Rachel S. Dickins

Towards rational design of fast water-exchanging Gd(dota-like) contrast agents? Importance of the M/m ratio.

1H NMR line-shape analysis and magnetisation-transfer experiments at variable temperature and pressure have been used to elucidate the solution dynamics of both M and m isomers of three [Eu(dota-tetraamide)(H2O)]3+ complexes. The direct 1H NMR observation of the bound water signal allows the water-exchange rates on each isomer to be measured individually. They are definitely independent of the ligand for both M and m isomers (M: k298(ex)=9.4+/-0.2 x 10(3) s(-1) for [Eu(dotam)(H2O)]3+, 8.2+/-0.2 x 10(3) s(-1) for [Eu(dtma)(H2O)]3+ and 11.2+/-1.4 x 10(3) s(-1) for [Eu(dotmam)-(H2O)]3+; m: k298(ex)=474+/-130 x 10(3) s(-1) for [Eu(dotam)(H2O)3+, 357+/-92 x 10(3) s(-1) for [Eu(dtma)(H2O)3+), and proceed through a dissociative mechanism (M isomers: deltaV++ = +4.9 cm3 mol(-1) for [Eu(dotam)(H2O)]3+ and + 6.9 cm3 mol(-1) for [Eu(dtma)(H2O)]3+). The overall water exchange only depends on the M/m isomeric ratio. The m isomer, which exchanges more quickly, is favoured by a-substitution of the ring nitrogen. Therefore the synthesis of DOTA-like ligands, which predominantly form complexes in the m form, should be a sufficient condition to ensure faster water exchange on potential Gd(III)-based contrast agents. Furthermore the activation parameters for the water-exchange and isomerisation processes are both compatible with a nonhydrated complex as intermediate.

Structural and NMR investigations of the ternary adducts of twenty α-amino acids and selected dipeptides with a chiral, diaqua–ytterbium complex

A detailed investigation of the nature of the binding of each of the 20 common alpha-amino acids and various selected dipeptides to a chiral, diaqua-ytterbium complex in aqueous solution has been carried out. Analysis of the dipolar 1H NMR paramagnetic shifts suggests that the alpha-amino acids form a common chelated structure within a nine-coordinate mono-capped square antiprismatic coordination environment, with the amine N axially disposed. Crystal structures of nine chelated YbL1-amino acid adducts (Gly, Ala, Ser, Thr, Met) confirm this. The ternary complexes with dipeptides (e.g. Gly-Ala, Gly-Ser, Gly-Met, Gly-Asp, Gly-Asn, Gly-His, Ser-Met, Asp-Phe, His-Gly) also favour the terminal amine as the axial donor with the proximate amide group binding to generate a five-ring chelate. Evidence for chelation through side-chain functionality was found only in the case of N-terminal Asp. The chiral environment about the ytterbium ion upon amino acid binding has also been probed using near-IR circular dichroism spectroscopy.

Closely diffusing O–H, amide N–H and methylene C–H oscillators quench the excited state of europium comlexes in solution

In octadentate complexes of europium(III) based on 1,4,7,10-tetraazacyclododecane, deuteriation studies and measurements of excited state lifetimes in solution reveal that amide N–H and methylene C–H oscillators afford an intramolecular vibronic deactivation pathway of the excited Eu 5D0 emissive state which, coupled with a reassessment of the effect of intermolecular OH oscillator quenching, allows more accurate estimates of complex solvation state, q, to be made.

Porphyrin sensitization of circularly polarised near-IR lanthanide luminescence: enhanced emission with nucleic acid binding

A palladium porphyrin has been covalently linked to a chiral lanthanide complex and effectively sensitises near-IR emission from Nd and Yb; sensitisation is enhanced in the absence of oxygen and in the presence of a nucleic acid.

LUMINESCENCE FROM YTTERBIUM(III) AND ITS COMPLEXES IN SOLUTION

Time-resolved studies of luminescence from ytterbium in solution are reported offering opportunities for luminescent imaging in the near IR, and allowing the use of a wide range of aromatic antennae to sensitise the metal centre; the luminescence of the solvated ion and of a wide variety of complexes is examined, both by direct excitation and by inter- and intra-molecular energy transfer.

