Polymeric Nanozyme with SOD Activity Capable of Inhibiting Self- and Metal-Induced α-Synuclein Aggregation.

Despite decades of research, Parkinson's disease is still an idiopathic pathology for which no cure has yet been found. This is partly explained by the multifactorial character of most neurodegenerative syndromes, whose generation involves multiple pathogenic factors. In Parkinson's disease, two of the most important ones are the aggregation of α-synuclein and oxidative stress. In this work, we address both issues by synthesizing a multifunctional nanozyme based on grafting a pyridinophane ligand that can strongly coordinate CuII, onto biodegradable PEGylated polyester nanoparticles. The resulting nanozyme exhibits remarkable superoxide dismutase activity together with the ability to inhibit the self-induced aggregation of α-synuclein into amyloid-type fibrils. Furthermore, the combination of the chelator and the polymer produces a cooperative effect whereby the resulting nanozyme can also halve CuII-induced α-synuclein aggregation.

Development and application of metallo-phthalocyanines as potent G-quadruplex DNA binders and photosensitizers.

Metallo-phthalocyanines (MPc) are common photosensitizers with ideal photophysical and photochemical properties. Also, these molecules have shown to interact with non-canonical nucleic acid structures, such as G-quadruplexes, and modulate oncogenic expression in cancer cells. Herein, we report the synthesis and characterisation of two metallo-phthalocyanines containing either zinc (ZnPc) or nickel (NiPc) in the central aromatic core and four alkyl ammonium lateral chains. The interaction of both molecules with G-quadruplex DNA was assessed by UV-Vis, fluorescence and FRET melting experiments. Both molecules bind strongly to G-quadruplexes and stabilise these structures, being NiPc the most notable G-quadruplex stabiliser. In addition, the photosensitizing ability of both metal complexes was explored by the evaluation of the singlet oxygen generation and their photoactivation in cells. Only ZnPc showed a high singlet oxygen generation either by direct observation or by indirect evaluation using a DPBF dye. The cellular evaluation showed mainly cytoplasmic localization of ZnPc and a decrease of the IC50 values of the cell viability of ZnPc upon light activation of two orders of magnitude. Two metallo-phthalocyanines containing zinc and nickel within the aromatic core have been investigated as G-quadruplex stabilizers and photosensitizers. NiPc shows a high G4 binding but negligible photosensitizing ability while ZnPc exhibits a moderate binding to G-quadruplex together with a high potency to generate singlet oxygen and photocytotoxicity. The interaction with G4s and capacity to be photosensitized is associated with the geometry adopted by the central metal core of the phthalocyanine scaffold.

Donor Radii in Rare-Earth Complexes.

We present a set of donor radii for the rare-earth cations obtained from the analysis of structural data available in the Cambridge Structural Database (CSD). Theoretical calculations using density functional theory (DFT) and wave function approaches (NEVPT2) demonstrate that the Ln-donor distances can be broken down into contributions of the cation and the donor atom, with the minimum in electron density (ρ) that defines the position of (3,-1) critical points corresponding well with Shannon's crystal radii (CR). Subsequent linear fits of the experimental bond distances for all rare earth cations (except Pm3+) afforded donor radii (rD) that allow for the prediction of Ln-donor distances regardless of the nature of the rare-earth cation and its oxidation state. This set of donor radii can be used to rationalize structural data and identify particularly weak or strong interactions, which has important implications in the understanding of the stability and reactivity of complexes of these metal ions. A few cases of incorrect atom assignments in X-ray structures were also identified using the derived rD values.

Selective recognition of neurotransmitters in aqueous solution by hydroxyphenyl aza-scorpiand ligands.

The synthesis, acid-base behaviour and anion recognition of neurotransmitters (dopamine, tyramine and serotonin) in aqueous solution of different aza-scorpiand ligands functionalized with hydroxyphenyl and phenyl moieties (L1-L3 and L4, respectively) have been studied by potentiometry, NMR, UV-Vis and fluorescence spectroscopy and isothermal titration calorimetry (ITC). The analysis of the potentiometric results shows the selective recognition of serotonin at physiological pH (Keff = 8.64 × 104) by L1. This selectivity has an entropic origin probably coming from a fine pre-organization of the interacting partners. Thus, the complementarity of the receptor and the substrate allows the reciprocal formation of hydrogen bonds, π-π and cation-π interactions, stabilizing the receptors and slowing the rate of oxidative degradation, and satisfactory results are obtained at acidic and neutral pH values. NMR and molecular dynamics studies reveal the rotation blockage in the neurotransmitter side chain once complexed with L1.

