Derivatization of the Peptidic Xxx-Zzz-His Motif toward a Ligand with Attomolar CuII Affinity under Maintaining High Selectivity and Fast Redox Silencing.

Cu chelation in biological systems is of interest as a tool to study the metabolism of this essential metal or for applications in the case of diseases with a systemic or local Cu overload, such as Wilson's or Alzheimer's disease. The choice of the chelating agent must meet several criteria. Among others, affinities and kinetics of metal binding and related metal selectivity are important parameters of the chelators to consider. Here, we report on the synthesis and characterization of Cu-binding properties of two ligands, L1 and L2, derivatives of the well-known peptidic CuII-binding motif Xxx-Zzz-His (also called ATCUN), where CuII is bound to the N-terminal amine, two amidates, and the imidazole. In either L, the N-terminal amine was replaced with a pyridine, and for L2, one amide was replaced with an amine compared to Xxx-Zzz-His. In particular, L2 showed several interesting features, including a CuII-binding affinity with a log KDapp = -16.0 similar to that of EDTA and stronger than all reported ATCUN peptides. L2 showed high selectivity for CuII over ZnII and other essential metal ions, even under the challenging conditions of the presence of human serum albumin. Further, L2 showed fast and efficient CuII redox silencing qualities and CuII-L2 was stable in the presence of mM GSH concentrations. Benefitting the fact that L2 can be easily elongated on its peptide part by standard SPPS to add other functions, L2 has attractive properties as a CuII chelator for application in biological systems.

Multifunctional cubic liquid crystalline nanoparticles for chemo- and photodynamic synergistic cancer therapy.

With the aim of engineering multifunctional nanoparticles useful for cancer therapy, a diketopyrrolopyrrole-porphyrin based photosensitizer was here conjugated to a block copolymer (Pluronic F108), and used to stabilize in water lipidic cubic liquid crystalline nanoparticles (cubosomes), also loaded with the antineoplastic agent docetaxel. The physicochemical characterization by SAXS, DLS, and cryo-TEM demonstrated that the formulation consisted of cubosomes, about 150 nm in size, possessing a bicontinuous cubic structure (space group Pn3m). The cellular imaging experiments proved that these nanoparticles localized in lysosomes and mitochondria, while cytotoxicity tests evidenced a slight but significant synergistic effect which, after irradiation, increased the toxicity induced by docetaxel alone, allowing further reduction of cell viability.

Synthesis and In Vitro Studies of a Gd(DOTA)-Porphyrin Conjugate for Combined MRI and Photodynamic Treatment.

With the aim of developing new molecular theranostic agents, a π-extended Zn(II) porphyrin as photosensitizer for photodynamic therapy (PDT) linked to two GdDOTA-type complexes for magnetic resonance imaging (MRI) detection was synthesized. The relaxivity studies revealed a much higher relaxivity value per Gd ion for this medium sized molecule (19.32 mM-1 s-1 at 20 MHz and 298 K) compared to clinical contrast agents-a value which strongly increases in the presence of bovine serum albumin, reaching 25.22 mM-1 s-1. Moreover, the photophysical studies showed the strong ability of the molecule to absorb light in the deep red (670 nm, ε ≈ 60000 M-1 cm-1) and in the near-infrared following two-photon excitation (920 nm, σ2 ≈ 650 GM). The conjugate is also able to generate singlet oxygen, with a quantum yield of 0.58 in DMSO. Promising results were obtained in cellular studies, demonstrating that the conjugate is internalized in HeLa cells at micromolar concentration and leads to 70% of cell death following 30 min irradiation at 660 nm. These results confirm the potential of the designed molecule as an imaging and therapeutic agent.

Tumour-targeting photosensitisers for one- and two-photon activated photodynamic therapy.

