Dipropionic Acid Research Articles

A 2-(2′-hydroxyphenyl)quinazolin-4(3H)-one derived fluorescence ‘turn on’ probe for recognition of Hg2+ in water solution and its live cell imaging

Abstract A new fluorescence “turn on” Hg 2+ probe 3,3′-(((2-hydroxy-5-methyl-3-(4-oxo-3,4-dihydroquinazolin-2-yl)phenyl)methylene)bis(sulfanediyl))dipropionic acid ( QBDA ) based on Hg 2+ -triggered transformation of dithioacetal to aldehyde has been developed. Probe QBDA exhibits high selectivity and sensitivity to Hg 2+ over other metal ions in PBS buffered (20 mM, pH = 7.4) solution, the detection limit of QBDA for Hg 2+ was estimated to be 2.04 × 10 −8 M and the potential interference from Ag + can be suppressed in PBS buffered normal saline solution. Living cell imaging investigations show that QBDA possesses good cell permeability, and can act as a light-up imaging probe for Hg 2+ ions in MCF-7 cell.

Mushroom-Derived Flow Battery Electrolytes

There is a strong and growing need for reliable, cost-effective grid storage to support a transition from fossil fuels. Non-aqueous redox-flow batteries (NRFB) are a promising technology to meet this need but they are currently limited by poor stability of solution-phase, charge-carrying metal complexes. A major mechanism of decomposition of these redox electrolytes is substitution of ligands that have weak interactions with substitution-labile metal ions. Presented herein is an approach to mitigate these thermodynamic and kinetic challenges with a naturally occurring compound that is produced biologically. Mushrooms of the genus Amanita synthesize a molecule known as Amavadin, in which a vanadium ion is tightly coordinated by a pair of 2,2’-(hydroxyimino)dipropionic acid (HIDPA) ligands. Millions of generations of evolution have optimized the stability of this molecule. As a result, under physiological conditions in which most vanadium compounds would decompose, ligand substitution is suppressed. The electrochemical properties of redox molecules based on Amavadin as NRFB electrolytes will be presented. This will include data on electrochemical reversibility and stability to deep redox-cycling under various conditions. In addition, we will present the results of computational investigations that have guided ligand-design efforts. These are focused on optimization of the properties of Amavadin-based compounds for application in energy storage devices without losing their extraordinary ability to bind metal ions.

Graphene oxide promoted synthesis of p-phenylenediamine antioxidants

Three p-phenylenediamine antioxidants (p-phenylenediamine-N,N,N′,N′-tetrapropionic acid tetramethyl ester, p-phenylenediamine-N,N,N′-tripropionic acid trimethyl ester, and p-phenylenediamine-N, N′-dipropionic acid dimethyl ester) were successfully synthesized via atom-economic aza-Michael addition of pphenylenediamine to methyl acrylate p-romoted by graphene oxide in water. The synthesized compounds were characterized by NMR, ESI-MS spectra, and elemental analyses. The effects of the solvent and graphene oxide on the reaction were investigated.

Biodistribution and Pharmacokinetic Study of 3,3' Diseleno Dipropionic Acid (DSePA), A Synthetic Radioprotector, in Mice.

3,3' Diseleno dipropionic acid (DSePA), a synthetic compound has been shown to have radioprotective activity, especially as a lung radioprotector. In this study, the pharmacokinetics and biodistribution of DSePA in MX-1 tumour bearing SCID mice were evaluated. Twenty SCID mice were administered DSePA (50mg/kg bodyweight) by oral gavage following which four animals each were sacrificed at 15, 30min, 1, 2 and 4h. Blood and tissue samples were collected for determination of DSePA concentration by graphite furnace atomic absorption spectrometry (GFAAS) method. The control group (n=4) was administered sterile water and sacrificed at 4h. Peak plasma concentration (C max) of 2.7µg/ml was observed at 15min which returned to near baseline (baseline=0.6µg/ml) at 1h following drug administration. Biphasic pharmacokinetics characterized by rapid distribution phase and a slower elimination phase were observed. Highest maximal concentration (C max) of the drug was observed in lung (19.2µg/g at 30min) followed by intestine (14.64µg/g at 15min) and kidney (12.96µg/g at 15min). There was negligible uptake in tumor tissue and no uptake in brain. DSePA has a favorable pharmacokinetic profile which makes it a potentially good candidate for further development as a radioprotective agent.