Development of potent tripodal G-quadruplex DNA binders and their efficient delivery to cancer cells by aptamer functionalised liposomes.

Two new ligands (TPB3P and TPB3Py) showing a strong stabilisation effect and good selectivity for G4 over duplex DNAs have been synthesised. The ligands hold three analogous polyamine pendant arms (TPA3P and TPA3Py) but differ in the central aromatic core, which is a triphenylbenzene moiety instead of a triphenylamine moiety. Both TPB3P and TPB3Py exhibit high cytotoxicity in MCF-7, LN229 and HeLa cancer cells in contrast to TPA-based ligands, which exhibit no significant cytotoxicity. Moreover, the most potent G4 binders have been encapsulated in liposomes and AS1411 aptamer-targeted liposomes reaching nanomolar IC50 values for the most cytotoxic systems.

Small Molecule Pytren-4QMn Metal Complex Slows down Huntington's Disease Progression in Male zQ175 Transgenic Mice.

Huntington's disease (HD) is an inherited neurodegenerative disorder considered a rare disease with a prevalence of 5.7 per 100,000 people. It is caused by an autosomal dominant mutation consisting of expansions of trinucleotide repeats that translate into poly-glutamine enlarged mutant huntingtin proteins (mHTT), which are particularly deleterious in brain tissues. Since there is no cure for this progressive fatal disease, searches for new therapeutic approaches are much needed. The small molecule pytren-4QMn (4QMn), a highly water-soluble mimic of the enzyme superoxide dismutase, has shown in vivo beneficial anti-inflammatory activity in mice and was able to remove mHTT deposits in a C. elegans model of HD. In this study, we assessed 4QMn therapeutic potential in zQ175 neo-deleted knock-in mice, a model of HD that closely mimics the heterozygosity, genetic injury, and progressive nature of the human disease. We provide evidence that 4QMn has good acute and chronic tolerability, and can cross the blood-brain barrier, and in male, but not female, zQ175 mice moderately ameliorate HD-altered gene expression, mHtt aggregation, and HD disease phenotype. Our data highlight the importance of considering sex-specific differences when testing new therapies using animal models and postulate 4QMn as a potential novel type of small water-soluble metal complex that could be worth further investigating for its therapeutic potential in HD, as well as in other polyglutamine diseases.

Antimicrobial Properties of New Polyamines Conjugated with Oxygen-Containing Aromatic Functional Groups.

Antibiotic resistance is now a first-order health problem, which makes the development of new families of antimicrobials imperative. These compounds should ideally be inexpensive, readily available, highly active, and non-toxic. Here, we present the results of our investigation regarding the antimicrobial activity of a series of natural and synthetic polyamines with different architectures (linear, tripodal, and macrocyclic) and their derivatives with the oxygen-containing aromatic functional groups 1,3-benzodioxol, ortho/para phenol, or 2,3-dihydrobenzofuran. The new compounds were prepared through an inexpensive process, and their activity was tested against selected strains of yeast, as well as Gram-positive and Gram-negative bacteria. In all cases, the conjugated derivatives showed antimicrobial activity higher than the unsubstituted polyamines. Several factors, such as the overall charge at physiological pH, lipophilicity, and the topology of the polyamine scaffold were relevant to their activity. The nature of the lipophilic moiety was also a determinant of human cell toxicity. The lead compounds were found to be bactericidal and fungistatic, and they were synergic with the commercial antifungals fluconazole, cycloheximide, and amphotericin B against the yeast strains tested.

Characterization of a Ferryl Flip in Electronically Tuned Nonheme Complexes. Consequences in Hydrogen Atom Transfer Reactivity.

