Near-Infrared Optical Imaging of Necrotic Cells by Photostable Lanthanide-Based Metallacrowns

Sensitive detection of cell necrosis is crucial for the determination of cell viability. Because of its high resolution at the cellular level and sensitivity, optical imaging is highly attractive for identifying cell necrosis. However, challenges associated with this technique remain present such as the rapid photobleaching of several types of organic fluorophores and/or the interference generated by biological autofluorescence. Herein, we synthesized novel biologically compatible Zn²⁺/Ln³⁺ metallacrowns (MCs) that possess attractive near-infrared (NIR) emission and are highly photostable. In addition, these MCs have the ability to label differentially necrotic HeLa cells from living cells. This work is also the first demonstration of (i) the use of the NIR emission arising from a single lanthanide­(III) cation for optical biological imaging of cells under single photon excitation, (ii) the first example of a lanthanide­(III)-based NIR-emitting probe that can be targeted to a specific type of cell

Functionalized Triptycene-Derived Tripodal Ligands: Privileged Formation of Tetranuclear Cage Assemblies with Larger Ln(III)

In this Article, we report the self-assembly of lanthanide complexes formed with two new tripodal ligands, <b>L2</b> and <b>L3</b>, where binding strands are connected to a rigid triptycene anchor. The pyridine moieties are functionalized with methoxy and PEG groups to enhance ligand solubility and to evaluate the effect of these substituents on lanthanide coordination. These ligands were successfully synthesized and characterized, and their coordination properties were examined along the lanthanide series through speciation studies with NMR and ESI-MS. Well-defined tetranuclear complexes are formed with both ligands, but their stabilities with heavier lanthanides are considerably reduced, especially for complexes with <b>L3</b>. This is attributed to a destabilizing effect of pending PEG arms in combination with increased steric hindrance between binding strands upon complexation with smaller cations. The sensitization of lanthanide luminescence in tetranuclear complexes occurs despite one water molecule being coordinated to a metal ion

A Postsynthetic Modification of II–VI Semiconductor Nanoparticles to Create Tb³⁺ and Eu³⁺ Luminophores

We describe a novel method for creating luminescent lanthanide-containing nanoparticles in which the lanthanide cations are sensitized by the semiconductor nanoparticle’s electronic excitation. In contrast to previous strategies, this new approach creates such materials by addition of external salt to a solution of fully formed nanoparticles. We demonstrate this postsynthetic modification for the lanthanide luminescence sensitization of two visible emitting lanthanides (Ln), Tb³⁺ and Eu³⁺ ions, through ZnS nanoparticles in which the cations were added postsynthetically as external Ln­(NO₃)₃·<i>x</i>H₂O salt to solutions of ZnS nanoparticles. The postsynthetically treated ZnS nanoparticle systems display Tb³⁺ and Eu³⁺ luminescence intensities that are comparable to those of doped Zn­(Ln)S nanoparticles, which we reported previously (<i>J. Phys. Chem. A</i>, <b>2011</b>, <i>115</i>, 4031–4041). A comparison with the synthetically doped systems is used to contrast the spatial distribution of the lanthanide ions, bulk versus surface localized. The postsynthetic strategy described in this work is fundamentally different from the synthetic incorporation (doping) approach and offers a rapid and less synthetically demanding protocol for Tb³⁺:ZnS and Eu³⁺:ZnS luminophores, thereby facilitating their use in a broad range of applications

Near-Infrared Optical Imaging of Necrotic Cells by Photostable Lanthanide-Based Metallacrowns

Sensitive detection of cell necrosis is crucial for the determination of cell viability. Because of its high resolution at the cellular level and sensitivity, optical imaging is highly attractive for identifying cell necrosis. However, challenges associated with this technique remain present such as the rapid photobleaching of several types of organic fluorophores and/or the interference generated by biological autofluorescence. Herein, we synthesized novel biologically compatible Zn²⁺/Ln³⁺ metallacrowns (MCs) that possess attractive near-infrared (NIR) emission and are highly photostable. In addition, these MCs have the ability to label differentially necrotic HeLa cells from living cells. This work is also the first demonstration of (i) the use of the NIR emission arising from a single lanthanide­(III) cation for optical biological imaging of cells under single photon excitation, (ii) the first example of a lanthanide­(III)-based NIR-emitting probe that can be targeted to a specific type of cell

