Development of Luminescent Dendrimeric Metallacrowns from Lanthanide-based Metallacrowns

Abstract

Dendrimeric metallacrowns (DMCs) combine both dendrimers and metallacrowns as viable luminescent probes. Three approaches were investigated, these included functionalizing luminescent Ln2Ga8 metallacrowns at either the bridging or ring sites, or simultaneously at both positions, to then use them as the core of dendrimers. Investigation of the physical and optical properties of each DMC was performed, their solution behavior characterized, and in some cases their ability to label cells was investigated. Ln2Ga8 metallacrowns were functionalized with maleimide appendages at the bridging ligands to undergo thiol-coupling reactions. Complete coupling of cysteamine to the functionalized metallacrown confirmed thiol-coupling reactivity and that there was no degradation of the luminescent signal. Toroidal-DMCs could then be prepared by coupling poly(amidoamine) dendrons (G0.5-2.0) to Yb2Ga8 metallacrown-cores. Increased solution stability in mixed-aqueous/organic media was observed in DMCs compared to metallacrowns. YbIII-sensitization yielded long lifetimes (62-64μs) and high quantum yields (7.03-9.38%) in solution. The observed luminescent enhancement of the metallacrown core was attributed to the solvent protection by the dendrons. Depending on the solvent, generation size, and sample preparation, these DMCs showed various degrees of self-aggregation as determined by dynamic light scattering. HeLa cells incubated with G0.5- and G1.5-DMCs exhibited strong luminescence from non-specific binding at the cell membrane, while G1.0 toroidal-DMCs were internalized with luminescent signals localized at cell nucleoli. Altogether, these results show that toroidal-DMCs are more viable as imaging probes than non-functionalized metallacrowns. The more challenging functionalization occurred at the ring position. Four new ligands with allyl- and propargyl-appendages at the para- or meta-position were synthesized, and then LnGa4 and Ln2Ga8 metallacrowns were prepared (SmIII and YbIII) with each ring ligand. It was shown that the functionalization position (para vs. meta) had an effect on the ligand-centric singlet (29412 vs 26667cm-1) and triplet (23450 vs 21630cm-1) energies, as well as on thiol-coupling reactivity (para>meta). The SmIII and YbIII metallacrowns exhibited quantum yields in solution ranging 1.4-2.9% and 3.7-8.1%, which includes the highest value among YbIII-compounds (e.g., DMSO: F15TPPYb-H (Yb-2) 3.5% and PAN-DOTA(Yb) 0.054%). Synthetic trials revealed that Yb2Ga8 metallacrowns with para-allyl ring ligands were the best cored for the photocatalytic synthesis of hyperboloidal-DMCs with G1.0 poly(amidoamine) dendrons based on completeness of coupling. Photophysical characterization confirmed sensitization of YbIII-emission and enhancement of the luminescent properties, resulting in long lifetimes (69μs) and high quantum yields (8.7%) in solution. Since the templating ligands were functionalized independently, bifunctional metallacrowns could be prepared, and the synthesis of symmetric and asymmetric molecules to form more versatile dendrimers constructs was achieved. Three different DMCs were prepared using bifunctionalized Yb-metallacrowns. The first was a symmetric-DMC with twelve poly(amidoamine) dendrons coupled to both ligand positions, matching the highest number of dendron-growth/attachment sites in the literature. Asymmetric coupling was then investigated by preparing Janus-DMCs with orthogonally-positioned biotin and G1.0-dendrons. Finally, controlling the degree of thiol-coupling by selecting redshifted ring ligands with low thiol-reactivity was investigated, yielding a redshifted Yb-metallacrown that selectively coupled thiol-groups at the bridges. Photophysical characterization of the Janus- and redshifted-DMCs exhibited excellent YbIII-emission, with long lifetimes (62-66μs) and high quantum yields (7.4-8.8%). In summary, functionalization of metallacrowns at the templating ring and bridging ligands with thiol-active groups allowed the preparation of DMCs, which have high quantum yields and long luminescent lifetimes for this molecular class. Altogether, this work provides a new strategy toward the versatile design of luminescent DMCs, metallacrowns, and dendrimers.