Synthesis and reversible photocleavage of novel polyurethanes containing coumarin dimer components

Six polyurethanes containing coumarin dimer components in the main chain have been prepared by polyaddition of diisocyanates with anti head-to-head 7-hydroxycoumarin dimer or anti head-to-tail 7-hydroxy-4-methylcoumarin dimer. 7-Acetoxycoumarin and 7-acetoxy-4-methylcoumarin were first prepared and then photodimerized under 350 nm UV light to give anti head-to-head 7-acetoxycoumarin dimer and anti head-to-tail 7-acetoxy-4-methylcoumarin dimer, respectively. After hydrolyzing under acidic conditions to 7-hydroxycoumarin dimer and anti head-to-head 7-hydroxycoumarin dimer, they were polymerized with aliphatic and aromatic diisocyanates in N,N-dimethylacetamide to give the polyurethanes. Addition of dibutyltin dilaurate (T-12) as catalyst increases the polymer yield with the viscosity remaining almost unchanged. It was also found that lithium chloride enhances both the yield and viscosity of the polyurethanes by increasing their solubility possibly through complexation. The polyurethanes are symmetrically photocleaved at cyclobutane rings under 254 nm UV light to dicoumarins. Reversible photodimerization of the photocleaved compounds have also been investigated under 300 and 350 nm UV light. The polyurethanes from aromatic diisocyanates or with 4-methyl substituent exhibit greater reactivity in the photocleavage reaction. © 1997 John Wiley & Sons, Inc.     

On-chip integrated hydrolysis, fluorescent labeling, and electrophoretic separation utilized for acetylcholinesterase assay

A sensitive on-chip acetylcholinesterase (AChE) assay that serves as a basis for the development of a fully integrated on-chip AChE-inhibitor detection assay is presented. The sequential steps required for the on-chip analysis process were integrated into a microchip. Transport and mixing of the reagents occurred by a combination of electroosmosis and electrophoresis using computer-controlled electrokinetic transport. AChE-catalyzed hydrolysis of acetylthiocholine to thiocholine was determined by on-chip reaction of thiocholine with eosinmaleimide, and the resulting thioether was electrophoretically separated and detected by laser-induced fluorescence (LIF). Enzyme-substrate mixing and reaction by confluent flow of reagents was compared with electrophoretically mediated microanalysis (EMMA), based on injection of an enzyme plug, and the utilization of differences in electrophoretic mobility as a driving force for efficient mixing and reaction. Both methods yielded similar results, however the EMMA-plug technique is preferable. The EMMA-plug technique was optimized for length and pushing time of enzyme plug, length of dyes mixture plug, acetylthiocholine concentration, and detector location. Detection of O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate (VX) and paraoxon, two AChE inhibitors, was demonstrated by off-chip mixing of the inhibitor and AChE, followed by the on-chip AChE assay. Limit of detection of VX for 5.5 min incubation and of paraoxon for 8 min incubation was 4 × 10⁻¹⁰ and 4 × 10⁻⁷ M, respectively. Utilization of the AChE microchip assay for inhibition kinetics was demonstrated also by evaluation of the inhibitor-enzyme bimolecular reaction constant (k_i). The evaluated k_i values for VX and paraoxon for AChE from the electric eel were 3.5 × 10⁷ and 1.7 × 10⁵ M⁻¹ min⁻¹, respectively, conforming well to reported values obtained by bulk methods.     

Synthesis and anti-HBV activity of S-substituted 7-mercapto-4-methylcoumarin analogs

Twelve S-substituted 7-mercapto-4-methylcoumarin analogs were synthesized and evaluated for the inhibition to HBV in HepG2 2.2.1.5 cell. Among them, ten compounds exhibited potent inhibition to HBsAg and/or HBeAg with the IC50 values of sub μmol/L level. The ICso of anti-HBsAg activities of 5c and 5j reached 0.01 μmol/L respectively which were 16 fold more potent than that of 3TC. Compounds 3, 5e, 5g, 5h and 5i showed admirable inhibitory activity to both HBsAg and HBeAg. The bioassay results indicated the S-substituted 7-mercapto-4-methylcoumarin analogs merit attention as novel anti-HBV agents.     

