2. This unusual bis(amide) complex is diamagnetic and displays an N-H resonance at 12.0 ppm in its 1H NMR spectrum. 1H-15N correlation experiments identified a 15N NMR spectroscopic resonance signal at -267 ppm. Experimental reactivity studies and density functional theory calculations support relatively weak N-H bonds of 73.3 kcal/mol for (TMP)OsII(NH3)2 and 74.2 kcal/mol for (TMP)OsIII(NH3)(NH2). Cyclic voltammetry experiments provide an estimate of the pKa of [(TMP)OsIII(NH3)2]+. In the presence of Barton's base, a current enhancement is observed at the Os(III/II) couple, consistent with an ECE event. Spectroscopic experiments confirmed (TMP)OsIV(NH2)2 as the product of bulk electrolysis. Double hydrogen atom abstraction is influenced by π donation from the amides of (TMP)OsIV(NH2)2 into the d orbitals of the Os center, favoring the formation of (TMP)OsIV(NH2)2 over N-N coupling. This π donation leads to a Jahn-Teller distortion that splits the energy levels of the dxz and dyz orbitals of Os, results in a low-spin electron configuration, and leads to minimal aminyl character on the N atoms, rendering (TMP)OsIV(NH2)2 unreactive toward amide-amide coupling.

Trigonal Copper(I) Complexes with Cyclic (Alkyl)(amino)carbene Ligands for Single-Photon Near-IR Triplet Emission.

Molecular near-IR (NIR) triplet-state emitters are of importance for the development of new, organic-electronics-based telecommunication technologies as optical fibers operating in the corresponding spectral bands allow for data transfer over much longer distances due to the significantly lower attenuation. However, achieving such low-energy triplet excited states with good radiative rate constants is very challenging, and studies regarding the single-photon emission of organometallics in this energy range are scarce. We have prepared a series of trigonal CuI CAAC complexes bearing chelating ligands with O, N, S, and Se donor atoms and studied their photophysical properties in this context. The compounds show weak low-energy absorption in solution between 400 and 500 nm due to mixed Cu → CAAC 1MLCT/LLCT states, resulting in yellow-green to orange appearance, which we have also correlated to the 15N NMR resonances of the π-accepting carbene ligand. In the solid state, phosphorescence from dominant 3(Cu → CAAC) CT states is observed at room temperature. The emission of the complexes is bathochromically shifted in comparison to structurally related linearly coordinated copper(I) CAAC complexes due to structural reorganization in the excited state to a T-shape. For [Cu(dbm)(CAACMe)], the broad phosphorescence with outstanding λmax = 760 nm tailors out to ca. 1100 nm and leads to its proof-of-concept application as a nonclassical single-photon light source, constituting key functional units for the implementation of tap-proof data transfer.

1H, 13C, 15N resonance assignment of the enzyme KdgF from Bacteroides eggerthii

To fully utilize carbohydrates from seaweed biomass, the degradation of the family of polysaccharides known as alginates must be understood. A step in the degradation of alginate is the conversion of 4,5-unsaturated monouronates to 4-deoxy-L-erythro-5-hexoseulose catalysed by the enzyme KdgF. In this study BeKdgF from Bacteroides eggerthii from the human gut microbiota has been produced isotopically labelled in Escherichia coli. Here the 1H, 13C, and 15N NMR chemical shift assignment for BeKdgF is reported.

Synthesis, characterization, DFT, antioxidant, antibacterial, pharmacokinetics and inhibition of SARS-CoV-2 main protease of some heterocyclic hydrazones

Three hydrazone derivatives have been synthesized using condensation reaction of 4-hydrazinylbenzoic acid with three aromatic aldehydes namely: thiophene-2-carbaldehyde, thiophene-3-carbaldehyde and 2-furaldehyde in ethanol at 78 °C reflux. The synthesized molecules have been characterized using spectroscopic and physicochemical methods including UV–Vis, IR, 1H NMR, 13C NMR, 15N NMR and melting point determination. Optimized molecular structures, UV–Vis and IR spectra modeling, the reactivity, the stability and some quantum chemical parameters of the synthesized molecules were modeled utilizing density functional theory (DFT). The obtained theoretical results were found in good agreement with the experimental results. On the other hand, the antioxidant and antibacterial activities of the molecules under study were evaluated to better understand the associated mechanisms of action specifically. Also, predicted ADME-T and pharmacokinetic parameters indicated that these compounds showed good oral bioavailability. Finally, molecular docking has been used to predict the inhibitory activity of the studied hydrazone derivatives on the SARS-CoV-2 main protease (Mpro).