Two oxoiron(IV) isomers (R 2a and R 2b) of general formula [FeIV (O)(R PyNMe3 )(CH3 CN)]2+ are obtained by reaction of their iron(II) precursor with NBu4 IO4 . The two isomers differ in the position of the oxo ligand, cis and trans to the pyridine donor. The mechanism of isomerization between R 2a and R 2b has been determined by kinetic and computational analyses uncovering an unprecedented path for interconversion of geometrical oxoiron(IV) isomers. The activity of the two oxoiron(IV) isomers in hydrogen atom transfer (HAT) reactions shows that R 2a reacts one order of magnitude faster than R 2b, which is explained by a repulsive noncovalent interaction between the ligand and the substrate in R 2b. Interestingly, the electronic properties of the R substituent in the ligand pyridine ring do not have a significant effect on reaction rates. Overall, the intrinsic structural aspects of each isomer define their relative HAT reactivity, overcoming changes in electronic properties of the ligand.

Assembly of Polyiodide Networks with Cu(II) Complexes of Pyridinol-Based Tetraaza Macrocycles.

Polyiodide networks are currently of great practical interest for the preparation of new electronic materials. The participation of metals in the formation of these networks is believed to improve their mechanical performance and thermal stability. Here we report the results on the construction of polyiodide networks obtained using Cu(II) complexes of a series of pyridinol-based tetraazacyclophanes as countercations. The assembly of these crystalline polyiodides takes place from aqueous solutions on the basis of similar structural elements, the [CuL]2+ and [Cu(H-1L)]+ (L = L2, L2-Me, L2-Me3) complex cations, so that the peculiarities induced by the increase of N-methylation of ligands, the structural variable of ligands, can be highlighted. First, solution equilibria involving ligands and complexes were analyzed (potentiometry, NMR, UV-vis, ITC). Then, the appropriate conditions could be selected to prepare polyiodides based on the above complex cations. Single-crystal XRD analysis showed that the coordination of pyridinol units to two metal ions is a prime feature of these ligands, leading to polymeric coordination chains of general formula {[Cu(H-1L)]}nn+ (L = L2-Me, L2-Me3). In the presence of the I-/I2 couple, the polymerization tendency stops with the formation of [(CuL)(CuH-1L)]3+ (L = L2-Me, L2-Me3) dimers which are surrounded by polyiodide networks. Moreover, coordination of the pyridinol group to two metal ions transforms the surface charge of the ring from negative to markedly positive, generating a suitable environment for the assembly of polyiodide anions, while N-methylation shifts the directional control of the assembly from H-bonds to I···I interactions. In fact, an extended concatenation of iodine atoms occurs around the complex dimeric cations, the supramolecular I···I interactions become shorter and shorter, fading into stronger forces dominated by the orbital overlap, which is promising for effective electronic materials.

Aza-Crown-Based Macrocyclic Probe Design for "PET-off" Multi-Cu2+ Responsive and "CHEF-on" Multi-Zn2+ Sensor: Application in Biological Cell Imaging and Theoretical Studies.

The work represents a rare example of an aza-crown-based macrocyclic chemosensor, H2DTC (H2DTC = 1,16-dihydroxy-tetraaza-30-crown-8) for the selective detection of both Zn2+ and Cu2+ in HEPES buffer medium (pH 7.4). H2DTC exhibits a fluorescence response for both Zn2+ and Cu2+ ions. The reversibility of the chemosensor in its binding with Zn2+ and Cu2+ ions is also examined using a Na2EDTA solution. H2DTC exhibits a chelation-enhanced fluorescence (CHEF) effect in the presence of Zn2+ ions and a quenching effect (CHEQ) in the presence of paramagnetic Cu2+ ions. Furthermore, the geometry and spectral properties of H2DTC and the chemosensor bound to Zn2+ have been studied by DFT and TDDFT calculations. The limit of detection (LOD) values are 0.11 × 10-9 and 0.27 × 10-9 M for Cu2+ and Zn2+, respectively. The formation constants for the Zn2+ and Cu2+ complexes have been measured by pH-potentiometry in 0.15 M NaCl in 70:30 (v:v) water:ethanol at 298.1 K. UV-vis absorption and fluorometric spectral data and pH-potentiometric titrations indicate 1:1 and 2:1 metal:chemosensor species. In the solid state H2DTC is able to accommodate up to four metal ions, as proved by the crystal structures of the complexes [Zn4(DTC)(OH)2(NO3)4] (1) and {[Cu4(DTC)(OCH3)2(NO3)4]·H2O}n (2). H2DTC can be used as a potential chemosensor for monitoring Zn2+ and Cu2+ ions in biological and environmental media with outstanding accuracy and precision. The propensity of H2DTC to detect intracellular Cu2+ and Zn2+ ions in the triple negative human breast cancer cell line MDA-MB-468 and in HeLa cells has been determined by fluorescence cell imaging.

