Potentiometric, luminescence and NMR study of the interaction of Eu with glyceryl phosphates

Complexation of europium(III) with glyceryl-1- and -2-phosphates has been studied by metal ion luminescence, ¹H and ¹³C NMR spectroscopy and potentiometry. From the luminescence and NMR studies, the formation of a 1:1 inner-sphere complex, in which the glyceryl phosphate is directly bound to the metal, is confirmed. Similar apparent binding constants at pH 2 were obtained by the three methods. Values obtained by NMR at pH 2 are 53 M⁻¹ and 12 M⁻¹ for glyceryl-1- and -2-phosphate, respectively. By comparison with literature data on related systems it is suggested that the ligands bind through the phosphate group. To obtain structural information from the NMR data, complexation has also been studied with the lanthanide ions Dy(III), Er(III) and Gd(III) using both chemical shift and relaxation data. From this, metal-proton distance ratios have been calculated. Comparison of ¹H and ¹³C NMR spectral data in the presence of paramagnetic lanthanides suggests conformational equilibria in the solutions. From the potentiometric studies, global formation constants have been determined, and speciation diagrams obtained over the pH range 1.5pH7.0 for ligand/metal ratios of 1 and 30. Implications of these results on lanthanide induced fusion of phospholipid membranes are discussed.     

Application of fluorescence reactions in the ring oven segment technique

Summary The ring oven segment technique already described earlier has been applied to the determination of ng- tog-amounts of organic and inorganic substances using fluorescence reactions. The methods proposed here are based either on self-fluorescence or on appearance or disappearance of fluorescence following a chemical reaction.

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Anwendung von Fluoreszenzreaktionen in der Ringofen-Segmenttechnik

Zusammenfassung Die bereits früher beschriebene Ringofen-Segmenttechnik wurde auf die Bestimmung organischer und anorganischer Substanzen im ng- bisg-Bereich mit Hilfe von Fluoreszenzreaktionen angewendet. Die hier vorgeschlagenen Methoden beruhen entweder auf Eigenfluoreszenz oder aber auf der Bildung bzw. dem Verschwinden von Fluoreszenz nach einer chemischen Reaktion.

     

Synthesis, biological activity and modelling studies of two novel anti HIV PR inhibitors with a thiophene containing hydroxyethylamino core

An efficient method has been developed for the synthesis of a versatile intermediate bearing azido, hydroxyl and ester functions, a useful precursor for peptidomimetic compounds. The two main features for this synthesis were the use of the Sharpless asymmetric dihydroxylation on thiophene acrylate and the subsequent regioselective ring opening by sodium azide of the cyclic sulfite. Highly chemoselective reduction of the azido alcohol led to a key compound which was utilized for the synthesis of two analogues of commercial anti HIV PR such as nelfinavir and saquinavir. The biological activity and molecular modelling study on these two new potential drugs have been evaluated.     

Investigation on the Interaction of Bendazac with β-, Hydroxypropyl-β-, and γ-, yclodextrins

The interactions of Bendazac, a topical non-steroidal anti-inflammatory drug, with-cyclodextrin, hydroxypropyl--cyclodextrin and -cyclodextrinwere investigated to evaluate possibilities to improve the drug's poor water solubilityand eventually to enhance the topical delivery of Bendazac. Phase solubility studiesdemonstrated the ability of the selected cyclodextrins to complex with Bendazac andincrease drug solubility. The amount of solubilized Bendazac increased linearly withthe addition of each cyclodextrin according toA_L type plots. ¹³C-NMR studiesshowed that the Bendazac A-ring was included in the cavity of the three cyclodextrins.The -cyclodextrin was also able to include the B-ring of Bendazac, forminga complex where one drug molecule fitted into two cyclodextrin molecules. Equimolarsolid systems of the drug with each cyclodextrin carrier were prepared using varioustechniques (physical mixing, spray-drying and freeze-drying). The results of differential scanning calorimetry and Fourier transform infrared analysis, performed on the solid systems, demonstrated that freeze-dried and spray-dried products had a high degree of amorphization and agreed with the hypothesis of the existence of drug–cyclodextrin interaction in the solid state. The cyclodextrins tested were able to improve the dissolution of Bendazac. The dissolution profile of the drug was also affected by the physico-chemical properties of each solid system, the freeze-dried products being the most rapidly dissolving forms.     

Aza-Diels-Alder reaction in fluorinated alcohols. A one-pot synthesis of tetrahydroquinolines

Hexafluoroisopropanol and trifluoroethanol are found to promote imino-Diels-Alder reactions of the N-aryl aldimine 1 with alkyl vinyl ethers to afford the corresponding tetrahydroquinolines in good yields without Lewis acid under mild and neutral conditions. The reaction is also efficient in a three component process from aldehyde, amine and vinyl ethers.     