The Cluster Polyazide Complexes: Synthesis, Crystal Structures, and 14N NMR Studies of [{Re3(μ-X)3}(N3)9]3– (X = Br or I)

Azide cluster complexes [{Re3(μ-Br)3}(N3)9]3- and [{Re3(μ-I)3}(N3)9]3- were obtained by reaction of Re3X9 (X = Br or I, respectively) with sodium azide in methanol. The complexes were crystallized as cesium salts of the compositions Cs3[{Re3(μ-Br)3}(N3)9]·H2O (1) and Cs3[{Re3(μ-I)3}(N3)9]·H2O (2) and characterized by X-ray single-crystal diffraction and elemental analyses, mass spectrometry, 14N NMR spectroscopy, and DFT calculations. In the anions, each rhenium atom is coordinated by three azide ligands. To the best of our knowledge, these compounds represent the first case of metal cluster polyazide complexes (i.e., where each metal atom bears more than one azide ligand). Both complexes are stable in air but are very shock sensitive, and spontaneous explosive decomposition is also possible.

Attached Nitrogen Test by 13C-14N Solid-State NMR Spectroscopy for the Structure Determination of Heterocyclic Isomers.

Differentiation of heterocyclic isomers by solution 1H, 13C, and 15N NMR spectroscopy is often challenging due to similarities in their spectroscopic signatures. Here, 13C{14N} solid-state NMR spectroscopy experiments are shown to operate as an "attached nitrogen test", where heterocyclic isomers are easy to distinguish based on one-dimensional nitrogen-filtered 13C solid-state NMR. We anticipate that these NMR experiments will facilitate the assignment of heterocyclic isomers during synthesis and natural product discovery.

Backbone resonance assignments and dynamics of S. cerevisiae SERF.

Abnormal protein aggregation and precipitation are associated with the perturbation of cellular function and underlie a variety of neurodegenerative diseases. S. cerevisiae SERF (ScSERF), a homolog of modifier of aggregation-4 (MOAG-4) and small EDRK-rich factor protein (SERF1a) is highly conserved and discovered as an enhancer of amyloid formation of Aβ40 and α-synuclein both in vitro and in vivo. However, the detailed molecular mechanism whereby ScSERF and its homologs accelerate amyloid formation is not well known yet. Herein, we present the 1H, 15N and 13C NMR assignments of the 68 amino acids long ScSERF. Although ScSERF displays a very high degree of disorder, secondary chemical shifts of Cα, Cβ, 15N{1H}-NOE values and the residue-specific secondary structure propensity (SSP) scores indicate the segment spanning residues 36E-65K has a strong helical propensity. This work sets the stage for further detailed structural and dynamic investigations of ScSERF and the molecular mechanism it utilizes in accelerating amyloid formation.

Structure and Framework Association of Lewis Acid Sites in MOR Zeolite.

