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Objective: Skin damage induced by ischemia/reperfusion (I/R) is a multifactorial process that often occurs in plastic surgery. The mechanisms of I/R injury include hypoxia, inflammation, and oxidative damage. Hydrogen gas has been reported to alleviate cerebral I/R injury by acting as a free radical scavenger. Here, we assessed the protective effect of hydrogen-rich saline (HRS) on skin flap I/R injury. Methods: Abdominal skin flaps of rats were elevated and ischemia was induced for 3 h; subsequently, HRS or physiological saline was administered intraperitoneally 10 min before reperfusion. On postoperative Day 5, flap survival, blood perfusion, the accumulation of reactive oxygen species (ROS), and levels of cytokines were evaluated. Histological examinations were performed to assess inflammatory cell infiltration. Results: Skin flap survival and blood flow perfusion were improved by HRS relative to the controls. The production of malondialdehyde (MDA), an indicator of lipid peroxidation, was markedly reduced. A multiplex cytokine assay revealed that HRS reduced the elevation in the levels of inflammatory cytokines, chemokines and growth factors, with the exception of RANTES (regulated on activation, normal T-cell expressed and secreted) growth factor. HRS treatment also reduced inflammatory cell infiltration induced by I/R injury. Conclusions: Our findings suggest that HRS mitigates I/R injury by decreasing inflammation and, therefore, has the potential for application as a therapy for improving skin flap survival.

In this study, we discussed an efficient approach for the synthesis of camphorquinone from camphor by the continuous reaction of bromination and oxidation. The oxidation of 3-bromocamphor was catalyzed by Fe-porphyrins with air. The catalytic activity of iron-metallated functional porphyrins was investigated under optimization conditions. The results showed that this method was a milder alternative to the reported methods, with a simple, greener procedure in which the advantages were the utilization of air as the oxidant and the use of metalloporphyrins as catalysts.

The relationship between carcinogenicity and DNA interstrand cross-links of nitrosoureas is poorly defined. 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3- (2-chloroethyl)- 3- nitrosourea (ACNU, nimustine) is one of nitrosoureas used in the treatment of high-grade gliomas. It has the capability of causing DNA interstrand cross-links (ICLs) to kill cancer cells. But it can also cause the generation of secondary tumors with carcinogenic side effects. In present study, we investigated DNA interstrand cross-links, DNA double-strand breaks and cell cycle phase in NIH/3T3 cells from the primary mouse embryonic fibroblast cells induced by ACNU. This result indicated that the concentration of 60 and 75μg/ml of ACNU could be detected significantly ICLs, and the γ-H2AX has the ability to be a biomarker for DNA damage associated with ICLs induced by ACNU. The subgroup of nitrosoureas (CNUs) including 1-(4-amino -2-methyl-5- pyrimidinyl) methyl-3 -(2- chloroethyl) -3- nitrosourea (ACNU, nimustine), 1,3- Bis(2- chloroethyl)- 1- nitrosourea (BCNU, carmustine), 1-(2- chloroethyl)- 3- cyclohexyl- nitrosourea (CCNU, lomustine)

The 4-aryl-1,4-dihydropyrazines were prepared via the cyclization of N,N-bisalkylated anilines with ammonium acetate. These reactions were aided by improvements in the synthesis of N,N-bisalkylated anilines which were alkylated with anilines using ethyl 2-diazo acetoacetate in a reaction catalyzed by rhodium acetate in the absence of oxygen. A possible mechanistic route is postulated on the basis of the isolation of the N-alkylation intermediates, which were determined to be N-aryloxamates by 1H NMR data and X-ray diffraction.

Tetraethyl 2,4,8,10-tetramethyl-6,12-bis(4-fluorophenyl)-3,9-dioxapentacyclo[6.4.0.0 2,7 .0 4,11 .0 5,10 ]dodecane-1,5,7,11-tetracarboxylate ( 1 , simplified as 6,12-bis(4-fluorophenyl)-3,9-dioxatetraasterane) was synthesized by [2 + 2] photocyclization of diethyl 2,6-dimethyl-4-(4-fluorophenyl)-4H-pyran-3,5-dicarboxylate ( 2 ) in solution. The NMR analysis of 1 is discussed in detail by the splittings and assignments of signals according to the three-dimensional structure. Single-crystal X-ray diffraction shows that 1 is situated on an inversion center. The molecular symmetry is close to C 2 h except for the terminal ethyl groups.

