The deprotonation and protonation equilibria of a hypericin derivative in aqueous solution

Summary A hypericin derivative ,'-appended at the methyl groups with two polyethylene glycol moieties (about 23 units long) and capped with acetyl groups was synthesized starting from emodin. This derivative proved to be soluble in water and was investigated by means of spectrophotometric titrations and electrophoresis experiments. Deprotonation at thebay-region hydroxyl group was observed atpK _a=1.6. This was followed by a second deprotonation step of aperi-hydroxyl group at apK _a value of 9.4. This derivative could be protonated at the carbonyl group characterized by apK _a value of –5.7. FrompK _a determinations in water-ethanol mixtures the correspondingpK _a values of hypericin itself determined in such mixtures were extrapolated to the aqueous phase. This resulted in estimatedpK _a values of 1.8, 9.2, and –6.

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Deprotonierungs- und Protonierungsgleichgewichte eines Hypericinderivates in wäßriger Lösung

Zusammenfassung Ein an den Methylgruppen von Hypericin mit endständig acetylierten Polyethylenglykolketten (ungefähr 23 Einheiten lang) ,'-disubstituiertes Derivat wurde ausgehend von Emodin synthetisiert. Dieses Derivat ist wasserlöslich, und es wurde mit Hilfe von spektrophotometrischen Titrationen und Elektrophorese untersucht. Die Deprotonierung derbay-Hydroxylgruppe erfolgt beipK _a=1.6. Diese wird von einem zweiten Deprotonierungsschritt an einerperi-Hydroxylgruppe bei einempK _a-Wert von 9.4 gefolgt. Dieses Derivat konnte an der Carbonylgruppe protoniert werden, was durch einenpK _a-Wert von –5.7 charakterisiert ist. Ausgehend vonpK _a-Messungen in Wasser-Ethanol-Mischungen wurden die entsprechendenpK _a-Werte auch für das Hypericin selbst in wäßriger Phase extrapoliert. Dies führte zu geschätztenpK _a-Werten von 1.8, 9.2 und –6.

     

Synthesis, pH-dependent structural characterization, and solution behavior of aqueous aluminum and gallium citrate complexes

Reactions of Al(III) and Ga(III) with citric acid in aqueous solutions, yielded the complexes (NH(4))(5)[M(C(6)H(4)O(7))(2)].2H(2)O (M(III) = Al (1), Ga (2)) at alkaline pH, and the complexes (Cat)(4)[M(C(6)H(5)O(7))(C(6)H(4)O(7))].nH(2)O (M(III) = Al (3), Ga (4), Cat. = NH(4)(+), n = 3; M(III) = Al (5), Ga (6), Cat. = K(+), n = 4) at acidic pH. All compounds were characterized by spectroscopic (FT-IR, (1)H, (13)C, and (27)Al NMR, (13)C-MAS NMR) and X-ray techniques. Complex 1 crystallizes in space group P1, with a = 9.638(5) A, b = 9.715(5) A, c = 7.237(4) A, alpha = 90.96(1) degrees, beta = 105.72(1) degrees, gamma = 119.74(1) degrees, V = 557.1(3) A(3), and Z = 1. Complex 2 crystallizes in space group P1, with a = 9.659(6) A, b = 9.762(7) A, c = 7.258(5) A, alpha = 90.95(2) degrees, beta = 105.86(2) degrees, gamma = 119.28(1) degrees, V = 564.9(7) A(3), and Z = 1. Complex 3 crystallizes in space group I2/a, with a = 19.347(3) A, b = 9.857(1) A, c = 23.412(4) A, beta = 100.549(5) degrees, V = 4389(1) A(3), and Z = 8. Complex 4 crystallizes in space group I2/a, with a = 19.275(1) A, b = 9.9697(6) A, c = 23.476(1) A, beta = 100.694(2) degrees, V = 4432.8(5) A(3), and Z = 8. Complex 5 crystallizes in space group P1, with a = 7.316(1) A, b = 9.454(2) A, c = 9.569(2) A, alpha = 64.218(4) degrees, beta = 69.872(3) degrees, gamma = 69.985(4) degrees, V = 544.9(2) A(3), and Z = 1. Complex 6 crystallizes in space group P1, with a = 7.3242(2) A, b = 9.4363(5) A, c = 9.6435(5) A, alpha = 63.751(2) degrees, beta = 70.091(2) degrees, gamma = 69.941(2) degrees, V = 547.22(4) A(3), and Z = 1. The crystal structures of 1-6 reveal mononuclear octahedral complexes of Al(III) (or Ga(III)) bound to two citrates. Solution NMR, on both 4- and 5- species, reveals rapid intramolecular exchange of the bound and unbound terminal carboxylates. Upon dissolution in water, the complexes, through a complicated reaction cascade, transform to oligonuclear 1:1 species that, in agreement with previous studies, represent the thermodynamically stable state in solution. The data provide, for the first time, structural details of low MW, mononuclear complexes of Al(III) (or Ga(III)) with citrate that are dictated, among other factors, by pH. The properties of 1-6 may provide clues relevant to their biological association with humans.     