Zeolites, although key materials used in industrial processes, remain poorly understood on a molecular level despite their well-defined crystal lattices. In fact, obtaining a direct spectroscopic signatures and resolving the structure of Lewis acid sites (LAS) has remained a challenge. In this work, thanks to 1D and 2D 1H, 15N, and 27Al MAS NMR spectroscopy, carried out at different temperatures (from 298 down to 107 K), we were able to obtain the NMR spectroscopic signatures of LAS and Brønsted acid sites (BAS) in mordenite zeolite in the presence and the absence of adsorbed pyridine (Py). Combined with DFT modeling, this information enabled the structure of LAS to be revealed, namely (≡SiO)3Al sites interacting with pyridine, thus indicating that the corresponding base-free framework-associated sites are pseudo tricoordinated Al sites, namely tricoordinated Al sites interacting with an additional coordinated adjacent siloxane bridge. With this information in hand, we propose a molecular-level understanding on how the AlIV and AlVI framework and framework-associated sites evolve upon dehydration and exposure to Py into BAS and LAS, and their associated Py adducts. By measuring and analyzing the changes in quadrupolar coupling constants (CQ) that reflect electrical charge distribution around the nuclei, we further show that the lower CQ values observed at 298 K are due to residual dynamics that makes the electric field around aluminum nuclei more symmetric. Thus, NMR spectroscopic signatures of 27Al greatly vary with temperature; this information illustrates the importance of accounting for the temperature effect when confronting experimental and calculated CQ values of the corresponding aluminum sites in zeolites in order to obtain accurate structural assessment.

1H, 13C, 15 N backbone and side-chain NMR assignments for three MAX effectors from Magnaporthe oryzae

Effectors are small and very diverse proteins secreted by fungi and translocated in plant cells during infection. Among them, MAX effectors (for Magnaporthe Avrs and ToxB) were identified as a family of effectors that share an identical fold topology despite having highly divergent sequences. They are mostly secreted by ascomycetes from the Magnaporthe genus, a fungus that causes the rice blast, a plant disease leading to huge crop losses. As rice is the first source of calories in many countries, especially in Asia and Africa, this constitutes a threat for world food security. Hence, a better understanding of these effectors, including structural and functional characterization, constitutes a strategic milestone in the fight against phytopathogen fungi and may give clues for the development of resistant varieties of rice. We report here the near complete 1H, 15N and 13C NMR resonance assignment of three new putative MAX effectors (MAX47, MAX60 and MAX67). Secondary structure determination using TALOS-N and CSI.3 demonstrates a high content of β-strands in all the three proteins, in agreement with the canonic ß-sandwich structure of MAX effectors. This preliminary study provides foundations for further structural characterization, that will help in turn to improve sequence predictions of other MAX effectors through data mining.

1-(Azidomethyl)-5H-Tetrazole: A Powerful New Ligand for Highly Energetic Coordination Compounds.

Highly energetic 1‐(azidomethyl)‐5H‐tetrazole (AzMT, 3) has been synthesized and characterized. This completes the series of 1‐(azidoalkyl)‐5H‐tetrazoles represented by 1‐(azidoethyl)‐5H‐tetrazole (AET) and 1‐(azidopropyl)‐5H‐tetrazole (APT). AzMT was thoroughly analyzed by single‐crystal X‐ray diffraction experiments, elemental analysis, IR spectroscopy and multinuclear (1H, 13C, 14N, 15N) NMR measurements. Several energetic coordination compounds (ECCs) of 3d metals (Mn, Fe, Cu, Zn) and silver in combination with anions such as (per)chlorate, mono‐ and dihydroxy‐trinitrophenolate were prepared, giving insight into the coordination behavior of AzMT as a ligand. The synthesized ECCs were also analyzed by X‐ray diffraction experiments, elemental analysis, and IR spectroscopy. Differential thermal analysis for all compounds was conducted, and the sensitivity towards external stimuli (impact, friction, and ESD) was measured. Due to the high enthalpy of formation of AzMT (+654.5 kJ mol−1), some of the resulting coordination compounds are extremely sensitive, yet are able to undergo deflagration‐to‐detonation transition (DDT) and initiate pentaerythritol tetranitrate (PETN). Therefore, they are to be ranked as primary explosives.

Molecular Rearrangement of Pyrazino[2,3-c]quinolin-5(6H)-ones during Their Reaction with Isocyanic Acid.

New tetrahydropyrazino[2,3-c]quinolin-5(6H)-ones were prepared from 3-chloroquinoline-2,4(1H,3H)-diones and ethylene diamine. In their reaction with HNCO, an unprecedented molecular rearrangement produced new types of hydantoin derivatives. All prepared compounds were characterized on the basis of their 1H, 13C, and 15N NMR and ESI mass spectra and some were authenticated by X-ray analysis of single crystalline material. A proposed mechanism for rearrangement is discussed in this essay. The CDK and ABL inhibition activity as well as in vitro cytotoxicity of the prepared compounds was also tested.

