别嘌醇质子迁移过程的理论研究

别嘌醇(Allopurinol)是次黄嘌呤的位置异构体,是唯一在临床上应用的黄嘌呤氧化酶抑制剂.     

Density functional study of neutral allopurinol tautomeric forms

Optimized structures and total molecular energy density functional theory calculations for the 14 possible neutral allopurinol tautomers give the decreasing stability order for the three most stable forms. Several molecular and electronic structure properties, the stabilities in oxidation and reduction processes, the tautomeric equilibrium constants, and the IR vibrational spectra were obtained for these. Those properties corresponding to the ketonic forms are discussed and compared with the theoretical ones for the two most stable species of the isomer hypoxanthine. A noticeable agreement is found between the predicted properties and the experimental behavior known up to date for both isomers. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 200–206, 1999     

Electrochemiluminescent behavior of allopurinol in the presence of Ru(bpy)(3)(2+)

The electrochemiluminescent (ECL) response of allopurinol was studied in aqueous media over a wide pH range (pH 2–13) using flow injection (FI) analysis. It was revealed that allopurinol itself had no ECL activity, but could greatly enhance the ECL of Ru(bpy)₃²⁺ in alkaline media giving rise to a sensitive FI-ECL response. The effects of experimental conditions including the mode of applied voltage signal, the potential of working electrode, pH value, the flow rate of carrier solution, and the concentration of Ru(bpy)₃²⁺ and allopurinol on the ECL intensity were investigated in detail. The most sensitive FI-ECL response of allopurinol was found at pH 12.0, where the FIA-ECL intensity showed a linear relationship with concentration of allopurinol in the range 1 × 10⁻⁸ mol L⁻¹ to 5 × 10⁻⁷ mol L⁻¹, and the detection limit was 5 × 10⁻⁹ mol L⁻¹.     

Synthesis of 2′-deoxyribonucleosides of allopurinol by phase-transfer glycosylation

Regioselective glycosylation of 4-methoxy-1H-pyrazolo[3,4-d]pyrimidine (6b) with the halogenose 7 was achieved by employing phase-transfer techniques. The N-1 glycosylation product 3a was formed in preponderance. It was converted into the allopurinol β-D-2′-deoxyribonucleoside 2.     

“On the complexation of allopurinol with β-cyclodextrin”

NMR diffusion coefficient measurements and PM3 theoretical calculations were employed in the study of the inclusion complexation of allopurinol with β-cyclodextrin (β-CD) at pH 6.5 and 10.0. Experimental findings revealed an increase in the association constant from 16 to 30 M⁻¹ as a consequence of guest deprotonation. PM3 quantum-mechanical calculations were performed to investigate the complexation process between β-CD and allopurinol, considering the most stable neutral and anionic tautomers of the guest. The binding energies obtained from the computational study were in agreement with the experimental observations, indicating that the anionic complex was more stable than the neutral one. Such unusual behavior was related to hydrogen bonding interactions between β-CD and the anionic guest, leading to the increase of the association constant as a consequence of guest deprotonation.     

Alkylation of allopurinol and inosine with dimethylformamide dimethylacetal or diethylacetal

The alkylation of allopurinol and inosine with dimethylformamide (DMF) dimethylacetal and diethylacetal was studied. Allopurinol is alkylated in both the pyrazole and pyrimidine rings. 1,5- and 2,5-Dimethyl derivatives are formed in the case of methylation. 1,5- and 2,5-Diethyl derivatives, as well as 1-ethyl-4-ethoxypyrazolo[3,4-d]pyrimidine, were obtained in the ethylation of allopurinol. The yields of the 1,5-substituted compounds are highest in both cases. The alkylation of inosine with DMF diethylacetal takes place in the 1 and 6 positions.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1526–1531, November, 1988.     

