First ¹⁷O NMR Observation of Coordinated Water on Both Isomers of [Eu(DOTAM)(H₂O)]³⁺:  A Direct Access to Water Exchange and its Role in the Isomerization¹

Abstract

A complete mechanistic study of the solution dynamics of [Eu(DOTAM)(H 2 O)] 3+ is performed through 1 H and 17 O NMR variable pressure and temperature studies. An unambiguous understanding of the water exchange was possible thanks to the first 17 O NMR observation of the bound water signal on both the M-and m-isomers (M:). The water exchange on m is about 50 times faster than on M, and even though the equilibrium constant K ) [M]/[m] equals 4.5, the contribution of m to the overall exchange rate is 90%. These results can be transferred to an aqueous solution since they agree with the overall exchange rate obtained by 17 O NMR for an aqueous solution of [Gd(DOTAM)(H 2 O)] 3+ . 2D-EXSY and variable temperature and pressure 1 H NMR experiments reveal that the interconversion between the M and m isomers happens mainly through a rotation of the amide arms in an interchange activated mechanism. (Interconversion rates measured by magnetization transfer: M f m: k a 250 ) 60 ( 10 s -1 ; m f M: k a 250 ) 260 ( 50 s -1 . Activation volumes: M f m: ∆V q ) -0.5 ( 0.3 cm 3 mol -1 , m f M: ∆V q ) -0.5 ( 0.7 cm 3 mol -1 and reaction volume ∆V°) 0 ( 1 cm 3 mol -1 ). In light of a simultaneous fitting of the water exchange and interconversion NMR data (M f m: ∆H q ) 39.1 ( 1.9 kJ mol -1 , ∆S q ) -52.1 ( 7.4 J K -1 mol -1 , k 250 ) 68 ( 5 s -1 ), as well as an interpretation of the activation and reaction volumes, we deduce a correlation between the two processes. A nonhydrated complex is proposed as a common intermediate for both the water exchange and the arm rotation processes, but only one M f m interconversion happens while two to three water exchanges take place.

Towards the Rational Design of Magnetic Resonance Imaging Contrast Agents: Isolation of the Two Coordination Isomers of Lanthanide DOTA‐Type Complexes

“…This difference is smaller than that observed by Dunand et al [13] for the more slowly exchanging [Eu(dotam)] 3+ ) isomers (dotam = 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane). However, the two complexes [Gd(S-RRRR-1)]…”

“…[9] Recent studies have suggested that the rate of water exchange in the two enantiomeric coordination isomers may differ by as much as two orders of magnitude. [10][11][12][13] The t M value measured for [Gd(dota)] À (244 ns) is a weighted average of the values for the coordination isomers present. [14] Although adequate for low-relaxivity agents, such a long average residence lifetime of water molecules is considered undesirable in the design of high-relaxivity contrast media.…”

Towards Binuclear Polyaminocarboxylate MRI Contrast Agents? Spectroscopic and MD Study of the Peculiar Aqueous Behavior of the LnIII Chelates of OHEC (Ln=Eu, Gd, and Tb): Implications for Relaxivity

“…[43] The kinetics for the isomerization a . [44] This may be the result of the important structural changes required for the interconversion. Firstly, the two water±Gd III bonds, which are also stabilized by hydrogen bonds, must be successively broken, and, secondly, the torsion of the macrocyclic skeleton needs to recover a steady state.…”

Structural and Chiroptical Properties of the Two Coordination Isomers of YbDOTA-Type Complexes

“…Of particular interest has been the nature of the two coordination isomers that exist naturally in a solution of LnDOTA. [1][2][3] Since the rate of water exchange is a critical parameter in contrast agent design 2 and one of the two coordination isomers of LnDOTA complexes exhibits substantially faster water exchange than the other, [4][5][6] understanding the physical characteristics of these two coordination isomers has been an important goal. Because they are in dynamic exchange in solution, the nature of each coordination isomer historically had to be deduced from measurements performed on mixtures of the two.…”