Synthesis and photophysical properties of azuleno[1′,2′:4,5]pyrrolo[2,1-b]quinazoline-6,14-diones: Azulene analogs of tryptanthrin

Azulene analog of tryptanthrin, azuleno[1′,2′:4,5]pyrrolo[2,1-b]quinazoline-6,14-dione, was successfully prepared by the condensation reaction of azuleno[2,1-b]pyrrole-2,3-dione with isatoic anhydride in the presence of sodium hydride or diisopropylethylamine (DIPEA). Its 2-halo derivatives were also obtained in high yields by the condensation reaction with 5-haloisatoic anhydrides in the presence of DIPEA. Reactivity toward electrophilic reagents was revealed by halogenation with N-bromosuccinimide (NBS) or N-iodosuccinimide (NIS) to afford 12-halo derivatives in high yields. Among the halo derivatives, 2-iodo and 12-iodo derivatives were reactive enough to afford phenylethynyl derivatives under Pd-catalyzed Sonogashira cross-coupling conditions. Within the phenylethynyl derivatives, only 12-phenylethynyl derivative was transformed into its 1,1,4,4-tetracyanobutadiene (TCBD) derivative by the reaction with TCNE. Amphoteric redox properties of the novel azulene analogs of tryptanthrin were characterized by spectroscopic and voltammetric analyses.     

Bandwidth of the strong product of two connected graphs

The bandwidth B(G) of a graph G is the minimum of the quantity max{|f(x)-f(y)|:xy∈E(G)} taken over all proper numberings f of G. The strong product of two graphs G and H, written as G(S_P)H, is the graph with vertex set V(G)×V(H) and with (u₁,v₁) adjacent to (u₂,v₂) if one of the following holds: (a) u₁ and v₁ are adjacent to u₂ and v₂ in G and H, respectively, (b) u₁ is adjacent to u₂ in G and v₁=v₂, or (c) u₁=u₂ and v₁ is adjacent to v₂ in H. In this paper, we investigate the bandwidth of the strong product of two connected graphs. Let G be a connected graph. We denote the diameter of G by D(G). Let d be a positive integer and let x,y be two vertices of G. Let denote the set of vertices v so that the distance between x and v in G is at most d. We define δ_d(G) as the minimum value of over all vertices x of G. Let denote the set of vertices z such that the distance between x and z in G is at most d-1 and z is adjacent to y. We denote the larger of and by . We define η(G)=1 if G is complete and η(G) as the minimum of over all pair of vertices x,y of G otherwise. Let G and H be two connected graphs. Among other results, we prove that if δ_D(H)(G)?B(G)D(H)+1 and B(H)=⌈(|V(H)|+η(H)-2)/D(H)⌉, then B(G(S_P)H)=B(G)|V(H)|+B(H). Moreover, we show that this result determines the bandwidth of the strong product of some classes of graphs. Furthermore, we study the bandwidth of the strong product of power of paths with complete bipartite graphs.     

Determination of (R)-xanthoanthrafil, a phosphodiesterase-5 inhibitor, in a dietary supplement promoted for sexual enhancement

We describe here the first case of the finding of xanthoanthrafil, a phosphodiesterase-5 inhibitor, in a dietary supplement. A methanol extract of the supplement product was first analyzed by TLC and HPLC. The results indicated that the extract contained an unknown compound. The molecular weight of the compound was 389 and the accurate mass showed its elemental composition to be C(19)H(23)N(3)O(6). Combined with this data, NMR analysis revealed the planar structure of the unknown compound to be N-(3,4-dimethoxybenzyl)-2-(1-hydroxypropan-2-ylamino)-5-nitrobenzamide. The R-configuration of this compound had been synthesized as a phosphodiesterase-5 inhibitor, formerly reported as FR226807 by Fujisawa Pharmaceutical Co., Ltd. The absolute configuration of the isolated compound was estimated to have R-configuration by its optical rotation. Considering its general properties, this compound is renamed as (R)-xanthoanthrafil with the agreement of Astellas Pharma Inc. which is the successor of Fujisawa Pharmaceutical Co., Ltd. Quantitative analysis revealed that the content of (R)-xanthoanthrafil in the product was about 31 mg/capsule.     

Synthesis, structures, and magnetic properties of face-sharing heterodinuclear Ni(II)-Ln(III) (Ln = Eu, Gd, Tb, Dy) complexes

Heterodinuclear [(Ni (II)L)Ln (III)(hfac) 2(EtOH)] (H 3L = 1,1,1-tris[(salicylideneamino)methyl]ethane; Ln = Eu, Gd, Tb, and Dy; hfac = hexafluoroacetylacetonate) complexes ( 1.Ln) were prepared by treating [Ni(H 1.5L)]Cl 0.5 ( 1) with [Ln(hfac) 3(H 2O) 2] and triethylamine in ethanol (1:1:1). All 1.Ln complexes ( 1.Eu, 1.Gd, 1.Tb, and 1.Dy) crystallized in the triclinic space group P1 (No. 2) with Z = 2 with very similar structures. Each complex is a face-sharing dinuclear molecule. The Ni (II) ion is coordinated by the L (3-) ligand in a N 3O 3 coordination sphere, and the three phenolate oxygen atoms coordinate to an Ln (III) ion as bridging atoms. The Ln (III) ion is eight-coordinate, with four oxygen atoms of two hfac (-)'s, three phenolate oxygen atoms of L (3-), and one ethanol oxygen atom coordinated. Temperature-dependent magnetic susceptibility and field-dependent magnetization measurements showed a ferromagnetic interaction between Ni (II) and Gd (III) in 1.Gd. The Ni (II)-Ln (III) magnetic interactions in 1.Eu, 1.Tb, and 1.Dy were evaluated by comparing their magnetic susceptibilities with those of the isostructural Zn (II)-Ln (III) complexes, [(ZnL)Ln(hfac) 2(EtOH)] ( 2.Ln) containing a diamagnetic Zn (II) ion. A ferromagnetic interaction was indicated in 1.Tb and 1.Dy, while the interaction between Ni (II) and Eu (III) was negligible in 1.Eu. The magnetic behaviors of 1.Dy and 2.Dy were analyzed theoretically to give insight into the sublevel structures of the Dy (III) ion and its coupling with Ni (II). Frequency dependence in the ac susceptibility signals was observed in 1.Dy.     

