A theoretical and spectroscopic study of conformational structures of piroxicam

Piroxicam (PRX) has been widely studied in an attempt to elucidate the causes and mechanisms of its side effects, mainly the photo-toxicity. In this paper fluorescence spectra in non-protic solvents and different polarities were carried out along with theoretical calculations. Preliminary potential surfaces of the keto and enol forms were obtained at AM1 level of theory providing the most stable conformers, which had their structure re-optimized through the B3LYP/CEP-31G(d,p) method. From the optimized structures, the electronic spectra were calculated using the TD-DFT method in vacuum and including the solvent effect through the PCM method and a single water molecule near PRX. A new potential surface was constructed to the enol tautomer at DFT level and the most stable conformers were submitted to the QST2 calculations. The experimental data showed that in apolar media, the solution fluorescence is raised. Based on conformational analysis for the two tautomers, keto and enol, the results indicated that the PRX-enol is the main tautomer related to the drug fluorescence, which is reinforced by the spectra results, as well as the interconvertion barrier obtained from the QST2 calculations. The results suggest that the PRX one of the enol conformers presents great possibility of involvement in the photo-toxicity mechanisms.     

Optical emission spectroscopy of benzyl radicals produced in a radio-frequency plasma

The benzyl radical was studied by optical emission spectroscopy in gas phase. This radical was produced in a radio-frequency (RF, 13.56 MHz) discharge, using benzyl alcohol (?CH(2)OH) as a precursor. The fluorescence from the first excited electronic state 1(2)A(2) to ground state 1(2)B(2) (450 nm) was studied as a function of several external parameters (pressure, RF power, electrodes and mixtures of the inert gases Ar, Ne, He, N(2), with the precursor). We also used a DC discharge to produce this radical but, in this case, the decomposition was fast. We observed changes in the electronic transitions of this radical, and found the best conditions to study it by optogalvanic spectroscopy.     

Electronic and atomic Collisions,proceedings of the XIth international conference on the physics of electronic and atomic collisions : Kyoto, 29 August–4 September 1979, edited by N. Oda and K. Takayanagi,North-Holland,Amsterdam, 1980, pp. xii + 844, price Dfl. 225

The dependence of volume fractions (%V) on the square of the refractive index (n²) has been determined for a series of intermolecular hydrogen-bonded systems. An additive linear relationship between %V and n² is obtained for weakly hydrogen-bonded solutions of acetone and methanol while mixtures of acetone/water and methanol/water give a parabolic shape for the refractive-index diagrams. Surprisingly, a quasi-linearity (but with singular and turning points not apparent on the refractive-index curves) is found for strongly hydrogen-bonded cases such as 2,2,2-trifluoroethanol(TFE)/water, TFE/acetone, TFE/methanol, 1,1,1,3,3,3-hexafluoro-2-propanol (HFP)/water, HFP/acetone and HPP/methanol. This unexpected observation is explained in terms of the coexistence of various stable hydrogen-bonded species corresponding to different geometrical isomers and polymer complexes in the mixtures. The proposed explanation is confirmed by MENDO/3 molecular orbital calculations.     

Spectroscopic (fluorescence, 1D-ROESY) and theoretical studies of the thiabendazole and β-cyclodextrin inclusion complex

The inclusion complex between the anti-helminthic drug thiabendazole (TBZ) and the β-cyclodextrin (βCD) was characterized in solution using fluorescence and ¹H-Nuclear Magnetic Resonance spectroscopy and studied theoretically by semi empirical PM3 and density functional theory (DFT) quantum mechanical calculations. Thermodynamic stability associated with the formation of the TBZ:βCD inclusion complex in aqueous solution was determined treating the drug’s fluorescence enhancement in the presence of cyclodextrin by a non-linear model, which indicated a moderate host–guest affinity at equilibrium (K 150 ± 31 at 25 °C). Its supramolecular structure in solution was studied through the 1D-ROESY NMR experiment, which produced evidence that the guest molecular encapsulation occurs preferably via the drug’s benzimidazole group. Theoretical study employing molecular optimization with the semi empirical PM3 method provided two energetic-equivalent complex structures that are in accordance with the NMR experimental evidences. Single point energy calculations with DFT at the B3LYP/6-31G (d,p) level suggest the most stable structure of the inclusion complex and further comprehension on the interactions and conformational strains involved in its formation.     

Host–guest interactions between dapsone and β-cyclodextrin (Part II): thermal analysis, spectroscopic characterization, and solubility studies

The complex of dapsone with β-cyclodextrin was prepared by the co-precipitation/freeze–drying method. The physical–chemical characteristics of the complex were investigated by different methods and compared with those of the physical mixture and of the isolated compounds. The methods used were infrared spectroscopy, X-ray diffractometry and differential scanning calorimetry. The stability constant was calculated from phase solubility diagram (Higuchi–Connors) and fluorescence spectroscopy. The stoichiometry of the complex was confirmed by Job’s plot. Fluorescence measurements at different temperatures provided the thermodynamic parameters of the complexation. The infrared spectrum showed the disappearance of the SO₂ asymmetric stretching band of the drug at 1275?cm^?1 after complexation. The amorphization of the samples, as revealed by the X-ray diffraction patterns, was an indirect proof of the inclusion complex. The thermal analysis showed that the curves of the physical mixture are combination of the curves of both constituents (dapsone and β-cyclodextrin) while the absence of the melting peak of the drug in the DSC curve of the complex suggests the inclusion of the drug molecule in the host cavity as a 1:1 complex as indicated by Job’s plot. There was a linear increase in its solubility with the increase of the cyclodextrin concentration and the complex was classified as an A_L-type. The value of the stability constant was 3,998?L?mol^?1 calculated by the Higuchi–Connors diagram and around 18,100?L?mol^?1 from the fluorescence method indicating a strong interaction between the host and the guest. Complex formation was a spontaneous and enthalpy directed process.     

