Nitrogen Position Research Articles

Electronic structure changes introduced by nitrogen on the N-doped VOx/TiO2 system: Consequences on partial oxidation catalysis

The catalytic activity for ethanol partial oxidation of supported vanadium oxide catalysts prepared on N doped TiO2 (VOx/N-TiO2) was correlated to the electronic structure of the vanadium clusters present in the catalyst surface. In situ Raman and UV–vis spectra together with ethanol temperature programmed desorption (TPD) profiles indicate that in all materials studied the average VOx cluster size is very similar, irrespective of the presence of nitrogen. However, the distribution of active sites and the reducibility of the VOx species are significantly affected by the presence of nitrogen in the support. The electronic structure of these materials was investigated using periodic density functional theoretical calculations. It was found that, compared to the nitrogen free materials, the electronic structure of reduced VOx is affected by the presence of N, as well as nitrogen position on the TiO2 supports (interstitial vs. substitutional). Our analysis revealed that after vanadia reduction during ethanol oxidation, reduced VOx sites (V+4) form, accompanied by the simultaneous reduction of adjacent Ti cations (Ti+3). Calculated optical absorption spectra are also provided and matched with experimental spectroscopic results, confirming these observations.

Synthesis and biological evaluation of alpha-bromoacryloylamido indolyl pyridinyl propenones as potent apoptotic inducers in human leukaemia cells

The combination of two pharmacophores into a single molecule represents one of the methods that can be adopted for the synthesis of new anticancer molecules. To investigate the influence of the position of the pyridine nitrogen on biological activity, two different series of α-bromoacryloylamido indolyl pyridinyl propenones 3a–h and 4a–d were designed and synthesized by a pharmacophore hybridization approach and evaluated for their antiproliferative activity against a panel of six human cancer cell lines. These hybrid molecules were prepared to combine the α-bromoacryloyl moiety with two series of indole-inspired chalcone analogues, possessing an indole derivative and a 3- or 4-pyridine ring, respectively, linked on either side of 2-propen-1-one system. The structure-activity relationship was also investigated by the insertion of alkyl or benzyl moieties at the N-1 position of the indole nucleus. We found that most of the newly synthesized displayed high antiproliferative activity against U-937, MOLT-3, K-562, and NALM-6 leukaemia cell lines, with one-digit to double-digit nanomolar IC50 values. The antiproliferative activities of 3-pyridinyl derivatives 3f–h revealed that N-benzyl indole analogues generally exhibited lower activity compared to N-H or N-alkyl derivatives 3a–b and 3c–e, respectively. Moreover, cellular mechanism studies elucidated that compound 4a induced apoptosis along with a decrease of mitochondrial membrane potential and activated caspase-3 in a concentration-dependent manner.

Heat and mass transfer of liquid nitrogen in coal porous media

Liquid nitrogen has been working as an important medium in fire extinguishing and prevention, due to its efficiency in oxygen exclusion and heat removal. Such a technique is especially crucial for coal industry in China. We built a tunnel model with a temperature monitor system (with 36 thermocouples installed) to experimentally study heat and mass transfer of liquid nitrogen in non-homogeneous coal porous media (CPM), and expected to optimize parameters of liquid nitrogen injection in engineering applications. Results indicate that injection location and amount of liquid nitrogen, together with air leakage, significantly affect temperature distribution in CPM, and non-equilibrium heat inside and outside of coal particles. The injection position of liquid nitrogen determines locations of the lowest CPM temperature and liquid nitrogen residual. In the deeper coal bed, coal particles take longer time to reach thermal equilibrium between their surface and inside. Air leakage accelerates temperature increase at the bottom of the coal bed, which is a major reason leading to fire prevention inefficiency. Measurement fluctuation of CPM temperature may be caused by incomplete contact of coal particles with liquid nitrogen flowing in the coal bed. Moreover, the secondary temperature drop (STD) happens and grows with the more injection of liquid nitrogen, and the STD phenomenon is explained through temperature distributions at different locations.