The Structure of Biologically Active Functionalized Azoles: NMR Spectroscopy and Quantum Chemistry

This review summarizes the data on the stereochemical structure of functionalized azoles (pyrazoles, imidazoles, triazoles, thiazoles, and benzazoles) and related compounds obtained by multipulse and multinuclear 1H, 13C, 15N NMR spectroscopy and quantum chemistry. The stereochemistry of functionalized azoles is a challenging topic of theoretical research, as the correct interpretation of their chemical behavior and biological activity depends on understanding the factors that determine the stereochemical features and relative stability of their tautomers. NMR spectroscopy, in combination with quantum chemical calculations, is the most convenient and reliable approach to the evaluation of the stereochemical behavior of, in particular, nitrogen-containing heteroaromatic and heterocyclic compounds. Over the last decade, 15N NMR spectroscopy has become almost an express method for the determination of the structure of nitrogen-containing heterocycles.

A Copper(II)‐Nitrite Complex Hydrogen‐Bonded to a Protonated Amine in the Second‐Coordination‐Sphere

AbstractNitrous acid (HONO) plays pivotal roles in various metal‐free as well as metal‐mediated routes relevant to biogeochemistry, atmospheric chemistry, and mammalian physiology. While the metastable nature of HONO hinders the detailed investigations into its reactivity at a transition metal site, this report herein utilizes a heteroditopic copper(II) cryptate [oC]CuII featuring a proton‐responsive second‐coordination‐sphere located at a suitable distance from a [CuII](ONO) core, thereby enabling isolation of a [CuII](κ1‐ONO⋅⋅⋅H+) complex (2H‐NO2). A set of complementary analytical studies (UV‐vis, 14N/15N FTIR, 15N NMR, HRMS, EPR, and CHN) on 2H‐NO2 and its 15N‐isotopomer (2H‐15NO2) reveals the formulation of 2H‐NO2 as {[oCH]CuII(κ1‐ONO)}(ClO4)2. Non‐covalent interaction index (NCI) based on reduced density gradient (RDG) analysis on {[oCH]CuII(κ1‐ONO)}2+ discloses a H‐bonding interaction between the apical 3° ammonium site and the nitrite anion bound to the copper(II) site. The FTIR spectra of [CuII](κ1‐ONO⋅⋅⋅H+) species (2H‐NO2) shows a shift of ammonium NH vibrational feature to a lower wavenumber due to the H‐bonding interaction with nitrite. The reactivity profile of [CuII](κ1‐ONO⋅⋅⋅H+) species (2H‐NO2) towards anaerobic nitration of substituted phenol (2,4‐DTBP) is distinctly different relative to that of the closely related tripodal [CuII]‐nitrite complexes (1‐NO2/3‐NO2/4‐NO2).

Synthesis, crystal structure and spectroscopic characterization of new anionic iridium(III) complexes and their interaction with biological targets

The synthesis and characterisation of new anionic iridium(II) complexes (NH4)2[IrCl4(κ2N,N'-H2biim)]2 · 5H2O (1) and ((CH3)2NH2)[IrCl4(κ2N,N’-PyBIm)] · H2O (2) are presented in this article. Spectroscopic methods (1H, 13C and 15N NMR, FTIR, UV–Vis) were used to characterize these new complexes. Solid-state structural analysis (SC-XRD) of complexes 1 and 2 shows a slightly distorted octahedral geometry of Ir(III) ions, which is constructed by one chelating κ2N,N’-2,2′-biimidazole (H2biim (1)) or 2-(2′-pyridyl)benzimidazole (PyBIm (2)) and four chloride ions. In the crystal structures, the presence of organic ligands containing NH groups favours the formation of strong hydrogen bonds (XH···Cl (X = O, N, C)), which have significant impact on the crystal structure forming 2D (1) and 3D (2) systems during the self-assembly process. Additionally, preliminary studies of the biological activity of the obtained complexes were performed. Considering the above properties, the observed stronger binding affinity of complex 1 to DNA and HSA can be interpreted in terms of changes in the number of hydrogen bonds that are potentially formed with the target molecule. Furthermore, higher reactivity towards NADH and the lower reactivity towards GSH were observed for complex 2. Both complexes showed moderate cytotoxicity against selected cancer cell lines (LoVo, MV-4–11, MCF-7) and did not show toxicity towards normal cells (BALB/3T3). The cytotoxicity of 2 may be compromised by a weaker interaction with DNA, HSA or GSH and a stronger reactivity towards NADH.