Copper(II) Cyclam Complexes with N‐­Propionic Acid Pendant Arms

AbstractFour cyclam (1,4,8,11‐tetraazacyclotetradecane) ligands with different numbers of N‐substituted propionic acid groups lead to pentacoordinate copper(II) complexes that adopt trans‐I configurations (4+1 geometry), that is, the complexes have a d ground state with significant rhombic distortion. From the structural data (X‐ray diffraction analysis and electron paramagnetic resonance, UV/Vis and IR spectroscopy), as the number of secondary amine groups of the macrocyclic ring substituted with propionic acid groups increases, the distortion from square pyramidal to trigonal bipyramidal increases, and this is expected to lead to relatively low complex stabilities. This is confirmed by in vitro studies with superoxide dismutase (SOD) and human serum challenge experiments as well as by biodistribution data with the 64Cu‐labelled complexes. The 64Cu‐labelled complexes with cyclam monopropionic and dipropionic acid show high in vitro and in vivo stabilities, and the latter provides a comparable biodistribution profile to that of 64Cu–TETA (TETA = 1,4,8,11‐tetraazacyclotetradecane‐1,4,8,11‐tetraacetic acid).

Singlet Oxygen Generation by the Genetically Encoded Tag miniSOG

The genetically encodable fluorescent tag miniSOG is expected to revolutionize correlative light- and electron microscopy due to its ability to produce singlet oxygen upon light irradiation. The quantum yield of this process was reported as ΦΔ = 0.47 ± 0.05, as derived from miniSOG's ability to photooxidize the fluorescent probe anthracene dipropionic acid (ADPA). In this report, a significantly smaller value of ΦΔ = 0.03 ± 0.01 is obtained by two methods: direct measurement of its phosphorescence at 1275 nm and chemical trapping using uric acid as an alternative probe. We present insight into the photochemistry of miniSOG and ascertain the reasons for the discrepancy in ΦΔ values. We find that miniSOG oxidizes ADPA by both singlet oxygen-dependent and -independent processes. We also find that cumulative irradiation of miniSOG increases its ΦΔ value ~10-fold due to a photoinduced transformation of the protein. This may be the reason why miniSOG outperforms other fluorescent proteins reported to date as singlet oxygen generators.

A Uranyl Hybrid Compound Designed from Urea‐Bearing Dipropionic Acid

AbstractA uranyl‐urea‐bearing dipropionate hybrid compound, in which the two acid groups are coordinated in different modes and the urea group serves as both a coordination functionality and a supramolecular synthon, is prepared. The effect of hydrogen‐bonding interactions on the luminescence properties of the compound was explored by lifetime measurements. Thermogravimetric analyses were performed under a nitrogen atmosphere and in air. The “uranophilicity” of this urea‐bearing ligand was examined by competition experiments in alkaline spring water.