Structure optimization of tetrahydropyridoindole-based aldose reductase inhibitors improved their efficacy and selectivity

In our previous study, tetrahydropyridoindoles carboxymethylated in position 8 were identified as aldose reductase (ALR2) inhibitors with mild efficacy and selectivity yet with significant antioxidant activity. In the present study we proceeded with optimization of the tetrahydropyridoindole scaffold by shifting the carboxymethyl pharmacophore from position 8 to position 5, with the aim to improve the biological activity. Commercial databases were screened for the presence of tetrahydropyridoindoles carboxymethylated in position 5 and an experimental set of eight compounds was created. Mild inhibition characterized by IC50 in micromolar range was recorded for compound 8 with the isopropyl substituent at the piperidine nitrogen (position 2). This alkylated tertiary nitrogen is characterized by a rather high basicity (pKa ∼ 10.4) with complete protonization at physiological pH. On the other hand, ALR2 inhibition activity of the low basicity derivatives 3–7 with an acyl substituted nitrogen in position 2 (pKa ∼ −1 to −3) was characterized with IC50 values in low and medium nanomolar region. Docking into the binding site of human recombinant enzyme AKR1B1 performed for 3 revealed an interaction network responsible for the high affinity and selectivity. In ex vivo experiment, sorbitol accumulation in isolated rat eye lenses was significantly inhibited by 3 in the presence of high glucose, starting at a concentration as low as 0.1 μM. Moreover, in streptozotocin-induced diabetic rats, compound 3 administered intragastrically (i.g., 50 mg/kg/day) for five consecutive days significantly inhibited sorbitol accumulation in red blood cells and the sciatic nerve. Molecular obesity indices predicted along with water solubility point an excellent “lead-likeness” of compound 3, with prospects of further structure optimizations.

Designing Zn(II) complexes as a support of bifunctional liquid crystal and luminescent materials

Four series of 1-(pyridyl)-3-(alkyloxyphenyl)propane-1,3-dione type ligands, named L2N1, L2N2, L4N1 and L4N2, have been prepared and their thermal behaviour studied. These compounds have been classified on the basis of the position of the pyridinic nitrogen atom (2- or 4-position, 2N or 4N) and the number of alkyl chains at the phenyl substituent (one or two). In each family the alkyl chains are increased from 12 to 18 carbon atoms. In contrast with the absence of mesomorphism of the monocatenar ligands L2N1 and L4N1, the dicatenar ones L2N2 and L4N2 have been found to be liquid crystals exhibiting lamellar columnar mesophases (ColL). Those were established through the columnar ordering of disc-like molecules, which is achieved by the approach of the complementary shape between two hemidiscotic molecules. The crystalline structures of selected prototype compounds have been solved. The dicatenar ligands exhibit a dimeric structure with a disc-like shape, which is in agreement with the above mentioned ColL mesophase. By contrast, monomeric compounds having a hockey-stick shape are found for the monocatenar species, which were not liquid crystals. Reactions of those diketone-based ligands with Zn(II) dichloride afforded to four new families of Zn(II) compounds. Two of them, containing the monocatenar ligands, are liquid crystal materials, showing smectic A (SmA) mesophases and so, indicating that mesomophic behaviour is induced by complexation with the metal. However, the Zn(II) complexes carrying dicatenar ligands were not liquid crystal materials. Most of the Zn(II) complexes also exhibit green/blue emission at room temperature in solution. Additionally, the ionochromic behaviour of selected ligands towards Zn2+ and Cu2+ ions has also been proved. The results of both the mesomorphic and photoluminescence behaviours are established and compared as a function of the nitrogen position on the pyridine substituent as well as the number of pheripherical chains on the diketone ligand.

The role of annular nitrogen in tuning the reactivity of bifunctional platinum(II) complexes appended to pyridyl spacers; A kinetic and mechanistic investigation

