Formation and structure of 1:1 complexes between aryl hydroxamic acids and vanadate at neutral pH

Although aryl hydroxamic acids are well-known to form coordination complexes with vanadate (V(V)), the nature of these complexes at neutral pH and submillimolar concentrations, the conditions under which such complexes inhibit various serine amidohydrolases, is not well established. A series of qualitative and quantitative experiments, involving UV/vis, (1)H NMR, and (51)V NMR spectroscopies, established that both 1:1 and 1:2 vanadate/hydroxamate complexes form at pH 7.5, with the former dominating at submillimolar concentrations. Formation constants for the complexes of several aryl and alkyl hydroxamic acids were determined; for example, for benzohydroxamic acid, the stepwise formation constants of the 1:1 and 1:2 complexes were 3000 and 400 M(-1), respectively. The (51)V chemical shift of the 1:1 4-nitrobenzohydroxamic acid complex was -497 ppm, and that of its unsubstituted analogue was -498 ppm. A (1)H-(15)N HSQC spectrum of the 4-nitrobenzo-(15)N-hydroxamic acid/vanadate complex indicated the presence of an N-H group with (15)N and (1)H chemical shifts of 115 and 5.83 ppm, respectively. A (13)C NMR spectrum of the complex of 4-nitrobenzo-(13)C-hydroxamic acid with vanadate displayed a resonance at 170.1 ppm and thus a coordination-induced shift (CIS) of +3.8 ppm. In contrast, the CIS value of an established 1:2 complex, thought to contain chelated hydroxamic acid ligands, was +11.9 ppm. These spectral data led to the following structural picture of 1:1 complexes of vanadate and aryl hydroxamic acids. They contain penta- or hexa-coordinated vanadium. The ligand is in the hydroxamate rather than hydroximate form. The ligand is presumably bound to vanadium through the hydroxamic hydroxyl oxygen, but the hydroxamic acid carbonyl oxygen interacts weakly with vanadium. These species are the most likely candidates for the inhibitors of serine amidohydrolases found in vanadate/hydroxamic acid mixtures.     

A facial microwave-assisted synthesis, spectroscopic characterization and preliminary complexation studies of calix[4]pyrroles containing the hydroxamic-acid moiety

The synthesis, spectroscopic characterization and preliminary complexation properties of functionalized calix[4]pyrroles are described. To date, two generalized preparative approaches have been pursued (i) modifying the basic pyrrole-plus-ketone synthesis of calix[4]pyrrole by using microwave irradiation protocol, (ii) the basic meso-tetra(methyl) meso-tetra(p-nitrophenyl) calix[4]pyrrole skeleton was functionalized to give hydroxamic acids, especially in the meso-position of the macrocycles. The structures of novel calix[4]pyrrole hydroxamic acid derivatives were confirmed on the basis of various physico-chemical techniques such as elemental analysis, FT-IR, ¹H NMR and FAB-Mass. The results of preliminary studies on the extraction of vanadium (V) with the host calix[4]pyrrole hydroxamic acids were elucidated by significant examination of UV–Vis spectroscopy and ICP-AES. Single crystal structure of basic meso-tetra(methyl) meso-tetra (p-nitro phenyl) calix[4]pyrrole moiety has also been reported.     

Thermodynamic cycle for the calculation of ab initio pKa values for hydroxamic acids

A thermodynamic cycle to calculate pK_a values (Minus log of acid dissociation constants) of hydroxamic acids is presented. Hydroxamic acids exist mainly as amide isomers in the aqueous medium. The amide form of hydroxamic acids has two deprotonation sites and may yield either an N-ion or an O-ion upon deprotonation. The thermodynamic cycle proposed includes the gas-phase N–H deprotonation of the hydroxamic acid, the solvent phase transformation of the N-ion to the O-ion and the solvation of the hydroxamic acid molecule and the O-ion in water. The CBS-QB3 method was employed to obtain gas-phase free energy differences between 12 hydroxamic acids and their respective anions. The aqueous solvation Gibbs free energy changes were calculated at the HF/6-31G(d)/CPCM and HF/6-31+G(d)/CPCM levels of theory using HF/6-31+G(d)/CPCM geometries. For the proton, literature values of the gas-phase free energy of formation and the solvation free energy change were used. The free energy change for the transformation of the N-ion to O-ion in the aqueous medium was calculated by employing CBS-QB3/CPCM in the aqueous medium. For this, the hydroxamic acids were divided in two classes according to the substituent at the carbonyl carbon. A common transformation free energy difference for aliphatic substituted hydroxamic acids and a separate common transformation free energy difference for aromatic substituted hydroxamic acids were obtained. The pK_a calculation yielded a root mean square error of 0.32 pK_a units.     