Improved Acid Stress Survival of Lactococcus lactis Expressing the Histidine Decarboxylation Pathway of Streptococcus thermophilus CHCC1524

Degradative amino acid decarboxylation pathways in bacteria generate secondary metabolic energy and provide resistance against acid stress. The histidine decarboxylation pathway of Streptococcus thermophilus CHCC1524 was functionally expressed in the heterologous host Lactococcus lactis NZ9000, and the benefits of the newly acquired pathway for the host were analyzed. During growth in M17 medium in the pH range of 5-6.5, a small positive effect was observed on the biomass yield in batch culture, whereas no growth rate enhancement was evident. In contrast, a strong benefit for the engineered L. lactis strain was observed in acid stress survival. In the presence of histidine, the pathway enabled cells to survive at pH values as low as 3 for at least 2 h, conditions under which the host cells were rapidly dying. The flux through the histidine decarboxylation pathway in cells grown at physiological pH was under strict control of the electrochemical proton gradient (pmf) across the membrane. Ionophores that dissipated the membrane potential (ΔΨ) and/or the pH gradient (ΔpH) strongly increased the flux, whereas the presence of glucose almost completely inhibited the flux. Control of the pmf over the flux was exerted by both ΔΨ and ΔpH and was distributed over the transporter HdcP and the decarboxylase HdcA. The control allowed for a synergistic effect between the histidine decarboxylation and glycolytic pathways in acid stress survival. In a narrow pH range around 2.5 the synergism resulted in a 10-fold higher survival rate.

Thermodynamic characteristics of protolytic equilibria of ethylenediamine-N,N′-diacetic-N,N′-dipropionic acid

Heat effects of protonation and neutralization of ethylenediamine-N,N′-diacetic-N,N′-dipropionic acid at 298.15 K and ion force values of 0.1, 0.5, and 1.0 (KNO3) were measured by the direct calorimetric method. Combined use of the results of thermochemical and potentiometric measurements carried out under the identical experimental conditions permitted to evaluate standard thermodynamic characteristics of the equilibria under study. The results obtained were compared with the corresponding data for related compounds considering the specific features of structure of the diamine complexones.

Carboxyalkylation of ethylene diamine with β-chloropropionic acid. A new approach to ethylene diamine-N,N′-di-and ethylene diamine-N,N,N′,N′-tetrapropionic acids

Reactive ethylene diamine-N,N'-dipropionic acid II is used as initial reagent for incorporating into chosen structures of organic compounds to obtain a number of reagents containing ethylene diamine propionate moieties. However, the most obvious way to obtain acid II by nucleophilic substitution of chlorine in βchloropropionic acid by amino-group did not lead to desired results: By the reaction of β-chloropropionic acid with ethylene diamine in alkaline medium followed by acidifying of the reaction mixture and conversion of the forming dihydrochloride into the acid we for the first time synthesized tertiary amine derivative I in 48% yield [2] irrespective of the starting materials molar ratio.

Determination of lead(II) in fly ash leachate using a newly developed simple spectrophotometric method

A new simple method for the spectrophotometric determination of Pb(II) in fly ash leachates was developed. These leachates tend to contain a large amount of Ca(II) and Zn(II); this interferes with spectrophotometric determination of Pb(II) when conventional colorimetric agents are used. A copolymer consisting of protoporphyrin IX disodium salt and acrylamide was synthesized as a colorimetric agent. A measuring reagent containing ethylenediamine-N,N′-dipropionic acid (EDDP) as a masking agent for Zn(II) and an appropriate amount of Ca(II) together with the copolymer was applied to determine Pb(II). The temporal change in the absorption spectrum of the measuring reagent was acquired with a newly developed portable spectrophotometer for this method. The composition of EDDP and Ca(II) in the measuring reagent was optimized to measure leachates contaminated with Ca(II) and Zn(II). The detection limit and relative standard deviation of Pb(II) measured using the optimized method were 0.05 mg L −1 and 2.3%, respectively. The tolerance limits for Ca(II) and Zn(II) contaminants, where errors of less than 10% were allowed at a concentration of 0.5 mg L −1 Pb(II), were 4000 and 4 mg L −1, respectively. The determination of Pb(II) in various samples of actual leachates from incinerator fly ash was examined with this method. The obtained values correlated well with those obtained by flame atomic absorption spectroscopy.

