DFT-calculated structures based on 1H NMR chemical shifts in solution vs. structures solved by single-crystal X-ray and crystalline-sponge methods: Assessing specific sources of discrepancies

DFT calculations of ¹H NMR chemical shifts, using various functionals and basis sets, the conductor-like polarizable continuum model and discrete solute-solvent hydrogen bond interactions have been used to derive the solution structures of methyl salicylate and methyl 2,5-dihydroxybenzoate. We demonstrate that very good agreement between experimental and computed ¹H NMR chemical shifts can be obtained for various basis sets. The DFT structures in solution were compared with the recently reported X-ray structure, solved by the crystalline-sponge method, of the methyl salicylate and the single-crystal X-ray structure of methyl 2,5-dihydroxybenzoate. It is demonstrated that the information provided by ¹H NMR chemical shifts about the solution structure is significantly more precise than that obtained by the single-crystal X-ray and the crystalline-sponge methods.     

Total synthesis of pawhuskin C: a directed ortho metalation approach

The total synthesis of the opioid modulator pawhuskin C has been accomplished in eight steps from methyl 3,5-dihydroxybenzoate. The key step in this sequence is a directed ortho metalation reaction conducted without protection of a benzylic alcohol and thus presumed to involve a formal dianion intermediate.     

One-pot synthesis of new functionalized azacryptands from resorcinol derivatives for advanced photonic materials

Functionalized azacryptands containing resorcinol derivatives such as orcinol (5-methylresorcinol), 3,5-dihydroxybenzoic acid (5-carboxyresorcinol), and methyl 3,5-dihydroxybenzoate (5-methoxycarbonylresorcinol) were synthesized by one-pot synthesis in the presence of potassium carbonate with moderately good yields for advanced photonic materials, such as optical amplifying and light-emitting materials, for the first time to our knowledge.     

合成聚芳酯树状分子的新方法

以３，５－二羟基 苯甲酸为起始原料，经甲醇酯化保护羧基，与苯甲酰氯反应，得到３，５－二苯甲酰氧基苯甲酸甲酯用ＡｌＣｌ３．ＮａＩ去掉保护基甲基，以高收率得到３，５－二苯甲酰氧基苯甲酸。其结构均是由ＩＲ，＾１ＨＮＭＲ，ＥＡ等方法证实。     

Lamellar organic thin films through self-assembly and molecular recognition.

Molecular clips possessing U-shaped cavities have been functionalized on their convex side with long aliphatic tails. These molecules form dimers which self-assemble into malleable lamellar thin films. Upon addition of a guest (methyl 3,5-dihydroxybenzoate), a 1:1 host-guest complex is formed, which prohibits clip dimerization. As a result, the lamellar structure of the material is lost. Complexation of 3,5-dihydroxybenzoic acid in the clip results in host-guest complexes which dimerize by hydrogen bonding interactions between the carboxylic acid functions of the bound guests. This dimerization restores the lamellar type architecture of the material.     

Synthesis of 4-chloro-7-ethoxy-2(3H)-benzoxazolone-6-carboxylic acid

As a part of metabolic studies of mosapride ( 1 ), a potential gastroprokinetic agent, the synthesis of 4-chloro-7-ethoxy-2(3H)-benzoxazolone-6-carboxylic acid ( 7 ) as a derivative of 4-amino-5-chloro-2-ethoxy-3-hydroxybenzoic acid ( 6 ), which has served a benzoic acid part of the metabolites 4 and 5 , is described. Treatment of methyl 3-amino-4-substituted amino-5-chloro-2-ethoxybenzoate derivatives 11a-c with sodium nitrate in acidic medium gave the benzotriazole derivatives 13x,y instead of the objective 3-hydroxy counterpart. The synthesis of 7 started from o-vanillin acetate ( 15 ) and proceeded through the intermediates 2-hydroxy-3-methoxy-4-nitrobenzaldehyde ( 18 ), methyl 4-amino-2,3-dihydroxybenzoate ( 23 ), and methyl 7-hydroxy-2(3H)-benzoxazolone-6-carboxylate ( 30 ). Compound 30 was alternatively prepared from 23 via methyl 4-ethoxycarbonylamino-2-ethoxycarbonyloxy-3-hydroxybenzoate ( 29 ), which is the product resulting from the migration of the ethoxycarbonyl group of methyl 4-amino-2,3-diethoxycar-bonyloxybenzoate ( 27 ).     

