N-oxide Molecules Research Articles

Exploring the Potential Link between Acute Central Serous Chorioretinopathy and Trimethylamine N-Oxide, Phoenixin, Spexin, and Alarin Molecules.

Acute central serous chorioretinopathy (ACSCR) is a condition characterized by decreased visual acuity, macular thickening, and edema under the retinal layer. Although the underlying mechanisms of the disease are not fully understood, oxidative stress is considered to be a critical risk factor. The aim of this study was to shed light on the pathophysiology of ACSCR by investigating the levels of circulating trimethylamine N-oxide (TMAO), phoenixin (PNX), alarin (ALA), and spexin (SPX) molecules in ACSCR patients. The study included 30 ACSCR patients and 30 healthy individuals as controls. ACSCR was diagnosed using optical coherence tomography (OCT) imaging. Five mL blood samples were collected from all participants following overnight fasting. The levels of TMAO, PNX, ALA, and SPX in the blood samples were measured using the ELISA method. Visual acuity was found to be significantly reduced in ACSCR patients compared to the control group (<0.05), while macular thickness was increased (<0.05). Furthermore, TMAO, PNX, and ALA levels were significantly higher in ACSCR patients (<0.05), while SPX levels were significantly lower compared to the control group (<0.05). In ACSCR patients, there was a positive correlation between macular thickness and TMAO, PNX, and ALA; there was, however, a negative correlation with SPX. Additionally, visual acuity was negatively correlated with TMAO, PNX, and ALA, while SPX levels decreased as visual acuity decreased. These results demonstrate a correlation between the TMAO, PNX, ALA, and SPX levels of ACSCR patients and their visual acuity and macular thickness. Given the role of these molecules in ACSCR's pathophysiology, they hold promise as potential diagnostic, therapeutic, and follow-up markers in the future.

Ultrafast excited state dynamics of pyridine N-oxide derivative in solution; femtosecond fluorescence up-conversion and theoretical calculations

In this study we have investigated 2-ethylamino-4-nitro-6-methyl pyridine N-oxide (2E6M) molecule that belongs to important group of Proton Coupled Electron Transfer (PCET) compounds where both the charge transfer (CT) and proton transfer processes in excited states may proceed. In this case, this is possible due to the donors and acceptors of electrons and protons in this system, as well as due to the presence of intramolecular {N-H… O [2,566(3) Å}, hydrogen bond.Using stationary and time-resolved spectroscopy, as well as quantum chemical calculations on the DFT and TD DFT B3LYP/6-31G (d,p) level of theory, a partial CT nature of the S0 → S1 transition in both tautomeric forms (N and T) has been revealed. Additionally, the excited state intramolecular proton transfer (ESIPT) process shown to be more favorable in apolar and weakly polar solvents than in strongly polar acetonitrile (EN(S1) > ET(S1). The displacement of charge from the amine group and the ring to the nitro group has been observed on the changing shapes of the HOMO and LUMO orbitals involved in this transition what further quantitatively allowed to realize the increase in the dipole moment of both forms in the electronic excited state. The calculations show that in two solvents with radically different polarity (heptane, acetonitrile), dipole moments of both forms are very similar [in acetonitrile uN(S1) and uT(S1) are 11.0 D and 11.5 D, respectively]. Hence, in polar media both forms can be stabilized in a comparable manner. This made it difficult for us to assign a single fluorescent band in acetonitrile to one of the tautomeric forms. However, it seems that due to application of time-resolved spectroscopy, this problem has been clarified. The TCSPC decay curve in acetonitrile with an ultrafast lifetime assigned to the (N) form, along with the femtosecond up-conversion signals that demonstrated only an ultrafast decay without any rise-time of a new excited (T) species, allowed us to conclude that in 2E6M in strongly polar solvent the ESIPT does not occur.The unique fluorescence band origins from the (N) form. In protic solvents, the significant kinetic isotopic effects have provided us with conclusive evidence for the presence of the solvent-assisted ESIPT process. Furthermore, it was noticed that the fluorescence lifetime in D2O (100–120 fs) estimated from the up-conversion signals is about 40 times shorter relative to methanol. This may suggest that the sine qua non for the ESIPT process in 2E6M in protic solvents is the formation of a complex with a solvent molecule in the hydrogen bridge between the proton donor and proton acceptor, respectively.

