Central Pyrazine Ring Research Articles

Second-order nonlinear optical properties of X-shaped pyrazine derivatives.

This work reports an investigation of the second-order NLO properties of two isomer series of X-shaped pyrazine derivatives, by means of HRS measurements and DFT calculations. The systems differ in the relative position of the donor and acceptor substituents with respect to the axis formed by the nitrogen atoms of the central pyrazine ring. Although the magnitude of the second harmonic signal is similar, HRS measurements revealed that the anisotropy of the NLO response strongly differs in the two chromophore series, the one of the 2,3-isomers being strikingly dipolar, while the one of the 2,6-isomers is mostly octupolar. The experimental observations are well supported by DFT calculations. In particular, the sum-over-states approach allows us to rationalize the different NLO anisotropies observed in the two isomer series through a detailed analysis of the symmetry of the low-lying excited states.

Cytochrome c oxidase is one of the key enzymes providing the ability to produce phenazines in Pseudomonas chlororaphis subsp. aurantiaca.

Phenazines are heteroaromatic compounds consisting of a central pyrazine ring fused with two benzenes. Different functional groups attached to the dibenzopyrasin core cause differences in the chemical, physical, and biological properties of phenazines. Interest in these compounds has not diminished for decades. New biological activities and practical applications discovered in recent years force researchers to investigate all aspects of the synthesis, degradation, and mechanisms of action of phenazines. In this study, we have demonstrated the involvement of the coxA gene product (cytochrome c oxidase, su I) in the production of phenazines in P. chlororaphis subsp. aurantiaca. Overlap PCR was used to knock out the coxA gene and the resulting mutants were screened for their ability to grow on rich and minimal culture media and for phenazine production. The reintroduction of the full-length coxA gene into the B-162/coxA strains was used to further confirm the role of this gene product in the ability to produce phenazines. We were able to show that the product of the coxA gene is necessary for phenazine production in rich growth media. At the same time, the CoxA protein does not seem to have any effect on phenazine production in M9 minimal salt medium. We could show that knocking down even one subunit of the cytochrome c oxidase complex leads to a significant reduction (to trace concentrations) or complete suppression of phenazine antibiotic production on rich PCA medium in P. chlororaphis subsp. aurantiaca.

Silver(I) nitrate two-dimensional coordination polymers of two new pyrazine-thio-phane ligands: 5,7-di-hydro-1H,3H-dithieno[3,4-b:3',4'-e]pyrazine and 3,4,8,10,11,13-hexa-hydro-1H,6H-bis-([1,4]di-thio-cino)[6,7-b:6',7'-e]pyrazine.

The two new pyrazine-ophanes, 5,7-di-hydro-1H,3H-dithieno[3,4-b:3',4'-e]pyrazine, C8H8N2S2, L1, and 3,4,8,10,11,13-hexa-hydro-1H,6H-bis-([1,4]di-thio-cino)[6,7-b:6',7'-e]pyrazine, C12H16N2S4, L2, both crystallize with half a mol-ecule in the asymmetric unit; the whole mol-ecules are generated by inversion symmetry. The mol-ecule of L1, which is planar (r.m.s. deviation = 0.008 Å), consists of two sulfur atoms linked by a rigid tetra-2,3,5,6-methyl-ene-pyrazine unit, forming planar five-membered rings. The mol-ecule of L2 is step-shaped and consists of two S-CH2-CH2-S chains linked by the central rigid tetra-2,3,5,6-methyl-ene-pyrazine unit, forming eight-membered rings that have twist-boat-chair con-fig-urations. In the crystals of both compounds, there are no significant inter-molecular inter-actions present. The reaction of L1 with silver nitrate leads to the formation of a two-dimensional coordination polymer, poly[(μ-5,7-di-hydro-1H,3H-dithieno[3,4-b;3',4'-e]pyrazine-κ2 S:S')(μ-nitrato-κ2 O:O')silver(I)], [Ag(NO3)(C8H8N2S2)] n , (I), with the nitrato anion bridging two equivalent silver atoms. The central pyrazine ring is situated about an inversion center and the silver atom lies on a twofold rotation axis that bis-ects the nitrato anion. The silver atom has a fourfold AgO2S2 coordination sphere with a distorted shape. The reaction of L2 with silver nitrate also leads to the formation of a two-dimensional coordination polymer, poly[[μ33,4,8,10,11,13-hexa-hydro-1H,6H-bis-([1,4]di-thio-cino)[6,7-b;6',7'-e]pyrazine-κ3 S:S':S''](nitrato-κO)silver(I)], [Ag(NO3)(C12H16N2S4)] n , (II), with the nitrate anion coordinating in a monodentate manner to the silver atom. The silver atom has a fourfold AgOS3 coordination sphere with a distorted shape. In the crystals of both complexes, the networks are linked by C-H⋯O hydrogen bonds, forming supra-molecular frameworks. There are additional C-H⋯S contacts present in the supra-molecular framework of II.