New polyfunctional spiropyran of 1,3-benzoxazin-4-one series with carbonyl-containing substituents in the [2H]-chromene moiety

A polyfunctional spiropyran of 1,3-benzoxazin-4-one series containing one hydroxy and two carbonyl substituents in the [2H]-chromene moiety was synthesized on the basis of a new analogue of 2,4-dihydroxyisophthalic aldehyde, methyl 3,5-diformyl-2,4-dihydroxybenzoate. The structure of resulting 6'-carbomethoxy-3,7-dimethyl-8'-formyl-5'-hydroxy-4-oxo-spiro-(1,3-benzoxazine-2,2'-[2H]-chromene) was unambiguously established by single crystal X-ray diffraction analysis. These data allowed us to reveal the route for the reaction of the new polyfunctional aldehyde with 1,3-benzoxazin-4-onium perchlorate.     

Calcium complex of 2,5-dihydroxybenzoic acid (gentisic acid): synthesis,crystal structure,and spectroscopic properties

The synthesis, crystal structure, and spectral characteristics (IR, Raman, and ¹H and ¹³C NMR) of a monomeric hexa(aqua)calcium compound, viz. [Ca(C₇H₅O₄)₂(H₂O)₆]·H₂O (C₇H₅O₄ = 2,5-dihydroxybenzoate), are reported. The central Ca(II) located on a twofold axis is eight coordinate in an approximate square antiprismatic environment, bonded to two monodentate 2,5-dihydroxybenzoate ligands via the carboxylate oxygen, and six waters. The adjacent monomeric units are linked with the aid of several O–H?O hydrogen bonds.     

Hydroxyl radical detection with a salicylate probe using modified CUPRAC spectrophotometry and HPLC

Reactive oxygen species (ROS) may attack biological macromolecules giving rise to oxidative stress-originated diseases, so it is important to establish efficient methods to screen hydroxyl radical scavengers for antioxidant therapy. Since *OH is very short-lived, secondary products resulting from *OH attack to various probes are measured. As a low-cost measurement technique, we used a salicylate probe for detecting hydroxyl radicals generated from an equivalent mixture of Fe(II)+EDTA with hydrogen peroxide. The produced hydroxyl radicals attacked both the probe and the water-soluble antioxidants in 37 degrees C-incubated solutions for 2 h. The CUPRAC (cupric ion reducing antioxidant capacity) assay absorbance of the ethylacetate extract due to the reduction of Cu(II)-neocuproine reagent by the hydroxylated probe decreased in the presence of *OH scavengers, the difference being proportional to the scavenging ability of the tested compound. Attack by *OH radicals upon salicylate produced 2,3-dihydroxybenzoate, 2,4-dihydroxybenzoate, and 2,5-dihydroxybenzoate as major products. HPLC separation combined with CUPRAC spectrophotometry was used to identify and quantify hydroxylated salicylate derivatives in the presence of synthetic water-soluble antioxidants and green tea infusion. The developed spectrophotometric method for *OH detection was validated with HPLC, i.e., the concentrations of dihydroxybenzoates produced by radical attack from the probe were determined by HPLC, and the sum of (concentrationxabsorptivity) products of these components approximately agreed with the experimentally found CUPRAC absorbances, confirming the validity of Beer's law for the selected system. Statistical comparison of the results found with the proposed methodology and HPLC was made with two-way ANOVA (analysis of variance) test. Under optimal conditions, about 53% of the probe (salicylate) was converted into dihydroxybenzoate isomers in the absence of *OH scavengers, and these isomers were more specific markers of hydroxyl radicals than the non-specific malondialdehyde end-product of the TBARS test. Thus, the more costly and less speedy HPLC method could advantageously be substituted with the proposed spectrophotometric assay of *OH detection, which was also of much higher yield than the TBARS colorimetric assay.     