Influence of the position of the methyl substituent and N-oxide formation on the geometry and intermolecular interactions of 1-(phenoxyethyl)piperidin-4-ol derivatives.

Aminoalkanol derivatives have attracted much interest in the field of medicinal chemistry as part of the search for new anticonvulsant drugs. In order to study the influence of the methyl substituent and N-oxide formation on the geometry of molecules and intermolecular interactions in their crystals, three new examples have been prepared and their crystal structures determined by X-ray diffraction. 1-[(2,6-Dimethylphenoxy)ethyl]piperidin-4-ol, C15H23NO2, 1, and 1-[(2,3-dimethylphenoxy)ethyl]piperidin-4-ol, C15H23NO2, 2, crystallize in the orthorhombic system (space groups P212121 and Pbca, respectively), with one molecule in the asymmetric unit, whereas the N-oxide 1-[(2,3-dimethylphenoxy)ethyl]piperidin-4-ol N-oxide monohydrate, C15H23NO3·H2O, 3, crystallizes in the monoclinic space group P21/c, with one N-oxide molecule and one water molecule in the asymmetric unit. The geometries of the investigated compounds differ significantly with respect to the conformation of the O-C-C linker, the location of the hydroxy group in the piperidine ring and the nature of the intermolecular interactions, which were investigated by Hirshfeld surface and corresponding fingerprint analyses. The crystal packing of 1 and 2 is dominated by a network of O-H...N hydrogen bonds, while in 3, it is dominated by O-H...O hydrogen bonds and results in the formation of chains.

The Diversity of Heterocyclic N-oxide Molecules: Highlights on their Potential in Organic Synthesis, Catalysis and Drug Applications

The synthesis and chemistry of heterocyclic N-oxide derivatives such as those from pyridine and indazole are very well-known due to their usefulness as versatile synthetic intermediates and their biological importance. These classes of organic compounds have been demonstrated in many interesting and amazing functionalities, particularly vital in the areas including metal complexes formation, catalysts design, asymmetric catalysis and synthesis, and medicinal applications (some potent N-oxide compounds with anticancer, antibacterial, anti-inflammatory activity, etc.). Therefore, the heterocyclic N-oxide motif has been successfully employed in a number of recent advanced chemistry and drug development investigations. In the present review, our primary aim was to provide a relevant summary focusing on the topics of organic synthesis and medical application potential of the compounds cited, which could be attractive and give some insights to researchers in the field. Therefore, we mainly highlight the importance of heterocyclic N-oxide derivatives including those synthesized from imidazole, indazole, indole, pyridazine, pyrazine, pyridine, and pyrimidine in organic syntheses and catalysis, and drug applications. Over the past years, a number of reviews have been published on the organic synthesis and catalysis of N-oxides. We thus concentrated on highlighting those rarely mentioned or recently reported systems.

Crystal structure, vibrational and optic properties of 2-N-methylamino-3-methylpyridine N-oxide – Its X-ray and spectroscopic studies as well as DFT quantum chemical calculations

The crystal and molecular structure and physicochemical properties of 2-N-methylamino-3-methylpyridine N-oxide (MA3MPO) have been studied. MA3MPO was synthesized from 2-amino-3-methylpyridine by several steps to form colorless crystals suitable for crystallographic analysis. The data reveal that MA3MPO crystallizes in the monoclinic space group P21/n. The studied compound contains a nearly flat triply substituted pyridine skeleton whose structure is stabilized by an intramolecular N–H⋅⋅⋅O hydrogen bond. The N-oxide molecules are connected together by weak C–H⋯O hydrogen bonds, an acceptor of which is the oxygen atom from the N-oxide group. This leads to creation of two-dimensional network of hydrogen bonds. Its IR, Raman, UV–Vis and luminescence spectra have been measured and analyzed on the basis of DFT and NBO quantum chemical calculations in which the B3LYP/6-311++G(d,p) approach was applied. The distribution of the electron levels in the studied compound has been analyzed in terms of the possibility of its participation in the ligand-to-lanthanide ion energy transfer.