Syntheses and crystal structures of a new pyrazine dicarboxamide ligand, N 2,N 3-bis-(quinolin-8-yl)pyrazine-2,3-dicarboxamide, and of a copper perchlorate binuclear complex.

The title pyrazine dicarboxamide ligand, N 2,N 3-bis-(quinolin-8-yl)pyrazine-2,3-dicarboxamide (H2L1), C24H16N6O2, has a twisted conformation with the outer quinoline groups being inclined to the central pyrazine ring by 9.00 (6) and 78.67 (5)°, and by 79.94 (4)° to each other. In the crystal, molecules are linked by C-H⋯O hydrogen bonds, forming layers parallel to the (10) plane, which are in turn linked by offset π-π inter-actions [inter-centroid distances 3.4779 (9) and 3.6526 (8) Å], forming a supra-molecular three-dimensional structure. Reaction of the ligand H2L1 with Cu(ClO4)2 in aceto-nitrile leads to the formation of the binuclear complex, [μ-(3-{hy-droxy[(quinolin-8-yl)imino]-meth-yl}pyrazin-2-yl)[(quinolin-8-yl)imino]-methano-lato]bis-[diaceto-nitrile-copper(II)] tris-(per-chlor-ate) aceto-nitrile disolvate, [Cu2(C24H15N6O2)(CH3CN)4](ClO4)3·2CH3CN or [Cu2(HL1-)(CH3CN)4](ClO4)3·2CH3CN (I). In the cation of complex I, the ligand coordinates to the copper(II) atoms in a bis-tridentate fashion. A resonance-assisted O-H⋯O hydrogen bond is present in the ligand; the position of this H atom was located in a difference-Fourier map. Both copper(II) atoms are fivefold coordinate, being ligated by three N atoms of the ligand and by the N atoms of two aceto-nitrile mol-ecules. The first copper atom has a perfect square-pyramidal geometry while the second copper atom has a distorted shape. In the crystal, the cation and perchlorate anions are linked by a number of C-H⋯O hydrogen bonds, forming a supra-molecular three-dimensional structure.

Synthesis and Aldose Reductase Inhibitory Activity of Botryllazine A Derivatives.

Aldose reductase (AR) is associated with the onset of diabetic complications. Botryllazine A and its analogues were synthesized and evaluated for human AR inhibitory activity. Analogues possessing aromatic bicyclic systems at the C5 position of the central pyrazine ring exhibited superior AR inhibiting activity relative to the parent botryllazine A. In addition, the benzoyl groups at positions C2 and C3 of the pyrazine ring were dispensable for this improved inhibitory activity. Conversely, a benzoyl group-containing phenolic hydroxyl groups-at either position C2 or C3 of the pyrazine ring was essential for attainment of high inhibitory activity approaching that of sorbinil (a highly effective AR inhibitor).