Despite the advantages of photodynamic therapy (PDT) over chemotherapy or radiotherapy such as low side effects, lack of treatment resistance and spatial selectivity inherent to light activation of the drug, several limitations especially related to the photosensitiser (PS) prevent PDT from becoming widespread in oncology. Herein, new folic acid- and biotin-conjugated PSs for tumour-targeting PDT are reported, with promising properties related to PDT such as intense absorption following one-photon excitation in the red or two-photon excitation in the near-infrared, and also high singlet oxygen quantum yield (close to 70% in DMSO). Cellular studies demonstrated that both targeted PSs induced phototoxicity, the folate-targeted PS being the most effective one with 80% of cell death following 30 min of irradiation and a phototoxicity four times higher than that of the non-targeted PS. This result is in accordance with the uptake of the folate-targeted PS in HeLa cells, mediated by the folate receptors. Moreover, this folate-targeted PS was also phototoxic following two-photon excitation at 920 nm, opening new perspectives for highly selective PDT treatment of small and deep tumours.

A Porphyrin Dimer-GdDOTA Conjugate as a Theranostic Agent for One- and Two-Photon Photodynamic Therapy and MRI.

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 π-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 (λmax = 746 nm, ε ≈ 105 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 the 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.

A Theranostic Agent Combining a Two-Photon-Absorbing Photosensitizer for Photodynamic Therapy and a Gadolinium(III) Complex for MRI Detection.

The convergent synthesis and characterization of a potential theranostic agent, [DPP-ZnP-GdDOTA](-), which combines a diketopyrrolopyrrole-porphyrin component DPP-ZnP as a two-photon photosensitizer for photodynamic therapy (PDT) with a gadolinium(III) DOTA complex as a magnetic resonance imaging probe, is presented. [DPP-ZnP-GdDOTA](-) has a remarkably high longitudinal water proton relaxivity (19.94 mm(-1) s(-1) at 20 MHz and 25 °C) for a monohydrated molecular system of this size. The Nuclear Magnetic Relaxation Dispersion (NMRD) profile is characteristic of slow rotation, related to the extended and rigid aromatic units integrated in the molecule and to self-aggregation occurring in aqueous solution. The two-photon properties were examined and large two-photon absorption cross-sections around 1000 GM were determined between 910 and 940 nm in DCM with 1 % pyridine and in DMSO. Furthermore, the new conjugate was able to generate singlet oxygen, with quantum yield of 0.42 and 0.68 in DCM with 1 % pyridine and DMSO, respectively. Cellular studies were also performed. The [DPP-ZnP-GdDOTA](-) conjugate demonstrated low dark toxicity and was able to induce high one-photon and moderate two-photon phototoxicity on cancer cells.

Four Gadolinium(III) Complexes Appended to a Porphyrin: A Water-Soluble Molecular Theranostic Agent with Remarkable Relaxivity Suited for MRI Tracking of the Photosensitizer.

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 Ï•Δ = 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.

Cyclic [4]rotaxanes containing two parallel porphyrinic plates: toward switchable molecular receptors and compressors.

Twenty years ago, researchers considered the synthesis of simple rotaxanes a challenging task, but with the rapid development of this field, chemists now view these interlocking molecules as accessible synthetic targets. In a major advance for the field, researchers have developed transition metals or organic molecules as templating structures, making it easier to construct these molecular systems. In addition, chemists have found ways to introduce new functional groups, which have given these compounds new properties. Today researchers can also construct multirotaxanes consisting of several individual components, but the synthesis of the most complex structures remains challenging. This Account primarily discusses the cyclic [4]rotaxanes incorporating porphyrins that the Strasbourg group has synthesized and studied during the past few years. These cyclic [4]rotaxanes consist of two rigid rods threaded through the four rings of two molecules of a bis-macrocycle, and the synthetic strategy used for making them relies on the copper(I)-driven "gathering-and-threading" reaction. The formation of the threaded precursors was mostly quantitative, and the quadruple stoppering reaction leading to the target compound produces high yields because of the efficient copper-catalyzed azide-alkyne cycloaddition (CuAAC) or click chemistry reaction. These rotaxanes behave as receptors for various ditopic guests. We prepared and studied two types of molecules: (i) a rigid compound whose copper(I) complex has a well-defined shape, with high selectivity for the guest geometry and (ii) a much more flexible [4]rotaxane host that could act as a distensible receptor. The rigid [4]rotaxane was crystallized, affording a spectacular X-ray structure that matched the expected chemical structure. In addition, metalation or demetalation of the rigid [4]rotaxane induces a drastic geometric rearrangement. The metal-free compound is flat without a binding pocket, while the copper-complexed species forms a rectangle-like structure. The removal of copper(I) also expels any complexed guest molecule, and this process is reversible, making the rigid porphyrinic [4]rotaxane a switchable receptor. The rigid [4]rotaxane was highly selective for short, ditopic guests in its copper(I)-complexed form, but the flexible copper(I)-complexed [4]rotaxane proved to be a versatile receptor. Its conformation can adjust to the size of the guest molecule similar to the induced fit mechanism that some enzymes employ with substrates.