8-（3-或4-氟苯甲酰基）-7-羟基-4-甲基香豆素的合成、晶体结构、抑菌活性、抗氧化活性及其与牛血清白蛋白的相互作用

设计并合成了两个新的氟代香豆素化合物8-（3-氟苯甲酰基）-7-羟基-4-甲基香豆素（3a）和8-（4-氟苯甲酰基）-7-羟基-4-甲基香豆素（3b）,其结构通过元素分析、IR和1HNMR进行了表征,通过X-射线单晶衍射测定了化合物3b的晶体结构,单晶结构分析表明,化合物3b的晶体属于单斜晶系.体外抑菌试验结果显示,目标化合物对大肠杆菌（E.coli）、枯草杆菌（B.subtilis）和金色葡萄球菌（S.aureus）有不同程度的抑制作用;体外抗氧化实验显示,目标化合物对超氧阴离子自由基（O2-·）和二苯代苦味肼基自由基（DPPH·）均有良好的清除能力;运用荧光光谱法研究了不同温度下目标化合物与牛血清白蛋白（BSA）的相互作用,结果表明,目标化合物对BSA的荧光猝灭均属于静态猝灭,相关热力学参数表明,化合物3a（H〈0,S〈0,G〈0）与BSA二者之间主要以氢键或范德华力相结合,化合物3b（H〉0,S〉0,G〈0）与BSA二者之间主要靠疏水作用力相结合;依据Fster＇s非辐射能量转移理论,求得BSA与化合物3a和化合物3b间的距离（r）分别为2.53和2.65nm,说明两个化合物与BSA之间可能发生了非辐射能量转移.     

A New Chemiluminescent Triazine Reagent

The determination of hydrogen peroxide is of great importance in biochemistry, environmental fields and clinical control1,2. Chemiluminescence method is commonly used in the determination of hydrogen peroxide because of its low detection limit and wide dynamic range that can be achieved with relatively simple instrumentation. Up to now, however, established systems for analytical purposes fall into one of a limited number of types and these systems lack selectivity due to the possible interfer…     

Crystal and molecular structure of the reaction product of 7-mercapto-4-methylcoumarin with iodine

Russian Chemical Bulletin - 4-Methyl-7-(4-methyl-2-oxo-2H-chromen-6-yl)disulfanyl-2H-chromen-2-one hydrotriiodide was synthesized by the reaction of 7-mercapto-4-methylcoumarin with iodine, and its...     

Electrochemical phosphorylation of coumarins catalyzed by transition metal complexes (Ni—Mn,Co—Mn)

Russian Chemical Bulletin - A possibility of electrochemical phosphorylation of coumarins (coumarin, 6-methylcoumarin, 7-methylcoumarin) with diethyl phosphite was shown. The approach is based on...     

Tyrosol 1,2,3-triazole analogues as new acetylcholinesterase (AChE) inhibitors

The present work proposed the preparation of triazolic analogues of tyrosol, a biophenol found in olive oil and whose wide range of bioactivities has been the target of many studies. We obtained fifteen novel tyrosol derivatives and the compounds of the series were later evaluated as acetylcholinesterase (AChE) inhibitors. The study of AChE inhibition is important for the development of new drugs and pesticides, and especially the research for managing Alzheimer's disease. The most active compound, namely 7-({1-[2-(4-hydroxyphenyl)ethyl]-1H-1,2,3-triazol-4-yl}methoxy)-4-methyl-2H-chromen-2-one (30), showed IC₅₀ value of 14.66 ± 2.29 μmol L⁻¹. Docking experiments corroborated by kinetic assay are suggestive of a competitive inhibition mechanism. Derivatives interacted with amino acids from the AChE active site associated to the development of Alzheimer's disease. The results indicate that the compounds synthesized have a high potential as prototypes for the development of new acetylcholinesterase inhibitors.     

Modified Coumarins. II. Mannich Reaction of Substituted 4-Phenylcoumarins

Aminomethylation of 5-hydroxy- and 7-hydroxy-4-phenylcoumarins by substituted 1,1-diaminomethanes is studied. Mannich condensation of amino acids and their esters with 7-hydroxy-4-phenylcoumarin gives a series of 8-aminoacylmethylcoumarins and 4-phenyl-9,10-dihydro-2H,8H-chromeno[8,7-e][1,3]oxazin-2-ones     

Synthesis and structure of indoline spiropyrans of the coumarin series

New indoline spiropyrans of the coumarin series were synthesized by the condensation of indoline and hydroxyformylcoumarin derivatives. Spiropyrans, viz., derivatives of 8-formyl-7-hydroxy-4-methylcoumarin and 5-formyl-6-hydroxy-4-methylcoumarin, under irradiation are transformed into open forms, which are recyclized in the dark. The compounds formed by the condensation of the indoline derivatives with 3-formyl-4-hydroxycoumarin have an open structure of the merocyanine dyes and are transformed into spiro forms neither in the dark nor under irradiation with the visible light. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2342–2349, October, 2005.     