Lead-selective poly(vinyl choride) membrane electrodes based on heterocyclic thiocarboxylic acid

Heterocyclic thiocarboxylic acids have been designed to prepare polymeric membrane ion-selective electrode (ISE) for Pb2+. Construction, response characteristic and application of the lead ISEs are investigated. Better results have been obtained with membranes containing ligands L1∼L3 with bis(2-ethylhexyl) sebacate (DOS) as a plasticizer. Ionophores L1∼L3 are [(4,6-dimethyl-2-pyrimidinyl) thio] acetic acid (L1), (1,3,4-thiadiazole-2,5-diyldithio) diacetic acid (L2) and (1,3,4-thiadiazole-2,5-diyldithio) dipropionic acid (L3). The optimum electrodes have the composition of L1 (1.6): PVC (32.7): DOS (65.3): KTp ClPB (0.4) (w/w), L2 (1.0): PVC (32.8): DOS (66.0): KTpClPB (0.2) (w/w), and L3 (1.0): PVC (32.7): DOS (65.4): KTpClPB (0.9) (w/w). The optimized membrane electrodes work well over a wide range of concentrations (1.0 × 10−5 ∼1.0 × 10−2 M, 1.0 × 10−6 ∼1.0 × 10−2 M, and 1.0 × 10−6 ∼1.0 × 10−2 M) with the response slope of 27.4, 30.1 and 29.2 mV/decade, respectively. Potentiometric selectivities of the ISEs based on L1 ∼ L3 for Pb2+ over other interfering ions are determined with the fix interference method. The electrodes display good selectivity over a number of alkali, alkaline earth, transition and heavy metal ions. The lifetime of the electrodes is about 2 months and their response time is 20 s. Applications of these electrodes for the determination of lead in real samples and as indicator electrodes for potentiometric titration of Na2SO4 using Pb2+ solution are reported.

Double-helix pattern in a model compound of non-linear optical polymers

Molecules of the title compound, 3,3'-[4-(4-nitrophenyl-diazenyl)phenylimino]dipropionic acid, C 18 H 18 N 4 O 6 , a model compound of second-order non-linear optically active polymers, form helicoidal rows via hydrogen bonding between carboxy groups. Pairs of helices are wrapped around the common axis in a double-helix arrangement unprecedented in dicarboxylic acids. The lateral packing of the helices shows an interdigitated antiparallel arrangement of the chromophore units.

Screening of d-amino acid oxidase inhibitor by a new multi-assay method

This paper describes an investigation of the inhibition of a d-amino acid oxidase (DAAO) activity in several kinds of food additives and fruit. To screen for an inhibitor of DAAO, the method employed checked for two kinds of indicators, namely, pyruvic acid (indicator-1) and hydrogen peroxide (indicator-2), both of which are formed by digestion by DAAO of d-alanine (the standard d-amino acid used in this study). For measurement of pyruvic acid, a reliable and authenticated method was employed: the presence of pyruvic acid was determined by converting it into a chromophore derivative by tagging with 2,4-dinitro phenylhydrazine (DNP), followed by measurement of absorbance at 445 nm. The pyruvic acid thus determined is referred to as “(colorimetric) indicator-1”. To measure hydrogen peroxide, a highly sensitive fluorogenic substrate, 3-( p-hydroxyphenyl)propionic acid (HPPA), was employed in the present study. Hydrogen peroxide was detected by measuring fluorescence intensity (Ex. = 320 nm, Em. = 405 nm) of 2,2′-dihydroxybipheny l-5,5′-dipropionic acid (oxidize-HPPA), which is produced by horseradish peroxidase (HRP)-catalyzed oxidation of HPPA with hydrogen peroxide. The hydrogen peroxide thus determined is referred to as “(flourometric) indicator-2” After optimizing the multi-assay procedures, the inhibition of DAAO activity against d-alanine (used as the standard d-amino acid) in 11 kinds of food additives and five kinds of fruit was evaluated, first in terms of indicator-1. Then, two substrates, potassium sorbate and apple juice, that were screened by indicator-1, were further evaluated by indicator-2 to conform the inhibition of DAAO activity. This is the first demonstration of the inhibition of DAAO activity by potassium sorbate, which is widely used as a synthetic preservative in food and apple juice.