Diketopyrrolopyrrole-porphyrin conjugates with high two-photon absorption and singlet oxygen generation for two-photon photodynamic therapy.

Two-photon photodynamic therapy is a promising therapeutic method which requires the development of sensitizers with efficient two-photon absorption and singlet-oxygen generation. Reported here are two new diketopyrrolopyrrole-porphyrin conjugates as robust two-photon absorbing dyes with high two-photon absorption cross-sections within the therapeutic window. Furthermore, for the first time the singlet-oxygen generation efficiency of diketopyrrolopyrrole-containing systems is investigated. A preliminary study on cell culture showed efficient two-photon induced phototoxicity.

Transition-metal-complexed catenanes and rotaxanes: from dynamic systems to functional molecular machines.

Transition metal-based catenanes and rotaxanes constitute a specific class of mechanically interlocked molecules whose metal centers are essential both as templates in the construction of the compounds and for their ability to induce large-amplitude motions. In the present chapter we will first present a historical perspective of the field of interlocking compounds in general, in relation to molecular machines, starting with old work dating back to the 1980s and 1990s. Copper was shown many years ago to be the metal of choice for synthesizing the compounds via a template approach and for setting the molecules in motion using a redox signal (Cu(II)/Cu(I)). In a second paragraph, we will discuss various rotaxanes able to undergo a pirouetting motion of the axis within the threaded ring. Two families of such molecules will be mentioned: (1) a porphyrin-containing [2]rotaxane whose pirouetting motion is induced by a chemical reaction and (2) electrochemically driven systems. In this second category of [2]rotaxanes, the rate of motion could be dramatically increased by gradually modifying structural parameters and, in particular, by making the metal center less and less hindered by its surrounding ligands. The third section will be devoted to molecular shuttles and muscles, both families of compounds being reminiscent of linear machines such as biological muscles. By replacing the classical 2,9-diaryl-1,10-phenanthroline chelate (highly shielding and hindering) used by our group since the 1980s by an endocyclic but non-sterically hindering 3,3'-biisoquinoline derivative, the shuttling rate was increased in spectacular fashion, demonstrating the importance of steric factors in transition metal-based molecular machines. The same 3,3'-biisoquinoline motif was also used in the elaboration of a three-station shuttle, leading to long-distance (>20 Å) transport of a ring along the axis on which it is threaded. Finally, porphyrin-containing [3]rotaxanes and [4]rotaxanes, the latter displaying an overall cyclic structure, will be discussed and shown to behave as adjustable and switchable receptors. The synthesis of such compounds is a particularly challenging task in itself. In addition, the new receptors display fascinating properties such as, in particular, their ability to compress various guests and to expel them from their binding site using a chemical signal.

Quest for a stable Cu-ligand complex with a high catalytic activity to produce reactive oxygen species.