Transition metal compounds of the purinic isomer allopurinol. Part 1

Summary The synthesis, spectral and magnetic properties of a series of new compounds of Co^II, Ni^II and Cu^II with the purinic isomer allopurinol (L) are reported. The counterions employed were Cl^–, Br^–, NO ₃ ^– , SO ₄ ^2– , ClO ₄ ^– and MeCO ₂ ^– . The metal:ligand stoichiometries found for the compounds range from 11 to 13. Allopurinol exhibits two classes of coordination behaviour: neutral monodentate (M^II=Co, Ni and Cu; X^–=Cl or Br) and monoanionic bidentate for the compound [CuL(OH)]_n. The latter was obtained when the counterion used in the syntheses was NO ₃ ^– , SO ₄ ^2– , ClO ₄ ^– or MeCO ₂ ^– . The coordination behaviour of theN-pyrazolic ring atoms may relate to the interaction mode of this heterocyclic fragment with the xanthine oxidase metalloenzyme.     

Penicillin G acylase catalyzed Markovnikov addition of allopurinol to vinyl ester

A new enzymatic process is reported, in which penicillin G acylase from Escherichia coli displays a promiscuous activity in catalyzing the Markovnikov addition of allopurinol to vinyl ester.     

Electrochemical determination of allopurinol based on its interaction with xanthine oxidase

Allopurinol was determined in the range 0.20–50 μM utilizing xanthine oxidase immobilized onto a carbon paste electrode. Alternative assay methods relying on either inhibition of enzymatic activity or direct formation of a product are evaluated. Regeneration of xanthine oxidase activity under various conditions is also surveyed.     

A direct electrochemical method for the determination of allopurinol and uric acid mixtures

Uric acid and allopurinol are both electrochemically oxidized at the pyrolytic graphite electrode (P.G.E.) in aqueous solution, the oxidation of allopurinol occurring at more positive potentials. Allopurinol is polarographically reducible at the dropping mercury electrode, and the wave is not affected by uric acid. Uric acid is strongly adsorbed at the P.G.E., so that concentrationvs. anodic peak current curves are not linear, but when the solution is saturated with allopurinol, these plots become linear. and changes in scan rate have less effect. It is shown that allopurinol is adsorbed at the P.G.E., and in saturated solutions, displaces adsorbed uric acid from the electrode surface. Allopurinol (0.1–1 mM) can be determined via its polarographic reduction wave at the D.M.E.; the solution is then saturated with allopurinol and uric acid (0.05–0.5 mM) is determined via its anodic peak at the P.G.E. The procedure is satisfactory in supporting electrolyte systems of pH 0–6.     

OH(3) (-) and O(2)H(5) (-) double Rydberg anions: predictions and comparisons with NH(4) (-) and N(2)H(7) (-)

A low barrier in the reaction pathway between the double Rydberg isomer of OH(3) (-) and a hydride-water complex indicates that the former species is more difficult to isolate and characterize through anion photoelectron spectroscopy than the well known double Rydberg anion (DRA), tetrahedral NH(4) (-). Electron propagator calculations of vertical electron detachment energies (VEDEs) and isosurface plots of the electron localization function disclose that the transition state's electronic structure more closely resembles that of the DRA than that of the hydride-water complex. Possible stabilization of the OH(3) (-) DRA through hydrogen bonding or ion-dipole interactions is examined through calculations on O(2)H(5) (-) species. Three O(2)H(5) (-) minima with H(-)(H(2)O)(2), hydrogen-bridged, and DRA-molecule structures resemble previously discovered N(2)H(7) (-) species and have well separated VEDEs that may be observable in anion photoelectron spectra.     

Mixed ligand titanium(IV) complexes. Chlorobis(dithiocarbamato)bis(methylsalicylato)titanium(IV) andbis(dithiocarbamato)bis(methylsalicylato)titanium(IV)

Summary Dichlorobis(methylsalicylato)titanium(IV) reacts with potassium or amine salts of dialkyl or diaryl dithiocarbamates in 11 and 12 molar ratios in anhydrous benzene (room temperature) or in boiling CH₂Cl₂ to yield mixed ligand complexes: (AcOC₆H₄O)₂ Ti(S₂CNR₂)Cl (1) and (AcOC₆H₄O)₂ Ti(S₂CNR₂)₂ (2), R=Et, n-Pr, n-Bu, cyclo-C₄H₈ and cyclo-C₅H₁₀. These compounds are moisture sensitive and highly soluble in polar solvents. Molecular weight measurement in conjunction with i.r.,¹H and¹³C n.m.r. spectral studies suggest coordination number 7 and 8 around titanium(IV) in (1) and (2) respectively.