Functionalized Triptycene-Derived Tripodal Ligands: Privileged Formation of Tetranuclear Cage Assemblies with Larger Ln(III)

In this Article, we report the self-assembly of lanthanide complexes formed with two new tripodal ligands, <b>L2</b> and <b>L3</b>, where binding strands are connected to a rigid triptycene anchor. The pyridine moieties are functionalized with methoxy and PEG groups to enhance ligand solubility and to evaluate the effect of these substituents on lanthanide coordination. These ligands were successfully synthesized and characterized, and their coordination properties were examined along the lanthanide series through speciation studies with NMR and ESI-MS. Well-defined tetranuclear complexes are formed with both ligands, but their stabilities with heavier lanthanides are considerably reduced, especially for complexes with <b>L3</b>. This is attributed to a destabilizing effect of pending PEG arms in combination with increased steric hindrance between binding strands upon complexation with smaller cations. The sensitization of lanthanide luminescence in tetranuclear complexes occurs despite one water molecule being coordinated to a metal ion

Rare Earth pcu Metal–Organic Framework Platform Based on RE₄(μ₃‑OH)₄(COO)₆²⁺ Clusters: Rational Design, Directed Synthesis, and Deliberate Tuning of Excitation Wavelengths

The T_<i>d</i> point group symmetry of rare earth (RE³⁺) metal clusters RE₄(μ₃-OH)₄(COO)₆²⁺ makes them attractive building blocks for creating metal–organic frameworks (MOFs) with controllable topologies. Herein, we describe the design and synthesis of a series of isoreticular MOFs featuring <b>pcu</b> topology [<b>MOF-1114­(RE)</b> and <b>MOF-1115­(RE)</b>] with variable rare earth metal ions (RE³⁺ = Y³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺, Dy³⁺, Ho³⁺, Er³⁺, Tm³⁺, Yb³⁺) and linear amino-functionalized dicarboxylate linkers of different lengths. In total, we report 22 MOFs that vary in both composition and structure yet share the same RE₄(μ₃-OH)₄ cluster motif. We demonstrate that these <b>pcu</b> MOFs are cationic and that anion exchange can be used to affect the MOF properties. We also investigate the luminescence properties of a representative member of this MOF series [<b>MOF-1114­(Yb)</b>] that exhibits near-infrared emission. We show that the excitation energy for Yb³⁺ sensitization can be carefully adjusted to lower energy via covalent postsynthetic modification at the amino group sites within the MOF

Rare Earth pcu Metal–Organic Framework Platform Based on RE₄(μ₃‑OH)₄(COO)₆²⁺ Clusters: Rational Design, Directed Synthesis, and Deliberate Tuning of Excitation Wavelengths

The T_<i>d</i> point group symmetry of rare earth (RE³⁺) metal clusters RE₄(μ₃-OH)₄(COO)₆²⁺ makes them attractive building blocks for creating metal–organic frameworks (MOFs) with controllable topologies. Herein, we describe the design and synthesis of a series of isoreticular MOFs featuring <b>pcu</b> topology [<b>MOF-1114­(RE)</b> and <b>MOF-1115­(RE)</b>] with variable rare earth metal ions (RE³⁺ = Y³⁺, Sm³⁺, Eu³⁺, Gd³⁺, Tb³⁺, Dy³⁺, Ho³⁺, Er³⁺, Tm³⁺, Yb³⁺) and linear amino-functionalized dicarboxylate linkers of different lengths. In total, we report 22 MOFs that vary in both composition and structure yet share the same RE₄(μ₃-OH)₄ cluster motif. We demonstrate that these <b>pcu</b> MOFs are cationic and that anion exchange can be used to affect the MOF properties. We also investigate the luminescence properties of a representative member of this MOF series [<b>MOF-1114­(Yb)</b>] that exhibits near-infrared emission. We show that the excitation energy for Yb³⁺ sensitization can be carefully adjusted to lower energy via covalent postsynthetic modification at the amino group sites within the MOF

