Solution Structures, Stabilities, Kinetics, and Dynamics of DO3A and DO3A鈥揝ulphonamide Complexes

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• 作者：Anett Tak谩cs ; Roberta Napolitano ; Mih谩ly Purgel ; Attila Csaba B茅nyei ; L谩szl贸 Z茅k谩ny ; Ern艖 Br眉cher ; Imre T贸th ; Zsolt Baranyai ; Silvio Aime
• 刊名：Inorganic Chemistry
• 出版年：2014
• 出版时间：March 17, 2014
• 年：2014
• 卷：53
• 期：6
• 页码：2858-2872
• 全文大小：512K
• 年卷期：v.53,no.6(March 17, 2014)
• ISSN：1520-510X

文摘

The Gd³⁺-DO3A鈥揳rylsulphonamide (DO3A鈥揝A) complex is a promising pH-sensitive MRI agent. The stability constants of the DO3A鈥揝A and DO3A complexes formed with Mg²⁺, Ca²⁺, Mn²⁺, Zn²⁺, and Cu²⁺ ions are similar, whereas the logK_LnL values of Ln(DO3A鈥揝A) 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鈥揝A) complexes are lower by about 4 logK units, indicating a strong interaction between the Ln³⁺ ions and the sulphonamide N atom. The Ln(HDO3A鈥揝A) complexes are formed via triprotonated *Ln(H₃DO3A鈥揝A) intermediates which rearrange to the final complex in an OH^{鈥?/sup>-assisted deprotonation process. The transmetalation reaction of Gd(HDO3A鈥揝A) with Cu2+ is very slow (t_1/2 = 5.6 脳 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鈥揝A) complexes have been assigned using 2D correlation spectroscopy (COSY, EXSY, HSQC). Two sets of signals are observed for Eu-, Y-, and Lu(DO3A鈥揝A), showing two coordination isomers in solution, that is, square antiprismatic (SAP) and twisted square antiprismatic (TSAP) geometries with ratios of 86鈥?4, 93鈥?7, and 94鈥?%, respectively. Line shape analysis of the 13C NMR spectra of La-, Y- , and Lu(DO3A鈥揝A) gives higher rates and lower activation entropy values compared to Ln(DOTA) for the arm rotation, which indicates that the Ln(DO3A鈥揝A) 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鈥揝A) have been confirmed by theoretical calculations in vacuo and by using the polarizable continuum model. The solid state X-ray structure of Cu(H₂DO3A鈥揝A) 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.}