Heteropolynuclear complexes of 3,5-dimethylpyrazolate [Pt2M4(Me2pz)8] (M = Ag, Cu). Highly luminescent character of the triplet excited state based on mixed-metal cores

The platinum dimer and heteropolynuclear platinum complexes of 3,5-dimethylpyrazolate, [Pt2M4(mu-Me2pz)8] [M = H (1), Ag (2), Cu (3)], were synthesized and structurally characterized. They exhibit yellow, sky-blue, and orange luminescence, respectively, in the solid state. The absorption bands of 2 and 3 are mainly assigned to the combination of the metal-metal-to-ligand charge-transfer and [Pt2 --> Pt2M4] transitions by the time-dependent density functional theory (DFT) method. DFT calculations also indicate that the emissive states of 2 and 3 are 3[Pt2 --> Pt2Ag4] and 3[Cu(d) --> Pt2Cu4], respectively.     

Direct Observation of Ordered High‐Spin–Low‐Spin Intermediate States of an Iron(III) Three‐Step Spin‐Crossover Complex

A neutral mononuclear Fe^III complex [Fe^III(H‐5‐Br‐thsa‐Me)(5‐Br‐thsa‐Me)]?H₂O ( 1 ; H₂‐5‐Br‐thsa‐Me=5‐bromosalicylaldehyde methylthiosemicarbazone) was prepared that exhibited a three‐step spin‐crossover (SCO) with symmetry breaking and a 14 K hysteresis loop owing to strong cooperativity. Two ordered intermediate states of 1 were observed, 4HS–2LS and 2HS–4LS, which exhibited reentrant phase‐transition behavior. This study provides a new platform for examining multistability in SCO complexes.     

UPLC-MS/MS detection of disaccharides derived from glycosaminoglycans as biomarkers of mucopolysaccharidoses

Mucopolysaccharidoses (MPSs) are a group of disorders resulting from primary defects in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Depending on the specific enzyme defect, the catabolism of one or more GAGs is blocked leading to accumulation in tissues and biological fluids. GAG measurements are important for high-risk screening, diagnosis, monitoring treatment efficacy, and patient follow up. The dimethylmethylene blue (DMB) spectrophotometric method commonly used in most biochemical genetics laboratories relies on a non-specific total GAG analysis which has led to false positive results, and even false negative results (mainly for MPS III and IV patients). The main objective of our project was to devise and validate a reliable tandem mass spectrometry multiplex analysis for the urine quantitation of four GAGs (dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and chondroitin sulfate (CS)) for an eventual technological transfer to the clinic. The developed methodology is rapid (7 min) and our results showed good intraday and interday precision (RSDs ≤ 8.7%) and accuracy (Biases range: −12.0%–18.4%). Linearity was good (r² > 0.995) for DS, HS, CS, and KS calibration curves. In comparison with the DMB spectrophotometric method, this multiplex tandem mass spectrometry method allows GAG fractionation, thus a differentiation of MPS types, except for MPS I and II which are characterized by the same GAG profile. The devised method is a useful and reliable tool for diagnosis of MPS patients, as well as their monitoring and follow up, as shown by longitudinal studies.     

Tris(pentafluorophenyl)borane‐Catalyzed Acceptorless Dehydrogenation of N‐Heterocycles

Catalytic acceptorless dehydrogenation is an environmentally benign way to desaturate organic compounds. This process is traditionally accomplished with transition‐metal‐based catalysts. Herein, a borane‐catalyzed, metal‐free acceptorless dehydrogenation of saturated N‐heterocycles is disclosed. Tris(pentafluorophenyl)borane was identified as a versatile catalyst, which afforded several synthetically important N‐heteroarenes in up to quantitative yield. Specifically, the present metal‐free catalytic system exhibited a uniquely high tolerance toward sulfur functionalities, and demonstrated superior reactivity in the synthesis of benzothiazoles compared to conventional metal‐catalyzed systems. This protocol can thus be regarded as the first example of metal‐free acceptorless dehydrogenation in synthetic organic chemistry.     

Analytical method for determination of disaccharides derived from keratan sulfates in human serum and plasma by high-performance liquid chromatography/turbo-ionspray ionization tandem mass spectrometry

We established a highly sensitive LC/MS/MS method for the analysis of the disaccharides produced from keratan sulfates (KS). It was revealed that the disaccharides produced by keratanase II enzymatic digestion of KS could be determined with high sensitivity by negative ion mode of multiple reaction monitoring. Furthermore, monosulfated and disulfated disaccharides can be separated using a Hypercarb (2.0 mm i.d. x 150 mm, 5 microm) with a gradient elution of acetonitrile-0.01 m ammonium bicarbonate (pH 10). This method was applied to the determination of KS in serum and plasma of control subjects. The intra-day precision expressed as %CV was within 6.8% for five replicate analyses with three different control serum. The inter-day (overall, n = 15) precision was within 7.3% for three days. This method is sensitive, reproducible and would be useful for clinical analysis.