A mechanistic study on trivalent metal complexes a model pharmaceuticals

[摘要] English: The aim of the study was to synthesize several novel Co(II)-, Co(III)- and Cr(III) complexes using an O,O-bidentate ligand, methylene diphosphonate, and to characterize these complexes by various means. Characterization of the complexes was done by elemental analysis, infrared spectroscopy, nuclear magnetic resonance spectroscopy (NMR), single X-ray crystallography and X-ray photoelectron spectroscopy (XPS).The methylene diphosphonate ligand was selected as it is a ligand employed in a bone imaging agent in the radiopharmaceutical sector. Little is known about the structure and coordination chemistry of metal complexes with methylene diphosphonate.Single crystal X-ray crystallographic structure determinations of six new structures were completed:(1) Pyridinium diaquabis(methylenediphosphonato)chromate(III) tetrahydrate(2) Potassium diaquabis(methylenediphosphonato)cobaltate(III)(3) Potassium diaquadihydroxy(methylenediphosphonato)cobaltate(III)(4) Diammonium diaquabis(methylenediphosphonato)cobaltate(II)(5) Disodium diaquabis(methylenediphosphonato)cobaltate(II) dihydrate(6) Dicesium diaquabis(methylenediphosphonato)cobaltate(II)Each complex has a slightly distorted octahedral geometry. The cobalt or chromium ion in each complex is coordinated to four oxygen atoms derived from two methylene diphosphonate ligands, except for K[Co(CH4O6P2)(OH)2(H2O)2] which has two oxygen atoms from one methylene diphosphonate ligand coordinated to it. Inaddition each complex has two aqueous molecules which are coordinated to the metal center. Two phosphonate oxygen atoms from the ligand, methylene diphosphonate define the equatorial plane, whereas the water molecules reside in the axial positions.See Table in full text PDF.These complexes correlate with other similar complexes but the occurrence of similar structures in literature is very limited, showing that this field is open to further study. We were unable to perform any meaningful studies on these complexes in solution due to its insolubility in water.The stability constants for the polyprotic ligand MDP were established by means of volumetric titrations. Three methodologies namely, the geometric method, the first derivative method and the second derivative method in combination with the program SPARC were employed to determine the protonation constants as well as the equivalence points.In order to investigate the effect of the ionic medium on the determination of the dissociation constants, it was decided to perform the volumetric titrations in an ionic medium of 0.1 M NaCl and compare these values with data obtained without any adjustments to the ionic medium, the temperature for all of the reactions was kept constant at 18.0 ºC. The Ka1 value could not be determined using the Compact Titrator G20 as it is unable to perform titrations below pH 2. The Ka2 value was 2.91(8) without and ionic medium and 2.95(1) with and ionic medium (0.1 M NaCl). The Ka3 value was 7.22(5) without and ionic medium and 6.81(5) with and ionic medium (0.1 M NaCl). The Ka4 value was 10.57(1) without and ionic medium and 10.41(2) with and ionic medium (0.1 M NaCl). These dissociation constants correlated to literature.

[发布机构] University of the Free State