The first enantioselective synthesis of the amavadin ligand and its complexation to vanadium

The ligand of the naturally occurring vanadium compound amavadin found in Amanita muscaria, (2 S, 2′ S)- N-hydroxyimino-2,2′-dipropionic acid ( 1), was synthesized stereoselectively in two steps with 43% overall yield. After complexation of this ligand to vanadyl acetate, amavadin was isolated in quantitative yield. Due to the chirality at vanadium amavadin consists of a mixture of Δ and Λ diastereoisomers. Directly after its synthesis, the Δ to Λ ratio of amavadin is 2.27 and it decreases to 0.80 after equilibrium has been reached. During this epimerization the optical rotation for V[(2 S,2′ S)- N-hydroxyimino-(2,2′)-dipropionate] 2 (=amavadin) changes from [ α ] D 25 = + 36 ° to + 114.0 ° ( c = 0.5, H 2O). For V[(2 R,2′ R)- N-hydroxyimino-(2,2′)-dipropionate] the optical rotation changes from [ α ] D 25 = - 36 ° to - 113.2 ° ( c = 0.5, H 2O).

A Porphyrin Based Potentiometric Sensor for Zn2+ Determination

PVC based membranes of disodium salt of porphyrin 3,7,12,17-tetramethyl-8, 13-divinyl 2,18-porphine dipropionic acid (I) as ionophore with sodium tetra phenyl borate (NaTPB) as anion excluder and dibutyl phthalate (DBP), dioctyl phthalate (DOP), dibutyl butyl phosphonate (DBBP), tris(2- ethyl hexyl)phosphate (TEP), tri-n-butylphosphate (TBP) and 1- chloronaphthalene (CN) as plasticizing solvent mediators were prepared and constructed for determination of Zn(II). The PVC based membrane of (I) with DBBP as plasticizer and having anion excluder, NaTPB in the ratio PVC: I: NaTPB: DBBP (150: 10: 2: 200) gave the best results in terms of working concentration range (1.3×10-5-1.0 ×10-1M) with a Nernstian slope (30.0 mV/decade of activity). The useful pH range of the sensor is 3.0 –7.4, beyond which a drift in potential was observed. The response time of the sensor is 10s and the lifetime was about 2 months during which it could be used without any measurable divergence. It had good stability and reproducibility. The membrane worked satisfactorily in non-aqueous medium up to 40% (v/v) non-aqueous content. The selectivity coefficient values indicate that the electrode is highly selective for Zn2+ over a number of other cations except Na+ and Cd2+. Although Na+ and Cd2+ are likely to cause some interference, they would not interfere if present at the concentrations < 1 ×10-5 and < 5 ×10-5 M, respectively. The electrode has been used as an indicator electrode to determine the end point in the potentiometric titration of Zn2+ with EDTA.

Kinetic determination of ultramicro amounts of As(III) in solution

A new catalytic reaction is proposed and a kinetic method developed for the determination of ultramicro amounts of As(III) on the basis of its catalytic activity in the oxidation of ethylenediamine-N,N?-diacetic-N,N? dipropionic acid (EAP) by KMnO4 in the presence of hydrochloric acid. Under optimal conditions, the sensitivity of the method is 20 ng/cm3. The probable relative error is 7.6 ? 14.5 % for the concentration range 50 ? 200 ng/cm3 As(III). The effect of certain foreign ions upon the reaction rate were determined for the assessment of the selectivity of the method. The method has relatively good selectivity. Kinetic equations were proposed for the investigated process.