Noncovalent Assembly and Catalytic Activity of Hybrid Materials Based on Pd Complexes Adsorbed on Multiwalled Carbon Nanotubes, Graphene, and Graphene Nanoplatelets.

Green catalysts with excellent performance in Cu-free Sonogashira coupling reactions can be prepared by the supramolecular decoration of graphene surfaces with Pd(II) complexes. Here we report the synthesis, characterization, and catalytic properties of new catalysts obtained by the surface decoration of multiwalled carbon nanotubes (MWCNTs), graphene (G), and graphene nanoplatelets (GNPTs) with Pd(II) complexes of tetraaza-macrocyclic ligands bearing one or two anchor functionalities. The decoration of these carbon surfaces takes place under environmentally friendly conditions (water, room temperature, aerobic) in two steps: (i) π-π stacking attachment of the ligand via electron-poor anchor group 6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxo-pyrimidine and (ii) Pd(II) coordination from PdCl42-. Ligands are more efficiently adsorbed on the flat surfaces of G and GNPTs than on the curved surfaces of MWCNTs. All catalysts work very efficiently under mild conditions (50 °C, aerobic, 7 h), giving a similar high yield (90% or greater) in the coupling of iodobenzene with phenylacetylene to form diphenylacetylene in one catalytic cycle, but catalysts based on G and GNPTs (especially on GNPTs) provide greater catalytic efficiency in reuse (four cycles). The study also revealed that the active centers of the ligand-Pd type decorating the support surfaces are much more efficient than the Pd(0) and PdCl42- centers sharing the same surfaces. All of the results allow a better understanding of the structural factors to be controlled in order to obtain an optimal efficiency from similar catalysts based on graphene supports.

Cucurbituril hosts as promoters of aggregation induced emission of triphenylamine derivatives.

Three ligands bearing triphenylamine as a core and one, two or three acyclic polyamine chains, TPA1p, TPA2p and TPA3p, respectively, have been studied by potentiometric and photophysical (UV-Vis, steady-state and time-resolved fluorescence) techniques. The host-guest interaction with cucurbit[7]uril, CB7, has been investigated in aqueous solution showing aggregation induced emission behaviour when encapsulated into a CB7 cavity. From fluorescence emission it is revealed that the charged polyamine chains are the unit entering into CB7 and from the Job plots the stoichiometries are found to vary from 1 : 1 to 1 : 3 L : CB7 ratios. Interactions of the charged amines with the portals of CB7 restrict rotation of the benzene units in the triphenylamine backbone (free rotor effect), decreasing the radiationless internal conversion channel at the expense of the enhancement of fluorescence. Dynamic light scattering and resonance Rayleigh scattering experiments show that TPA3p-CB7 complexes involve formation of aggregates with a mean size of 126 ± 5 nm and a dispersity factor of 0.117, indicating a monodisperse distribution and supporting the important conclusions of this work: formation of emissive aggregates through the AIE effect.

Mn(II) Quinoline Complex (4QMn) Restores Proteostasis and Reduces Toxicity in Experimental Models of Huntington's Disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder, of the so-called minority diseases, due to its low prevalence. It is caused by an abnormally long track of glutamines (polyQs) in mutant huntingtin (mHtt), which makes the protein toxic and prone to aggregation. Many pathways of clearance of badly-folded proteins are disrupted in neurons of patients with HD. In this work, we show that one Mn(II) quinone complex (4QMn), designed to work as an artificial superoxide dismutase, is able to activate both the ubiquitin-proteasome system and the autophagy pathway in vitro and in vivo models of HD. Activation of these pathways degrades mHtt and other protein-containing polyQs, which restores proteostasis in these models. Hence, we propose 4QMn as a potential drug to develop a therapy to treat HD.

Unravelling the modus operandi of phytosiderophores during zinc uptake in rice: the importance of geochemical gradients and accurate stability constants.