Investigation of nitrogen- and sulfur-containing heterocycles

The corresponding N-(3-pyridyl)hydroxamic acid derivatives were obtained by reductive desulfuration of [2-(ethoxycarbonylmethylthio)-6-chloro-3-pyridyl]hydroxamic acid amide, benzylamide, and morpholide. The amides were synthesized by reaction of [2-(ethoxycarbonylmethylthio)-6-chloro-3-pyridyl]hydroxamic acid ester with diethylaminoethylamine and pyrrolidine. Heating of the ester and morpholide of [2-(ethoxycarbonylmethylthio)-6-chloro-3-pyridyl]hydroxamic acid with H₂SO₄ gives 2-chloropyrido[2,3-b] [1,4]thiazin-6-one.See [1] for communication XXVI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 676–678, May, 1973.     

Functional monomers and polymers. LXXI. Conformation and interaction studies of poly-L-lysine derivatives with pendant nucleic acid bases

Copolymers of L -lysine and L -lysine derivatives which contained nucleic acid bases substituted on the N^ε position were synthesized by grafting nucleic acid derivatives onto poly-L -lysine. The conformation and interaction of these copolymers in solution were studied by using spectroscopic measurements. They existed in helical conformation at neutral pH values, and the polymer complex formation among them was examined by ultraviolet (UV) measurements in organic solvents. A decrease in the nucleic acid base content of the copolymers resulted in a decrease in helical structures and also in interactions with the polymer-containing complementary bases.     

亚硝基化合物与甲醛的反应机理和溶剂效应的理论研究

采用密度泛函方法B3LYP/6-311++G(d,p)研究了亚硝基苯C₆H₅-NO和2-甲基-2-亚硝基丙烷(CH₃)₃C-NO与甲醛分别在气相和溶剂中的反应机理. 在气相中均找到两条反应通道, 即协同机理和分步机理, 均生成实验产物氧肟酸, 而且分步机理均为优势通道; 除2-甲基-2-亚硝基丙烷的反应没有协同途径外, 在溶剂中反应机理与气相中的类似. 采用导电极化连续介质模型分别研究了在乙腈与水溶液中反应的溶剂化效应, 发现这些溶剂可降低反应的活化能, 但降低的程度比较小, 反应速率变化不大.     

Hydroxamic acids as weak base indicators: protonation in strong acid media.

The protonation equilibria of N-phenylbenzohydroxamic, benzohydroxamic, salicylhydroxamic, and N-p-tolylcinnamohydroxamic acids have been studied at 25 degrees C in concentrated sulfuric, hydrochloric, and perchloric acid media; the UV-vis spectral measurements were analyzed using the Hammett equation and the Bunnett-Olsen and excess acidity methods. The medium effects observed in the UV spectral curves were corrected with the Cox-Yates and vector analysis methods. The H(A) acidity function based on benzamides provided the best results. The range of variation of the solvation coefficient m is similar to that of amides, this indicating similar solvation requirements for amides and hydroxamic acids. For the same substrate, the observed variations of pK(BH)(+) with the mineral acid used was justified by formation of solvent-separated ion pairs; for the same mineral acid, the observed changes in pK(BH)(+) can be explained by the solvation of BH(+). The change of the pK(BH)(+) values was in reasonably good agreement with the sequence of the catalytic efficiency of the mineral acids used, HCl > H(2)SO(4) > HClO(4).     

