Structural and thermodynamic analysis of heteroassociation of daunomycin and flavin mononucleotide molecules in water by <Superscript>1</Superscript>H NMR spectroscopy

Heteroassociation of the antitumor antibiotic daunomycin (DAU) with flavin mononucleotide (FMN) has been investigated by one-and two-dimensional ¹H NMR spectroscopy (500 MHz) in a water solution to determine the molecular mechanism of the combined action of the antibiotic and vitamin in the FMN-DAU system. The equilibrium constants of the reactions, induced proton chemical shifts, and thermodynamic parameters (ΔH, ΔS) of heteroassociation were determined from the concentration and temperature dependences of the proton chemical shifts in the interacting aromatic molecules. Analysis of the results indicate that heterocomplexes of riboflavin mononucleotide and daunomycin are formed due to stacking interactions between aromatic chromophores. The most probable spatial structure of the 1:1 DAU-FMN heterocomplex was determined by the molecular dynamics method using the X-PLOR program and the results of the analysis of the induced proton chemical shifts in molecules. Calculation of the relative content of self-and hetero-complexes of daunomycin for different values of the ratio (r) between the concentrations of flavin mononucleotide and daunomycin demonstrated that for r > 3, the contribution of DAU-FMN heterocomplexes to the equilibrium distribution of associates in aqueous solution is dominant. It is concluded that the aromatic molecules of vitamins, in particular, riboflavin, can form energetically strong heteroassociates with antitumor antibiotics in water solution and can thereby affect their medical and biological activity.     

1H nmr study of heteroassociation of caffeine with acridine orange in aqueous solution

The molecular mechanism of the action of caffeine (CAF) as a complexing interceptor of aromatic ligands intercalated in DNA is considered using a typical intercalant — acridine orange (AO) dye. Hetero-association of CAF and AO was investigated by one- and two-dimensional H NMR spectroscopy (500 MHz). The concentration (at 298 and 308 K) and temperature dependences of the proton chemical shifts of molecules in aqueous solution were measured. The equilibrium constants of the CAF-AO hetero-association reactions at different temperatures and the limiting chemical shifts of the protons of the aromatic ligands of the associates were determined. The most plausible structure of the 1:1 CAF-AO helerocomplex in aqueous solution is suggested based on the calculated values of the induced proton chemical shifts of the molecules and the quantum mechanical screening curves for CAF and AO. The thermodynamic parameters of CAF-AO helerocomplex formation art calculated. The structural and thermodynamic analyses indicate that dispersion forces and hydrophobic interactions play a significant role in heterocomplex formation in aqueous salt solution. The relative contents of different types of associate in a mixed solution containing CAF and AO are estimated. The equilibrium of CAF-AO heteroassociates in solution is characterized in relation to temperature. Heteroassociation of CAF and AO molecules leads to decreased effective concentration of intercalant in solution and hence to decreased mutagenic activity of the dye. Translated from Zhumal Struktumoi Khimii, Vol. 41, No. 1, pp. 86-96, January–February, 2000.     

Potentiometric studies of the thermodynamics of iodine disproportionation from 4 to 209°C

The equilibrium constant for the disproportionation of iodine in aqueous solution was determined as a function of temperature from 3.8 to 209.0°C using emf measurements in low ionic strength media. The equilibrium constant and associated molal thermodynamic quantities at 25°C are: K₁=1.17±0.62×10^–47, H^o=273±3 kJ-mol^–1, S^o=16±9 J-K^–1-mol^–1, and C _p ^o =–1802±41 J-K^–1-mol^–1. Although the value of K₁ is in excellent agreement with a previous emf measurement at 25°C, these results conflict with the corresponding parameters obtained from the NBS tables. Moreover, at temperatures above ca. 100°C, our measured values for the equilibrium constant diverge strongly from all previous estimates and predictions.     