A kinetic and mechanistic study on ligand substitution reactions of pyridine functionalized dinuclear Pt(II) complexes visa-viz., N,N,N’,N’-tetrakis(2-pyridyl)-2,3 pyridinediaminetetraquaplatinum(II) (PtL1); N,N,N’,N’-tetrakis(2-pyridyl)-2,4-pyridinediaminetetraquaplatinum(II) (PtL2); N,N,N’,N’-tetrakis(2-pyridyl)-2,6-pyridinediaminetetraquaplatinum(II) (PtL3); N,N,N’,N’-tetrakis(2-pyridyl)-2,5-pyridinediaminetetraquaplatinum(II) (PtL4) and N,N,N’,N’-tetrakis(2-pyridylaminomethyl)-2,6-pyridinediaminetetraquaplatinum(II) (PtL5) complexes with thiourea (TU), N,N’-dimethylthiourea (DMTU) and N,N,N’N’-tetramethylthiourea (TMTU) as the entering nucleophiles was carried out under pseudo-first-order conditions by stopped-flow and UV–Vis spectrophotometric techniques. Substitution reactions proceeds via a two-step pathway with the rate law kobs(1,2) = k2(1st/2nd)[Nu]. The first substitution step is attributed to simultaneous displacement of one water molecule at each platinum(II) center. The second step is attributed to the slow phase substitution of the second water molecule occurring concurrently with the slow displacement of the bridging linker. The steps were confirmed by 1H and 195Pt NMR spectroscopy. The reactivity of the complexes is governed by the position of the annular nitrogen in the pyridine spacer. The Low positive values of enthalpy of activation and significantly large negative values of entropy of activation parameters for both steps indicate an associative mechanism of substitution.

Measurement of protein backbone 13CO and 15N relaxation dispersion at high resolution

Peak overlap in crowded regions of two-dimensional spectra prevents characterization of dynamics for many sites of interest in globular and intrinsically disordered proteins. We present new three-dimensional pulse sequences for measurement of Carr-Purcell-Meiboom-Gill relaxation dispersions at backbone nitrogen and carbonyl positions. To alleviate increase in the measurement time associated with the additional spectral dimension, we use non-uniform sampling in combination with two distinct methods of spectrum reconstruction: compressed sensing and co-processing with multi-dimensional decomposition. The new methodology was validated using disordered protein CD79A from B-cell receptor and an SH3 domain from Abp1p in exchange between its free form and bound to a peptide from the protein Ark1p. We show that, while providing much better resolution, the 3D NUS experiments give the similar accuracy and precision of the dynamic parameters to ones obtained using traditional 2D experiments. Furthermore, we show that jackknife resampling of the spectra yields robust estimates of peak intensities errors, eliminating the need for recording duplicate data points.

Smart activatable and traceable dual-prodrug for image-guided combination photodynamic and chemo-therapy.

Activatable photosensitizers (PSs) and chemo-prodrugs are highly desirable for anti-cancer therapy to reduce systemic toxicity. However, it is difficult to integrate both together into a molecular probe for combination therapy due to the complexity of introducing PS, singlet oxygen quencher, chemo-drug, chemo-drug inhibitor and active linker at the same time. To realize activatable PS and chemo-prodrug combination therapy, we develop a smart therapeutic platform in which the chemo-prodrug serves as the singlet oxygen quencher for the PS. Specifically, the photosensitizing activity and fluorescence of the PS (TPEPY-SH) are blocked by the chemo-prodrug (Mitomycin C, MMC) in the probe. Meanwhile, the cytotoxicity of MMC is also inhibited by the electron-withdrawing acyl at the nitrogen position next to the linker. Upon glutathione activation, TPEPY-S-MMC can simultaneously release active PS and MMC for combination therapy. The restored fluorescence of TPEPY-SH is also used to report the activation for both PS and MMC as well as to guide the photodynamic therapy.

Antiparasitic activity against trypanosomatid diseases and novel metal complexes derived from the first time characterized 5-phenyl-1,2,4-triazolo[1,5-a]pyrimidi-7(4H)-one

A serie of isostructural complexes with general formula [M(ftpO)2(H2O)4] have been obtained from reaction between the first time characterized triazolopyrimidine derivative 5-phenyl-1,2,4-triazolo[1,5-a]pyrimidi-7(4H)-one (HftpO) (1) and first row transition nitrates (M=Cu (2), Co (3), Ni (4) and Zn (5)). A copper complex with formula [Cu(HftpO)2(NO3)2(H2O)2]·H2O (6) was also isolated. HftpO and their metal complexes have been characterized by spectroscopic and thermal analysis and their crystal structures have been solved by X-ray diffraction methods. The isostructural compounds are mononuclear complexes where the triazolopyrimidine ligand acts as monodentate ligand through N3 nitrogen position. The crystal structure of these novel bis-5-phenyl-1,2,4-triazolo[1,5-a]pyrimidin-7(4H)-one-tetraaquo metal complexes offers an excellent opportunity at these complexes to acts as potential building blocks. Also, the antiparasitic activity of HftpO ligand against different leishmania and trypanosome strains has been studied.