Selective carbon dioxide sorption and heterogeneous catalysis by a new 3D Zn-MOF with nitrogen-rich 1D channels

We prepared a new C2h-symmetric bridging ligand, 3,3′-(pyrazine-2,5-diyl)dibenzoic acid (3,3′-PDBA), through a Suzuki coupling reaction. 3,3′-PDBA contains a central pyrazine ring instead of the phenyl ring of 3,3′-terphenyldicarboxylic acid (3,3′-TPDC). Despite the geometrical similarity of the two bridging ligands, the reaction between Zn(NO3)2·6H2O and 3,3′-PDBA in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) yielded a structurally different Zn-based metal-organic framework (Zn-MOF). The Zn-MOF, [Zn2(3,3′-PDBA)2(DABCO)1.5]·2DMF·H2O, had two-dimensional (2D) layers, and the interlocked 2D layers formed a porous 3D framework. Interestingly, one of the two available N atoms of DABCO remained intact. The uncoordinated N atoms of the dangling DABCO ligand and the pyrazinyl N atoms of the 3,3′-PDBA bridging ligand were fully exposed toward the 1D channels. Therefore, the 1D channels represented a highly nitrogen-rich environment. Gas sorption analysis indicated that the Zn-MOF was selective for adsorption of CO2 at 196 K over N2 (77 K) and H2 (77 K). The exceptionally high zero surface coverage heat of CO2 adsorption (Qst = 79.5 kJ mol−1) was attributable to the openly accessible multiple Lewis basic sites in the nitrogen-rich 1D channels. Zn-MOF also showed good Lewis base catalytic activities in three model aldol-type reactions with good recyclability due to chemically accessible 3° amine sites.

N,N′-Bis(pyrazin-2-ylmethyl)pyrazine-2,3-dicarboxamide

The title compound, C16H14N8O2, was prepared by a condensation reaction between the dimethyl ester of pyrazine-2,3-dicarboxylic acid and an excess of 2-(aminomethyl)pyrazine. The molecule is approximately V-shaped with the central pyrazine ring joined through amide linkages to two pyrazin-2-ylmethyl substituents. In the crystal, molecules are linked by N—H...O, N—H...N and C—H...O hydrogen bonds, forming a three-dimensional framework.

Structurally Diverse Polynuclear Copper(I) Complexes Bridged by Pyrimidine–, Pyrazine–, and Triazine–based Ligands with Several 2–Pyridyl Groups

AbstractThe reactions of [Cu(MeCN)4]BF4 or [Cu(C2H4)n]ClO4 complexes with 4,6–bis(2–pyridyl)pyrimidine (bppym) in Me2CO under C2H4 afforded dinuclear Cu(I)–bppym/C2H4 adducts [Cu2‐(bppym)(C2H4)2](BF4)2•Me2CO (1) and [Cu2(bppym)2(C2H4)2](ClO4)2•Me2CO (2), respectively. One Cu(I) atom is coordinated by bppym and C2H4 in a distorted trigonal–planar geometry. The other Cu(I) atom is coordinated by bppym, Me2CO, and C2H4 toward a distorted tetrahedral geometry. The reaction of [Cu(MeCN)4]BF4 with 2,3–bis(2–pyridyl)pyrazine (bppz) in MeOH under C2H4 afforded a Cu(I)–bppz coordination polymer {[Cu2(bppz)2](BF4)2•MeOH}n (3). Two Cu(I) atoms are alternately bridged by two bppz to form a 1–D zigzag–chain structure. Each Cu(I) coordination sphere is largely distorted from a normal tetrahedral structure toward a square planar structure. The reaction of [Cu(MeCN)4]PF6 with 2,4,6–tris(2–pyridyl)–s–triazine (tptz) in MeEtCO under C2H4 afforded a tetranuclear Cu(I)–tptz/C2H4 adduct [Cu4(tptz)2(C2H4)2(MeCN)2](PF6)4•MeEtCO (4 b). Two Cu(I) atoms are bridged by the central triazine ring, the 2–pyridyl group, the central triazine ring, and the 2–pyridyl group in a different tptz to form a double helical structure. The other Cu(I) atom is coordinated by the central triazine ring, the 2–pyridyl group, MeCN, and C2H4 in a distorted tetrahedral geometry. The reaction of [Cu(MeCN)4]PF6 with tetra–2–pyridylpyrazine (tppz) in MeOH under C2H4 afforded a tetranuclear Cu(I)–tppz complex [Cu4(tppz)2(MeCN)4](PF6)4•MeOH (5 a). Each Cu(I) atom is coordinated by the central pyrazine ring, the 2–pyridyl group, the 2–pyridyl group in a different tppz, and MeCN in a distorted tetrahedral geometry. These four Cu(I) atoms are bridged by the two opposite tppz ligands to form a unique tetranuclear Cu(I) cage structure.