Aminium cation radical of glycylglycine and its deprotonation to aminyl radical in aqueous solution

The photochemical reaction between glycylglycine and triplet 4-carboxybenzophenone has been investigated using time-resolved chemically induced dynamic nuclear polarization (CIDNP). It is shown that the mechanism of the peptide reaction with triplet excited carboxybenzophenone is electron transfer from the amino group of the peptide, leading to the formation of an aminium cation radical that deprotonates to a neutral aminyl radical. Simulation of the CIDNP kinetics leads to an estimation of the paramagnetic relaxation time for the alpha-protons at the N-terminus at 20 to 40 mus with the best-fit value of 25 mus.     

Study on chemical speciation in aluminum chloride solution by ESI-Q-MS

AlCl(3) solution was analyzed at concentrations from 0.02 to 100 mM using an electrospray ionization quadrupole mass spectrometer (ESI-Q-MS), and the dissolution state of aluminum ions is discussed. Results obtained using ESI-Q-MS were consistent with those obtained using (27)Al nuclear magnetic resonance ((27)Al NMR). Aluminum species existed mainly as positively charged monomeric aluminum hydroxide coordinated with several water molecules in solution. The complexation of chloride ions by aluminum ions differed between the positive and negative ion modes. Chemical reactions that partially modified chemical forms of species through ESI-Q-MS measurement were also observed. In the same aluminum chloride solution, using ESI-TOF-MS and ESI-Q-MS/MS studies, the disagreement of the reports is discussed. It is concluded that ESI-TOF-MS might show also the gas-phase reaction in the mass spectrometer but the dissolution state of aluminum species can be shown by ESI-Q-MS.     

A computational study of the intramolecular deprotonation of a carbon acid in aqueous solution

Proton transfer reactions are the rate-limiting steps in many biological and synthetic chemical processes, often requiring complex cofactors or catalysts to overcome the generally unfavourable thermodynamic process of carbanion intermediate formation. It has been suggested that quantum tunnelling processes enhance the kinetics of some of these reactions, which when coupled to protein motions may be an important consideration for enzyme catalysis. To obtain a better fundamental and quantitative understanding of these proton transfer mechanisms, a computational analysis of the intramolecular proton transfer from a carbon acid in the small molecule, 4-nitropentanoic acid, in aqueous solution is presented. Potential-energy surfaces from gas-phase, implicit and QM/MM (quantum mechanical/molecular mechanical) explicit solvation quantum chemistry models are compared, and the potential of mean force, for the full reaction coordinate, using umbrella-sampling molecular dynamics is analysed. Semi-classical multidimensional tunnelling corrections are also used to estimate the quantum tunnelling contributions and to understand the origin of the primary deuterium kinetic isotope effects (KIEs). The computational results are found to be in excellent agreement with the KIEs and the energetics obtained experimentally.     

The stability of the acetic acid dimer in microhydrated environments and in aqueous solution

The thermodynamic stability of the acetic acid dimer conformers in microhydrated environments and in aqueous solution was studied by means of molecular dynamics simulations using the density functional based tight binding (DFTB) method. To confirm the reliability of this method for the system studied, density functional theory (DFT) and second order M?ller-Plesset perturbation theory (MP2) calculations were performed for comparison. Classical optimized potentials for liquid simulations (OPLS) force field dynamics was used as well. One focus of this work was laid on the study of the capabilities of water molecules to break the hydrogen bonds of the acetic acid dimer. The barrier for insertion of one water molecule into the most stable cyclic dimer is found to lie between 3.25 and 4.8 kcal mol(-1) for the quantum mechanical methods, but only at 1.2 kcal mol(-1) for OPLS. Starting from different acetic acid dimer structures optimized in gas phase, DFTB dynamics simulations give a different picture of the stability in the microhydrated environment (4 to 12 water molecules) as compared to aqueous solution. In the former case all conformers are converted to the hydrated cyclic dimer, which remains stable over the entire simulation time of 1 ns. These results demonstrate that the considered microhydrated environment is not sufficient to dissociate the acetic acid dimer. In aqueous solution, however, the DFTB dynamics shows dissociation of all dimer structures (or processes leading thereto) starting after about 50 ps, demonstrating the capability of the water environment to break up the relatively strong hydrogen bridges. The OPLS dynamics in the aqueous environment shows--in contrast to the DFTB results--immediate dissociation, but a similar long-term behavior.     

