RESUMO
Air oxidation of ortho-fluorodithizone resulted in the first X-ray resolved structure of a disulfide of dithizone, validating the last outstanding X-ray structure in the oxidation of dithizone, H(2)Dz, which proceeds via the disulfide, (HDz)(2), to the deprotonated dehydrodithizone tetrazolium salt, Dz. Density functional theory calculations established the energetically favored tautomers along the entire pathway; in gas phase and in polar as well as nonpolar solvent environments. DFT calculations using the classic pure OLYP and PW91, or the newer B3LYP hybrid functional, as well as MP2 calculations, yielded the lowest energy structures in agreement with corresponding experimental X-ray crystallographic results. Atomic charge distribution patterns confirmed the cyclization reaction pathway and crystal packing of Dz. Time dependent DFT for the first time gave satisfactory explanation for the solvatochromic properties of dithizone, pointing to different tautomers that give rise to the observed orange color in methanol and green in dichloromethane. Concentratochromism of H(2)Dz was observed in methanol. Computed orbitals and oscillators are in close agreement with UV-visible spectroscopic experimental results.
Assuntos
Ditizona/análogos & derivados , Ditizona/química , Teoria Quântica , Cristalografia por Raios X , Modelos Moleculares , Estrutura Molecular , Oxirredução , Espectrofotometria UltravioletaRESUMO
Synthesis, characteristics and radioiodination of the new carboxylic derivatives of dithizone are described in this paper. We have applied the carboxy dithizones for preparation of radioactive compounds by coupling with [131I]-histamine. Preliminary biological studies of the new radiodithizone were done in rats after two different application routs: peripheral i.v. injection and direct injection to splenic artery. Biodistribution of the carboxy dithizone-[131I]-histamine conjugate (i.v. injection) was quite different than that for free [131I]-histamine. However, uptake of activity in pancreas was low (0.81% g-1 of tissue). Direct application of the conjugate to splenic artery resulted in high activity retention in pancreas after 30 and 45 min post injection (respectively 8.8 and 12.4% g-1 of tissue) indicating potential usefulness of the new radiodithizone for in vivo monitoring of pancreas.
Assuntos
Ácidos Carboxílicos/farmacocinética , Ditizona/análogos & derivados , Ditizona/síntese química , Ditizona/farmacocinética , Radioisótopos do Iodo , Animais , Histamina/farmacocinética , Radioisótopos do Iodo/farmacocinética , Ratos , Iodeto de Sódio , Fatores de Tempo , Distribuição TecidualAssuntos
Ditizona/análogos & derivados , Transplante das Ilhotas Pancreáticas/fisiologia , Ilhotas Pancreáticas/citologia , Alanina Transaminase/sangue , Amilases/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Glicemia/metabolismo , Sobrevivência Celular , Creatinina/sangue , Técnicas de Cultura/métodos , Glucose/farmacologia , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Transplante das Ilhotas Pancreáticas/patologia , Ratos , Ratos Endogâmicos , Coloração e RotulagemRESUMO
The mono and diiodo-derivatives of dithizone labelled with radioactive 131I isotope were obtained. Those compounds can be used for diagnostic of pancreas and other organs to monitor pathological states.