Crystal structure of 2,5-bis-(4-methyl-pyridin-2-yl)pyrazine chloro-form disolvate.

The heterocyclic molecule in the title solvate, C16H14N4·2CHCl3, possesses inversion symmetry, with the inversion centre situated at the centre of the pyrazine ring. The outer pyridine rings are inclined to the central pyrazine ring by 4.89 (9)°. The compound crystallized as a chloro­form disolvate with the solvent mol­ecules linked to the title mol­ecule by C—H⋯N hydrogen bonds. In the crystal, mol­ecules are further linked by π–π inter­actions involving the pyrazine and pyridine rings of neighbouring mol­ecules [inter-centroid distance = 3.5629 (12) Å; symmetry code: x, y + 1, z + 1].

Dividing the Spoils: Role of Pyrazine Ligands and Perchlorate Counterions in the Magnetic Properties of Bis(pyrazine)diperchloratecopper(II), [Cu(pz)2](ClO4)2

A complete first-principles bottom-up computational study of the magnetic properties of [Cu(pz)2](ClO4)2 is presented. A remarkable agreement is observed in the whole range of temperatures between simulated and experimental magnetic susceptibility data. Interestingly, the simulated heat capacity values show an anomaly close to the Néel temperature of 4.21 K associated with a transition from a two-dimensional (2D) antiferromagnet to a three-dimensional (3D) ordered state. The antiferromagnetic behavior of [Cu(pz)2](ClO4)2 is due to a 2D magnetic topology owing to two antiferromagnetic J(AB) interactions through pyrazine ligands. Although presenting a very similar molecular arrangement, the numerical values of the two magnetically significant J(AB) couplings differ by 25% (-10.2 vs -7.3 cm(-1)). This difference can be ascribed to three main contributions: (i) the central pyrazine ring shearing-like distortion, (ii) the effect of the orientation of the perchlorate counterions, and (iii) a hitherto unrecognized skeleton-counterion cooperation arising from different hydrogen bonding contributions in the two most significant J(AB) couplings. The impact of the orientation of the perchlorate counterions is disclosed by comparison to J(AB) studies using structurally similar ligands but with different electronegativity (namely, BF4(-), BCl4(-), and BBr4(-)). Pyrazine ligands and perchlorate counterions prove to be noninnocent.

ChemInform Abstract: Cephalostatins and Ritterazines

AbstractReview: 146 refs.

Bis(μ-azido-κ2N1:N1)bis{(acetato-κ2O,O′)[2,4,6-tris(2-pyridyl)-1,3,5-triazine-κ3N2,N1,N6]lead(II)}

The complete dinuclear title complex, [Pb2(C2H3O2)2(N3)2(C18H12N6)2], is generated by the application of a crystallographic centre of inversion. The PbII atom is coordinated by three N atoms of the tridentate ligand, two O atoms derived from an asymmetrically coordinating acetate ligand, and two azido-N atoms derived from two asymmetrically bridging azido ligands. The metal coordination geometry can be described as a square anti-prism with one position occupied by an unseen lone pair of electrons. In the ligand, the two coordinating pyridine rings are almost co-planar with the central pyrazine ring [dihedral angles = 0.47 (17) and 0.83 (18)°], but the terminal ring is twisted [dihedral angle = 19.76 (18)°]. In the crystal, the presence of π–π inter­actions [ring centroid distance between pyridyl rings = 3.581 (2) Å] leads to supra­molecular chains along the a-axis direction.