Overview on Developed Synthesis Methods of Triazepane Heterocycles

Triazepanes are important seven‐membered heterocyclic compounds with nitrogen at different positions in the ring, and have many pharmaceutical activities. Compounds with the triazepane core have attracted much attention as a result of their interesting biological properties. A study of the literature shows that there are various methods for the preparation of triazepanes. In this review, we have classified the methods based on the nitrogen position in the final triazepine products into four triazepine classes, namely TAP‐1,2,3, TAP‐1,2,4, TAP‐1,2,5, and TAP‐1,3,5.

Cationic dipyridylamine substituted zinc tetrapyrazinoporphyrazine derivatives for photodynamic therapy

Two kinds of cationic zinc tetrapyrazinoporphyrazine derivatives substituted with ortho- or para- methylpyridinium groups on the peripheral position were synthesized and characterized. The solubility and aggregation behavior of each material were estimated in various solvents, which show different aspect depending on the position of nitrogen on methylpyridinium groups. The fluorescence quantum yield (ΦF) values of both cationic tetrapyrazinoporphyrazines were measured and the singlet oxygen quantum (ΦΔ) yield value were measured by indirect method with DPBF (1,3-diphenylisobenzofuran) in DMSO. Both ΦF and ΦΔ of cationic zinc tetrapyrazinoporphyrazine derivatives exhibited reasonable values for photodynamic therapy application. The cationic zinc tetrapyrazinoporphyrazine derivatives substituted methylpyridinium groups increased solubility in aqueous solvent but also showed the suitable properties as the photosensitizers for photodynamic therapy.

Modular Approach to Tricyclic Heterocycles through Copper Catalysis and Functionalization by Palladium‐Catalyzed C–H Arylation

A copper‐catalyzed Ullman reaction accompanied with oxidative C–N bond formation was used to access tricyclic heterocycles in a one‐pot operation by using atmospheric air as the terminal oxidant. This modular synthesis approach was used to synthesize previously known and novel azole‐containing heterocycles with different nitrogen position isomers. Fused heterocycles were further functionalized by palladium‐catalyzed direct C–H arylation methodology. Various electron‐rich and electron‐poor functional groups were tolerated in the ortho, meta, and para positions of the aryl bromides.

Mechanisms of Energy Transfer and Enhanced Stability of Carbidonitride Phosphors for Solid-State Lighting

Phosphor-converted light emitting diodes (pcLEDs) produce white light through the use of phosphors that convert blue light emitted from the LED chip into green and red wavelengths. Understanding the mechanisms of degradation of the emission spectra and quantum yields of the phosphors used in pcLEDs is of critical importance to fully realize the potential of solid-state lighting as an energy efficient technology. Toward this end, time-resolved photoluminescence spectroscopy was used to identify the mechanistic origins of enhanced stability and luminescence efficiency that can be obtained from a series of carbidonitride red phosphors with varying degrees of substitutional carbon. The increasing substitution of carbon and oxygen in nitrogen positions of the carbidonitride phosphor (Sr2Si5N8-[(4x/3)+z]CxO3z/2:Eu2+) systematically changed the dimensions of the crystalline lattice. These structural changes caused a red shift and broadening of the emission spectra of the phosphors due to faster energy transfer from higher to lower energy emission sites. Surprisingly, in spite of broadening of the emission spectra, the quantum yield was maintained or increased with carbon substitution. Aging phosphors with lowered carbon content under conditions that accurately reflected thermal and optical stresses found in functioning pcLED packages led to spectral changes that were dependent on substitutional carbon content. Importantly, phosphors that contained optimal amounts of carbon and oxygen possessed luminescence spectra and quantum yields that did not undergo changes associated with aging and therefore provided a more stable color point for superior control of the emission properties of pcLED packages. These findings provide insights to guide continued development of phosphors for efficient and stable solid-state lighting materials and devices.