Study on the Kinetics of Non-isothermal Dehydration of Alkaline Earth Metal Selenites

The dehydration kinetics of crystallohydrates of beryllium, magnesium and calcium selenites were studied under non-isothermal conditions. The values of the activation energy of dehydration, the pre-exponential factor in Arrhenius equation and the change of entropy for the formation of the activated complex were calculated using the calculation procedure of Coats and Redfern. Thermal stability and activation energy of dehydration of the crystallohydrates were found to increase by the same order. The relationships observed were interpreted using Klopman’s generalized perturbation theory of chemical reactivity. The same theory was applied to explain the differences in the IR spectra of the selenite crystallohydrates studied.     

Eptastigmine,nicotinamide and nicotinic acid determination using an inhibition enzyme sensor; application to pharmaceutical analysis

An enzyme inhibition biosensor, developed in our laboratory and previously used for the analysis of compounds with anticholinesterase activity (e.g. physostigmine, neostigmine, pyridostigmine nicotine and organophosphorus compounds) has now been tested for the analysis of another recently synthesized cholinesterase inhibitor, i.e. eptastigmine. In addition nicotinic acid and nicotinamide, although displaying weaker inhibition properties, were also tested in pharmaceutical products using the same inhibition enzyme sensor. The biosensor consisted of a hydrogen peroxide amperometric electrode coupled to a functionalised nylon membrane chemically bonding both the enzymes butyrylcholinesterase and choline oxidase; a butyrylcholine standard solution in glycine buffer acted as substrate. The response of the system to all the inhibitors considered was characterised completely and the analysis of several pharmaceutical formulations containing nicotinamide or nicotinic acid was also performed.     

The CuII−CuI−Cu0(Hg) system in the presence of benzotriazole: Part II. A chronocoulometric investigation

Both the oxidation of Cu⁰ at dropping amalgam electrodes immersed in solutions of benzotriazole (BTA) and the reduction of Cu^II at a dropping mercury electrode from BTA solutions have been investigated by the single potential-step chronocoulometric technique. The dependence of the charge Q(t) flowing as a consequence of a given potential jump E_i→E_f upon the initial and final potentials E_i and E_f, as well as upon the time t elapsed from the instant of the potential jump provides direct evidence for the presence of a single adsorbed monolayer of a Cu^I compound on a mercury electrode immersed in a Cu^II solution containing BTA, at applied potentials positive to ≈?0.4 V/SCE. Analogous measurements carried out at dropping amalgam electrodes reveal the presence of a single adsorbed monolayer of a Cu^I compound, or else of an adsorbed multilayer, depending on the potential range investigated. The results of the chronocoulometric measurements are in agreement with those of the polarographic measurements of Part I.     

Harmonic oscillator tensors in contact transformation theory

The application of contact transformation theory to the perturbed harmonic oscillator is reexamined in the light of the harmonic oscillator tensors previously presented. It is found that the recasting of the formalism of this problem in terms of harmonic oscillator tensors results in great simplifications, most of which stem from the introduction of the additional algebraic quantum numbers (l, m). The order of magnitude of each fragment of the Hamiltonian is easily recognizable, and the diagonal and nondiagonal parts contained therein are readily identifiable. The determination of the contact transformation operator is reduced to a simple formula. First, an analysis is made for a single mode of vibration, and it is subsequently extended to a multimode case. The perturbed diatomic vibrator is presented as an example.     

Multistep mass spectrometry of heterocyclic amines in a quadrupole ion trap mass analyser

The fragmentation of heterocyclic amines (HAs) in an ion trap was studied by means of the infusion of methanolic solutions containing the compounds under assay, and using an atmospheric pressure chemical ionization (APCI) as ion source. The MS(n) spectra obtained for compounds included in the same family, either aminoimidazoazaarenes (AIAs) or carbolines, were compared in order to propose fragmentation pathways for each HA. Moreover, labelled AIAs were used to establish the mechanisms. The protonated molecule was always obtained, but subsequent fragmentation was different for both families. In the case of AIAs, major product ions came from the fragmentation of the aminoimidazole moiety, thus the base peak in MS(2) corresponded to the loss of the methyl group, and losses of C(2)NH(3) and CN(2)H(2) were also observed. Further fragmentation occurred in the heterocyclic rings, mainly with losses of HCN and CH(3)CN. For carbolines, the most important product ions came from the loss of ammonia, except for harman and norharman, the loss of a methyl group for methylated carbolines or the loss of diverse fragments from the heterocyclic rings. In some cases, ion-molecule reactions into the ion trap were observed. For instance, for AalphaC or MeAalphaC one ion originating from these reactions corresponded to the base peak.