Metal ion-catalyzed overproduction of reactive oxygen species (ROS) is believed to contribute significantly to oxidative stress and be involved in several biological processes, from immune defense to development of diseases. Among the essential metal ions, copper is one of the most efficient catalysts in ROS production in the presence of O2 and a physiological reducing agent such as ascorbate. To control this chemistry, Cu ions are tightly coordinated to biomolecules. Free or loosely bound Cu ions are generally avoided to prevent their toxicity. In the present report, we aim to find stable Cu-ligand complexes (Cu-L) that can efficiently catalyze the production of ROS in the presence of ascorbate under aerobic conditions. Thermodynamic stability would be needed to avoid dissociation in the biological environment, and high ROS catalysis is of interest for applications as antimicrobial or anticancer agents. A series of Cu complexes with the well-known tripodal and tetradentate ligands containing a central amine linked to three pyridyl-alkyl arms of different lengths were investigated. Two of them with mixed arm length showed a higher catalytic activity in the oxidation of ascorbate and subsequent ROS production than Cu salts in buffer, which is an unprecedented result. Despite these high catalytic activities, no increased antimicrobial activity toward Escherichia coli or cytotoxicity against eukaryotic AGS cells in culture related to Cu-L-based ROS production could be observed. The potential reasons for discrepancy between in vitro and in cell data are discussed.

Impact of human serum albumin on CuII and ZnII complexation by ATSM (diacetyl-bis(N4-methylthiosemicarbazone)) and a water soluble analogue.

The chelator diacetyl-bis(N4-methylthiosemicarbazone) (ATSM) and its complexes with CuII and ZnII are becoming increasingly investigated for medical applications such as PET imaging for anti-tumour therapy and the treatment of amyotrophic lateral sclerosis. However, the solubility in water of both the ligand and the complexes presents certain limitations for in vitro studies. Moreover, the stability of the CuII and ZnII complexes and their metal exchange reaction against the potential biological competitor human serum albumin (HSA) has not been studied in depth. In this work it was observed that the ATSM with an added carboxylic group into the structure increases its solubility in aqueous solutions without altering the coordination mode and the conjugated system of the ligand. The poorly water-soluble CuII- and ZnII-ATSM complexes were prevented from precipitating due to the binding to HSA. Both HSA and ATSM show a similar thermodynamic affinity for ZnII. Finally, the CuII-competition experiments with EDTA and the water-soluble ATSM ligands yielded an apparent log Kd at pH 7.4 of about -19. When ATSM was added to CuII- and ZnII-loaded HSA, withdrawing of ZnII was kinetically favoured, but this metal is slowly substituted by the CuII afterwards taken from HSA so that this protein could be considered as a source of CuII for ATSM.

Three in One: In Vitro and In Vivo Evaluation of Anticancer Activity of a Theranostic Agent that Combines Magnetic Resonance Imaging, Optical Bioimaging, and Photodynamic Therapy Capabilities.

Cancer treatment is a crucial area of research and development, as current chemotherapeutic treatments can have severe side effects or poor outcomes. In the constant search for new strategies that are localized and minimally invasive and produce minimal side effects, photodynamic therapy (PDT) is an exciting therapeutic modality that has been gaining attention. The use of theranostics, which combine diagnostic and therapeutic capabilities, can further improve treatment monitoring through image guidance. This study explores the potential of a theranostic agent consisting of four Gd(III) DTTA complexes (DTTA: diethylenetriamine-N,N,N″,N″-tetraacetate) grafted to a meso-tetraphenylporphyrin core for PDT, fluorescence, and magnetic resonance imaging (MRI). The agent was first tested in vitro on both nonmalignant TIB-75 and MRC-5 and tumoral CT26 and HT-29 cell lines and subsequently evaluated in vivo in a preclinical colorectal tumor model. Advanced MRI and optical imaging techniques were employed with engineered quantitative in vivo molecular imaging based on dynamic acquisition sequences to track the biodistribution of agents in the body. With 3D quantitative volume computed by MRI and tumoral cell function assessed by bioluminescence imaging, we could demonstrate a significant impact of the molecular agent on tumor growth following light application. Further exhaustive histological analysis confirmed these promising results, making this theranostic agent a potential drug candidate for cancer.