Micronutrient deficiencies threaten global food production. Attempts to biofortify crops rely on a clear understanding of micronutrient uptake processes. Zinc deficiency in rice is a serious problem. One of the pathways proposed for the transfer of zinc from soils into rice plants involves deoxymugineic acid (DMA), a phytosiderophore. The idea that phytosiderophores play a wider role in nutrition of Poaceae beyond iron is well established. However, key mechanistic details of the DMA-assisted zinc uptake pathway in rice remain uncertain. In particular, questions surround the form in which zinc from DMA is taken up [i.e. as free aqueous Zn(II) or as Zn(II)-DMA complexes] and the role of competitive behaviour of other metals with DMA. We propose that an accurate description of the effect of changes in pH, ligand concentration, and ionic strength on the stability of Zn(II)-DMA complexes in the presence of other metals in the microenvironment around root cells is critical for understanding the modus operandi of DMA during zinc uptake. To that end, we reveal the importance of geochemical changes in the microenvironment around root cells and demonstrate the effect of inaccurate stability constants on speciation models.

Ditopic Aza-Scorpiand Ligands Interact Selectively with ds-RNA and Modulate the Interaction upon Formation of Zn2+ Complexes.

Nucleic acids are essential biomolecules in living systems and represent one of the main targets of chemists, biophysics, biologists, and nanotechnologists. New small molecules are continuously developed to target the duplex (ds) structure of DNA and, most recently, RNA to be used as therapeutics and/or biological tools. Stimuli-triggered systems can promote and hamper the interaction to biomolecules through external stimuli such as light and metal coordination. In this work, we report on the interaction with ds-DNA and ds-RNA of two aza-macrocycles able to coordinate Zn2+ metal ions and form binuclear complexes. The interaction of the aza-macrocycles and the Zn2+ metal complexes with duplex DNA and RNA was studied using UV thermal and fluorescence indicator displacement assays in combination with theoretical studies. Both ligands show a high affinity for ds-DNA/RNA and selectivity for ds-RNA. The ability to interact with these duplexes is blocked upon Zn2+ coordination, which was confirmed by the low variation in the melting temperature and poor displacement of the fluorescent dye from the ds-DNA/RNA. Cell viability assays show a decrease in the cytotoxicity of the metal complexes in comparison with the free ligands, which can be associated with the observed binding to the nucleic acids.

A Metal-Based Receptor for Selective Coordination and Fluorescent Sensing of Chloride.

A scorpionate Zn2+ complex, constituted by a macrocyclic pyridinophane core attached to a pendant arm containing a fluorescent pyridyl-oxadiazole-phenyl unit (PyPD), has been shown to selectively recognize chloride anions, giving rise to changes in fluorescence emission that are clearly visible under a 365 nm UV lamp. This recognition event has been studied by means of absorption, fluorescence, and NMR spectroscopy, and it involves the intramolecular displacement of the PyPD unit by chloride anions. Moreover, since the chromophore is not removed from the system after the recognition event, the fluorescence can readily be restored by elimination of the bound chloride anion.

Development of Polyamine-Substituted Triphenylamine Ligands with High Affinity and Selectivity for G-Quadruplex DNA.

Currently, significant efforts are devoted to designing small molecules able to bind selectively to guanine quadruplexes (G4s). These noncanonical DNA structures are implicated in various important biological processes and have been identified as potential targets for drug development. Previously, a series of triphenylamine (TPA)-based compounds, including macrocyclic polyamines, that displayed high affinity towards G4 DNA were reported. Following this initial work, herein a series of second-generation compounds, in which the central TPA has been functionalised with flexible and adaptive linear polyamines, are presented with the aim of maximising the selectivity towards G4 DNA. The acid-base properties of the new derivatives have been studied by means of potentiometric titrations, UV/Vis and fluorescence emission spectroscopy. The interaction with G4s and duplex DNA has been explored by using FRET melting assays, fluorescence spectroscopy and circular dichroism. Compared with previous TPA derivatives with macrocyclic substituents, the new ligands reported herein retain the G4 affinity, but display two orders of magnitude higher selectivity for G4 versus duplex DNA; this is most likely due to the ability of the linear substituents to embrace the G4 structure.

Hybrid GMP-polyamine hydrogels as new biocompatible materials for drug encapsulation.