(E,E,E,E)-2,3,5,6-Tetrakis{2-[4-(dimethylamino)phenyl]ethenyl}pyrazine

In the title compound, C44H48N6, the essentially planar mol­ecule [maximum deviation from the mean plane of the π system of 0.271 (3) Å] is located on a crystallographic centre of inversion. The almost planar (angle sums at N atoms = 357.6 and 357.1°) dimethyl­amino groups and short C—N bonds of the aniline groups [both 1.379 (4) Å] indicate strong electronic coupling between these groups and the central pyrazine ring.

2,5-Bis[4-(dimethylamino)phenyl]-3,6-dimethylpyrazine

The title compound, C22H26N4, was prepared from p-dimethyl­amino­propiophenone in six steps. The mol­ecule has no crystallographic symmetry. The dihedral angles between the pyrazine ring and the phenyl rings are 35.81 (6) and 37.11 (8)°. The dimethyl­amino groups are essentially planar (sum of the bond angles at N = 359.3 and 359.9°) and nearly coplanar with the adjacent aromatic ring [dihedral angles = 5.54 (11) and 7.40 (3)°]. This effect and the short aniline C—N bonds can be rationalised in terms of charge transfer from the amino groups to the central pyrazine ring.

Diiodido(2,3,5,6-tetrapyridin-2-yl-pyrazine-κN,N,N)zinc(II).

In the title compound, [ZnI2(C24H16N6)], the ZnII ion is five-coordinated in a distorted trigonal-bipyramidal geometry by an N,N,N-tridentate 2,3,5,6-tetra-2-pyridinylpyrazine ligand and two iodide ions. The I− ions both occupy equatorial sites. Within the ligand, the dihedral angles between the central pyrazine ring and the two chelating pyridine (py) rings are 14.74 (17) and 26.72 (18)°. The equivalent angles for the non-coordinating py rings are 28.63 (16) and 42.19 (17)°. There is no aromatic π–π stacking in the crystal.

1,2,4,5-Tetrafluoro-3,6-diiodobenzene–2,3-bis(pyridin-2-yl)pyrazine (1/1)

The components of the title 1:1 co-crystal, C14H10N4·C6F4I2, are connected via an N⋯I [2.959 (4) Å] halogen bond, in which the N atom is part of the relatively electron-rich pyrazine ring. The C6F4I2 mol­ecule is almost planar [r.m.s. deviation = 0.038 Å] but there are significant twists in the pyrazine derivative, as seen in the dihedral angles [31.3 (2) and 54.6 (2)°] formed between the pendant pyridyl rings and the central pyrazine ring. The bimolecular aggregates are sustained in the crystal by C—H⋯F and π–π inter­actions [ring centroid(pyrid­yl)–ring centroid(benzene) = 3.678 (3) Å].

Carboxylate Tolerance of the Redox-Active Platform [Ru(μ-tppz)Ru]n, where tppz = 2,3,5,6-Tetrakis(2-pyridyl)pyrazine, in the Electron-Transfer Series [(L)ClRu(μ-tppz)RuCl(L)]n,n= 2+, +, 0, −, 2−, with 2-Picolinato, Quinaldato, and 8-Quinolinecarboxylato Ligands (L−)