Copper(I)-catalyzed terminal alkyne-azide 1,3-cycloaddition reaction has emerged as one of the main strategies for the rapid creation and screening of a small molecular library. The present work describes the design and synthesis of a series of 1,2,3-triazol-4-yl-substituted 1,4-dihydro-4-oxo-1,5-napthyridine-3-carboxylic acids in which the hydrophobic and hydrophilic domains were efficiently incorporated by a click reaction. The structures of the desired products 8 and 12 were characterized by spectroscopic methods and their HIV integrase inhibitory activities were also screened.

Electrochemical synthesis of o -benzoquinone derivatives and their in situ transformation are one of the versatile approaches for the synthesis of derivatized catechols. In the present work, electrochemical oxidation of catechols 1a – 1d in the presence of a unique nucleophile, 4-amino-3-methyl-5-mercapto-1,2,4-triazole 3 , bearing two nucleophilic groups (–NH 2 and –SH), have been studied in phosphate buffer solutions using cyclic voltammetry and controlled-potential electrolysis (CPE) methods. The results show that only the mercapto group participated selectively in the Michael addition reaction and led to the formation of catechol substituted products of types 4 and 5 , bearing a free amino group, potentially useful for further chemical modifications, e.g. of interest in biomedical applications. Various electrolytic conditions, such as the nature of anode material, amount of passed charge, pH of the electrolytic solution and cell configuration (divided or undivided cell), were also investigated to optimize the yields of corresponding products.

Polyhydroxylated aromatic pyrimidinyl thioethers are important compounds due to their potential anti-HIV integrase activity. The present work describes an electrochemical synthetic strategy and environmentally benign approach for the synthesis of these compounds, superior to conventional chemical reactions. Thus, the electrochemical oxidation of 4-substituted catechols and caffeic acid, in the presence of 2-mercaptopyrimidine derivatives 2 , generates monopyrimidinylthio-substituted polyhydroxylated aromatics 3a – f in moderate yields. In the case of catechol itself and 3-substituted catechols, both mono- ( 3g – l ) and dipyrimidinylthio-substituted derivatives ( 4g – l ) were produced. Apparently, the anodic oxidation of catechol derivatives leads to nucleophilic addition products of types 3 and 4 , which are different from the traditional nucleophilic substitution reaction of aryl halides and thiols. The electrochemically induced reaction mechanism is also discussed.

The electrochemical synthesis of 5-purin-6′-ylthiocatechols was carried out by anodic oxidation of catechol derivatives 1a–1d in the presence of 6-mercaptopurine (2) in aqueous solution. Results of cyclic voltammetry and controlled-potential electrolysis indicated that the starting catechols were first oxidized to the corresponding o-benzoquinone, which underwent further Michael addition with 6-mercaptopurine to produce titled products 3a–3d following an EC (E=electrochemical and C=chemical step) mechanism. Such work further demonstrates the versatility of the anodic oxidation of catechols and their in-situ transformation for the synthesis of derivatized catechols.

The anodic oxidation of caffeic acid in the presence of sodium benzenesulfinate in aqueous solution was studied by cyclic voltammetry and controlled potential coulometry. The results showed that similar to other simple catechol derivatives where the substituents attached directly to the benzene ring, caffeic acid was oxidized to the corresponding o-benzoquinone which underwent further Michael-addition with sodium benzenesulfinate or sodium p-methyl benzenesulfinate to produce 6-arylsulfonyl caffeic acid derivative 7a or 7b.

Diketo acid derivatives are potent and selective HIV-1 integrase inhibitors. To investigate the detailed synthesis of those derivatives, a series of p/m-[p-(un)substituted phenylsulfonamido]phenyl β-diketo acid derivatives have been designed and synthesized. The quinoxalone derivatives as the potential bioisosteres of the biologically labile β-diketoacid pharmacophores have also been synthesized from reactions of the corresponding diketo acids with o-phenylenediamine. The structures of all diketo acid (ester) and quinoxalone derivatives were confirmed by 1H NMR, 13C NMR, IR, HRMS and/or MS (ESI). X-ray crystallographic analysis of 11b demonstrates a similar arrangement of the side chain of quinoxalone derivatives with the parent diketoacids due to the intramolecular hydrogen bond (O···H–N) and the sp2 hybridization configuration of the two nitrogen atoms of the quinoxalone ring.