Analysis by Means of <Superscript>1</Superscript>H NMR Spectroscopy of Heteroassociaion in Water Solution of Antitumor Antibiotics Daunomycin and Actinomycin D

Heteroassociation of aromatic antitumor antibiotics daunomycin (DAU) and actinomycin D (AMD) was investigated using 1D and 2D ¹H NMR spectroscopy (at 500 MHz) and molecular mechanics procedure with the goal of establishing the mechanism of the combined action of antibiotics in the system AMD-DAU. The experimental data were processed applying a modified statistical and thermodynamic model of the molecules heteroassociation. Proceeding from this model the values were obtained of induced proton chemical shifts, equilibrium constant and thermodynamic parameters of complexing reaction between DAU and AMD. By means of molecular mechanics with the use of X-PLOR software and of the analysis results of the induced proton chemical shifts in the molecules the most probable spatial structure, 1:1, was established for the heterocomplex of DAU and AMD. Heterocomplexes of daunomycin and actinomycin D form due to stacking interaction between the aromatic chromophores with possible additional stabilization of the complexes by an intermolecular hydrogen bond.     

Preparation and Thermochemistry of Complexes of Zinc Nitrate with Threonine

The solubility property of Zn(NO₃)₂–Thr–H₂O system (Thr—threonine) at 25°C in the entire concentration range has been investigated by the phase equilibrium semimicromethod. The corresponding phase diagram and refractive index diagram were constructed. From the phase equilibrium results, the incongruently soluble compounds of Zn(Thr)(NO₃)₂ · 2H₂O, Zn(Thr)₂(NO₃)₂ · H₂O, and Zn(Thr)₃(NO₃)₂ · H₂O were synthesized and characterized by IR, XRD, TG–DTG, chemical and elemental analyses. The constant-volume combustion energies of the compounds, _c E, determined by precision rotating bomb calorimeter at 298.15 K, were –6266.88 ± 3.72, –9263.28 ± 2.23, and –11 423.11 ± 6.81 J/g, respectively. The standard enthalpies of combustion for these compounds, _c H _m ^° (complex, s., 298.15 K), were calculated as –2147.40 ± 1.28, –4120.83 ± 0.99, and –6444.68 ± 3.85 kJ/mol and the standard enthalpies of formation, _f H _m ^° (complex, s., 298.15 K), are –1632.82 ± 1.43, –1885.55 ± 1.50, and –2770.25 ± 4.21 kJ/mol. The enthalpies of dissolution of the complexes in a medium of simulated human gastric juice (37°C, pH 1, in the solution of hydrochloric acid), _dis H _m ^° (complex, s., 310 K), which were also measured by a microcalorimeter to be 13.36 ± 0.06, 15.53 ± 0.06, and 17.04 ± 0.05 kJ/mol, respectively.     

Spectrofluorimetric determination of clioquinol in pharmaceutical preparations

Summary The absorption spectrum of the nitrate radical (NO₃) in aqueous solution and the kinetic of the reactions with Cl^– and OH^– have been determined using laser-spectrometric techniques. The maximum absorption was found at 635 nm with a decadic absorption coefficient of =(530±110) l/mol·cm. At 298 K rate constants of k₁=(1.0±0.2)·10⁷ l/mol·s for the reaction with chloride and of k₂=(8.2±0.9)·10⁷ l/mol·s for the reaction with hydroxide were obtained.     

Thermodynamics of lonization of aqueous lodic acid,an “almost-strong” electrolyte