O,N,S-tris-chelating ligand scaffolds flanked with cyclohexyl or adamantyl substituents anchored with diorganotin(IV) moieties: synthesis, structures and cytotoxicity

The O,N,S-tris-chelating ligand, H2NSCN-N-C(H)ArO− constitutes an attractive scaffold in coordination chemistry and we have expanded this scaffold by installing an alkyl group of different steric hindrance. Thus, the ligand scaffolds containing O,N,S (Ln) differ with respect to the chemical link between the coordinating O atoms, which is either a phenol or a naphthol moiety and carrying a cyclohexyl or a adamantyl groups (L1, phenol and cyclohexyl; L2, naphthol and cyclohexyl; L3, phenol and adamantyl; L4, naphthol and adamantyl). Six novel diorganotin(IV)-Ln compounds 1–6 were synthesized and structurally characterized. The solid-state structures were deduced from single crystal X-ray diffraction data, and revealed the Sn(IV) cations adopting square pyramid (in 2, 3 and 4) or trigonal bipyramid (in 1, 5 and 6) geometries with coordination spheres comprising κ-N,O,S (κ-N,S in 1) ligand chelators and two methyl or phenyl groups (plus a hydrosulfide in 1) co-ligands. Solution state characterizations were achieved by detailed 1H, 13C, 15N and 119Sn NMR analysis including selected 2D experiments. In vitro cytotoxic activities of the compounds were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against human histiocytic lymphoma U-937 cells. The IC50 values revealed better activities of diphenyltin(IV) compounds 4–6 as compared to the respective pro-ligands and doxorubicin. More importantly, compounds 4–6 demonstrated maximum inhibition in U-937 cells (IC50 = 0.47–0.99 μM), with negligible effect on human peripheral blood mononuclear cells (PBMC). Compounds 4–6 effectively inhibited cell viability event, which was confirmed by detecting cytotoxicity, Live & Dead and Lactate dehydrogenase (LDH) release assays.

Synthesis and characterization of 2,5-dibutylthio-2,3-dihydro-2-formyl-4H-pyran thiosemicarbazones and their copper complexes

Previously unknown derivatives of thiosemicarbazide were obtained in high yields by the condensation reaction of 2,5-dibutylthio-2,3-dihydro-2-formyl-4H-pyran with 4-phenylthiosemicarbazide or thiosemicarbazide when boiling in EtOH. The reaction products are represented by colored oils. Cu(II) complexes based on 2,5-dibutylthio-2,3-dihydro-2-formyl-4H-pyran carbazones were synthesized by their interaction with copper (II) chloride. All these complexes are soluble in dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) and, according to elemental analysis, have a 1:1 metal-ligand stoichiometry. The obtained compounds were studied using IR and 1H, 13C, 15N NMR spectroscopy, as well as elemental analysis. The obtained copper-containing complexes with thiosemicarbazones are of particular interest due to their pronounced biological activity. The thiosemicarbazone 2,5-dibutylthio-2,3-dihydro-2-formyl-4H-pyran compound was subjected to primary screening for acute toxicity. The obtained results showed that, when taken intragastricaly, the studied compound can be characterized as a substance with a low risk of acute toxicity. According to the DL50 parameter, the compound belongs to the V hazard class (DL50>2000 mg/kg).

STRUCTURE INVESTIGATION OF 5,5,6-TRIHYDROXY-6-METHYLDIHYDROPYRIMIDINE-2,4(1H,3H)-DIONE IN DMSO-d6 SOLUTION BY NMR-SPECTROSCOPY

The structure of 5,5,6-trihydroxy-6-methyldihydropyrimidine-2,4(1Н,3Н)-dione in dimethyl sulfoxide was proved by 13С, 1Н, and 15N NMR spectroscopy. It was shown that this compound has a structure similar to 5,5,6-trihydroxy-6-methyldihydropyrimidine-2,4(1Н,3Н)-dione.

