We have created unique near-infrared (NIR)-emitting nanoscale metal-organic frameworks (nano-MOFs) incorporating a high density of Yb 3+ lanthanide cations and sensitizers derived from phenylene. We establish here that these nano-MOFs can be incorporated into living cells for NIR imaging. Specifically, we introduce bulk and nano-Yb-phenylenevinylenedicarboxylate-3 (nano-Yb-PVDC-3), a unique MOF based on a PVDC sensitizer-ligand and Yb 3+ NIRemitting lanthanide cations. This material has been structurally characterized, its stability in various media has been assessed, and its luminescent properties have been studied. We demonstrate that it is stable in certain specific biological media, does not photobleach, and has an IC 50 of 100 μg/mL, which is sufficient to allow live cell imaging. Confocal microscopy and inductively coupled plasma measurements reveal that nano-Yb-PVDC-3 can be internalized by cells with a cytoplasmic localization. Despite its relatively low quantum yield, nano-Yb-PVDC-3 emits a sufficient number of photons per unit volume to serve as a NIR-emitting reporter for imaging living HeLa and NIH 3T3 cells. NIR microscopy allows for highly efficient discrimination between the nano-MOF emission signal and the cellular autofluorescence arising from biological material. This work represents a demonstration of the possibility of using NIR lanthanide emission for biological imaging applications in living cells with single-photon excitation.uminescent reporters emitting in the near-infrared (NIR) region of the electromagnetic spectrum are highly advantageous for biological imaging applications for several reasons. Biological material has low autofluorescence in the NIR window, which allows facile discrimination between the desired signal of the reporter and the background, leading to an enhanced signalto-noise ratio and improved detection sensitivity (1). Additionally, NIR light scatters less than visible light, and therefore results in increased optical imaging resolution (2, 3). Finally, NIR photons interact less with biological material compared with visible photons, thus decreasing the risk of disturbing or damaging the biological systems being observed.NIR reporters, such as cyanine dyes (4, 5) and quantum dots (6), have previously been shown to be useful for biological imaging applications. However, these materials have broad emission bands that limit their ability to be easily discriminated from the background fluorescence. Additionally, cyanine dyes exhibit limited photostability and quantum dots can display blinking emission, making it difficult to conduct repeated or long-term experiments for such purposes as tracking a moiety or monitoring a process.Several lanthanide cations emit in the NIR and have some advantages with respect to organic fluorophores and semiconductor nanocrystals. Lanthanide cations have narrower emission bandwidths than organic fluorophores and semiconductor nanocrystals. Their emission wavelengths are not affected by the environment, allowing them to be used in a broad ra...

The search for more biocompatible alternatives to Gd 3+-based MRI agents,a nd the interest in 52 Mn for PET imaging call for ligands that form inert Mn 2+ chelates.G iven the labile nature of Mn 2+ ,h igh inertness is challenging to achieve.The strongly preorganized structure of the 2,4-pyridyldisubstituted bispidol ligand L 1 endows its Mn 2+ complex with exceptional kinetic inertness.I ndeed, MnL 1 did not showa ny dissociation for 140 days in the presence of 50 equiv.o fZ n 2+ (37 8 8C, pH 6), while recently reported potential MRI agents MnPyC3A and MnPC2A-EA have dissociation half-lives of 0.285 ha nd 54.4 hu nder similar conditions.I na ddition, the relaxivity of MnL 1 (4.28 mm À1 s À1 at 25 8 8C, 20 MHz) is remarkable for am onohydrated, small Mn 2+ chelate.I nvivo MRI experiments in mice and determination of the tissue Mn content evidence rapid renal clearance of MnL 1 .Additionally, L 1 could be radiolabeled with 52 Mn and the complex revealed good stability in biological media.

A molecular theranostic agent for magnetic resonance imaging (MRI) and photodynamic therapy (PDT) consisting of four [GdDTTA](-) complexes (DTTA(4-) = diethylenetriamine-N,N,N″,N″-tetraacetate) linked to a meso-tetraphenylporphyrin core, as well as its yttrium(III) analogue, was synthesized. A variety of physicochemical methods were used to characterize the gadolinium(III) conjugate 1 both as an MRI contrast agent and as a photosensitizer. The proton relaxivity measured in H2O at 20 MHz and 25 °C, r1 = 43.7 mmol(-1) s(-1) per gadolinium center, is the highest reported for a bishydrated gadolinium(III)-based contrast agent of medium size and can be related to the rigidity of the molecule. The complex displays also a remarkable singlet oxygen quantum yield of ϕΔ = 0.45 in H2O, similar to that of a meso-tetrasulfonated porphyrin. We also evidenced the ability of the gadolinium(III) conjugate to penetrate in cancer cells with low cytotoxicity. Its phototoxicity on Hela cells was evaluated following incubation at low micromolar concentration and moderate light irradiation (21 J cm(-2)) induced 50% of cell death. Altogether, these results demonstrate the high potential of this conjugate as a theranostic agent for MRI and PDT.