A convenient parallel synthesis of low molecular weight hydroxamic acids using polymer-supported 1-hydroxybenzotriazole

A convenient two-step procedure for the parallel synthesis of hydroxamic acids from carboxylic acids and hydroxylamine in good to high yields is reported. It involves the formation of a polymer-bound HOBt active ester and subsequent reaction with O-protected or free hydroxylamine. The hydroxamates are isolated with high purities by simple evaporation of volatile solvents. The use of free hydroxylamine leads to increased yields while maintaining high purities. Recycling of the spent resin to produce the same or a different hydroxamic acid has been achieved by a three-step protocol which is easily amenable to automation and cost-economical. The method presented here is well suited to the preparation of the title compounds and can be used effectively to synthesise large molecules containing a hydroxamic acid group.     

Determination of tetraethyl ammonium by ion-pair chromatography with indirect ultraviolet detection using 4-aminophenol hydrochloride as background ultraviolet absorbing reagent

A method was developed for the determination of tetraethyl ammonium (TEA) by reversed-phase ionpair chromatography with indirect ultraviolet detection. Chromatographic separation was achieved on a reversed-phase C18 column using background ultraviolet absorbing reagent - ion-pair reagent - organic solvent as mobile phase. The effects of the background ultraviolet absorbing reagents, detection wavelength, ion-pair reagents, organic solvents and column temperature on the determination method were investigated and the retention rules discussed. Results found that TEA could be successfully analyzed by using 0.7 μmol/L 4-aminophenol hydrochloride and 0.15 μmol/L 1-heptanesulfonic acid sodium mixed with 20% (v/v) methanol asmobile phase at a UV detection wavelength of 230 nm. Under these conditions, the retention time of tetraethyl ammonium was 2.85 min. The detection limit (S/N = 3) for TEA was 0.06 mg/L. The relative standard deviations (n = 5) for peak area and retention time were 0.35% and 0.02%, respectively. The method has been successfully applied to the determination of synthesized tetraethyl ammonium bromide. Recovery of tetraethyl ammonium after spiking was 99.1%.     

Solvent colorimetric paper-based polydiacetylene sensors from diacetylene lipids

A well known unique property of polydiacetylenes (PDAs) is the colorimetric response to external stimuli making it one of the most studied conjugated polymers for sensing applications. Here we report the synthesis of a novel series of diacetylene acids from the condensation of pentacosa-10,12-diynylamine (PCDAmine) and dicarboxylic acid or its anhydrides. One of these diacetylene lipids, 4-(pentacosa-10,12-diynylamino)-4-oxobutanoic acid (PCDAS), is used in combination with pentacosa-10,12-diynoic acid (PCDA) for dropcasting on pieces of filter paper which are consequently irradiated by UV light to generate a paper based sensor array for solvent detection and identification. Upon the exposure to various types of organic solvents, the blue colored sensors colorimetrically respond to give different shades of colors between blue to red. The color patterns of the sensor array are recorded as RedGreenBlue (RGB) values and statistically analyzed by principal component analysis (PCA). The PCA score plot reveals that the array is capable of identifying eleven common organic solvents.     

Asymmetric Transfer Hydrogenation of Ketones Catalyzed by Amino Acid Derived Rhodium Complexes: On the Origin of Enantioselectivity and Enantioswitchability

Amino acid based thioamides, hydroxamic acids, and hydrazides have been evaluated as ligands in the rhodium‐catalyzed asymmetric transfer hydrogenation of ketones in 2‐propanol. Catalysts containing thioamide ligands derived from L ‐valine were found to selectively generate the product with an R configuration (95 % ee), whereas the corresponding L ‐valine‐based hydroxamic acids or hydrazides facilitated the formation of the (S)‐alcohols (97 and 91 % ee, respectively). The catalytic reduction was examined by performing a structure–activity correlation investigation with differently functionalized or substituted ligands and the results obtained indicate that the major difference between the thioamide and hydroxamic acid based catalysts is the coordination mode of the ligands. Kinetic experiments were performed and the rate constants for the reduction reactions were determined by using rhodium–arene catalysts derived from amino acid thioamide and hydroxamic acid ligands. The data obtained show that the thioamide‐based catalyst systems demonstrate a pseudo‐first‐order dependence on the substrate, whereas pseudo‐zero‐order dependence was observed for the hydroxamic acid containing catalysts. Furthermore, the kinetic experiments revealed that the rate‐limiting steps of the two catalytic systems differ. From the data obtained in the structure–activity correlation investigation and along with the kinetic investigation it was concluded that the enantioswitchable nature of the catalysts studied originates from different ligand coordination, which affects the rate‐limiting step of the catalytic reduction reaction.     