3-[2-Oxo-2-(4-methyloxyphenylsulfonamidophenyl)ethylidene]-3,4-dihydro-1H-quinox-alin-2-one (4) was synthesized and characterized by 1H NMR,13C NMR, IR, and single-crystal X-ray diffraction techniques. The crystallographic results show that the composition of the title compound is C23H19N3O5S. It belongs to triclinic crystal system and P-1 space group, with a=7.273(6) A, b=9.092(7) A, c=15.928(13) A; α=85.135(11)°, β=78.297(10)°, γ=84.619(11)°, V=1024.4(14) A3, Z=2, D c=1.457 mg/m3, μ = 0.201 mm−1, F(000)=468, R=0.0597, wR=0.1438.

The reactivity of N -phosphoryl f -alanine differs from N -phosphoryl g -alanine and N -phosphoryl n -amino butyric acid enormously. N -phospho- f -alanine could self-activate to yield N -phosphopeptides either in aqueous or nonaqueous media, but not g - or n -amino acid analogues. The mechanism of the reaction is discussed.

In recent years β-amino acids have increased their importance enormously in defining secondary structures of β-peptides. Interest in β-amino acids raises the question: Why and how did nature choose α-amino acids for the central role in life? In this article we present experimental results of MS and 31P NMR methods on the chemical behavior of N-phosphorylated α-alanine, β-alanine, and γ-amino butyric acid in different solvents. N-Phosphoryl α-alanine can self-assemble to N-phosphopeptides either in water or in organic solvents, while no assembly was observed for β- or γ-amino acids. An intramolecular carboxylic–phosphoric mixed anhydride (IMCPA) is the key structure responsible for their chemical behaviors. Relative energies and solvent effects of three isomers of IMCPA derived from α-alanine (2a–c), with five-membered ring, and five isomers of IMCPA derived from β-alanine (4a–e), with six-membered ring, were calculated with density functional theory at the B3LYP/6-31G** level. The lower relative energy (3.2 kcal/mol in water) of 2b and lower energy barrier for its formation (16.7 kcal/mol in water) are responsible for the peptide formation from N-phosphoryl α-alanine. Both experimental and theoretical studies indicate that the structural difference among α-, β-, and γ-amino acids can be recognized by formation of IMCPA after N-phosphorylation. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 232–241, 2003

The anodic oxidation of caffeic acid in the presence of acetylacetone or methyl acetoacetate in aqueous solution has been studied by cyclic voltammetry and controlled-potential electrolysis techniques. The result showed that caffeic acid was oxidized to the corresponding o -benzoquinone, which underwent further Michael-addition with acetylacetone or methyl acetoacetate to produce caffeic acid derivative 3,4-dihydroxy-6-(1-acetylacetone)-yl cinnamic acid 4a or 3,4-dihydroxy-6-(1-acetyl-methylacetate)-yl cinnamic acid 4b .

The reaction of monocyclic oxyphosphorane compounds 1a, 1b, 1c, with ethylene glycol in pyridine was studied by 31P NMR. The results showed that compound 1a, with an unsaturated five-membered ring reacts slightly faster than compound lb with a saturated ring attached by two trans p-nitro phenyl groups, which reacts 100 times faster than the cis compound lc. To interpret the mechanism, hexacoordinated intermediates 3, and 4, were proposed. The properties of 3b, and 3c, as well as 1b, and 1c, were investigated on the basis of PM3 calculations. The calculations showed that there was about 2.9 kcal/mol difference between the active energy of the ester exchange reaction for compound 1b, and 1c, which matched well with our experimental results and provided more support to the proposed mechanism.

The title compound, C23H19N3O4S, a quinoxalone derivative, is the product of the condensation reaction of 4-[4-(4-methyl­phenyl­sulfonamido)phen­yl]-2,4-dioxobutanoic acid with o-phenyl­enediamine. Inter­molecular N—H⋯O hydrogen bonds and π–π stacking inter­actions stabilize the solid structure.

The title compounds (IV) are formed via cyclization of N,N-bisalkylated aniline derivatives (III) with ammonium acetate.

A general and cost-effective method for the environmentally friendly oxidation of bromomethyl-substituted pyridine, quinoline and phenanthroline derivatives to the corresponding carboxylic acids is developed using less toxic Ph-I(O-Ac)2 and biologically relevant iron(III)porphyrins as catalysts.

