Cationic Biphotonic Lanthanide Luminescent Bioprobes Based on Functionalized Cross-Bridged Cyclam Macrocycles

Abstract

<p>Cationic lanthanide complexes are generally able to spontaneously internalize into living cells. Following our previous works based on diMe-cyclen framework, a second generation of cationic water-soluble lanthanide complexes based on a constrained cross-bridged cyclam macrocycle functionalized with donor-p-conjugated picolinate antennas has been prepared with europium(III) and ytterbium(III). Their spectroscopic properties were thoroughly investigated in various solvents and rationalized with the help of DFT calculations. A significant improvement is observed in the case of the Eu<sup>3+</sup> complex, while the Yb<sup>3+</sup> analogous conserve an excellent brightness in aqueous solvent. Two-photon (2P) microscopy imaging experiments on living T24 human cancer cells confirmed the spontaneous internalization of the probes and images with good signal-to-noise have been obtained in the classical NIR-to-visible configuration with Eu<sup>3+</sup> luminescent bioprobe and in the NIR-to-NIR with the Yb<sup>3+</sup> one.</p>

Pyclen-Based Ln(III) Complexes as Highly Luminescent Bioprobes for In Vitro and In Vivo One- and Two-Photon Bioimaging Applications

“…15 The pioneering works of Bunzli and Parker underlining the role of the cationic charge on the internalization process 16,17 prompted us to explore the potential of two eight-coordinated macrocyclic scaffolds for the design of 2P-LLBs, namely Medo2pa and the more rigid cross-bridged cyclam dipicolinate (cb-te2pa), both leading to highly luminescent and stable monocationic complexes (Figure 1). 10c,d, 18 Their analogues with π-extended picolinate antennas, [EuL 2a ], 19 [EuL 3a ], 21 [YbL 2b ], 20 and [YbL 3b ], 21 were obtained (Figure 1). The photophysical properties of the Yb 3+ complexes are excellent, in contrast to the Eu 3+ ones.…”

Tuning the excited state properties of [2.2]paracyclophane-based antennas to ensure efficient sensitization of lanthanide ions or singlet oxygen generation.

“…400 cm -1 , close to that of threefold symmetry complexes reported in the literature (LFS max in the range 340-370 cm -1 ). 34,59, 69-71 The slightly higher value confirms the distortion from the threefold symmetry already mentioned for EuL 1 . The absence of singlet oxygen emission at 1270 nm further indicates a preferable intramolecular energy transfer from the triplet of the ligand to the 7 F5/2 of the central Yb 3+ ion above an intermolecular energy transfer to the molecule of O2.…”

“…These values are close to that obtained for other related C3 symmetric TACN complexes (R 2 = 79%, r = 10.9) but the more intense J=4 transition suggests a slight distortion from this threefold symmetry. 59 At low temperature the spectra is better resolved, giving more indications about the complex symmetry (Figure 7). Here, the fine splitting of the bands (2 for J=1, and 3 for J=2) suggests a high symmetry around the Eu(III) ion, typically D3h symmetry expected for TACN-trispicolinate derivatives.…”

Design of Polyazamacrocyclic Gd3+ Theranostic Agent Combining MRI and Two-Photon PDT

“…Just like the molar extinction coefficient, the two-photon absorption cross-section is known to be an additive values depending only on the nature of the antenna chromophore. 31,36 Keeping in mind that the parent antenna ligand L1, featuring three brominated antennas, present a two-photon cross-section of 540 GM at 810 nm, 38 it can be anticipated that 9 and 11 present an estimated cross-section of ca 360 GM and 180 GM, respectively (2/3 and 1/3 of L1, respectively). All ligands present a similar typical broad CT ligand emission band centred around 580 nm in the case of dichloromethane and above 600 nm in water, associated with the brominated antenna, which undergoes a minor shift upon coordination ( Figure S16).…”

“…Besides showing improved performances in terms of metal complexation over cyclen-based chelators, they also allow the easier introduction of π-conjugated antennas to permit optical modalities. We, among others, have used such chemical modifications to design cyclen, 29,30 cyclam 31 but, especially, tacn [32][33][34][35] and pyclen 36,37 frameworks functionalised by picolinate functions for the development of both gadolinium(III) CA (GdCA) and lanthanide(III) luminescent bioprobes (LLB). More recently we presented a lanthanide(III) (Yb 3+ and Gd 3+ ) two-photon photosensitizer for PDT 38 that opened the way for the design of an "all-in-one" probe combining MRI and PDT.…”