RESUMEN
We synthesized iron(III), cobalt(II), copper(II) and zinc(II) complexes [Fe(III)(HBPClNOL)Cl(2)]·H(2)O (1), [Co(II)(H(2)BPClNOL)Cl(2)] (2), [Cu(II)(H(2)BPClNOL)Cl]Cl·H(2)O (3), and [Zn(II)(HBPClNOL)Cl] (4), where H(2)BPClNOL is the ligand (N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)[(3-chloro)(2-hydroxy)]propylamine). The complexes obtained were characterized by elemental analysis, IR and UV-visible spectroscopies, electrospray ionization mass spectrometry (ESI-MS), tandem mass spectrometry (MS/MS), and cyclic voltammetry. X-ray diffraction studies were performed for complexes (3) and (4) revealing the presence of mononuclear and dinuclear structures in solid state for (3). However, the zinc complex is mononuclear in solid state. Biological studies of complexes (1)-(4) were carried out in vitro for antimicrobial activity against nine Gram-positive bacteria (Staphylococcus aureus strains RN 6390B, COL, ATCC 25923, Smith Diffuse, Wood 46, enterotoxigenic S. aureus FRI-100 (SEA+), FRI S-6 (SEB+) and SEC FRI-361) and animal strain S. aureus LSA 88 (SEC/SED/TSST-1+). The following sequence of inhibition promoted by the complexes was observed: (4)>(2)>(3)>(1), showing the effect of the metal on the biological activity. To directly observe the morphological changes of the internal structure of bacterial cells after the treatment, transmission electron microscopy (TEM) was employed. For the most active complex [Zn(II)(HBPClNOL)Cl] (4), granulation deposits around the genetic material and internal material leaking were clearly detected.
Asunto(s)
Antibacterianos/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Microscopía Electrónica de Transmisión/métodos , Cobalto/química , Cobalto/farmacología , Complejos de Coordinación/síntesis química , Cobre/química , Cobre/farmacología , Compuestos Férricos/síntesis química , Compuestos Férricos/química , Compuestos Férricos/farmacología , Ligandos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/ultraestructura , Difracción de Rayos X , Zinc/química , Zinc/farmacologíaRESUMEN
We report herein the characterization by electrospray ionization (ESI) mass spectrometry (MS), matrix assisted laser desorption ionization (MALDI-MS) and potentiometric titration of three iron(III) compounds: [Fe(III)(HPClNOL)Cl2]·NO3 (1), [Cl(HPClNOL)Fe(III)-(µ-O)-Fe(III)(HPClNOL)Cl]·Cl2·H2O (2) and [(SO4)(HPClNOL)Fe(III)-(µ-O)-Fe(III)(HPClNOL)(SO4)]·6H2O (3), where HPClNOL= 1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol). Despite the fact that the compounds have distinct structures in solid state and non-buffered solution, all compounds present similar ESI and MALDI mass spectra in a buffered medium (pH 7.0). At this pH, the species [(PClNOL)Fe(III)-(µ-O)-Fe(III)(PClNOL)](2+) (m/z 354) was observed for all the compounds under investigation. Potentiometric titration confirms a similar behavior for all compounds, indicating that the dihydroxo form [(OH)(HPClNOL)Fe(III)-(µ-O)-Fe(III)(HPClNOL)(OH)](2+) is the major species at pH 7.0, for all the compounds. The products of the interaction between compounds (1), (2) and (3) and dAMP (2'-deoxyadenosine-5'-monophosphate) in a buffered medium (pH 7.0) were identified by MALDI-MS/MS. The fragmentation data obtained by MS/MS allow one to identify the nature of the interaction between the iron(III) compounds and dAMP, revealing the direct interaction between the iron center and phosphate groups.