Self-assembly between dicarboxylate ions and binuclear europium complexes: moving to water—pH dependence and effects of buffers

Abstract

Binuclear lanthanide complexes consisting of two lanthanide binding domains in kinetically stable DO3A binding pockets linked by a 3-functionalized meta-xylyl bridge form stable 1:1 adducts with isophthalate and dinicotinate in water. The influence of buffer, pH and ligand structure on the binding of dinicotinate has been investigated.The nature of the f-electron configurations of the trivalent lanthanide ions results in long lived, high intensity luminescence and strong paramagnetic perturbation of proton resonances as well as highly reduced relaxation times in NMR. Bioassays based on lanthanide chemistry, where the long lived lanthanide centred emission allows for separation of fluorescence background and signal, exploit self-assembly on both the immunology side and to develop the highly emissive lanthanide species that supply the readout for the assay. 1 Lanthanide luminescence is also used in optical imaging, 2-5 where time-gating methodologies can be applied to reduce background noise and detection limit. 6 Gadolinium complexes have been extensively used as MRI contrast agents, 7-10 while bimodal lanthanide based imaging agents have been demonstrated that combine approaches to imaging. 11Self-assembled helicates, relying o n thermodynamic stability, have been prepared and studied in great detail. 5,[12][13][14] We and others have exploited the formation of ternary complexes between kinetically stable lanthanide complexes and simple carboxylates to probe energy transfer, 15 Self-complementary lanthanide complexes of DO3A with benzoate pendent arms exhibit pH-dependent self-association that modulates the luminescence intensity of the lanthanide emission by a combination of water displacement and an increase in of sensitisation efficiency. 18 Such modulation has been used as the basis for lanthanide luminescence sensors, 19-23 a number of which work in aqueous and biological media. 3,[24][25][26] The binding pocket of the binuclear complexes Eu 2 .1-3 consists of the seven-coordinate europium centres and the flat aromatic bridge (Scheme 1). The coordination number of europium is nine, which offers the possibility of both mono-and bi-dentate binding of carboxylates to each europium centre. We have recently shown that isophthalate ions are ideally suited to bind in this binding pocket (Scheme 2), in a study where the association of α, α'-bis(Eu.DO3A)-5-amino-m-xylene (Eu 2 .2) and isophthalate (5) was investigated.Isophthalate is not water-soluble, and we were obliged to use the terbium complex Tb.4 to study assembly processes with Eu 2 .2 in water. 27 In this work, we explore the binding of dinicotinate (6), the simplest water-soluble analogue of isophthalate, with three binuclear lanthanide complexes, and show that small changes in structure and solvation can have a profound impact upon binding. Figure 1 shows the changes in the europium centred luminescence upon titrating bis(Eu.DO3A)-3,5-dimethylpyridine (Eu 2 .1) with 6 in TRIS buffer, maintaining [Eu 2 .1] constant. These dramatic changes, make it...

Thermodynamics of Self‐Assembly of Dicarboxylate Ions with Binuclear Lanthanide Complexes

“…Furthermore, the difference between these parameters in BBS and HEPES buffer strongly suggests that HEPES buffer is a competitive buffer in this system. Such effects have been observed for the pyridine‐bridged system, where HEPES is a more competitive ion than phosphate …”

“…5‐nitro‐α,α′‐(DO3Ayl)‐ m ‐xylene (H 6 ⋅ 1 ) and its binuclear europium complex (Eu 2 ⋅ 1 ) were prepared as previously described . Although this ligand was among the first m ‐xylyl‐bridged bismacrocycles to be prepared, we have previously only carried out very limited studies upon the binding of anionic guest species beyond establishing the affinity for dinicotinate in tris(hydroxymethyl)aminomethane (TRIS) buffer . In this study, we report a much broader range of data and establish the affinity for four different anions, and define the binding in methanolic and aqueous media at a range of temperatures.…”

“…Initially, we established that lanthanide complexes of α,α′‐(DO3Ayl)‐ m ‐xylene are selective for isophthalate over terephthalate and phthalate . Subsequently, we have explored the binding of water‐soluble guests in such systems, and established that such complexes can be recruited to isophthalate‐functionalised surfaces . The isophthalate motif can also be used to direct the assembly of more complicated multimetallic f,f ’ and d , f complexes .…”

Ligation driven 19F relaxation enhancement in self-assembled Ln(iii) complexes

“…S5, ESI †), ¶ and concomitant changes in R 2 indicate the potential utility of these materials as 19 F contrast agents. [33][34][35][36] We postulated that effective ligation of ethoxy-fluorinated isophthalic acid analogues to binuclear gadolinium adducts would facilitate effective, and distance-optimised, PRE. 5 Recent investigations into the chelation of binuclear lanthanide chelates with dicarboxylate species have demonstrated that strongly bound adducts can be formed due to the unique binding pocket available, where both mono-and bi-dentate binding of carboxylate groups can occur with 7-coordinate lanthanide centres.…”

“…2 and Table S1, ESI †). 34,37,38 These conformational changes will, of course, have direct consequences on the relaxation through self-assembly. Somewhat counter-intuitively, relaxometric characteristics were less strongly enhanced at high solution pH (9)(10)(11)(12) also.…”