Isoquinoline-Based Lanthanide Complexes: Bright NIR Optical Probes and Efficient MRI Agents

In the objective of developing ligands that simultaneously satisfy the requirements for MRI contrast agents and near-infrared emitting optical probes that are suitable for imaging, three isoquinoline-based polyaminocarboxylate ligands, <b>L1</b>, <b>L2</b> and <b>L3</b>, have been synthesized and the corresponding Gd³⁺, Nd³⁺ and Yb³⁺ complexes investigated. The specific challenge of the present work was to create NIR emitting agents which (i) have excitation wavelengths compatible with biological applications and (ii) are able to emit a sufficient number of photons to ensure sensitive NIR detection for microscopic imaging. Here we report the first observation of a NIR signal arising from a Ln³⁺ complex in aqueous solution in a microscopy setup. The lanthanide complexes have high thermodynamic stability (log <i>K</i>_LnL =17.7–18.7) and good selectivity for lanthanide ions versus the endogenous cations Zn²⁺, Cu²⁺, and Ca²⁺ thus preventing transmetalation. A variable temperature and pressure ¹⁷O NMR study combined with nuclear magnetic relaxation dispersion measurements yielded the microscopic parameters characterizing water exchange and rotation. Bishydration of the lanthanide cation in the complexes, an important advantage to obtain high relaxivity for the Gd³⁺ chelates, has been demonstrated by ¹⁷O chemical shifts for the Gd³⁺ complexes and by luminescence lifetime measurements for the Yb³⁺ analogues. The water exchange on the three Gd³⁺ complexes is considerably faster (<i>k</i>_ex²⁹⁸ = (13.9–15.4) × 10⁶ s^–1) than on commercial Gd³⁺-based contrast agents and proceeds <i>via</i> a dissociative mechanism, as evidenced by the large positive activation volumes for Gd<b>L1</b> and Gd<b>L2</b> (+10.3 ± 0.9 and +10.6 ± 0.9 cm³ mol^–1, respectively). The relaxivity of Gd<b>L1</b> is doubled at 40 MHz and 298 K in fetal bovine serum (<i>r</i>₁ = 16.1 vs 8.5 mM^–1 s^–1 in HEPES buffer), due to hydrophobic interactions between the chelate and serum proteins. The isoquinoline core allows for the optimization of the optical properties of the luminescent lanthanide complexes in comparison to the pyridinic analogues and provides significant shifts of the excitation energies toward lower values which therefore become more adapted for biological applications. <b>L2</b> and <b>L3</b> bear two methoxy substituents on the aromatic core in ortho and para positions, respectively, that further modulate their electronic structure. The Nd³⁺ and Yb³⁺ complexes of the ligand <b>L3</b>, which incorporates the <i>p</i>-dimethoxyisoquinoline moiety, can be excited up to 420 nm. This wavelength is shifted over 100 nm toward lower energy in comparison to the pyridine-based analogue. The luminescence quantum yields of the Nd³⁺ (0.013–0.016%) and Yb³⁺ chelates (0.028–0.040%) are in the range of the best nonhydrated complexes, despite the presence of two inner sphere water molecules. More importantly, the 980 nm NIR emission band of Yb<b>L3</b> was detected with a good sensitivity in a proof of concept microscopy experiment at a concentration of 10 μM in fetal bovine serum. Our results demonstrate that even bishydrated NIR lanthanide complexes can emit a sufficient number of photons to ensure sensitive detection in practical applications. In particular, these ligands containing an aromatic core with coordinating pyridine nitrogen can be easily modified to tune the optical properties of the NIR luminescent lanthanide complexes while retaining good complex stability and MRI characteristics for the Gd³⁺ analogues. They constitute a highly versatile platform for the development of bimodal MR and optical imaging probes based on a simple mixture of Gd³⁺ and Yb³⁺/Nd³⁺ complexes using an identical chelator. Given the presence of two inner sphere water molecules, important for MRI applications of the corresponding Gd³⁺ analogues, this result is particularly exciting and opens wide perspectives not only for NIR imaging based on Ln³⁺ ions but also for the design of combined NIR optical and MRI probes

