Solution Structures, Stabilities, Kinetics, and Dynamics of DO3A and DO3A–Sulphonamide Complexes

• Published in: Inorganic chemistry Vol. 53; no. 6; pp. 2858 - 2872
• Main Authors: Takács, Anett, Napolitano, Roberta, Purgel, Mihály, Bényei, Attila Csaba, Zékány, László, Brücher, Ernő, Tóth, Imre, Baranyai, Zsolt, Aime, Silvio
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 17.03.2014
• Subjects: Carbon-13 Magnetic Resonance Spectroscopy; Kinetics; Models, Molecular; Molecular Structure; Proton Magnetic Resonance Spectroscopy; Sulfonamides - chemistry
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/ic4025958

The Gd3+-DO3A–arylsulphonamide (DO3A–SA) complex is a promising pH-sensitive MRI agent. The stability constants of the DO3A–SA and DO3A complexes formed with Mg2+, Ca2+, Mn2+, Zn2+, and Cu2+ ions are similar, whereas the logK LnL values of Ln(DO3A–SA) complexes are 2 orders of magnitude higher than those of the Ln(DO3A) complexes. The protonation constant (log K MHL) of the sulphonamide nitrogen in the Mg2+, Ca2+, Mn2+, Zn2+, and Cu2+ complexes is very similar to that of the free ligand, whereas the logK LnHL values of the Ln(DO3A–SA) complexes are lower by about 4 logK units, indicating a strong interaction between the Ln3+ ions and the sulphonamide N atom. The Ln(HDO3A–SA) complexes are formed via triprotonated *Ln(H3DO3A–SA) intermediates which rearrange to the final complex in an OH–-assisted deprotonation process. The transmetalation reaction of Gd(HDO3A–SA) with Cu2+ is very slow (t 1/2 = 5.6 × 103 h at pH = 7.4), and it mainly occurs through proton-assisted dissociation of the complex. The 1H and 13C NMR spectra of the La-, Eu-, Y-, and Lu(DO3A–SA) complexes have been assigned using 2D correlation spectroscopy (COSY, EXSY, HSQC). Two sets of signals are observed for Eu-, Y-, and Lu(DO3A–SA), showing two coordination isomers in solution, that is, square antiprismatic (SAP) and twisted square antiprismatic (TSAP) geometries with ratios of 86–14, 93– 7, and 94–6%, respectively. Line shape analysis of the 13C NMR spectra of La-, Y- , and Lu(DO3A–SA) gives higher rates and lower activation entropy values compared to Ln(DOTA) for the arm rotation, which indicates that the Ln(DO3A–SA) complexes are less rigid due to the larger flexibility of the ethylene group in the sulphonamide pendant arm. The fast isomerization and the lower activation parameters of Ln(DO3A–SA) have been confirmed by theoretical calculations in vacuo and by using the polarizable continuum model. The solid state X-ray structure of Cu(H2DO3A–SA) shows distorted octahedral coordination. The coordination sites of Cu2+ are occupied by two ring N- and two carboxylate O-atoms in equatorial position. The other two ring N-atoms complete the coordination sphere in axial positions. The solid state structure also indicates that a carboxylate O atom and the sulphonamide nitrogen are protonated and noncoordinated.