Thermal behaviour of nitrogen oxides relevant to oxidative denitrogenation

Nitrogen compounds in crude oil are known to cause several problems during refining including catalyst deactivation and gum formation. Industrially, nitrogen is removed by hydro-treating, which requires ring saturation prior to denitrogenation and makes hydro-treating an expensive process for heavy crude oils or coal liquids with high nitrogen content. Oxidative denitrogenation is an alternative method to hydro-treating, where the nitrogen compounds are oxidized to form nitrogen oxides, which can be separated from the oil by extraction with a polar solvent. During this separation process there is a loss of hydrocarbon material which can be between (10–20) wt% for an oil containing 1 wt% of N. The possibility to release nitrogen as NOx by thermal treatment and consequently recover the hydrocarbon portion from the N-oxide molecule is the topic explored in this work. The thermochemistry of the N-oxides of pyridine, 3-picoline, 2-mercaptopyridine, quinoline, 4-nitropyridine, 3,5-dimethylpyridine, picolinic acid, 4-picoline, 3-hydroxypyridine, nicotinic acid, isonicotinic acid, and nicotinamide was studied. The results showed that the N-oxides of pyridine and 3-picoline evaporated at atmospheric pressure while the other compounds decomposed after or during melting or during evaporation. Decomposition temperatures could be determined for all the N-oxides during thermal analysis at 5 MPa gauge. Infra-red spectroscopy of the residues after thermal treatment indicated that the compounds still contained nitrogen. The suggested chemistry taking place upon thermal decomposition in the liquid phase was discussed. N-oxides may form an oxaziridine intermediate, which results in formation of polymeric structures that still contain the nitrogen. Therefore, pyrolysis of the N-oxides subsequent to oxidation seems to be inefficient to liberate the nitrogen as NOx.

Oxidation of 2-mercaptopyridine N-oxide upon iodine agent: structural and FT-IR studies on charge-assisted hydrogen bonds CAHB(+) and I\u2026I halogen interactions in 2,2\u2032-dithiobis(pyridine N-oxide) ionic cocrystal

2-Mercaptopyridine N-oxide (I) undergoes spontaneous dimerization to the disulfide form due to reaction with iodine acting as an oxidizing reagent. As a result, a di-N-oxide disulfide derivative of pyridine is obtained. During the process of crystallization, one of N-oxide groups undergoes protonation and a cation form of disulfide moiety cocrystallizes with I3− counterion forming a salt structure. Therefore, in the crystalline state, the 2,2′-dithiobis(pyridine N-oxide) molecule exists in a not observed previously form of monocation. Interestingly, the protonated N-oxide group does not form hydrogen-bonded salt bridges (of the CAHB(±) type with I3− anions) but prefers to be involved in intermolecular interactions with the unprotonated N-oxide group of the adjacent molecule This results in formation of intermolecular CAHB(+) hydrogen bridges finally linking molecules into infinite chains. The crystal structure is also stabilized by other various noncovalent interactions, including iodine...iodine and sulfur...iodine contacts.

Подвижность молекул воды, мочевины и триметиламиноксида вблизи глобулярного белка

C использованием полноатомного молекулярно-динамического моделирования исследовали подвижность молекул в гидратной оболочке глобулярного белка SNase в водном растворе с косольвентами (мочевина и триметиламиноксид). Для молекул, изначально расположенных в последовательных слоях вокруг белка, рассчитывали средние смещения за один и тот же короткий промежуток времени. Это позволило характеризовать диффузионную подвижность молекул в зависимости от расстояния до белка. Показано, что молекулы растворителя имеют пониженную подвижность вблизи белка, а при удалении от него подвижность молекул увеличивается неравномерно, коррелируя с положением максимумов функции распределения соответствующих молекул вокруг белка. За пределами второго максимума этих функций подвижность достигает своих объемных значений как для воды, так и для косольвентов.