Ga³⁺/Ln³⁺ Metallacrowns: A Promising Family of Highly Luminescent Lanthanide Complexes That Covers Visible and Near-Infrared Domains

Luminescent lanthanide­(III)-based molecular scaffolds hold great promises for materials science and for biological applications. Their fascinating photophysical properties enable spectral discrimination of emission bands that range from the visible to the near-infrared (NIR) regions. In addition, their strong resistance to photobleaching makes them suitable for long duration or repeated biological experiments using a broad range of sources of excitation including intense and focalized systems such as lasers (e.g., confocal microscopy). A main challenge in the creation of luminescent lanthanide­(III) complexes lies in the design of a ligand framework that combines two main features: (i) it must include a chromophoric moiety that possesses a large molar absorptivity and is able to sensitize several different lanthanide­(III) ions emitting in the visible and/or in the near-infrared, and (ii) it must protect the Ln³⁺ cation by minimizing nonradiative deactivation pathways due to the presence of −OH, −NH and −CH vibrations. Herein, a new family of luminescent Ga³⁺/Ln³⁺ metallacrown (MC) complexes is reported. The MCs with the general composition [LnGa₄(shi)₄(C₆H₅CO₂)₄(C₅H₅N) (CH₃OH)] (<b>Ln-1</b>, Ln = Sm³⁺–Yb³⁺) were synthesized in a one pot reaction using salicylhydroxamic acid (H₃shi) with Ga³⁺ and Ln³⁺ nitrates as reagents. The molecular structure of [DyGa₄(shi)₄(C₆H₅CO₂)₄(C₅H₅N) (CH₃OH)] was obtained by X-ray analysis of single crystals and shows that the complex is formed as a [12-MC_Ga(III)shi-4] core with four benzoate molecules bridging the central Dy³⁺ ion to the Ga³⁺ ring metals. The powder X-ray diffraction analysis demonstrates that all other isolated complexes are isostructural. The extended analysis of the luminescence properties of these complexes, excited by the electronic states of the chromophoric ligands, showed the presence of characteristic, sharp f–f transitions that can be generated not only in the NIR (Sm, Dy, Ho, Er, Yb) but also in the visible (Sm, Eu, Tb, Dy, Tm). All <b>Ln-1</b> complexes possess very high quantum yield values with respect to other literature compounds, indicating a good sensitization efficiency of the [12-MC_Ga(III)shi-4] scaffold. Especially, as of today, the <b>Yb-1</b> complex exhibits the highest NIR quantum yield reported for a lanthanide­(III) complex containing C–H bonds with a value of 5.88(2)% in the solid state. This work is a significant step forward toward versatile, easily prepared luminescent lanthanide­(III) complexes suitable for a variety of applications including highly in demand biological imaging, especially in the NIR domain

Enzyme-Catalyzed Oxidation Facilitates the Return of Fluorescence for Single-Walled Carbon Nanotubes

In this work, we studied enzyme-catalyzed oxidation of single-walled carbon nanotubes (SWCNTs) produced by the high-pressure carbon monoxide (HiPco) method. While oxidation via strong acids introduced defect sites on SWCNTs and suppressed their near-infrared (NIR) fluorescence, our results indicated that the fluorescence of SWCNTs was restored upon enzymatic oxidation, providing new evidence that the reaction catalyzed by horseradish peroxidase (HRP) in the presence of H₂O₂ is mainly a defect-consuming step. These results were further supported by both UV–vis–NIR and Raman spectroscopy. Therefore, when acid oxidation followed by HRP-catalyzed enzyme oxidation was employed, shortened (<300 nm in length) and NIR-fluorescent SWCNTs were produced. In contrast, upon treatment with myeloperoxidase, H₂O₂, and NaCl, the oxidized HiPco SWCNTs underwent complete oxidation (i.e., degradation). The shortened, NIR-fluorescent SWCNTs resulting from HRP-catalyzed oxidation of acid-cut HiPco SWCNTs may find applications in cellular NIR imaging and drug delivery systems