Characterization of crystalline and amorphous forms of irbesartan by multi-nuclear solid-state NMR

Irbesartan (IRB) is an antihypertensive drug which exhibits the rare phenomenon of desmotropy; its 1H- and 2H- tetrazole tautomers can be isolated as distinct crystalline forms. The crystalline forms of IRB are poorly soluble, hence the amorphous form is potentially of interest for its faster dissolution rate. The tautomeric form and the nature of hydrogen bonding in amorphous IRB are unknown. In this study, crystalline form A and amorphous form of irbesartan were studied using 13C, 15N and 1H solid-state NMR. Variable-temperature 13C SSMNR studies showed alkyl chain disorder in the crystalline form of IRB, which may explain the conflicting literature crystal structures of form A (the marketed form). 15N NMR indicates that the amorphous material contains an approximately 2:1 ratio of 1H- and 2H-tetrazole tautomers. Static 1H SSNMR and relaxation time measurements confirmed different molecular mobilities of the samples and provided molecular-level insight into the nature of the glass transition. SSNMR is shown to be a powerful technique to investigate the solid state of disordered active pharmaceutical ingredients.

Energetic Polymers: A Chance for Lightweight Reactive Structure Materials?

AbstractToday's ammunition still consists of about 70 wt% structure‐providing materials such as metals providing no energetic contribution. Therefore, reactive structure materials (RSMs) offer tremendous room for improvement. While current research focuses on rather heavy, metal‐based materials (e. g., alloys, thermites), energetic polymers appear as an under‐recognized opportunity for very lightweight RSMs. Unfortunately, suitable polymers are unavailable as energetic polymer research has almost exclusively focused on elastic binders with the least possible glass transition temperature. An application as RSM, however, requires rigid polymers with a glass transition above operational temperatures. Accordingly, monomers with fundamentally different structures are required. The first step in this particular direction is 3‐(2,4,6‐trinitrophenoxy)oxetane (TNPO). Herein, we report the synthesis of its homopolymer and investigate its polymerization behavior by copolymerization with prior art energetic oxetanes. All polymers were intensively studied by vibrational and multinuclear (1H, 13C, 14N) NMR spectroscopy, elemental analysis, gel permeation chromatography, and differential scanning calorimetry (DSC). Hereby, DSC revealed the high effect of the TNPO repeating unit on the glass transition temperature. The performance of all polymers was calculated using the EXPLO5 code to evaluate the potential performance range of polymeric RSMs. Further, their shock and friction sensitivity was determined by BAM standard procedures.

Comparative study of cyclic polyaniline oligomers with linear and bent structures

In the present work, Grimme’s D3 dispersion corrected density functional theory (DFT-D3) is used for the comparative study of cyclic polyaniline oligomers with linear and bent structures, for the first time. Molecular design and spectral characterisation of these compounds are performed at the B3LYP-D3/6-311G(d,p) and the B3LYP-D3/6-311++G(d,p) levels of theory. The formation mechanism of cyclic polyaniline oligomers compared to the linear and bent structures is discussed. Molecular orbital (MO) calculations are applied to study the electronic structure, and estimate the energy gap between the highest occupied (HOMO) and the lowest unoccupied (LUMO) molecular orbitals. The density of states (DOS) diagrams are used to evaluate the nature of valence and conduction bands and investigate the electrical conductivity. The calculated infrared (IR), ultraviolet-visible (UV-Vis) and nitrogen-15 nuclear magnetic resonance (15N NMR) spectra of these compounds are compared to the theoretical and experimental spectra of polyaniline. Results show that cyclic polyanilines are nonpolar in comparison to the linear and bent structures. The band gap of these molecules is larger than the linear and bent ones. The band gap of cyclic oligomers increases with the increasing size of the rings. These results provide useful information for the characterisation of these novel compounds.