New molybdenum(v) analogues of Amavadin and their redox properties

Reactions of [MoO2(acetylacetonate)2] with the proligands (N-hydroxyimino)diacetic acid (H3hidpa), R,R-2,2′-(N-hydroxyimino)dipropionic acid (R,R-H3hidpa) or R,S-2,2′-(N-hydroxyimino)dibutyric acid (R,S-H3hidba) yielded the compounds [PPh4][Δ,Λ-Mo(hida)2]·CH2Cl21, [H5O2][Δ-Mo(R,R-hidpa)2] 2, [PPh4][Mo(R,S-hidba)2]·2H2O 3a and Na[Δ,Λ-Mo(R,S-hidba)2]·¼iPr2O 3b, respectively. Reactions of H3hida with a methanolic solution of [PPh4][MoOCl4(H2O)] in the presence of NaOH (ca. pH 8) provided an alternative synthesis for 1. The complex of 1 when transferred into CH2Cl2 using [PPh4]Br yielded brown block-like crystals from a CH2Cl2–EtOH solution, however, 2 and 3b were crystallised from H2O and MeCN solutions with [H5O2]+ and [Na]+ counter cations, respectively. X-Ray crystallography confirmed the same distinctive eight-co-ordinate geometry of the complex anions of 1, 2 and 3b as identified for Amavadin, the form in which vanadium(IV) is bound in Amanita muscaria mushrooms. EPR and UV/vis spectra recorded for 1, 2 and 3a are consistent with the presence of molybdenum(V). Cyclic voltammetric studies using a glassy carbon working electrode in CH2Cl2 for 1 exhibited a reversible MoVI/MoV and a quasi-reversible MoV/MoIV redox couple at E1/2 = +0.96 and −0.99 V (vs. a saturated calomel electrode), respectively. Complex 3a also displayed a reversible MoVI/MoV redox couple at E1/2 = +0.77 V, whereas the MoV/MoIV couple was irreversible (Epc = −1.28 V). Additional electrochemical studies with 2 recorded a reversible MoVI/MoV redox couple in Me2SO (E1/2 = +0.77 V), however in H2O this one-electron oxidation process is irreversible.

Simultaneous Determination of the Complexing Capacity and Conditional Stability Constant of Soluble Copper(II) Complexes in Natural-Water Samples by Using a Chelate Extraction Technique

Based on a back-extraction of bis(4,4,4-trifluoro-1-(2-thienyl)-1,3-butanedionato)copper(II), a method for the simultaneous determination of the copper(II) complexing capacity of natural water and the conditional stability constant of copper(II) complex with naturally occurring ligands was developed. The feasibility of the proposed method was confirmed using nitrilotriacetic acid and ethylenediamine-N,N'-dipropionic acid instead of naturally occurring ligands. It was then applied to a pond-water sample. The results indicated that two types of copper(II) complexes having different stabilities were formed upon the addition of copper(II) to the sample. By using the copper(II) complexing capacity and the conditional stability constant, the distribution of copper(II) species in pond water was calculated. It was found that most of the copper(II) in pond water exists as a complex with a naturally occurring ligand, and that the concentration of free copper(II) ion is extremely low.

NMR studies on natural and synthetic Amavadin

The stereochemistry of isolated natural product Amavadin, which contains a 1:2 complex of V(IV) with N-hydroxyimino-2,2′-dipropionic acid (HIDPAH 3), and some synthetic complexes have been investigated. Amavadin was isolated from Amanita muscaria and oxidized with [NH 4] 2[Ce(NO 3) 6]. H 2[Δ-V( S,S-HIDPA) 2].3H 2O, H 2[Δ,Λ-V( S,S-HIDPA) 2].3H 2O and their equivalent oxidized species have been synthesized and characterized spectroscopically. A combination of COSY, NOE, 1H, 13C-NMR and CD spectroscopy have been used to prove that the isolated natural product Amavadin consists of an almost equal mixture of the Δ- and Λ-isomers of [V( S,S-HIDPA) 2] 2−.