Highly efficient construction of large molecular cavity using 1,3-alternate tetraoxacalix[2]arene[2]triazine as a platform

In the presence of K(2)CO(3) in refluxing THF, dichloro-substituted tetraoxacalix[2]arene[2]triazine, a readily available macrocyclic compound from cyanuric acid chloride and benzyl 1,3-dihydroxybenzoate, underwent highly efficient nucleophilic displacement reactions with bis-nucleophilic reagents of different geometry, length and chirality in a 2+2 fashion to produce large and size-tunable cavity bis-tetraoxacalix[2]arene[2]triazines in good to excellent yields.     

Monitoring Humic Acid Photodegradation by CUPRAC Colorimetric and HPLC Determination of Dihydroxybenzoate Isomers Produced From a Salicylate Probe

Abstract

Novel analytical methods were designed for monitoring humic acid photodegradation in environmental waters. Modified CUPric Reducing Antioxidant Capacity (CUPRAC) spectrophotometric and chromatographic methods were used for the determination of dihydroxybenzoate isomers (DHBAs) produced from a salicylate probe, which was hydroxylated by hydroxyl radicals (^?OH) produced from the photodegradation of humic acid under ultraviolet A-radiation. The combined use of CUPRAC colorimetry and HPLC was shown to effectively monitor humic acid photodegradation and ^?OH generation for the first time. The formation of 2,5-dihydroxybenzoate and 2,3-dihydroxybenzoate, as major and minor products, respectively, from the hydroxylation of a salicylate probe was demonstrated by HPLC and confirmed by a modified CUPRAC method to indicate ^?OH formation from humic acid, which acted as both a generator and absorber of hydroxyl radicals. Salicylate hydroxylation showed an increase between 30 and 50?min of illumination, and was affected by the initial concentration of humic acid up to 0.01% but not by solution pH around the neutral values. Traces of Fe(III) and Mn(II) present in natural waters decreased the ^?OH production, but EDTA partly restored the probe hydroxylation by chelating these metal cations. Since humic acid-mediated ^?OH generation may aid in natural disinfection processes, this work may extend our comprehension of concentration- and time-dependent generation of ^?OH in environmental waters and of the possible effects of other antioxidants.     

Solid-state changes in ligand-to-metal charge-transfer spectra of (NH3)5Ru(III)(2,4-dihydroxybenzoate) and (NH3)5Ru(III)(xanthine) chromophores

Five distorted-octahedral complexes containing (NH3)5Ru(III)L ions, where L = 2,4-dihydroxybenzoate or a xanthine, have been studied using a combination of X-ray crystallography, solution and polarized single-crystal electronic absorption spectroscopy, and first principles electronic structure computational techniques. Both yellow (2) and red (3) forms of the complex (NH3)5Ru(III)L, where L = 2,4-dihydroxybenzoate, as well as three xanthine complexes in which L = hypoxanthine-kappaN(7) (4), 7-methylhypoxanthine-kappaN(9) (5), and 1,3,9-trimethylxanthine-kappaN(7) (6) were examined. In the solid state, some of these complexes exhibit split low-energy ligand-to-metal charge-transfer (LMCT) bands. Traditional solid-state effects, such as ligand pi-pi overlap or hydrogen bonding that might lead to splitting of electronic absorption bands, were probed in an attempt to identify the origins of these unusual observations. For comparison, companion studies were carried out for spectroscopically normal reference complexes of the same ligands. Time-dependent density-functional theory (TD-DFT) calculations, employing modified B3LYP-type functionals with increased contributions of exact exchange, attribute the color change in the crystalline complexes 2 and 3 to pi(ligand) --> Ru[d(pi)] LMCT bands which, in the red form (3), arise from ligand donor pi-orbitals split by strongly overlapping phenyl moieties in centrosymmetric (NH3)5Ru(III)(2,4-dihydroxybenzoate) dimers. Complex 5 does not show split visible absorptions, whereas both the polarizations and energies of the split visible absorptions shown by 4 and 6 also suggest assignment as LMCT. No support is found for relating the split absorptions of 4 and 6 to the details of pi-pi xanthine overlap in the solid state; indeed, complex 4 enjoys considerably less pi-stacking overlap than does 5. We feel compelled to attribute the split absorptions in crystalline 4 and 6 to the emergence of a LMCT transition originating in the carbonyl lone pair, potentially deriving intensity from the significant intramolecular N-H...O hydrogen bonding present in both 4 and 6 (but not in 5). The electronic structure calculations suggest an O(n) --> Ru[d(sigma*)] LMCT transition; however, this novel assignment must be considered tentative.     