An ultrasound-assisted preparation of 1,4-diazabutadienes via smooth condensation of diketones with amines under solvent-free conditions is described. The generality of this method was examined by the synthesized N,N'-diaryl- and N,N'-dialkyl-1,4-diazabutadiene derivatives. In addition to experimental simplicity, the main advantages of the procedure are mild conditions, short reaction time (2-15 min) and high yields (71-98%).

Using iron(III)porphyrins in combination with (diacetoxyiodo)benzene allows for the conversion of 2,9-bis(bromomethyl)-4,7-diphenyl-1,10-phenanthroline into 4,7-diphenyl-1,10-phenanthroline-2,9-dicarboxylic acid. This method provides a cost-effective and environmentally-friendly oxidation procedure using less toxic PhI(OAc)2 and biologically relevant iron(III)porphyrins. The catalytic activity of five kinds of iron-metallated functional porphyrins were investigated using different oxidants, including air, H2O2, PhI(OAc)2, PhIO and NaClO. Our results showed that the use of T(p-NO2)PPFeCl with PhI(OAc)2 as the oxidant in the presence of water displays remarkable activity for the desired oxidation reaction. The generality of this method was examined by synthesizing the carboxylic acids of pyridines and quinolines.

The electrochemical synthesis of 5-purin-6′-ylthiocatechols was carried out by anodic oxidation of catechol derivatives 1a–1d in the presence of 6-mercaptopurine (2) in aqueous solution. Results of cyclic voltammetry and controlled-potential electrolysis indicated that the starting catechols were first oxidized to the corresponding o-benzoquinone, which underwent further Michael addition with 6-mercaptopurine to produce titled products 3a–3d following an EC (E=electrochemical and C=chemical step) mechanism. Such work further demonstrates the versatility of the anodic oxidation of catechols and their in-situ transformation for the synthesis of derivatized catechols.

Diethyl 2,6-dimethyl-4-aryl-4H-pyran-3,5-dicarboxylates (1) have been synthesized by the reaction of aryl aldehyde and 1,3-diketone catalyzed by ZnCl(2) under ultrasound irradiation. The effects of changes in the ultrasonic power, temperature, and reaction time are discussed. With the optimized reaction conditions, various aryl aldehydes were used to synthesize 4H-pyrans (1) under the influence of ultrasound irradiation. Compared with the conventional thermal methods, the remarkable advantages of this method are the simple experimental procedure, shorter reaction time and high yield of product.

Diketo acid derivatives are potent and selective HIV-1 integrase inhibitors. To investigate the detailed synthesis of those derivatives, a series of p/m-[p-(un)substituted phenylsulfonamido]phenyl β-diketo acid derivatives have been designed and synthesized. The quinoxalone derivatives as the potential bioisosteres of the biologically labile β-diketoacid pharmacophores have also been synthesized from reactions of the corresponding diketo acids with o-phenylenediamine. The structures of all diketo acid (ester) and quinoxalone derivatives were confirmed by 1H NMR, 13C NMR, IR, HRMS and/or MS (ESI). X-ray crystallographic analysis of 11b demonstrates a similar arrangement of the side chain of quinoxalone derivatives with the parent diketoacids due to the intramolecular hydrogen bond (O···H–N) and the sp2 hybridization configuration of the two nitrogen atoms of the quinoxalone ring.

Chloroethylnitrosoureas (CENUs) are clinically useful anticancer agents. Their cytotoxicity has been proved to be associated with the generation of DNA interstrand crosslinks. In the present work, QM/MM computations are carried out to investigate the crosslinks of DNA complementary bases by the CENUs with ONIOM hybrid method. DNA double helix containing crosslinked base pairs are established as the computational models. The crosslinked DNA are subdivided into three layers, each of which are described at B3LYP/6-311+G(d,p), AM1 and UFF level of theory respectively. The result shows that the covalent crosslink between guanine N1 and complementary cytosine N3 is the most favorable crosslinking product. This crosslink is characterized by its less deformation of DNA double helix and higher stability than the other crosslinks on the complementary base pairs. The results of the ONIOM computations explain the phenomenon that 1-(N3-deoxycytidyl)-2-(N1-deoxyguanosinyl)ethane is the main crosslink product in the in vivo an the in vitro experiments.