We have made calorimetric measurements of enthalpies of dilution of aqueous iodic acid and have used these results for evaluation of the standard enthalpy of ionization of HIO₃(aq.). We have also made calorimetric measurements of enthalpies of addition of perchloric acid solution to aqueous solutions of KIO₃, KNO₃, NaIO₃, and NaNO₃ and have used these results to obtain further values for the standard enthalpy of ionization of HIO₃(aq.). On the basis of all these results, we have selected H^o=–660±125 cal-mole^–1 as the best available standard enthalpy of ionization of HIO₃(aq.) at 298.15°K, compared to the previously accepted –2400 cal-mole^–1. Using the best available K=0.157 for ionization, we also obtain G^o=1097 cal-mole^–1 and S^o=–5.9 cal-^oK^–1-mole^–1 for ionization of HIO₃(aq) at 298.15°K.On study leave from Department of Inorganic and Analytical Chemistry, LaTrobe University, Bundoora, Victoria, 3083, Australia, to University of Lethbridge.On study leave from Department of Chemistry, University of Wollongong, Wollongong, N.S.W. 2500, Australia, to University of Lethbridge.     

Structure of tetraphenylarsonium tricyano- 2,2′,6′,2′′-terpyridylferrate(II), AsPh4[FeII(terpy)(CN)3]; and kinetics of oxidation of the complex anion by peroxodisulfate in water and in binary aqueous mixtures

The structure of the title compound has been determined by X-ray crystallography. The octahedral arrangement of ligands about the iron(II) centre is somewhat distorted, with the axial NC–Fe–CN bond angle being 174.3(4)°. The oxidation of the tricyano-2,2,6,2- terpyridylferrate(II) anion by the peroxodisulfate anion has been investigated in water and in binary aqueous mixtures. The reaction follows a second order rate law, with a second-order rate constant of 0.126± 0.001dm3mol–1s–1 at 295.2K. The enthalpy and entropy of activation in water are 51.3±1.8kJmol–1 and –89±5JK–1mol–1 respectively. The rate is retarded on addition of organic cosolvent. The transfer chemical potential of the initial state from water into mixed solvents has been determined from solubility measurements, and compared with the transfer potential of the transition state. Solvent effects on the reaction are discussed in terms of initial state versus transition state solvation.     

<Superscript>1</Superscript>H NMR Study of Heteroassociation of Ethidium Homodimer and Propidium Iodide in Water

1D and 2D ¹H NMR spectroscopy (500 MHz) was used to study heteroassociation of the bifunctional intercalator ethidium homodimer (EBH) with a phenanthridine dye propidium iodide (PI) in an aqueous salt (0.1 mol/l NaCl). A physical model of equilibrium between various associated forms of ethidium homodimer and propidium in solution is suggested, the most probable forms being 1:1 and 1:2 complexes of PI with the EBH monomer and dimer. The chemical shifts of the EBH molecule in heterocomplexes, as well as the equilibrium constants and the thermodynamic parameters (enthalpy, entropy) of heteroassociations, were calculated from the concentration and temperature dependences of the proton chemical shifts. It is concluded that the propidium molecule is built (intercalated) into the EBH monomer and dimer to form 1:1 and 1:2 complexes mainly stabilized by dispersive and hydrophobic interactions.Original Russian Text Copyright © 2004 by A. N.Veselkov, M. P. Evstigneev, S. A. Hernandez, O. V. Rogova, D. A. Veselkov, and D. B. Davies__________Translated from Zhurnal Strukturnoi Khimii, Vol. 45, No. 5, pp. 837–843, September–October, 2004.     

Photolysis of water-carbon tetrachloride and water-chlorobenzene saturated solutions and their two-phase systems. Quantum yields of chloride ions

The quantum yields of formation of chloride ions were determined in photolysis (=254 nm) of watercarbon tetrachloride organic phase of CCl₄(Cl^–)=0.89±0.04 water-chlorobenzene (_PhCl(Cl^–)=0.137± ±0.005) two-phase systems and saturated aqueous solutions of carbon tetrachloride (_CCl4(Cl^–)=18.9±5.6 and chlorobenzene _PhCl(Cl^–)=0.56±0.03. The quantum yields of chloride ions obtained from these systems are compared with partial radiation yields in the same systems. A mechanism for formation of Cl^– ions is proposed.     

