Monitoring proton dissociation and solution conformation of chiral ytterbium complexes with near‐IR CD

Abstract

The ytterbium complex [Yb((S)-THP)](3+) ((S)-THP = (1S,4S,7S,10S-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane) is investigated in solution through NMR, near-IR absorption, and CD spectroscopy. Quantitative analysis of the paramagnetic pseudocontact NMR shift shows Lambda helicity of the ligand cage around the metal. The NIR CD spectrum recorded at acidic pH is found to be very similar to that of [Yb((R)-DOTMA)](-) ((R)-DOTMA = (1R,4R,7R,10R)-alpha,alpha',alpha'',alpha'''-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), which in solution assumes a twisted square antiprism (TSA) conformation. The similarity of the NIR CD spectra is discussed, and it is the first proof of the Lambda(lambda,lambda,lambda,lambda) conformation of [Yb((S)-THP)](3+). NIR CD spectra recorded in the pH range of 2-9 allow one to easily follow proton dissociation and to calculate the pK of this equilibrium in water (pK(A) = 6.4 +/- 0.1). This value agrees well with that determined for [Lu((S)-THP)](3+) using potentiometric methods. This demonstrates once again that NIR CD spectroscopy is a powerful technique for investigating the solution structure and dynamics of these complexes.

Static and Dynamic Stereochemistry of Chiral Ln DOTA Analogues

“…Interestingly, the chiral centre in THP is more distant from the macrocycle than in DOTMA, but in this case there is no evidence of a TSA/SA equilibrium: apparently the ring conformation appears to be locked to a large extent in Yb THP. [39,40] One can tentatively extend these findings to the whole Ln THP series, on account of the similar behaviour of the paramagnetic shifts recently reported for the Ce, Nd, Eu derivatives. [41] Chirality has been introduced at an even more remote position, outside the first coordination sphere, by derivatizing the carboxyl group with a chiral amine, as occurs for example with the amide DOTAMNp (Scheme 2).…”

“…The NIR-ECD spectrum of (SSSS) Yb THP in acidic solution. [40] Jacobus van't Hoff Because the first element can be regarded as inert and completely stereodefined, only the other two give rise to dynamics, between two pairs of TSA and SA forms (which in this case are in diastereomeric relation). For Yb, the SA form is prevalent, in analogy to what is discussed above.…”

“…Naturally, this cannot be achieved on the sp 2 carboxylic carbon, but it becomes possible on a carbinolic derivative, THP (THP = 1,4,7,10tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane), depicted in Figure 7. [37][38][39][40][41] Following a procedure similar to what outlined for DOTMA in Figure 5, we can predict that the (SSSS)configuration of the ligand will lead to D coordination, as shown in Figure 7.…”

“…The NIR-ECD spectrum of (SSSS) Yb THP in acidic solution. [40] Jacobus van't Hoff ChemPhysChem 2011ChemPhysChem , 12, 1490ChemPhysChem -1497ChemPhysChem 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim…”

Activation of a PARACEST Agent for MRI through Selective Outersphere Interactions with Phosphate Diesters

“…Under conditions where the non-ionized Eu( S-THP )(OH 2 ) 3+ is the major complex, the nonalcoholic macrocycle proton resonances do not change upon addition of DEP as would be expected for an outersphere interaction 24. In contrast, the ionized Yb( S-THP D)(OH 2 ) 2+ is the major complex in solution at pH 7.0 due to the low p K a values of late Ln( S-THP ) 3+ complexes 36,41. The 1 H NMR spectrum of Yb( S-THP ) 3+ changes dramatically at high and low pH because the ionized and non-ionized species have distinct hyperfine shifted macrocycle proton resonances (Figure S5).…”