Ion-Pairing Interactions between Co(en)3 3+ and the 23Na NMR Frequency Shift Reagent TmDOTP5- 1

Jimin Ren, Charles Jr Springer, A. Dean Sherry

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Three new formulations of TmDOTP5- (DOTP8- = 1,4,7,10-tetraazacyclododecane-1,4,7,11-tetrakis(methylenephosphonate)) have been prepared in an effort to develop a low-osmolality form of the 23Na frequency shift reagent (SR). Equally concentrated (0.32 M) solutions of (MegH)4HTmDOTP (Meg = N-methylglucamine or meglumine), Na4HTmDOTP, and [Co(en)3]4/3HTmDOTP have solution osmolalities of 1245, 1040, and 707 mOsm/ kg, respectively, comparable to the ionic and non-ionic gadolinium-based MRI contrast agent preparations in clinical use. An analysis of 23Na and 59Co frequency shifts induced by TmDOTP5- indicated that Co(en)3 3+ can form both 1:1 and 2:1 adducts with TmDOTP5- with (log) binding constants of 3.1 ± 0.4 and 2.5 ± 0.4, respectively. These values were comparable with those obtained by analysis of the 2H frequency shifts observed for Co(en)3 3+ upon binding to HoDOTP5-. The 1H shifts of Co(en)3 3+ signals induced by YbDOTP5- at pH 7.4 were fitted best by a 1:1 binding model with a conditional binding constant of 3.1 ± 2. The 59Co and 1H limiting frequency shifts of Co(en)3 3+ could be fitted with a dipolar shift model in which the Co atom of the Co(en)3 3+ cation is located 5.0 ± 0.3 Å from the Ln atom of the LnDOTP5- chelate, and with an angle of 40 ± 0.2° between the Co-Ln vector and the 4-fold symmetry axis of the LnDOTP5- complex. Ion pairing of Co(en)3 3+ and TmDOTP5- was significant enough in both saline and human blood plasma to reduce the effectiveness of the 23Na frequency SR. Comparisons between all formulations suggested that Na4TmDOTP represents the best compromise of lower osmolality with minimal reduction of SR shift potency.

Original languageEnglish (US)
Pages (from-to)3493-3498
Number of pages6
JournalInorganic Chemistry
Volume36
Issue number16
StatePublished - 1997
Externally publishedYes

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Meglumine
frequency shift
reagents
Nuclear magnetic resonance
Ions
nuclear magnetic resonance
shift
Atoms
ions
Gadolinium
interactions
Magnetic resonance imaging
Contrast Media
Cations
Blood
blood plasma
formulations
Plasmas
gadolinium
chelates

ASJC Scopus subject areas

  • Inorganic Chemistry

Cite this

Ion-Pairing Interactions between Co(en)3 3+ and the 23Na NMR Frequency Shift Reagent TmDOTP5- 1. / Ren, Jimin; Springer, Charles Jr; Sherry, A. Dean.

In: Inorganic Chemistry, Vol. 36, No. 16, 1997, p. 3493-3498.

Research output: Contribution to journalArticle

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abstract = "Three new formulations of TmDOTP5- (DOTP8- = 1,4,7,10-tetraazacyclododecane-1,4,7,11-tetrakis(methylenephosphonate)) have been prepared in an effort to develop a low-osmolality form of the 23Na frequency shift reagent (SR). Equally concentrated (0.32 M) solutions of (MegH)4HTmDOTP (Meg = N-methylglucamine or meglumine), Na4HTmDOTP, and [Co(en)3]4/3HTmDOTP have solution osmolalities of 1245, 1040, and 707 mOsm/ kg, respectively, comparable to the ionic and non-ionic gadolinium-based MRI contrast agent preparations in clinical use. An analysis of 23Na and 59Co frequency shifts induced by TmDOTP5- indicated that Co(en)3 3+ can form both 1:1 and 2:1 adducts with TmDOTP5- with (log) binding constants of 3.1 ± 0.4 and 2.5 ± 0.4, respectively. These values were comparable with those obtained by analysis of the 2H frequency shifts observed for Co(en)3 3+ upon binding to HoDOTP5-. The 1H shifts of Co(en)3 3+ signals induced by YbDOTP5- at pH 7.4 were fitted best by a 1:1 binding model with a conditional binding constant of 3.1 ± 2. The 59Co and 1H limiting frequency shifts of Co(en)3 3+ could be fitted with a dipolar shift model in which the Co atom of the Co(en)3 3+ cation is located 5.0 ± 0.3 {\AA} from the Ln atom of the LnDOTP5- chelate, and with an angle of 40 ± 0.2° between the Co-Ln vector and the 4-fold symmetry axis of the LnDOTP5- complex. Ion pairing of Co(en)3 3+ and TmDOTP5- was significant enough in both saline and human blood plasma to reduce the effectiveness of the 23Na frequency SR. Comparisons between all formulations suggested that Na4TmDOTP represents the best compromise of lower osmolality with minimal reduction of SR shift potency.",
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