Here we present the preparation and characterization of new biocompatible materials for drug encapsulation. These new gels are based on positively charged [1+1] 1H-pyrazole-based azamacrocycles which minimise the electrostatic repulsions between the negatively charged GMP molecules. Rheological measurements confirm the electroneutral hydrogel structure as the most stable for all the GMP-polyamine systems. Nuclear magnetic resonance (NMR) was employed to investigate the kinetics of the hydrogel formation and cryo-scanning electron microscopy (cryo-SEM) was used to obtain information about the hydrogel morphology, which exhibited a non-homogeneous structure with a high degree of cross-linking. It is possible to introduce isoniazid, which is the most employed antibiotic for tuberculosis treatment, into the hydrogels without disrupting the hydrogel structure at appropriate concentrations for oral administration.

Macrocyclic Pyclen-Based Gd3+ Complex with High Relaxivity and pH Response.

We report the synthesis and characterization of the macrocyclic ligand 2,2'-((2-(3,9-bis(carboxymethyl)-3,6,9-triaza-1(2,6)-pyridinacyclodecaphane-6-yl)ethyl)azanediyl)diacetic acid (H4L) and several of its complexes with lanthanide ions. The structure of the free ligand was determined using X-ray diffraction measurements. Two N atoms of the pyclen moiety in the trans position are protonated in the solid state, together with the exocyclic N atom and one of the carboxylate groups of the ligand. The relaxivity of the Gd3+ complex was found to increase from 6.7 mM-1 s-1 at pH 8.6 to 8.5 mM-1 s-1 below pH ≈ 6.0. Luminescence lifetime measurements recorded from H2O and D2O solutions of the Eu3+ complex evidence the presence of a single complex species in solution at low pH (∼5.0) that contains two inner-sphere water molecules. DFT calculations suggest that the coordination environment of the Ln3+ ion is fulfilled by the four N atoms of the pyclen unit, two oxygen atoms of the macrocyclic acetate groups, and an oxygen atom of an exocyclic carboxylate group. The two inner-sphere water molecules complete coordination number nine around the metal ion. At high pH (∼9.3), the lifetime of the excited 5D0 level of Eu3+ displays a biexponential behavior that can be attributed to the presence of two species in solution with hydration numbers of q = 0 and q = 1. The 1H NMR and DOSY spectra recorded from solutions of the Eu3+ and Y3+ complexes reveal a structural change triggered by pH and the formation of small aggregates at high pH values.

Tripyridinophane Platform Containing Three Acetate Pendant Arms: An Attractive Structural Entry for the Development of Neutral Eu(III) and Tb(III) Complexes in Aqueous Solution.

We report a detailed characterization of Eu3+ and Tb3+ complexes derived from a tripyridinophane macrocycle bearing three acetate side arms (H3tpptac). Tpptac3- displays an overall basicity (∑ log KiH) of 24.5, provides the formation of mononuclear ML species, and shows a good binding affinity for Ln3+ (log KLnL = 17.5-18.7). These complexes are also thermodynamically stable at physiological pH (pEu = 18.6, pTb = 18.0). It should be noted that the pGd value of Gd-tpptac (18.4) is only slightly lower than that of commercially available MRI contrast agents such as Gd-dota (pGd = 19.2). Moreover, a very good selectivity for these ions over the endogenous cations (log KCuL = 14.4, log KZnL = 12.9, and log KCaL = 9.3) is observed. The X-ray structure of the terbium complex shows the metal coordinated by the nine N6O3 donor set of the ligand and one inner-sphere water molecule. DFT calculations result in two Eu-tpptac structures with similar bond energies (ΔE = 0.145 eV): one structure in which the water is coordinated to the metal ion and one structure in which the water molecule is farther away from the ion, bound to the ligand with an OH-π bond. By detailed luminescence experiments, we demonstrate that the europium complex in aqueous solution presents a hydration equilibrium between nine-coordinate, dehydrated [Eu-tpptac]0 and ten-coordinate, monohydrated [Eu-tpptac(H2O)]0 species. A similar trend is observed for the terbium complex. Despite the presence of this hydration equilibrium, the H3tpptac ligand sensitizes Eu3+ and Tb3+ luminescence efficiently in buffered water at physiological pH. Particularly, the terbium complex displays a long excited-state lifetime of 2.24 ms and an overall quantum yield of 33% with a brightness of 3600 M-1 cm-1. Such features of Ln3+ complexes of H3tpptac indicate that this platform appears to be particularly appealing for the further development of luminescent lanthanide labels.