Intermolecular interactions in dioxane-water solutions of substituted coumarins according to ultrasonic data

Density, ultrasonic velocity of pure dioxane (Dx) and ligands, 4,6-dimethyl-7-hydroxycoumarin (L₁), 6-ethyl-7-hydroxy-4-methylcoumarin (L₂), and 3-chloro-7-hydroxy-4-methylcoumarin (L₃) in different percent of Dx-water mixture have been investigated at 303.15 K. Acoustical parameters such as adiabatic compressibility (β), intermolecular free length (L _f ), acoustical impedance (Z), relative association (R _A ), apparent molar compressibility (Φ_β), and apparent molar volume (Φ _V ) have also been evaluated from the experimental data of density and ultrasonic velocity. An excellent correlation between a given parameters is observed at all percent of dioxane-water and the result suggests nature of intermolecular interactions between the components.     

PHOTOCHEMICAL REACTIONS OF AZIDOCOUMARINS

Abstract— Photochemical reactions of 6-azidocoumarin and 7-azido-4-methylcoumarin in the presence of secondary amines have been investigated for their potential applications in photoaffinity labeling. It was found that the singlet nitrene generated from 6-azidocoumarin isomerized to a dehydroazepine intermediate that reacted with an amine to yield two isomeric adducts. Photolysis of 7-azido-4-meth-ylcoumarin, in contrast, gave a triplet nitrene that abstracted hydrogen atoms from secondary amine molecules to form 7-amino-4-methylcoumarin as the major product. The difference in the intersystem crossing rate between the two compounds originates from the azido position relative to the carbonyl group. Because of its ability to form a covalent linkage with a nucleophile, 6-azidocoumarin is deemed to have a greater potential as a photoaffinity label than 7-azido-4-methylcoumarin.     

Design, synthesis and evaluation of new α-nucleophiles for the hydrolysis of organophosphorus nerve agents: application to the reactivation of phosphorylated acetylcholinesterase

A series of new α-nucleophiles including oximes and amidoximes have been synthesized, and their ability to efficiently and selectively cleave the P-S bond of organophosphorus nerve agents has been evaluated. The relationship between the chemical structure of the α-nucleophiles and their reactivity towards PhX hydrolysis is reported. A significant effect induced by an ortho-hydroxyl group of aryl- and pyridyl-oximes, amidoximes on their organo-phosphono-thioase reactivity was discovered. The evaluation of the initial rates of PhX hydrolysis reaction in the presence of α-nucleophiles allowed the discovery of new uncharged molecules with increased reactivity compared to positively charged 2-pralidoxime used as antidote. The mechanism of their action was studied in details by kinetic analysis, HPLC and LC-MS methods. The most promising structures were then considered as potent in vitro reactivators of phosphylated acetylcholinesterase (AChE), which was confirmed by the preliminary results of AChE reactivation initially inhibited by VX.     

Improved and rapid synthesis of new coumarinyl chalcone derivatives and their antiviral activity

Two closely structurally related coumarins, 4-hydroxy-8-isopropyl-5-methylcoumarin and 4-hydroxy-6-chloro-7-methylcoumarin were acylated at C-3 and further converted to the respective chalcones and two series of eighteen new compounds, which were evaluated for possible antiviral activity.     

Nerve Agents Assay Using Cholinesterase Based Biosensor

Electrochemical biosensor based on electric eel acetylcholinesterase (AChE) (EC 3.1.1.7) was performed for assay of nerve agents – tabun, sarin, soman, cyclosarin, and VX. The biosensor used AChE as biorecognition element. The presence of nerve agents was accompanied by a strong inhibition of AChE activity. Enzyme activity is easily measurable by electrochemical oxidation of thiocholine created from acetylthiocholine (ATChCl) by AChE‐catalyzed hydrolysis. The tested nerve agents were successfully assayed. The best limits of detection were achieved for sarin (5.88×10^?10 M) and VX (8.51×10^?10 M) after one‐minute assay. The biosensor was found long term stable at low as well as laboratory temperature.     