Voacalgines A–E,new indole alkaloids from Voacanga grandifolia

Five new indole alkaloids, voacalgines A–E (1–5) consisting of a C-mavacurine type of skeleton with 2,3-dihydroxybenzoate moiety, a macroline-type of skeleton, or a macroline-type of skeleton with C₆ unit, were isolated from the bark of Voacanga grandifolia. Their relative structures were determined by means of NMR data. Voacalgine A showed moderate cell growth inhibitory activities against HL-60 and HCT116 cells.     

Nonlinear analysis of dynamic binding in affinity capillary electrophoresis demonstrated for inclusion complexes of beta-cyclodextrin

The stability of the molecular host-guest inclusion complexes of beta-cyclodextrin with benzoate and four different hydroxybenzoates is investigated. For the measurement of the binding constants an experimental method is devised that is based on affinity capillary electrophoresis (ACE) with indirect UV absorbance detection. We derive an explicit equation for effective mobilities in ACE experiments without violation of rigorous mass balance. This equation is employed in the nonlinear least-squares analyses of the experimental data yielding binding constants of 48+/-2 M(-1) for benzoate, 299+/-38 M(-1) for 2-hydroxybenzoate, 37+/-1 M(-1) for 3-hydroxybenzoate, 228+/-9 M(-1) for 4-hydroxybenzoate, and 895+/-110 M(-1) in the case of 2,4-dihydroxybenzoate.     

Structure of the EntB multidomain nonribosomal peptide synthetase and functional analysis of its interaction with the EntE adenylation domain

Nonribosomal peptide synthetases are modular proteins that operate in an assembly line fashion to bind, modify, and link amino acids. In the E. coli enterobactin NRPS system, the EntE adenylation domain catalyzes the transfer of a molecule of 2,3-dihydroxybenzoic acid to the pantetheine cofactor of EntB. We present here the crystal structure of the EntB protein that contains an N-terminal isochorismate lyase domain that functions in the synthesis of 2,3-dihydroxybenzoate and a C-terminal carrier protein domain. Functional analysis showed that the EntB-EntE interaction was surprisingly tolerant of a number of point mutations on the surface of EntB and EntE. Mutational studies on EntE support our previous hypothesis that members of the adenylate-forming family of enzymes adopt two distinct conformations to catalyze the two-step reactions.     

Matrix-assisted laser desorption/ionization analysis of lipids and high molecular weight hydrocarbons with lithium 2,5-dihydroxybenzoate matrix

Lithium 2,5-dihydroxybenzoate (LiDHB) is shown to be a very effective matrix for matrix-assisted laser desorption/ionization (MALDI) analysis of nonpolar long-chain lipids, hydrocarbons and polymers. Under standard desorption and ionization conditions using a conventional nitrogen UV laser (337 nm), hydrocarbons (C(24)-C(40)), diverse lipids (triglycerides, diglycerides, wax esters from leaves) and saturated polymers are effectively lithiated providing [M+Li](+) ions. The formation of lithiated hydrocarbons is not accompanied by an elimination of hydrogen or other fragmentation reactions and, due to the relatively simple isotopic distribution of lithium, seems to be more useable for analysis of hydrocarbon mixtures than the previously used silver cationization agents. The mass calibration can be conveniently performed either externally or internally using poly(ethylene glycol) commercial standards.     