Molecular switch triggered by solvent polarity: synthesis,Acid-base behavior,alkali metal ion complexation,and crystal structure

The synthesis and characterization of the new tetraazamacrocycle L, bearing two 1,1'-bis(2-phenol) groups as side-arms, is reported. The basicity behavior and the binding properties of L toward alkali metal ions were determined by means of potentiometric measurements in ethanol/water 50:50 (v/v) solution (298.1+/-0.1 K, I=0.15 mol dm(-3)). The anionic H(-1)L(-) species can be obtained in strong alkaline solution, indicating that not all of the acidic protons of L can be removed under the experimental conditions used. This species behaves as a tetraprotic base (log K(1)=11.22, log K(2)=9.45, log K(3)=7.07, log K(4)=5.08), and binds alkali metal ions to form neutral [MH(-1)L] complexes with the following stability constants: log K(Li)=3.92, log K(Na)=3.54, log K(K)=3.29, log K(Cs)=3.53. The arrangement of the acidic protons in the H(-1)L(-) species depends on the polarity of the solvents used, and at least one proton switches from the amine moiety to the aromatic part upon decreasing the polarity of the solvent. In this way two different binding areas, modulated by the polarity of solvents, are possible in L. One area is preferred by alkali metal ions in polar solvents, the second one is preferred in solvents with low polarity. Thus, the metal ion can switch from one location to the other in the ligand, modulated by the polarity of the environment. A strong hydrogen-bonding network should preorganize the ligand for coordination, as confirmed by MD simulations. The crystal structure of the [Na(H(-1)L)].CH(3)CN complex (space group P2(1)/c, a=12.805(1), b=20.205(3), c=14.170(2) A, beta=100.77(1) degrees, V=3601.6(8) A(3), Z=4, R=0.0430, wR2=0.1181), obtained using CH(2)Cl(2)/CH(3)CN as mixed solvent, supports this last aspect and shows one of the proposed binding areas.     

Synthesis of 4-hydroxy-4,5-dihydro-1,2,4-triazol-5-ones

Summary A series of hydroxamic acid ethoxycarbonylhydrazides was obtained by reactions of ester ethoxycarbonylhydrazones with hydroxylamine. The corresponding 3-substituted 4-hydroxy-4,5-dihydro-1,2,4-triazol-5-ones were synthesized by cyclization of these hydroxamic acid derivatives in basic medium.

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Synthesen von 4-Hydroxy-4,5-dihydro-1,2,4-triazol-5-onen

Zusammenfassung Durch Reaktion von Esterethoxycarbonylhydrazonen und Hydroxylamin wurde eine Reihe von Hydroxamsäureethoxycarbonylhydraziden gewonnen; Cyclisierung dieser Verbindungen durch Base gab die entsprechenden 3-substituierten 4-Hydroxy-4,5-dihydro-1,2,4-triazol-5-one.

     

Cyclic hydroxamic acids derived from α-amino acids 2. Regioselective synthesis,crystal structure,and antitumor activity of spiropiperidine-imidazolidine hydroxamic acids based on glycine and dl-alanine

Regioselective cyclocondensation of glycine hydroxamic and dl-alanine hydroxamic acids with 1-methylpiperidin-4-one gave 1-hydroxy-8-methyl-1,4,8-triazaspiro[4.5]decan-2-one (5) and (±)-1-hydroxy-3,8-dimethyl-1,4,8-triazaspiro[4.5]decan-2-one (6), respectively. The X-ray diffraction data showed that acid 6 formed racemic crystals with two independent molecules, whose structure was studied and compared with the analog obtained earlier. The in vivo tests on the leukemia P388 and L1210 models showed that the low-toxic spirocyclic hydroxamic acids 5 and 6 were the adjuvants of clinic cytostatics cisplatin and cyclophosphamide. Chemotherapy of the leukemias P388 and L1210 was more efficient with the combination of acid 6 with cisplatin and cyclophosphamide, respectively.     

