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

Abstract

Cationic lanthanide complexes are generally able to spontaneously internalize into living cells. Following our previous works based on a diMe-cyclen framework, a second generation of cationic water-soluble lanthanide complexes based on a constrained cross-bridged cyclam macrocycle functionalized with donor-π-conjugated picolinate antennas was 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 was observed in the case of the Eu 3 + complex, while the Yb 3 + analogue conserved photophysical properties 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 ratio were obtained in the classic NIR-tovisible configuration with the Eu 3 + luminescent bioprobe and in the NIR-to-NIR with the Yb 3 + one.[a] J.

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

“…Due to the presence of good to excellent quantum yields and strong ILCT transitions, all the functionalized complexes present very high brightness for each central metal ion (Table ). In the particular case of europium, the brightness compares well with that of the best complexes also presenting the same type of antennas, the number of antennas per complex controlling the extinction coefficient and, hence, the brightness. ,,, In the case of Tb, the brightness is comparable (although 50% lower) with that of the corresponding tacn derivative featuring three antennas and with that of the benchmark TbLumi4 derivative . For Dy and Sm, the comparison is mainly restricted to the tacn analogues and, once again, the number of antennas controls the global efficiency.…”

“…The pioneering works of Bünzli and Parker underlining the role of the cationic charge on the internalization process , 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 ). ,, Their analogues with π-extended picolinate antennas, [Eu L 2a ], [Eu L 3a ], [Yb L 2b ], and [Yb L 3b ], were obtained (Figure ). The photophysical properties of the Yb 3+ complexes are excellent, in contrast to the Eu 3+ ones.…”

Electron transfer pathways in photoexcited lanthanide(iii) complexes of picolinate ligands

“…21 The push-pull systems obtained by para-functionalization with electron-donating alkynes yield chromophores that are excellent sensitisers for Eu(III), [38][39][40][41][42] and have large two-photon absorption crosssections. [43][44][45][46][47] Thus, the near infrared-emitting YbL VII and related structures can be excited in the red at  ex = 760 nm. 48,49 Sensitising antennae can also be grafted onto the pyridine using a linker, [50][51][52][53][54] or both pyridine ligand and antenna can be assembled around a macrocyclic core.…”

Pyclen Based Ln(III) Complexes as Highly Luminescent Bioprobes for in Vitro and in Vivo 1P and 2P Bioimaging Applications

“…In the particular case of europium, the brightness compares well with that of the best complexes also presenting the same type of antennas, the number of antennas per complex controlling the extinction coefficient hence the brightness. [11,19,21,30] In the case of Tb, the brightness is in the same order of magnitude than that of the corresponding tacn derivative featuring three antennas [8] and that of the benchmark TbLumi4 derivative. [12] For Dy and Sm, the comparison is mainly restricted to the tacn analogous and once again, the number of antennas controls the global efficiency.…”

“…[4a, 16, 17] This idea prompted us to explore the potential of two eight coordinate macrocyclic scaffolds for the design of 2P-LLBs, namely the Medo2pa and the more rigid cross-bridged cyclam dipicolinate (cb-te2pa), both leading to highly luminescent and stable monocationic complexes ( Figure 1). [18, 10c, 10d] Their analogues with -extended picolinate antennas [EuL 2a ], [EuL 3a ], [19,21] [YbL 2b ] and [YbL 3b ] [20,21] were obtained ( Figure 1). The photophysical properties of the Yb 3+ complexes are excellent contrarily to that of the bigger size Eu 3+ one where non-radiative de-excitation pathways, due to partial dynamic water coordination, limit the overall brightness.…”