Sub-nanometer resolution XPS depth profiling: Sensing of atoms

The development of a method capable of distinguishing a single atom in a single molecule is important in many fields. The results reported herein demonstrate sub-nanometer resolution for angularly resolved X-ray photoelectron spectroscopy (ARXPS). This is made possible by the incorporation of a Maximum Entropy Method (MEM) model, which utilize density corrected electronic emission factors to the X-ray photoelectron spectroscopy (XPS) experimental results.In this paper we report on the comparison between experimental ARXPS results and reconstructed for both inorganic and organic thin film samples. Unexpected deviations between experimental data and calculated points are explained by the inaccuracy of the constants and standards used for the calculation, e.g. emission factors, scattering intensity and atomic density through the studied thickness.The positions of iron, nitrogen and fluorine atoms were determined in the molecules of the studied self-assembled monolayers. It has been shown that reconstruction of real spectroscopic data with 0.2nm resolution is possible.

Synthesis of Azanucleosides by Anodic Oxidation in a Lithium Perchlorate–Nitroalkane Medium and Diversification at the 4′‐Nitrogen Position

Azanucleosides, in which the 4'-oxygen atom has been replaced with a nitrogen atom, have drawn much attention owing to their anticancer and antivirus activity, and tolerance towards nucleases. However, the traditional synthetic strategy requires multiple steps and harsh conditions, thereby limiting the structural and functional diversity of the products. Herein we describe the synthesis of azanucleosides by an electrochemical reaction in a lithium perchlorate-nitroethane medium, followed by postmodification at the 4'-N position. N-Acryloyl prolinol derivatives were converted into azanucleosides by anodic activation of the N-α-C-H bond. Moreover, the use of nitroethane instead of nitromethane lowered the oxidation potential of the N-acryloyl prolinols and increased the Faradic yield. The prepared azanucleosides were efficiently functionalized at the 4'-N-acryloyl group with a lipophilic alkanethiol and a fluorescent dye by conjugate addition and olefin cross-metathesis, respectively.

Synthesis of Azanucleosides by Anodic Oxidation in a Lithium Perchlorate–Nitroalkane Medium and Diversification at the 4′‐Nitrogen Position

AbstractAzanucleosides, in which the 4′‐oxygen atom has been replaced with a nitrogen atom, have drawn much attention owing to their anticancer and antivirus activity, and tolerance towards nucleases. However, the traditional synthetic strategy requires multiple steps and harsh conditions, thereby limiting the structural and functional diversity of the products. Herein we describe the synthesis of azanucleosides by an electrochemical reaction in a lithium perchlorate–nitroethane medium, followed by postmodification at the 4′‐N position. N‐Acryloyl prolinol derivatives were converted into azanucleosides by anodic activation of the N‐α‐C−H bond. Moreover, the use of nitroethane instead of nitromethane lowered the oxidation potential of the N‐acryloyl prolinols and increased the Faradic yield. The prepared azanucleosides were efficiently functionalized at the 4′‐N‐acryloyl group with a lipophilic alkanethiol and a fluorescent dye by conjugate addition and olefin cross‐metathesis, respectively.

Near-UV Photodissociation of Tryptic Peptide Cation Radicals. Scope and Effects of Amino Acid Residues and Radical Sites.

Peptide cation-radical fragment ions of the z-type, [●AXAR+], [●AXAK+], and [●XAR+], where X = A, C, D, E, F, G, H, K, L, M, N, P, Y, and W, were generated by electron transfer dissociation of peptide dications and investigated by MS3-near-ultraviolet photodissociation (UVPD) at 355 nm. Laser-pulse dependence measurements indicated that the ion populations were homogeneous for most X residues except phenylalanine. UVPD resulted in dissociations of backbone CO─NH bonds that were accompanied by hydrogen atom transfer, producing fragment ions of the [yn]+ type. Compared with collision-induced dissociation, UVPD yielded less side-chain dissociations even for residues that are sensitive to radical-induced side-chain bond cleavages. The backbone dissociations are triggered by transitions to second (B) excited electronic states in the peptide ion R-CH●-CONH- chromophores that are resonant with the 355-nm photon energy. Electron promotion increases the polarity of the B excited states, R-CH+-C●(O-)NH-, and steers the reaction to proceed by transfer of protons from proximate acidic Cα and amide nitrogen positions. Graphical Abstract ᅟ.