Synthesis of aluminum oxide nanoparticles in an aqueous ammonium-formaldehyde solution

A method of synthesis of the organic-inorganic nanocomposite consisting of a paraformaldehyde matrix and aluminum oxide nanoparticles is developed. Spontaneous dispersion of the composite in water at various component ratios makes it possible to prepare a sol or gel of hydrated aluminum oxide. No changes in the oxide particle dimensions are observed during storage of the composite.     

Colorimetric and fluorescent detection of biological thiols in aqueous solution

A new colorimetric and fluorescent probe,2-(2,4-dinitrostyryl)-1,3,3-trimethyl-3H-indolium iodide (DTI),for selective and sensitive detection of biological thiols is reported.In aqueous solution at physiological pH 7.4,biological thiols react with DTI via Michael addition to give the brownish red adduct concomitant with fluorescence emission decrease.     

Radiation-induced reduction of mixed copper and aluminum ionic aqueous solution

Colloidal Cu–Al nanoparticles were prepared in an aqueous polyvinyl alcohol solution containing copper chloride and aluminum chloride as precursors, isopropanol as a scavenger of hydroxyl radicals, and distilled water as a solvent. The gamma irradiations were carried out in a ⁶⁰Co gamma source chamber with different doses up to 120 kGy. The formation of Cu–Al nanoparticles has been observed initially by the change in color of the colloidal samples from colorless to brown. The nanoparticles properties were characterized by transmission electron microscopy, energy dispersive X-ray spectrometry, and UV–Vis spectrophotometer. At a constant Cu/Al molar ratio, size of the nanoparticles can be well controlled by varying the precursors concentration and radiation dose. The average particle diameter increases with increase of precursors concentration and decreases with increase of dose. This is owing to the competition between nucleation process, aggregation process, and ions association in the formation of nanoparticles during irradiation.     

Photophysical properties of fluorescent DNA-dyes bound to single- and double-stranded DNA in aqueous buffered solution.

The absorption and fluorescence spectra, fluorescence quantum yields, lifetimes and time-resolved fluorescence spectra are reported for nine different fluorescent DNA-dyes. The work was initiated in search of a quantitative method to detect the ratio of single-to-double stranded DNA (ssDNA/dsDNA) in solution based on the photophysics of dye-DNA complexes; the result is a comprehensive study providing a vast amount of information for users of DNA strains. The dyes examined were the bisbenzimide or indole-derived stains (Hoechst 33342, Hoechst 33258 and 4',6-diamidino-2-phenylindole), phenanthridinium stains (ethidium bromide and propidium iodide) and cyanine dyes (PicoGreen, YOYO-1 iodide, SYBR Green I and SYBR Gold). All were evaluated under the same experimental conditions in terms of ionic strength, pH and dye-DNA ratio. Among the photophysical properties evaluated only fluorescence lifetimes for the cyanine stilbene dyes allowed a convenient differentiation between ssDNA and dsDNA. The bisbenzimide dyes showed multiexponential decays when bound to either form of DNA, making lifetime-based analysis cumbersome with inherent errors. These dyes also presented biexponential decay when free in aqueous buffered solutions at different pH. A mechanism for their deactivation is proposed based on two different conformers decaying with different kinetics. The phenanthridinium dyes showed monoexponential decays with ssDNA and dsDNA, but there was no discrimination between them. High dye-DNA ratios (e.g. 1:1) resulted in multiexponential decays for cyanine dyes, resulting from energy transfer or self-quenching deactivation. Shifts in both absorption and fluorescence maxima for both ssDNA and dsDNA DNA-cyanine dye complexes were small. Broadening of dye-ssDNA absorption and fluorescence bands for the cyanine dyes relative to dye-dsDNA bands was detected and attributed to higher degrees of rotational freedom in the former.     