Effects of Supramolecular Architecture on Halogen Bonding between Diiodine and Heteroaromatic N-Oxides

Cocrystallization of diiodine with a series of heteroaromatic N-oxides produced three types of halogen-bonded associates: (a) alternating chains comprising I2 molecules bridged by oxygen atoms of N-oxides of pyridine, quinoline, or 4-methylpyridine; (b) discrete 2:1 complexes, in which diiodine links a pair of acridine N-oxide molecules; and (c) amphoteric 1:1 adducts, in which one end of each diiodine molecule is halogen-bonded to N-oxide of 4-methoxypyridine or 4-chloroquinoline, and another diiodine’s end forms contacts with the other I2 molecules. In all cases, halogen bonds between diiodine and N-oxides are characterized by nearly linear I–I···O angles, close to perpendicular dihedral C–N–O···I angles and N–O···I angles of about 110°. The halogen bond length in the 1:1 adducts is about 0.3 A shorter than those in the 2:1 associates and in the infinite chains. Computational analyses confirmed that the variations in I···O separations are related predominantly to the distinct effects of halogen bond com...

Stabilization of Allylic Amine N-Oxide through Cocrystallization with Pyrogallol[4]arene

An active allylic amine N-oxide (ANO) molecule was cocrystallized with pyrogallol[4]arene through intermolecular hydrogen bonds and π···π interactions. Interestingly, [2,3]-Meisenheimer rearrangement of the ANO was suppressed, which was analyzed in detail in the solid state by single crystal X-ray crystallography in varying temperatures. Additionally, this work provides not only a new strategy to stabilize reactive chemicals, but also a unique method to elucidate their structures.

Soft-Cavity-type Host–Guest Structure of Cocrystals with Good Luminescence Behavior Assembled by Halogen Bond and Other Weak Interactions

The host cocrystal 1 with a soft-cavity-type structure unit has been assembled by 1,4-diiodotetrafluorobenzene and 4-phenylpyridine N-oxide (PPNO) molecules mainly using the robust C–I···–O–N+ halogen bond. The results indicate that the host cavity has the capacity to envelope functional guests, Car, Nap, Phe, and BhQ molecules, to further form the host–guest cocrystals 2–5 by halogen bonds, hydrogen bonds, and other weak noncovalent interactions. The supramolecular cavity can be adjusted in size or shape to a certain degree by the bound guest molecule, reflecting its softness, openness, and inclusiveness. Moreover, compared to the pristine PPNO and guest molecules, the prepared cocrystals 1–5 display tunable luminescence behaviors at room temperature. The present work may pave a new platform for developing host–guest solid materials which have potential applications in the fields of luminescent sensor, light-emitting display, pharmaceutical encapsulation, and separation chemistry.

Structural study of the novel deuterated calix[4]pyrrole complex d12-meso-tetrakis(4-methoxyphenyl)-meso-tetramethylcalix[4]pyrrole-pyridine N-oxide-acetonitrile (1/1/1).

Calix[4]pyrroles act as powerful receptors for electron-rich neutral guests and anionic guests in organic solvents. For the electron-rich neutral guest pyridine N-oxide, calix[4]pyrrole, with a deep cavity, provides an appropriate environment. The ability of calix[4]pyrrole to host binding guest molecules is the result of hydrogen bonding, π-π, C-H...π and hydrophobic interactions of the cavity. The novel title complex, C52H40D12N4O4·C5H5NO·C2H3N, based on d12-meso-tetrakis(4-methoxyphenyl)-meso-tetramethylcalix[4]pyrrole, has been assembled using an excess of pyridine N-oxide and is the first deuterated complex of calix[4]pyrrole. A single-crystal X-ray study shows that the receptor adopts a cone conformation with the N-oxide fragment encapsulated deep within the cavity. 1H NMR spectroscopy was used to probe the molecular binding formation in CD3CN. The results are consistent with the single-crystal X-ray study in identifying that the pyridine N-oxide molecule occupies the cavity of the calix[4]pyrrole molecule. UV-vis spectroscopy revealed that the calix[4]pyrrole receptor molecules are able to form 1:1 inclusion complexes in CH3CN.