The neutral title complexes [(L(1-3))ClRu(II)(mu-tppz)Ru(II)Cl(L(1-3))] [tppz = 2,3,5,6-tetrakis(2-pyridyl)pyrazine with L(1) = 2-picolinate, L(2) = 2-quinolinecarboxylate (quinaldate) and with the hitherto little used L(3) = 8-quinolinecarboxylate] have been structurally characterized as approximately anti- (1 and 3) and syn-configured isomers (2) with L ligand N (1 and 3) or O atoms (2) trans to the pyrazine N atoms of tppz. In contrast to 1 and 2 with five-membered chelate rings, complex 3 (which is isomeric with 2) contains six-membered chelate rings. Each system 1-3 thus features a significantly different coordination situation, and all complexes exhibit a considerably distorted tppz bridge, including a twisted central pyrazine ring. In spite of this, double one-electron reduction of the bridge is always possible, as is evident from electron paramagnetic resonance (EPR) and UV/vis spectroelectrochemistry. Two separate (DeltaE approximately 0.4 V and K(c) approximately 10(7)) one-electron oxidations occur on the metals, producing invariably EPR-silent (4 K) Ru(III)Ru(II) intermediates with moderately intense near-IR absorptions, ranging from 1500 to 1900 nm. IR spectroelectrochemistry of the carboxylato carbonyl stretching bands did not result in any noticeable shift, in contrast to what was observed with dipyridyl ketones and related coligands. Density functional theory (DFT)/time-dependent DFT calculations confirm the experimental structures and explain the noted spectroscopic trends: destabilized and closer-spaced frontier orbitals for 3 over 2, with the comparison to 1 suggesting that the configuration is a major factor. Nevertheless, the rather unperturbed electronic structure of the [Ru(mu-tppz)Ru](n) entity, despite different coordination situations at the metal sites, is remarkable and suggests further use of this entity as a robust, carboxylate-tolerant redox-active platform in extended frameworks.

Oxidation of 5,6-Diamino-1,3-dimethyl-2,4-dioxopyrimidine by Perrhenate: the crystal structure of 1,3,6,8-Tetramethylpyrimidopteridine-2,4,5,7-tetrone

The oxidation of 5,6-diamino-1,3-dimethyl-2,4-dioxopyrimidine (H2ddd) by perrhenate (ReO4-) led to the formation of 1,3-dimethylalloxan, which condenses with unoxidized H2ddd to yield the product 1,3,6,8-tetramethylpyrimidopteridine-2,4,5,7-tetrone (tppt). The structure of tppt consists of a central pyrazine ring and two terminal pyrimidine rings in cis positions. The dihedral angles between the pyrazine and pyrimidine rings are 1.08° and 1.20°.

3-[(E)-4-(2-Nitrophenyl)vinyl]-1-(trifluoromethyl)-1,2,4-triazolo[4,3-a]quinoxaline

In the title mol­ecule, C18H10F3N5O2, the 1,2,4-triazolo[4,3-a]quinoxaline unit is nearly planar. The central pyrazine ring makes dihedral angles of 1.67 (6) and 2.44 (5)° with the 1,2,4-triazole and fused benzene ring, respectively. The nitro­phenyl ring makes dihedral angles of 2.82 (6), 3.15 (6) and 3.63 (6)° with the triazole, pyrazine and benzene rings, respectively. The nitro group is slightly twisted away from the plane of the attached benzene ring. C—H⋯O and C—H⋯F hydrogen bonds are found in the crystal structure.

Discovery of 3,3‘-(2,4-Diaminopteridine-6,7-diyl)diphenol as an Isozyme-Selective Inhibitor of PI3K for the Treatment of Ischemia Reperfusion Injury Associated with Myocardial Infarction

In studies aimed toward identifying effective and safe inhibitors of kinase signaling cascades that underlie ischemia/reperfusion (I/R) injury, we synthesized a series of pteridines and pyridopyrazines. The design strategy was inspired by the examination of naturally occurring PI3K inhibitors such as wortmannin and quercetin, and building a pharmacophore-based model used for optimization. Structural modifications led to hybrid molecules which incorporated aminopyrimidine and aminopyridine moieties with ATP mimetic characteristics into the pharmacophore motifs to modulate kinase affinity and selectivity. Elaborations involving substitutions of the 2 and 4 positions of the pyrimidine or pyridine ring and the 6 and 7 positions of the central pyrazine ring resulted in in vivo activity profiles which identified potent inhibitors of vascular endothelial growth factor (VEGF) induced vascular leakage. Pathway analysis identified a diaminopteridine-diphenol as a potent and selective phosphatidylinositol-3-kinase (PI3K) inhibitor. The structure-activity relationship studies of various analogues of diaminopteridine-diphenol-based on biochemical assays resulted in potent inhibitors of PI3K.