Correlation of optical and NMR spectral information with coordination variation for axially symmetric macrocyclic Eu(III) and Yb(III) complexes: axial donor polarisability determines ligand field and cation donor preference

In Bleaneys theory of magnetic anisotropy, the second-order crystal field coefficient, Bo2, is predicted to determine the dipolar NMR shift of paramagnetic lanthanide complexes in solution. This parameter has been measured directly, by analysing the europium emission spectra for a series of eight- and nine-coordinate axially symmetric complexes based on cyclen including aza-carboxylate ligands (e.g. DOTA), phosphonates (DOTP), phosphinates and several carboxamides (e.g. DOTAM). For both Yb and Eu complexes with a common coordination number and geometry (square antiprism (SAP) or twisted square antiprism (TSAP)), the dipolar NMR shift correlates very well with this parameter, which also determines the sign and magnitude of a major CD band in the near-IR CD spectra of a series of enantiopure Yb complexes. Measurements of the free energy change associated with axial ligand exchange in a cationic europium tetraamide complex, [Eu(DOTAMPh)](CF3SO3)3 supported by a simple electrostatic perturbation model, have been interpreted in terms of a predominant donor atom polarisation model which affords a simple assessment of Ln ion donor atom preference and ranks the axial second-order ligand field coefficient.

Nuclear magnetic resonance, luminescence and structural studies of lanthanide complexes with octadentate macrocyclic ligands bearing benzylphosphinate groups

The solution and solid-state structures of lanthanide complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetryltetramethylenetetra(benzylphosphinate), L1a, and of its o-, m- and p-methoxybenzyl analogues (L2, L3, L4) have been investigated by NMR, relaxometry, crystallographic and photophysical methods. It has been shown that the number of proximate water molecules is dependent on the size of the bound lanthanide ion: the complex [LaL1a]– is nine-co-ordinate and adopts a twisted square-antiprismatic structure with one bound water molecule. The analogous [YL1a]–, [YbL1a]–, [GdL1a]– and [EuL1a]– complexes also adopt a twisted square-antiprismatic geometry, but are eight-co-ordinate, with no metal-bound water. Relaxivity studies with the gadolinium complexes showed that they are purely ‘outer-sphere’ contrast agents, but they associate strongly with proteins leading to a pronounced relaxivity enhancement. Detailed biodistribution studies with [GdL1a]– revealed avid biliary uptake at low doses and a well defined tendency for the complex to be cleared more slowly from tumour tissue, allowing tissue differentiation.

Reversible anion binding in aqueous solution at a cationic heptacoordinate lanthanide centre: selective bicarbonate sensing by time-delayed luminescence

Reversible displacement of up to two metal bound water molecules at a coordinately unsaturated, cationic lanthanide centre is signalled by increases in the luminescence intensity or lifetime of the emissive lanthanide: selective chelation of hydrogencarbonate is consistent with emission spectroscopic, ESMS and CPL measurements.

Generating a Warm Glow: Lanthanide Complexes Which Luminesce in the Near-IR

This article reviews and expands upon our observations of neodymium and ytterbium-centered luminescence in the near-IR. A variety of neodymium (III) and ytterbium (III) complexes with aminocarboxylate ligands was synthesized and their photophysical properties were investigated in aqueous solutions. Metal-centered emission was observed in the near-IR for complexes of both ions and time-resolved studies were used to show how quenching of the excited states is dependent on both inner and outer sphere coordinated water molecules.

A new chiral lanthanide NMR probe for the determination of the enantiomeric purity of α-hydroxy acids and the absolute configuration of α-amino acids in water

A water-soluble, enantiopure lanthanide complex, SSS-[Ln·L3], has been assessed as an effective chiral derivatising agent for the determination of the enantiomeric purity of α-hydroxy acids in aqueous solution. The complex displays superior chemical shift non-equivalence (ΔΔδ ∼2–11 ppm) for the diastereomeric resonances of interest compared to lanthanide shift reagents reported in the literature (ΔΔδ <0.1 ppm, typically). 1H NMR studies have also revealed that SSS-[Ln·L3] can be used to determine the absolute configuration of α-amino acids at physiological pH, in water. The ability of SSS-[Ln·L3] to signal anion binding and, in particular, to distinguish between diastereomers through optical techniques such as lanthanide luminescence and circular dichroism has also been assessed.