Enthalpies of solution of thymine and uracil in water and dimethylsulfoxide

Enthalpies of solution of thymine and uracil in water and in dimethylsulfoxide (DMSO) were measured calorimetrically in the temperature range 25–40°C. H _s ^o at 25°C for thymine and uracil in water were found to be 23.1±0.5 and 29.5±0.3 kJ-mol^–1, respectively. In DMSO, H _s ^o were 7.9±0.1 and 10.2±0.1 kJ-mol^–1, respectively. In aqueous solution C _p ^o for the two nucleic acid bases were relatively large and positive with C _p ^o of thymine being larger. Both transfer quantities H _t ^o and C _p,t ^o for the proceses H₂ODMSO for the two nucleic acid bases were negative. It is proposed that, the differences in the values obtained for the two bases is due principally to increased order in the water adjacent to the methyl group in thymine.     

Tensimetric investigation of the CrCl<Subscript>3</Subscript>—Cl<Subscript>2</Subscript> system in the temperature range of 600–1200 K

The sublimation pressure of chromium trichloride was measured by the static method with a quartz membrane-gauge manometer in the temperature range of 875–1230 K. An approximating equation for the sublimation pressure vs. temperature was found. The enthalpy (259.4±4 kJ mol^–1) and the entropy (224.2±3.5 J mol^–1 K^–1) of sublimation at 298 K were calculated. For the process 2 CrCl₃(g) + Cl₂(g) = 2 CrCl₄(g), the following values were obtained: _r H°₂₉₈ = –207.1±11.6 kJ mol^–1 and _r S°₂₉₈ = –173.6±10 5 J mol^–1 K^–1.Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1561–1564, August, 2004.     

Solvent effect and temperature dependence in the interaction of singlet oxygen with α-phenyl-N-tert-butyl nitrone

The solvent effect on the quenching of singlet oxygen by -phenyl-N-tert-butyl-nitrone /PBN/ has been investigated by laser flash photolysis technique registrating luminescence kinetics of¹O₂. The values of the rate constant /k_q/ of the quenching were at 293 K: /9.0±0.4/×10⁶, /4.4±0.3/×10⁶ and /18.3±0.5/×10^{6 –}M^–1 s^–1 in toluene, chloroform and acetonitrile, respectively. The rate constant for the chemical interaction between¹O₂ and PBN, was k_r<1×10⁵ M^–1 s^–1k_q independently of the solvent. At temperatures between 223 and 293 K in toluene E_q=0.4±0.4 kJ mol^–1.     

Dissociation quotients of succinic acid in aqueous sodium chloride media to 225°C

The first and second molal dissociation quotients of succinic acid were measured potentiometrically with a hydrogen-electrode, concentration cell. These measurements were carried out from 0 to 225°C over 25° intervals at five ionic strengths ranging from 0.1 to 5.0 molal (NaCl). The dissociation quotients from this and two other studies were combined and treated with empirical equations to yield the following thermodynamic quantities for the first acid dissociation equilibrium at 25°C: log K_1a=–4.210±0.003; H _1a ⁰ =2.9±0.2 kJ-mol^–1; S _1a ⁰ =–71±1 J-mol^–1-K^–1; and C _p1a ⁰ =–98±3 J-mol^–1-K^–1; and for the second acid dissociation equilibrium at 25°C: log K_2a=–5.638±0.001; H _2a ⁰ = –0.5±0.1 kJ-mol^–1; S _2a ⁰ =–109.7±0.4 J-mol^–1-K^–1; and C _p2a ⁰ = –215±8 J-mol^–1-K^–1.     

Investigation of the self-association of proflavine and acridine orange molecules in aqueous solution by 1H NMR

The chemical shifts of the protons in the proflavine and acridine orange molecules in aqueous solution were measured by ¹H NMR spectroscopy. The equilibrium constants for the association of the molecules and the chemical shifts of the protons in the monomers and associates were obtained from the concentration dependence of the proton chemical shifts. The most probable structures for the dimers of the dyes were calculated on the basis of the obtained chemical shifts, and a comparative analysis was made.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 23, No. 3, pp. 373–376, May–June, 1987.     