A new series of amphiphilic polymers (amphipols) with varied molecular characteristics was prepared, and their properties in aqueous media were examined by static and dynamic light scattering techniques. These polymers are short poly(sodium methacrylate) chains of various molecular weights and tacticities, modified with different degrees of n-octylamine as copolymers of two distinct hydrophobe distribution sequences (random vs multiblocky). To synthesize the parent poly(methacrylic acid) (PMAA) prior to hydrophobic modification, tert-butyl methacrylate was polymerized under the controlled conditions of atom transfer radical polymerization (ATRP) to yield after deprotection the syndiotactic-rich PMAA of targeted molar masses (12-28 kg mol -1 ) and low polydispersity indexes (1.08-1.19). Under similar conditions of ATRP and deprotection, a well-defined isotactic-rich PMAA was obtained from triphenylmethyl methacrylate. The amphipol carrying octyl side chains randomly distributed along the polymer main chain was produced by coupling the parent PMAA with n-octylamine in an organic medium (N-methylpyrrolidone). In contrast, the coupling reaction of PMAA in aqueous media, with the n-octylamine solubilized by sodium dodecyl sulfate, gave the amphipols bearing octyl groups distributed in a multiblocky fashion. The highly controlled hydrophobe distribution sequence and polymer tacticity were confirmed by 1 H and 13 C NMR spectroscopic techniques. All polymers in aqueous solutions form nanoparticles with the structure strongly determined by the polymer microstructure and composition. In the case of random graft amphipol, the polymer self-assembles and preferentially forms small aggregates of 1-2 polymer chains on average with a hydrodynamic radius of ∼3 nm. In cases of the multiblocky graft amphipols, well-defined nanoscaled self-assemblies are formed but from multiple polymer chains (aggregation number ) ∼17), with a drastic increase in the hydrodynamic radius (∼13 nm). Comparing to the effects due solely to the hydrophobe distribution sequence, the increments in structural parameters of the amphipol self-assemblies are only slightly enhanced when concurrently improving the polymer isotacticity or increasing the polymer molar mass. All results point to the critical impact of hydrophobe distribution sequence on the self-assembly of methacrylate-based amphipols in aqueous solutions.

A molecular theranostic agent designed for photodynamic therapy (PDT) treatment in the near-infrared and for imaging tissue tumors with magnetic resonance imaging (MRI) is reported. It consists of a linear p-conjugated Zn(II)-porphyrin dimer linked at each extremity to a GdDOTA-type complex. This agent has shown very promising potential for PDT applications with good singlet oxygen generation in DMSO and high linear absorption in the near-infrared (lmax = 746 nm, e ≈ 10 5 M -1 cm -1 ). Moreover, this molecule has a propensity for two-photon excited PDT with high two-photon cross-sections (≈ 8000 GM in 880-930 nm range), which should allow for deeper tumor treatments and higher spatial precision as compared to conventional one-photon PDT. Regarding the MRI contrast agent properties, the molecule has shown superior relaxivity (14.4 mM -1 s -1 at 40 MHz, 298 K) in comparison to clinical contrast agents and ability to be internalized in cells, thanks to its amphiphilic character.Irradiation of HeLa cells using either one-photon (740 nm) or two-photon excitation (910 nm) has led in both cases to important cell death.

We report two macrocyclic ligands containing a 1,10-diaza-18-crown-6 fragment functionalized with either two picolinamide pendant arms (bpa18c6) or one picolinamide and one picolinate arm (ppa18c6(-)). The X-ray structure of [La(ppa18c6)(H2O)](2+) shows that the ligand binds to the metal ion using the six donor atoms of the crown moiety and the four donor atoms of the pendant arms, 11-coordination being completed by the presence of a coordinated water molecule. The X-ray structure of the [Sr(bpa18c6)(H2O)](2+) was also investigated due to the very similar ionic radii of Sr(2+) and Eu(2+). The structure of this complex is very similar to that of [La(ppa18c6)(H2O)](2+), with the metal ion being 11-coordinated. Potentiometric measurements were used to determine the stability constants of the complexes formed with La(3+) and Eu(3+). Both ligands present a very high selectivity for the large La(3+) ion over the smaller Eu(3+), with a size-discrimination ability that exceeds that of the analogous ligand containing two picolinate pendant arms reported previously (bp18c6(2-)). DFT calculations using the TPSSh functional and the large-core pseudopotential approximation provided stability trends in good agreement with the experimental values, indicating that charge neutral ligands derived from 1,10-diaza-18-crown-6 enhance the selectivity of the ligand for the large Ln(3+) ions. Cyclic voltammetry measurements show that the stabilization of Eu(2+) by these ligands follows the sequence bp18c6(2-) < ppa18c6(-) < bpa18c6 with half-wave potentials of -753 mV (bp18c6(2-)), -610 mV (ppa18c6(-)), and -453 mV (bpa18c6) versus Ag/AgCl. These values reveal that the complex of bpa18c6 possesses higher stability against oxidation than the aquated ion, for which an E1/2 value of -585 mV has been measured.

A series of novel pyridine-based Gd(3+) complexes have been prepared and studied as potential MRI contrast agents for Zn(2+) detection. By independent assessment of molecular parameters affecting relaxivity, we could interpret the relaxivity changes observed upon Zn(2+) binding in terms of variations of the rotational motion.

A water-soluble fluorinated MnIII/II porphyrin responds reversibly to ascorbate redox state as a turn-on MRI probe.