A flexible copper(I)-complexed [4]rotaxane containing two face-to-face porphyrinic plates that behaves as a distensible receptor.

A new cyclic [4]rotaxane composed of two flexible bis-macrocycles and two rigid axles is described. Each bis-macrocycle consists of two rings attached to antipodal meso positions of a central Zn porphyrin through single C-C bonds. Each ring incorporates a 2,9-diphenyl-1,10-phenanthroline chelation site. The axles contain two coplanar bidentate sites derived from the 2,2'-bipyridine motif. The building blocks were assembled by using a one-pot threading-and-stoppering reaction, which afforded the [4]rotaxane in 50% yield. The "gathering-and-threading" effect of copper(I) was utilised in the formation of a [4]pseudorotaxane, which was immediately converted to the corresponding [4]rotaxane by a quadruple CuAAC stoppering reaction. The rotaxane contains two face-to-face zinc porphyrins, which allowed the coordination of ditopic guest substrates. The rotaxane host showed remarkable flexibility and was able to adjust its conformation to the guest size. It can be distended and accommodate rod-like guests of 2.6 to 15.8 Å in length.

[2]Catenanes built around octahedral transition-metal complexes that contain two intertwined endocyclic but non-sterically hindering tridentate ligands.

Sterically hindering bidentate chelates, such as 2,9-diphenyl-1,10-phenanthroline, form entwined complexes with copper(I) and other tetrahedrally coordinated transition-metal centres. To prepare octahedral complexes containing two entwined tridentate ligands and thus apply a strategy similar to that used for making catenanes with tetrahedral metal centres, the use of the classical terpy ligand (terpy=2,2':6',2''-terpyridine) appears to be attractive. In fact, 6,6''-diphenyl-2,2':6',2''-terpyridine (dp-terpy) is not appropriate due to strong "pinching" of the organic backbone by coordination to the metal and thus stable entwined complexes with this ligand cannot be obtained. Herein, we report the synthesis and coordination properties of a new family of tridentate ligands, the main features of which are their endocyclic nature and non-sterically hindering character. The coordinating fragment consists of two 8'-phenylisoquinolin-3'-yl groups attached at the 2 and 6 positions of a pyridine nucleus. Octahedral complexes containing two such entangled ligands around an octahedral metal centre, such as Fe(II) , Ru(II) or Co(III) , are highly stable, with no steric congestion around the metal. By using functionalised ligands bearing terminal olefins, double ring-closing metathesis leads to [2]catenanes in good yield with Fe(II) or Co(III) as the templating metal centre. The X-ray crystallography structures of the Fe(II) precursor and the Fe(II) catenane are also reported. These show that although significant pinching of the ligand is observed in both Fe(II) complexes, the system is very open and no steric constraints can be detected.

Computational, structural, and mechanistic analysis of the electrochemically driven pirouetting motion of a copper rotaxane.

A mechanism for the electrochemically driven reorganization of a model copper [2]pseudorotaxane is proposed on the basis of density functional theory computations and validated by comparing to experimental results. We investigate in detail the ligand reorganization around the Cu ion from a 4 to 5 coordination number that follows the conversion of the oxidation state from +1 to +2. It is found that for both the oxidation and the reduction processes the rearrangement proceeds in a concerted fashion via a single transition state. Energy paths involving stable decoordinated-coordinated intermediates are computed to be higher in energy. The cyclic voltammogram simulated using the computed transition theory state rate constants in solvent medium is in good agreement with the experimental voltammogram. Further, we report on the computed concentration change of stable (Cu(+)(4), Cu(2+)(5)) and metastable species (Cu(2+)(4), Cu(+)(5)) during single cyclic voltammetry (CV) cycle as a function of the applied voltage or time (the subscripts 4 and 5 refer to the coordination number of the copper center).

Reversible turn-on fluorescent Cu(ii) sensors: rather dream than reality?