Sensitive determination of nitrophenol isomers by reverse-phase high-performance liquid chromatography in conjunction with liquid–liquid extraction

A method for the highly sensitive determination of 2-, 3- and 4-nitrophenols was developed using reverse-phase high-performance liquid chromatography (RP-HPLC) with a UV photodiode array detector. Using a reverse-phase column and 40% aqueous acetonitrile as an eluent (i.e. isocratic elution), the integrated peak area of detector output was linear up to 300 mg/L and the detection limit was 150 µg/L. The sensitivity of this detection method was improved by pretreating the sample solutions with a solvent extraction procedure that makes use of the high partition coefficient of ethyl acetate (EA)/water system. To find an optimum condition for the extraction procedure, this process was simulated by plotting the concentration of nitrophenol extracted in organic solvent against the volume multiplication factor at various partition coefficient of solute. This simulation demonstrated that EA is a superior extractant to other organic solvents. With the newly developed method, the detection limit was extended to 0.3 µg/L. This method offers fast, reliable and more sensitive determination of nitrophenol isomers than any other HPLC method.     

Chromium(V) complexes of hydroxamic acids: formation, structures, and reactivities

A new family of relatively stable Cr(V) complexes, [Cr(V)O(L)(2)](-) (LH(2) = RC(O)NHOH, R = Me, Ph, 2-HO-Ph, or HONHC(O)(CH(2))(6)), has been obtained by the reactions of hydroxamic acids with Cr(VI) in polar aprotic solvents. Similar reactions in aqueous solutions led to the formation of transient Cr(V) species. All complexes have been characterized by electron paramagnetic resonance spectroscopy and electrospray mass spectrometry. A Cr(V) complex of benzohydroxamic acid (1, R = Ph) was isolated in a pure form (as a K(+) salt) and was characterized by X-ray absorption spectroscopy and analytical techniques. Multiple-scattering analysis of X-ray absorption fine structure spectroscopic data for 1 (solid, 10 K) point to a distorted trigonal-bipyramidal structure with trans-oriented Ph groups and Cr-ligand bond lengths of 1.58 A (Cr-O), 1.88 A (Cr-O(C)), and 1.98 A (Cr-O(N)). Under ambient conditions, 1 is stable for days in aprotic solvents but decomposes within minutes in aqueous solutions (maximal stability at pH approximately 7), which leads predominantly to the formation of Cr(III) complexes. Complex 1 readily undergoes ligand-exchange reactions with biological 1,2-diols, including D-glucose and mucin, in neutral aqueous solutions. It differs from most other types of Cr(V) complexes in its biological activity, since no oxidative cleavage of plasmid DNA in vitro and no significant bacterial mutagenicity (in the TA 102 strain of Salmonella typhimurium) was observed for 1. In natural systems, stabilization of Cr(V) by hydroxamato ligands from bacterial-derived siderophores (followed by ligand-exchange reactions with more abundant carbohydrate ligands) may occur during the biological reduction of Cr(VI) in contaminated soils.     

Sensitive determination of phenylarsenic compounds based on a dual preconcentration method with capillary electrophoresis/UV detection