天花粉蛋白溶液构象与稳定性及生物活性的关系

用圆二色性研究了天花粉蛋白在不同PH,不同温度和不同的时间条件下的溶液构象变化.阐明了天花粉蛋白溶液的外部环境,并研究了天花粉蛋白的溶液构象与抗生育活性的关系,结果表明随着溶液中a-helix含量的增加,抗生育活性也相应增加,当a-helix含量减少到15%以下,其抗生育活性也就丧失.     

A novel dinuclear species in the aqueous distribution of aluminum in the presence of citrate

The chemistry of aluminum was explored in the presence of the physiological ligand citric acid and in low-pH aqueous media. As a result, the first dinuclear aluminum-citrate complex (NH4)4[Al2-(C6H4O7)(C6H5O7)2].4H2O was isolated at low pH (approximately 3.5), and was characterized by FT-IR spectroscopy and X-ray crystallography. The structural analysis reveals the presence of a dinuclear assembly of two aluminum ions octahedrally coordinated to three citrate ligands of differing protonation state. The NMR solution behavior of this complex emphasizes its time-dependent transformation into a number of variable nature species, ultimately leading to the thermodynamically stable trinuclear species. It also establishes the participation of the dinuclear complex as a viable component of the aqueous Al(III)-citrate speciation. The chemical and structural features of this novel low molecular mass species provide considerable insight into citrate's ability, as a natural ligand, to influence the chemistry of aluminum in a pH-dependent fashion, and potentially affect aluminum's (bio)distribution, absorption, accumulation, and biotoxicity at sensitive biological sites.     

Photoinitiated free radical polymerization of vinyl compounds in aqueous solution

A new method for the photochemical initiation of polymerization of vinyl compounds in aqueous solution is described. The photochemically active species is an ion pair complex of the formula Fe³⁺X⁻(X⁻ = OH⁻, CI⁻, N⁻₃, etc.). The light absorption by the ion pair leads to an electron transfer causing reduction of the cation and oxidation of the anion to an atom or free radical X. The latter leads to the initiation of polymerization in accordance with X + CH₂CHR→XCH₂ CHR . The kinetics of the reaction were studied by the measurement of: (a) ferrous ion formed (colorimetrically), (b) monomer disappearance (by titration and by weighting the polymer), (c) the chain length of the polymer (in the case of methyl methacrylate). The dependence of the quantum yield on the light intensity, light absorption fraction, and the concentration of vinyl monomer and ferrous ion added initially was investigated. A complete mechanism, both with regard to the formation of free radicals and the polymerization reaction, was put forward involving: (1) light absorption, (2) a primary dark back reaction, (3) dissociation of the primary product, (4) a secondary dark back reaction, (5) initiation of polymerization by free radicals, (6) propagation of polymerization, and (7) termination by recombination of active polymer endings. The mechanism was verified by the experimental results and some constant ratios were estimated quantitatively.     

Meso-substituted cationic porphyrins of biological interest. Photophysical and physicochemical properties in solution and bound to liposomes

A series of cationic porphyrins with 1-4 positive charges are studied: mono(N-methyl-4-pyridyl)triphenylporphine chloride [Mono], cis(N-methyl-4-pyridyl)diphenylporphine chloride [Cis], tri(N-methyl-4-pyridyl)monophenylporphine chloride [Tri] and tetra(N-methyl-4-pyridyl)porphine chloride [Tetra]. Their photophysical properties are measured in small unilamellar vesicles and compared with those in homogeneous solution. Liposomes of L-alpha-dimyristoyl-phosphatidylcholine (100 nm diameter) and L-alpha-dipalmitoyl-phosphatidylcholine (50 nm diameter) in phosphate-buffered saline (pH = 7.4) or D2O 0.15 M NaCl were used. The effect of the medium microheterogeinity is discussed. The triplet quantum yields in liposomes for all the porphyrins are about 0.7, similar to the value obtained for Tetra in aqueous media. The singlet molecular oxygen quantum yields for the hydrophilic compounds Tri and Tetra are greater than those of the hydrophobic ones, Mono and Cis. Also, association constants (KL) of the dyes to liposomes and their localization within the membranes are determined from fluorescence and fluorescence polarization measurements, respectively. KL values are in the range of 10(4)-10(5) M-1 for all the compounds, indicating that hydrophobic and coulombic interactions between porphyrins and liposomes are responsible for the dye association. Fluorescence polarization experiments indicate that Mono and Cis can penetrate into the lipidic phase, and that Tri and Tetra are located near the polar heads of the lipidic molecules.     