Reversible turn-on fluorescent sensors of Cu(ii) are of high interest for biological studies. We re-investigate a reported sensor, showing that turn-on occurs via irreversible Cu(ii)-induced sensor oxidation only in the presence of acetonitrile. This prevents its application in biological studies and highlights the challenge of establishing a reversible Cu(ii) turn-on sensor.

Photoinduced Electron and Energy Transfer in Rigidly Bridged Ru(II)-Rh(III) Binuclear Complexes.

A series of binuclear Ru(II)-Rh(III) complexes of general formula (ttpy)Ru-tpy-(ph)(n)-tpy-Rh(ttpy)(5+) (n = 0-2) have been synthesized, where ttpy = 4'-p-tolyl-2,2':6,2"-terpyridine and tpy-(ph)(n)-tpy represents a bridging ligand where two 2,2':6',2"-terpyridine units are either directly linked together (n = 0) or connected through one (n = 1) or two (n = 2) phenyl spacers in the 4'-position. This series of complexes is characterized by (i) rigid bridge structures and (ii) variable metal-metal distances (11 Å for n = 0, 15.5 Å for n = 1, 20 Å for n = 2). The photophysics of these binuclear complexes has been investigated in 4:1 methanol/ethanol at 77 K (rigid glass) and 150 K (fluid solution) and compared with that of mononuclear [Ru(ttpy)(2)(2+) and Rh(ttpy)(2)(3+)] or binuclear [(ttpy)Ru-tpy-tpy-Ru(ttpy)(4+)] model compounds. At 77 K, no quenching of the Ru(II)-based excited state is observed, whereas energy transfer from excited Rh(III) to Ru(II) is observed for all complexes. At 150 K, energy transfer from excited Rh(III) to Ru(II) is again observed for all complexes, while quenching of excited Ru(II) by electron transfer to Rh(III) is observed, but only in the complex with n = 0. The reasons for the observed behavior can be qualitatively understood in terms of standard electron and energy transfer theory. The different behavior between n = 0 and n = 1, 2 can be rationalized in terms of better electronic factors and smaller reorganizational energies for the former species. The freezing of electron transfer quenching but not of energy transfer, in rigid glasses reflects the different reorganizational energies involved in the two processes. Unusual results arising from multiphotonic and conformational effects have also been observed with these systems.

A ruthenium-based metallostar: synthesis, sensitized luminescence and (1)H relaxivity.

Ru-based metallostars Na(4){Ru[Ln(2)bpy-DTTA(2)(H(2)O)(4)](3)} (Ln = Y, Gd, and Eu) have been self-assembled in aqueous solution and their relaxivity and optical properties unravelled. The synthesis and the purification of the new, highly stable heptametallic entities have been optimized for the diamagnetic Y(3+) complex and followed by (1)H NMR. The europium(iii) ruthenium-based metallostar {Ru[Eu(2)bpy-DTTA(2)(H(2)O)(4)](3)}(4-) displays sensitized (5)D(0)-->(7)F(J) luminescence upon excitation of the tris(2,2'-bipyridyl)ruthenium(ii) unit in the ultraviolet around 293 nm, as well as in the visible around 450 nm ((1)MLCT state). NMRD profiles at two temperatures (25 degrees C and 37 degrees C) were performed on {Ru[Gd(2)bpy-DTTA(2)(H(2)O)(4)](3)}(4-). NMRD profiles of the ruthenium-based {Ru[Gd(2)bpy-DTTA(2)(H(2)O)(4)](3)}(4-) and the iron-based {Fe[Gd(2)bpy-DTTA(2)(H(2)O)(4)](3)}(4-) metallostars were fitted with SBM theory coupled to the model-free Lipary-Szabo method for internal motion as well as with the modified Florence approach. Comparison of both fitting methods shows that the Florence approach is able to fit NMRD profiles up to 100 MHz, fails however at higher frequencies because it does not account for internal motion. Overall, the results detailed point to the heptametallic self-assembled edifices being potential relaxivity and luminescence bimodal bioprobes for use in animal models.