Host–guest interactions between dapsone and β-cyclodextrin (part I): study of the inclusion compound by nuclear magnetic resonance techniques

Dapsone (4,4′diaminodiphenylsulfone) is a very effective drug to treat leprosy and a broad range of infectious conditions such as Pneumocystis carinii pneumonia, toxoplasmosis and tuberculosis. However, the oral administration of this drug generally is related to serious side effects and treatment failures. It is believed that the inclusion compound of this drug and cyclodextrins would increase the wettability and the solubility of the encapsulated drug for a supported and gradual release, maximizing its biodisponibility over time. The encapsulation of dapsone in β-cyclodextrin was investigated by five nuclear magnetic resonance spectroscopy techniques. The data obtained for the complex in aqueous solution and in solid-state revealed a strong interaction between host and guest, showing that the drug molecule is deeply inserted in the CD cavity. The diffusion experiments (diffusion ordered spectroscopy) showed a high percentage of complexation (86 %) and that the drug molecule is preferentially interacting with the large side of the β-cyclodextrin cavity.     

Time-resolved luminescence studies in hydrogen uranyl phosphate intercalated with amines

Time-resolved luminescence decays of intercalated compounds of hydrogen uranyl phosphate (HUP) with p-toluidinium (HUPPT), benzylaminium (HUPBZ), α-methylbenzylaminium (HUPMBZ) and hydroxylaminium (HUPHAM) were studied. The prepared compounds belong to the tetragonal P4/ncc space group and showed 00 l reflections shifted to lower angles relative to HUP, indicating that the intercalation increases the c parameter of the unit cell. The luminescence decays of the compounds with 100% of intercalation ratio (HUPHAM and HUPBZ) were analyzed by Global Analysis, assuming Lianos’ stretched exponential as the model function, which can be applied to compounds with restricted geometry and mobile donor and quencher molecules. It was remarkable that the luminescence decays showed that the quenching of the emission of the uranyl ions by the intercalated protonated amines is not restricted by low dimensionality of the host uranyl phosphate, and that a diffusion mechanism occurs. Benzylaminium cation efficiently quenches the excited energy of the uranyl ions at close distance, but the long-range and long-lifetime quenching is hindered. A different situation is found in the case of the small hydroxylaminium cation, where the long distance diffusion of the species is fast, playing an important role in the quenching of the excited uranyl ions at longer times.     

Synthesis and characterization of inclusion complex of the vasodilator drug minoxidil with β-cyclodextrin

The inclusion complex of β-cyclodextrin and minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide) was synthesized using two methods—kneading and freeze-drying—and characterized by UV-Vis spectroscopy, infrared spectroscopy, powder X-ray diffractometry, differential scanning calorimetry, thermal gravimetric analysis, and nuclear magnetic resonance spectroscopy. These techniques have demonstrated the existence of inclusion compound formation between the host and guest with a molar ratio of 1:1. The studies of solubility and the data obtained by nuclear magnetic resonance spectroscopy showed a weak interaction between the guest and the cyclodextrin molecules in solution.     

Asymmetrical hippocampal connectivity in mesial temporal lobe epilepsy: evidence from resting state fMRI

Background

Recent studies have shown that the human right-hemispheric auditory cortex is particularly sensitive to reduction in sound quality, with an increase in distortion resulting in an amplification of the auditory N1m response measured in the magnetoencephalography (MEG). Here, we examined whether this sensitivity is specific to the processing of acoustic properties of speech or whether it can be observed also in the processing of sounds with a simple spectral structure. We degraded speech stimuli (vowel /a/), complex non-speech stimuli (a composite of five sinusoidals), and sinusoidal tones by decreasing the amplitude resolution of the signal waveform. The amplitude resolution was impoverished by reducing the number of bits to represent the signal samples. Auditory evoked magnetic fields (AEFs) were measured in the left and right hemisphere of sixteen healthy subjects.

Results

We found that the AEF amplitudes increased significantly with stimulus distortion for all stimulus types, which indicates that the right-hemispheric N1m sensitivity is not related exclusively to degradation of acoustic properties of speech. In addition, the P1m and P2m responses were amplified with increasing distortion similarly in both hemispheres. The AEF latencies were not systematically affected by the distortion.

Conclusions

We propose that the increased activity of AEFs reflects cortical processing of acoustic properties common to both speech and non-speech stimuli. More specifically, the enhancement is most likely caused by spectral changes brought about by the decrease of amplitude resolution, in particular the introduction of periodic, signal-dependent distortion to the original sound. Converging evidence suggests that the observed AEF amplification could reflect cortical sensitivity to periodic sounds.