Theoretical Design of a New Allosteric Switch and Fluorescence Chemosensor Double Functional Devices of Aza-Crown Ether

A novel molecular device (trans-azobenzene embedded N-(11-pyrenyl methyl)aza-21-crown-7) with double functional devices was designed on the basis of theoretical calculations. Pyrenyl methyl covalently bonded to aza-21-crown-7 at the nitrogen position interacting with a series of alkaline-earth metal cations (Mg2+, Ca2+, Sr2+, and Ba2+) was investigated. The fully optimized geometries and real frequency calculations were investigated using a computational strategy based on density functional theory at B3LYP/6-31G(d) level. Free ligand (L) and their metal cation complexes (L/M2+) were studied using mixed basis set (6-31G(d) for the atoms C, H, O, and N and LANL2DZ for alkaline-earth metal cations Mg2+, Ca2+, Sr2+, and Ba2+. The natural bond orbital analysis that is based on optimized geometric structures was used to explore the interaction of L/M2+ molecules. The absorption spectra of L and L/M2+, excitation energies, and absorption wavelength for their excited states were studied by time-dependent density ...

Flying-seed-like liquid crystals 7: Synthesis and mesomorphism of novel octakis(m-chloropyridyloxy) phthalocyanato copper(II) complexes

We have synthesized three novel octakis([Formula: see text]-chloropyridyloxy)phthalocyaninato copper(II) complexes, [x-PyO(m-Cl)][Formula: see text]PcCu([Formula: see text] [Formula: see text] 2, 3, 4: 2a–2c), keeping a chlorine atom at the meta position on the 2-, 3- and 4-pyridyloxy group, in which the nitrogen atom is located at the 2-, 3- and 4-positions, respectively. Their phase transition behavior and the mesophase structure have been established by using a polarizing optical microscope, a differential scanning calorimeter, and a temperature-dependent small angle X-ray diffractometer. Very interestingly, the mesomorphism appears with strong dependence of the position of nitrogen in [Formula: see text]-chloropyridyloxy group. The derivative [3-PyO(m-Cl)][Formula: see text]PcCu (2b) introduced a nitrogen atom at the 3-position is not mesogenic but crystalline. On the other hand, the derivative [2-PyO(m-Cl)][Formula: see text]PcCu (2a) introduced a nitrogen atom at the 2-position shows columnar mesomorphism only at very high temperatures over 325°C. The derivative [4-PyO(m-Cl)][Formula: see text]PcCu (2c) introduced a nitrogen atom at the 4-position shows columnar mesomorphism in a very wide temperature region from rt to the decomposition temperature at 306°C. From the viewpoint of N…Cl halogen bond, we have discussed about relationship between their mesomorphism and the position of nitrogen atom in [Formula: see text]-chloropyridyloxy group.

Perturbation of cationic equilibrium by cucurbit-7-uril.

The effect of cucurbit-7-uril (CB-7) on a cationic mixture with same charge has been investigated by studying monocationic mixtures of 2-(4'-N,N-dimethylaminophenyl)imidazo[4,5-b]pyridine (DMAPIP-b) and 2-(4'-N,N-dimethylaminophenyl)imidazo[4,5-c]pyridine (DMAPIP-c). The pKa of both the guests increases in CB-7. DMAPIP-b forms all three monocations in the ground and the excited states in aqueous as well as in CB-7 solution. However, CB-7 shifts the equilibrium more towards the less polar MC2 and MC3. On the other hand, DMAPIP-c exists only as MC1 and MC3 in aqueous solution, however, in CB-7 it exists not only as MC1 and MC3 but also as MC2 in CB-7 in the ground state. In the excited state, as in aqueous solution MC1 forms MC2 by biprotonic phototautomerism in CB-7. The association constants of monocations suggest a pyridyl nitrogen position dependence. All the MC-CB-7 complexes are optimized by density functional theory (DFT).