Structural and Stability Studies of a Series of para-Phenylenediboronic and para-Hydroxyphenylboronic Acid Cocrystals with Selected Aromatic N-Oxides

Nine new cocrystals of para-phenylenediboronic or para-hydroxyphenylboronic acids with a series of aromatic N-oxides are reported. All of the complexes form centrosymmetric crystal structures. They are stabilized by an extended net of hydrogen bonds further supported by effective π-stacking interactions. In the studied structures four main synthons were distinguished. Only in the 3,10-phenanthroline-3-N-oxide and 3,10-N,N-dioxide cocrystals from the series, an acid–acid dimeric motif characteristic for arylboronic acid crystals was observed. The majority of the obtained cocrystals exhibit layered architectures, where the N-oxide molecules are separated by boronic acid slabs. Furthermore, most of the cocrystals form hydrates, where water molecules play the role of a “molecular glue”. Water contribution to the lattice stability is significant, and energy gain per water molecule ranges from 66.8 to 117.6 kJ·mol–1. The cocrystal cohesive energies seem to be more favorable when compared to the corresponding values for crystals of their components. However, the presence of various asymmetric unit contents and numerous hydrated crystal structures indicates that the crystallization process and the final products are highly dependent on kinetic and entropy factors. Finally, the calculated energetic features are compared with the experimental thermogravimetric analysis–differential scanning calorimetry results obtained for selected cocrystals.

Reversible Structural Changes of Strong Hydrogen Bond-Supported Organic Networks Using Neutral 3,5-Pyridinedicarboxylic Acid N-oxide through Solvent Release/Uptake

Abstract Crystallization of neutral 3,5-pyridinedicarboxylic acid N-oxide (H2-3,5-pydcao) molecules in the presence/absence of solvent molecules affords neutral hydrogen bond-supported one-dimensional, two-dimensional, and three-dimensional molecular networks of H2-3,5-pydcao·DMF (1·DMF), H2-3,5-pydcao·H2O (1·H2O), and H2-3,5-pydcao (1), respectively, that have strong intermolecular hydrogen bonds of Nδ+–Oδ−⋯HOOC. These molecular networks were found to show reversible structural changes among 1, 1·H2O, and 1·DMF driven by solvent release/uptake.

Development of multicomponent hybrid density functional theory with polarizable continuum model for the analysis of nuclear quantum effect and solvent effect on NMR chemical shift.

We have developed the multicomponent hybrid density functional theory [MC_(HF+DFT)] method with polarizable continuum model (PCM) for the analysis of molecular properties including both nuclear quantum effect and solvent effect. The chemical shifts and H/D isotope shifts of the picolinic acid N-oxide (PANO) molecule in chloroform and acetonitrile solvents are applied by B3LYP electron exchange-correlation functional for our MC_(HF+DFT) method with PCM (MC_B3LYP/PCM). Our MC_B3LYP/PCM results for PANO are in reasonable agreement with the corresponding experimental chemical shifts and isotope shifts. We further investigated the applicability of our method for acetylacetone in several solvents.

Experimental IR and Raman spectra and quantum chemical studies of molecular structures, conformers and vibrational characteristics of nicotinic acid and its N-oxide

FTIR and Raman spectra of nicotinic acid and its N-oxide have been recorded and analyzed. The stabilities, optimized molecular geometries, APT charges and vibrational characteristics for the two possible conformers of nicotinic acid and its N-oxide have been computed using DFT method. The E (trans) conformers of both the molecules are found to be more stable and less polar than their respective Z (cis) conformers. Due to addition of an O atom at the N 1 site in nicotinic acid the magnitudes of atomic charges on all the H atomic sites of the nicotinic acid N-oxide molecule are found to increase. Most of the vibrational frequencies have nearly the same magnitude for the two conformers of both the molecules. However, significant changes are noticed in their IR intensities, Raman activities and depolarization ratios of the Raman bands. The calculated frequencies have been correlated with the experimental frequencies.