New polymer syntheses 84. Synthesis of functional polyethers by alkylation of silylated diphenols

4,4′-Bistrimethylsiloxy diphenylsulfone was polycondensed with six different alkylating agents in N-Methylpyrrolidone/K₂CO₃ mixtures and polyethers were isolated from all experiments. The best results were obtained with the mesylate of bis(2-hydroxyethyl)hydroquinone, BHEH. Similar results were found when silylated n-butyl-3,5-dihydroxybenzoate was used. A comparison of five different reaction media revealed that NMP gives the highest molecular weights. Finally, various silylated diphenols containing functional groups were polycondensed with the mesylate of BHEH. In this way polyethers with pending ester, aldehyde, keto, and amide groups were obtained. © 1996 John Wiley & Sons, Inc.     

Combinative improving effect of increased solubility and the use of absorption enhancers on the rectal absorption of uracil in beagle dogs

An improvement of the rectal absorption of uracil was examined by the application of absorption enhancers in addition to the increased solubility of uracil. Uracil was ground with additives such as MgO, sodium 2,6-dihydroxybenzoate, human serum albumin or hydroxypropylmethylcellulose acetate succinate. Aqueous, oily and powdery formulations, which consisted of the ground mixtures, nicotinamide, urea and absorption enhancers such as polyoxyethylene (23) cetylether (BC-23) or sodium caprate, were prepared. Uracil solubility in the aqueous formulations was increased about 4-13 times that in the corresponding control formulations. When rectally administered to beagle dogs, marked increases in the plasma uracil level were observed in some of the cases of aqueous and oily formulations. In the powdery formulations and formulations containing macromolecular additives, however, absorption improvements was not observed. The results indicated that an improvement in the absorption of uracil was caused by the combinative improving effect of the increased uracil solubility and the promoting effect of absorption enhancers.     

Thermodynamics of guest-induced structural transitions in hybrid organic-inorganic frameworks

We provide a general thermodynamic framework for the understanding of guest-induced structural transitions in hybrid organic-inorganic materials. The method is based on the analysis of experimental adsorption isotherms. It allows the determination of the free energy differences between host structures involved in guest-induced transitions, especially hard to obtain experimentally. We discuss the general case of adsorption in flexible materials and show how a few key quantities, such as pore volumes and adsorption affinities, entirely determine the phenomenology of adsorption, including the occurrence of structural transitions. On the basis of adsorption thermodynamics, we then propose a taxonomy of guest-induced structural phase transitions and the corresponding isotherms. In particular, we derive generic conditions for observing a double structural transition upon adsorption, often resulting in a two-step isotherm. Finally, we show the wide applicability and the robustness of the model through three case studies of topical hybrid organic-inorganic frameworks: the hysteretic hydrogen adsorption in Co(1,4-benzenedipyrazolate), the guest-dependent gate-opening in Cu(4,4'-bipyridine)(2,5-dihydroxybenzoate)2 and the CO2-induced "breathing" of hybrid material MIL-53.     

Diterpenoide Drüsenfarbstoffe aus Labiaten: 6 neue p-Chinomethane aus Plectranthus parviflorus WILLD

Leaf-gland Pigments: 6-Novel p-Quinomethanes of the Abietane Series from Plectranthus parviflorus WILLD The above mentioned plant accumulates in its red coloured leaf-glands a complex mixture of strongly dehydrogenated abietanols. They were separated (with difficulties) to yield 6 novel compounds. Spectroscopic and chiroptic data show them to be esters of either 11, 19-dihydroxy- or 2 α, 11-dihydroxy-abieta-5, 7, 9 (11), 13-tetraen-12-one 2a and 3a , respectively. Specifically, the 19-O-p-hydroxybenzoate ( 2d ) parvifloron C, the 19-O-vanilloate ( 2c ) parvifloron B, the 19-O-p-hydroxy-benzoate ( 2d ) parvifloron C, the 19-O-3′,4′-dihydroxybenzoate ( 2e ) parvifloron E, the 2 α-O-p-hydroxybenzoate ( 3b ) parvifloron D, and the 2 α-O-3′,4′-dihydroxy-benzoate ( 3c ) parvifloron F. Reduction by LiAlH₄ splits the ester function and reduces the p-quinomethane to a colourless pyrocatechol derivative which, by air oxidation, regenerates the red p-quinomethane system of 2a and 3a .