Crystal structure of 7,8-dihydroxy-4-methylcoumarin.

The structure of 7,8-dihydroxy-4-methylcoumarin was determined by an X-ray diffraction method. The compound crystallized in the triclinic space group P1, Z = 2, with a = 7.631(2), b = 9.456(5), c = 7.075(3)A, alpha = 103.13(3), beta = 91.84(3), gamma= 68.21(3) degrees, and V= 460.9(3)A3. The X-ray crystal structure was also compared with those of 5,7-dihydroxy-4-methylcoumarin and 7-hydroxy-4-methylcoumarin.     

Photochromism of indoline spiropyrans of the coumarin series in polymeric matrices

The photochromic properties and aggregation processes of merocyanine forms of indoline spiropyrans of the coumarin series in the block and film poly(methyl methacrylate) (PMMA) were studied and compared by spectral and kinetic methods. Photochromism of the synthesized compounds depends on their structure. The efficient formation of J-aggregates was observed for indoline spiropyrans of the coumarin series based on 8-formyl-7-hydroxy-4-methylcoumarin and 3-formyl-4-hydroxycoumarin. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 870–875, May, 2007.     

Solvent-induced <Emphasis Type="Italic">E/Z</Emphasis>(C=N)-isomerization of imines of some hydroxy-substituted formylcoumarins

Aromatic imines, namely, 5-formyl-6-hydroxy-4-methyl- and 8-formyl-7-hydroxy-4-methylcoumarin derivatives, have been synthesized. A dependence of their spectral characteristics (¹H NMR spectra, electronic absorption spectra) from the solvent (DMSO, CHCl₃, DMF, acetonitrile, MeOH) has been studied. The solvatochromic effects observed for a number of imines, first of all, for 7-hydroxy-4-methyl-8-(4′-nitrophenylimino)methyl-2H-1-benzopyran-2-one, were related to their E/Z-isomerization with respect to the C=N bond based on the quantum chemical calculations by the AM1, PM3, PPP CI methods. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1954–1960, September, 2008.     

Probing chemical transformations in organic solids via NMR techniques: The solid-state photodimerization reaction of 7-methoxy-4-methylcoumarin

It has been reported that crystalline 7-methoxy-4-methylcoumarin undergoes a [2 + 2] photodimerization reaction to give two different products; the major product is thesyn head-head dimer, whereas the minor product is thesyn head-tail dimer. In this paper, high-resolution solid-state¹³C NMR and solution-state¹H and¹³C NMR techniques have been applied to investigate various structural issues relating to this solid-state photodimerization reaction. In particular, spectra have been recorded at various stages during the progress of the photodimerization reaction with the aim of charting the structural changes in the system as a function of reaction progress, with particular interest in assessing the potential of this technique for investigating the structural reasons for the production of the minor product. Conformational and dynamic properties of the product obtained in this solid-state photodimerization reaction have also been assessed.     

Reversible photodimerization of coumarin derivatives dispersed in poly(vinyl acetate)

Four photoreactive coumarin derivatives were successfully synthesized from 7-hydroxy-coumarin and 7-hydroxy-4-methylcoumarin, i.e., 7-propionyloxy-4-methylcoumarin (M₁), 7-palmitoyloxy-4-methylcoumarin (M₂), 7-propionyloxycoumarin (M₃), and 7-palmitoy-loxycoumarin (M₄). Reversible photodimerization (350 or 300 nm) and photocleavage (254 nm) of these coumarin derivatives dispersed in poly(vinyl acetate) (PVAc) were investigated by tracing their UV absorbance variations at 310 nm. The M₂ and M₄ with long palmitoyl chain show much better photoreaction reversibility than M₁ and M₃ with short propionyl chain. Moreover, photodimerization rate (under 350 nm) of M₂ is greater than 200 times of that of M₁. This has been explained by the formation of suitable conformation for revers-ible photodimerization due to the hydrophobic interactions. Photodimerization of M₂ is ca. 3 times quicker than that of M₄, indicating 4-methyl substitution enhances pho-todimerization. The influence of photodimerization wavelength (350 and 300 nm) and photosensitizer (benzophenone) have also been investigated in detail. © 1995 John Wiley & Sons. Inc.