Thermochemistry of Amines: Experimental Standard Molar Enthalpies of Formation of N-Alkylated Piperidines

The standard molar enthalpies of formation _f H _m ^° (l) at the temperature T = 298.15 K were determined using combustion calorimetry for N-methylpiperidine (A), N-ethylpiperidine (B), N-propylpiperidine (C), N-butylpiperidine (D), N-cyclopentylpiperidine (E), N-cyclohexylpiperidine (F), and N-phenylpiperidine (G). The standard molar enthalpies of vaporization _l ^g H ^{m °} of these compounds were obtained from the temperature variation of the vapor pressure measured in a flow system. From these data the following standard molar enthalpies of formation in gaseous phase _f H _m ^° (g) were derived for: A –(61.39 ± 0.88); B –(88.1 ± 1.3); C –(105.81 ± 0.66); D –(126.2 ± 1.3); E ( –88.21 ± 0.75); F –(135.21 ± 0.94); G (70.3 ± 1.4) kJ · mol^–1. They are used to determine the strain enthalpies of the cyclic amines A–G. The N-alkylated piperidine rings have been found to be about strainless.     

Spectral and kinetic characteristics of the α-propionic acid methyl ester radical in cyclohexane and water

The -propionic acid methyl ester radical was produced in dissociative electron capture reaction of 2-chloropropionic acid methyl ester. The absorption maxima of the radical are at 310 and 300 nm in cyclohexane and water with extinction coefficients of 440±50 and 400±50 mol^–1 dm³ cm^–1. The second order decay rate parameter in water is (2.3±0.5)×10⁹ mol^–1 dm³ s^–1. The peroxy radicals have the characteristics: _max=265–270 nm, _max=700–900 mol^–1 dm³ and 2k=(7±2)·10⁸ mol^–1 dm³ s^–1.     

Rate Constant for the Reaction of the OH-Radical with CH2F2

The rate constant value of k ₁ = (6.05 ± 0.20)×10⁹ cm³ mol^–1 s^–1 (with ± 1 error) has been determined for the reaction OH + CH₂F₂ (1) by applying the discharge-flow/resonance-fluorescence method at 298 K.     

Concentration Dependence of Thermoelectric Power in Aqueous Tetra-n-Butylammonium Hydroxide Using Hydrogen Electrodes

Using a hydrogen-electrode thermocell with a temperature difference of 8 K, initialthermoelectric power _in has been determined in aqueous tetra-n-butylammoniumhydroxide solutions for concentrations ranging from 0.001 to 0.2 molal at meantemperatures of 25 and 35°C. Graphs of a function of _in vs. m ^1/2/(1 + m ^1/2) yieldintercepts and infinite-dilution limiting slopes as m ^1/2 0. Using the value = 68.8±0.3 J-K^–1for the standard transported entropy of the hydroxideion, values for the enthalpy of transport of tetra-n-butylammonium hydroxide atinfinite dilution were determined to be 36.5±1.5 kJ-mol^–1 at25° and 37.7±2.0kJ-mol^–1 at 35°C.     

étude thermodynamique de certains médicaments

Two compounds of sulphamide type:p-amino-benzene sulphonamide (I) and 3,4-dimethylisoxazol 5-sulphanylamide (II) were studied by combustion calorimetry and by differential scanning calorimetry (DSC).The enthalpies in solid state at 298,15 K of combustion, _c H _m ^o (I)=-2788,5±1,6 kJ mol^–1, _c H _m ^o (II)=-5036±3,8 kJ mol^–1 and of formation, _f H _m ^o (I)=-458,3±1,6 kJ mol^–1, _fH _m ^o (II)=-180,1±3,8 kJ mol^–1 were determined.The thermal effects concerning the melting and phase transition of this compounds were also measured.