2,5-Dimethylpyrazine 1,4-dioxide

The title compound, C6H8N2O2, was prepared from 2,5-dimethyl­pyrazine, acetic acid, and hydrogen peroxide. The 2,5-dimethyl­pyrazine 1,4-dioxide mol­ecule is located on an inversion center. π–π inter­actions between neighboring 2,5-dimethyl­pyrazine 1,4-dioxide mol­ecules are observed with an inter­planar distance of 3.191 Å. Each 2,5-dimethyl­pyrazine 1,4-dioxide mol­ecule is linked to four neighboring N-oxide mol­ecules through C—H⋯O hydrogen-bonding inter­actions, forming two-dimensional layers.

Lewis acid effects on donor–acceptor associations and redox reactions: ternary complexes of heteroaromatic N-oxides with boron trifluoride and organic donors

Structural and spectral features of the novel supramolecular [D·NXO·BF3] complexes formed via simultaneous n-coordination of a Lewis acid (BF3) and π-complexation of organic donors (D) to polyfunctional nitrosubstituted N-oxide molecules (NXO = 4-nitropyridine-N-oxide or 4-nitroquinoline-N-oxide) are reported. X-Ray studies of [pyrene·NPO·BF3]·CH2Cl2 and [(pyrene)2·NQO·BF3] salts revealed that the Lewis acid is coordinated to the oxygen atom of the N-oxide group with O–B distance of ∼1.52 Å similar to that in the separate [NXO·BF3] adducts. Aromatic rings of N-oxide molecules in the ternary systems are π-stacked with pyrene moieties, and their interplanar separations of ∼3.35 Å are common for conventional charge-transfer complexes. In dichloromethane, associations between [NXO·BF3] adduct and organic donors are characterized by higher formation constants (and charge-transfer bands of [D·NXO·BF3] complexes are red-shifted) as compared to the complexes between the same donors and NXO acceptors. Spectral data and electrochemical measurements point out enhanced acceptor abilities of [NXO·BF3] adducts relative to the separate N-oxides which correspond to ∼0.5 V positive shift of reduction potentials of acceptors. Synergetic oxidation of strong organic donors by [NXO·BF3] dyads (which results in the formation of the corresponding cation radicals and products of transformation of both BF3 and NXO components) is discussed.

Versatility of p-sulfonatocalix[5]arene in building up multicomponent bilayers

The ability of pyridine N-oxide molecules to form host–guest complexes with p-sulfonatocalix-[5]arene was probed and resulted in the formation of europium complexes incorporating 2- or 4-picoline N-oxide, and 4,4′-dipyridine N,N′-dioxide. Relative to lanthanide complexes of p-sulfonatocalix[5]arene incorporating pyridine N-oxide, the presence of a methyl group on the aromatic ring for the picoline N-oxides, or a larger dipyridine dioxide guest dramatically alters the self-assembly, resulting in the formation of three new supramolecular motifs for the calixarene.

Three-centre hydrogen bonds in 4-picolineN-oxide–hydroquinone (1/1)

The title compound, C6H7NO·C6H6O2, belongs to a series of mol­ecular systems based on methylpyridine N-oxides. The N-oxide molecule is located on a crystallographic twofold rotation axis, while the hydroquinone molecule is located on an inversion centre. The two components are linked by an O—H⋯O hydrogen bond with a distance of 2.675 (2) Å. In the crystalline environment, three-centre hydrogen bonds involving the N-oxide O atom with two hydro­quinone mol­ecules related by symmetry in the [001] direction are observed.