title: Solution structures, stabilities, kinetics, and dynamics of DO3A and DO3A-sulphonamide complexes.
abstract: The Gd(3+)-DO3A-arylsulphonamide (DO3A-SA) complex is a promising pH-sensitive MRI agent. The stability constants of the DO3A-SA and DO3A complexes formed with Mg(2+), Ca(2+), Mn(2+), Zn(2+), and Cu(2+) ions are similar, whereas the logKLnL values of Ln(DO3A-SA) complexes are 2 orders of magnitude higher than those of the Ln(DO3A) complexes. The protonation constant (log KMHL) of the sulphonamide nitrogen in the Mg(2+), Ca(2+), Mn(2+), Zn(2+), and Cu(2+) complexes is very similar to that of the free ligand, whereas the logKLnHL values of the Ln(DO3A-SA) complexes are lower by about 4 logK units, indicating a strong interaction between the Ln(3+) 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 Cu(2+) is very slow (t1/2 = 5.6 × 10(3) h at pH = 7.4), and it mainly occurs through proton-assisted dissociation of the complex. The (1)H and (13)C 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 (13)C 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 Cu(2+) 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.
authors.affiliation: Department of Inorganic and Analytical Chemistry, ‡MTA-DE Homogeneous Catalysis and Reaction Mechanisms Research Group, §Department of Physical Chemistry, University of Debrecen , H-4032 Debrecen, Egyetem tér 1, Hungary.
authors.forename: Anett
authors.initials: A
authors.lastname: Takács
authors.forename: Roberta
authors.initials: R
authors.lastname: Napolitano
authors.forename: Mihály
authors.initials: M
authors.lastname: Purgel
authors.forename: Attila Csaba
authors.initials: AC
authors.lastname: Bényei
authors.forename: László
authors.initials: L
authors.lastname: Zékány
authors.forename: Ernő
authors.initials: E
authors.lastname: Brücher
authors.forename: Imre
authors.initials: I
authors.lastname: Tóth
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Baranyai
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D066241:Carbon-13 Magnetic Resonance Spectroscopy; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D066244:Proton Magnetic Resonance Spectroscopy; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D013449:Sulfonamides