Dioxouranium(VI)--carboxylate complexes. Interaction with dicarboxylic acids in aqueous solution: speciation and structure

In this paper we report the results of an investigation performed by potentiometric (H+-glass electrode) and visible spectrophotometric measurements on the interaction of UO2(2+) ion towards some carboxylic ligands (acetate, malonate, succinate, azelate). The measurements were carried out at T= 25 degrees C in different ionic media (KNO3 and NaCl) at different ionic strengths (0.1 < or = I/mol L(-1) < or = 1.0, NaCl; I/mol L(-1) = 0.1, KNO3). The dependence on ionic strength of formation constants was taken into account by using both a simple Debye-Hückel type equation and the SIT (Specific ion Interaction Theory) approach. Different speciation models (depending on concentration of reagents, ionic strength, pH-range) both for different carboxylates and different ionic media have been obtained. Linear combinations between formation constants, stoichiometric coefficients and length of alkyl chain of dicarboxylates have been observed and predicted formation constants at I= 0 mol L(-1) are reported for the interaction of UO2(2+) with HOOC-(CH2)n-COOH with 1 < or = n < or = 7. Finally, a visible absorption spectrum for each complex reaching a significant percentage of formation in solution (KNO3 medium) has been calculated to characterise the compounds found by pH-metric refinement.     

A fluorescent and colorimetric chemosensor for selective detection of aluminum in aqueous solution

We have synthesized a new Schiff base 1, which detects Al³⁺ through fluorescence and naked eye in aqueous solution. The sensor 1 exhibited selective and sensitive recognition toward Al³⁺ via significant fluorescence enhancement (31-fold). Moreover, it showed a significant color change from colorless to yellow. The complex formation was proposed to be 1:1 ratio, based on the Job plot, ESI-mass spectrometry analysis, ¹H NMR titration, and IR analysis. The detection limit was 1.00 μM, which is below the WHO acceptable limit (1.85 μM) in drinking water. In addition, the sensor 1 could be recyclable simply through treatment with a proper reagent such as EDTA.     

Spectral analysis of naringenin deprotonation in aqueous ethanol solutions

The deprotonation of 5,7-dihydroxy-2-(4-hydroxyphenyl)chroman-4-one (naringenin) was studied in aqueous solutions of ethanol and 0.1 mol L^?1 sodium perchlorate at 25°C. The chemical species that contributed to deprotonation were evaluated together with their pure spectral characteristics and concentration profiles by some chemometric methods. The deprotonation constants assigned by pK ₁, pK ₂, and pK ₃ were determined by multivariate curve analysis of spectral data at different pcH values. The pure spectral analysis concordant with the theoretical prediction of deprotonation constants indicates that the acidity of hydroxyl groups in naringenin decreases in the order: 7-OH, 4′-OH, 5-OH. The effects of the solvent on deprotonation were analysed in terms of the linear solvation energy relationships using the model of Kamlet, Abboud, and Taft (KAT). Multiple linear regressions were aimed towards correlating the deprotonation constants with the microscopic parameters containing hydrogen-bond acidity (α), dipolarity/polarisability (π*), and hydrogen-bond basicity (β). The most significant parameter was found to be the hydrogen-bond acidity of binary mixtures.     

Organometallic catalysis in aqueous and biological environments: harnessing the power of metal carbenes

Translating the power of transition metal catalysis to the native habitats of enzymes can significantly expand the possibilities of interrogating or manipulating natural biological systems, including living cells and organisms. This is especially relevant for organometallic reactions that have shown great potential in the field of organic synthesis, like the metal-catalyzed transfer of carbenes. While, at first sight, performing metal carbene chemistry in aqueous solvents, and especially in biologically relevant mixtures, does not seem obvious, in recent years there has been a growing number of reports demonstrating the feasibility of the task. Either using small molecule metal catalysts or artificial metalloenzymes, a number of carbene transfer reactions that tolerate aqueous and biorelevant media are being developed. This review intends to summarize the most relevant contributions, and establish the state of the art in this emerging research field.

Metal-catalyzed carbene transformations can be implemented in aqueous mixtures, and even under the stringent conditions of living cells, provided substrates and catalysts are properly tuned to present a good balance between stability and reactivity.