A novel method based on off-line hollow fiber based liquid liquid liquid microextraction (HF-LLLME) combined with on-column anion selective exhaustive injection (ASEI)-capillary electrophoresis/ultraviolet (CE/UV) detection was proposed for the speciation of five phenylarsenic compounds including phenylarsonic acid (PAA), 4-aminophenylarsonic acid (4-APAA), 4-hydroxyphenylarsonic acid (4-HPAA), 4-nitrophenylarsonic acid (4-NPAA) and 3-nitro-4-hydroxyphenylarsonic acid (NHPAA) in this paper. In HF-LLLME, the target analytes were extracted from 5 mL aqueous samples (donor solution pH 2.15) through a thin phase of tributyl phosphate (TBP) inside the pores of a polypropylene hollow fiber and finally into an 18 μL 0.8 mmol/L Tris acceptor solution inside the lumen of the hollow fiber. Following HF-LLLME, the acceptor solutions were directly analyzed by ASEI-CE/UV. For ASEI, a large plug of water (91% length of total capillary) was introduced into the separation capillary before sample injection in order to prolong the sample injection time, and thus enhance the stacking efficiency. Under the optimized ASEI conditions, up to 236-fold of enrichment factor (EF) was obtained for the ASEI-CE/UV determination of target phenylarsenic compounds. By combining HF-LLLME with ASEI-CE/UV, EFs ranging from 155 to 1780-fold were achieved and the limits of detection (LODs) (at a signal-to-noise ratio of 3) were in the range of 0.68-6.90 μg/L for five phenylarsenic compounds; the relative standard deviations (RSDs) of corrected peak area were 5.6-11.8%. The proposed HF-LLLME-ASEI-CE/UV method was applied for the determination of five target phenylarsenic compounds in pig feed from a local pig farm, and storage pig litter, soil in agricultural field and lake water collected near this pig farm, the recoveries for the spiked samples were in the range of 85.7-104.5%, 66.7-96.2%, 28.9-46.9% and 86.9-107.8% for pig feed, pig litter, soil and lake water, respectively.     

Determination of UV-filters in sunscreens by HPLC

Simultaneous determination of six internationally authorised organic UV-filters in sunscreen formulations was performed by HPLC with UV spectrophotometric detection. The filters determined were: sulisobenzone, oxybenzone, octyl dimethyl PABA, octyl methoxycinnamate, octyl salicylate and homosalate. A C18 stationary phase and a mobile phase of ethanol water acetic acid (70:29.5:0.5) were used with a flow rate of 0.5 mL/min. UV measurements were carried out at 313 nm. The time required for the analysis was 25 min and the limits of detection were between 0.2 and 2 mg/L, except for sulisobenzone, which gave a limit of detection of 20 mg/L. The procedure proposed provides an accurate, fast and green analytical method, that does not involve toxic organic solvents.     

漂浮液滴固化分散液液微萃取与高效液相色谱联用检测环境水样中的3种烷基苯酚

建立了漂浮液滴固化分散液液微萃取(DLLME-SFO)方法,以脂肪酸作为萃取剂,以甲醇作为分散剂,与高效液相色谱联用检测了环境水样中3种烷基苯酚。对影响前处理方法的因素进行了详细考察,在最佳萃取条件(60μL萃取剂辛酸、600μL分散剂甲醇、pH值为2.0~8.0、10 mL水样中加入0.5 g NaCl)下,3种烷基苯酚在20~1 500μg/L范围内具有良好的线性关系,相关系数不小于0.998 5,3种目标化合物的检出限为0.45~0.61μg/L,富集倍数为145~169,实际样品中3个水平的加标回收率为80.1%~109.9%。该方法将脂肪酸作为萃取剂,与HPLC联用实现了烷基苯酚的富集与检测,为环境水样中烷基苯酚的检测提供了对环境友好的前处理新方法。     

电堆集富集非水毛细管电泳同时测定水杨酸、肉桂酸、阿魏酸和香草酸

建立了同时分离测定水杨酸、肉桂酸、阿魏酸和香草酸的电堆集富集-非水毛细管电泳(NACE)的新方法。运行缓冲溶液为40mmol/L乙酸钠-2.5mmol/L氢氧化钠甲醇溶液,电压-25kV,在225nm波长下紫外检测。对电压、乙酸钠浓度、氢氧化钠浓度、进样时间、样品溶液等因素对电堆集及分离的影响做了系统的研究。水杨酸、肉桂酸、阿魏酸和香草酸分别在1.4~28mg/L、0.40~8.0mg/L、0.7~18mg/L和0.7~30mg/L范围内线性关系良好(r=0.9999、r=0.9997、r=0.9994、r=0.9997);回收率分别为95.8~99.6%、96.2~98·2%、95.7~105%和98.9~103%,基于3倍信噪比(S/N=3),4种有机酸的检出限分别为0.069、0.051、0.107和0.089mg/L。