Octadentate Ligand Research Articles

Chelation approach to long-lived and reversible chromium anolytes for aqueous flow batteries

Iron chromium flow battery (ICFB) has the advances of low cost, safety, and independent design of power and capacity, but is restricted by the deactivation of chromium anolytes. Here, a complex of diethylenetriaminepentaacetic acid with chromium ion (CrDTPA) is designed with minimum capacity loss rate and best cycling stability. DTPA is an octadentate ligand and chelates with chromium ions in a seven-coordinated manner. The coordination structure was studied by Nuclear Magnetic Resonance, Fourier transform infrared and UV–vis absorption spectra, and identified as a robust structure. CrDTPA has good electrochemical activity and reversibility with a redox potential of −1.145 V versus saturated calomel electrode. A novel iron chromium flow battery (NICFB) is designed by coupling CrDTPA anolytes and Fe(CN)6 catholytes. NICFB displays high energy conversion efficiency with coulombic efficiency of 99.0 % and energy efficiency of 82.2 % at 40 mA cm−2. Importantly, NICFB shows superior cycling stability without performance decay for 160 cycles, ranking the best among recently reported ICFBs. This chelation approach provides a simple and practical method to solve chromium anolytes deactivation and improve cycling stability.

Zirconium Coordination Chemistry and Its Role in Optimizing Hydroxymate Chelation: Insights from Molecular Dynamics.

In the past decade, there has been a growth in using Zirconium-89 (89Zr) as a radionuclide in nuclear medicine for cancer diagnostic imaging and drug discovery processes. Although one of the most popular chelators for 89Zr, desferrioxamine (DFO) is typically presented as a hexadentate ligand, our work suggests a different scenario. The coordination structure of the Zr4+-DFO complex has primarily been informed by DFT-based calculations, which typically ignore temperature and therefore entropic and dynamic solvent effects. In this work, free energy calculations using molecular dynamics simulations, where the conformational fluctuations of both the ligand and the solvent are explicitly included, are used to compare the binding of Zr4+ cations with two different chelators, DFO and 4HMS, the latter of which is an octadentate ligand that has been recently proposed as a better chelator due to the presence of four hydroxymate groups. We find that thermally induced disorder leads to an open hexadentate chelate structure of the Zr4+-DFO complex, leaving the Zr4+ metal exposed to the solvent. A stable coordination of Zr4+ with 4HMS, however, is formed by involving both hydroxamate groups and water molecules in a more closely packed structure.

Comparative Study of a Decadentate Acyclic Chelate, HOPO-O10, and Its Octadentate Analogue, HOPO-O8, for Radiopharmaceutical Applications.

Radiolanthanides and actinides are aptly suited for the diagnosis and treatment of cancer via nuclear medicine because they possess unique chemical and physical properties (e.g., radioactive decay emissions). These rare radiometals have recently shown the potential to selectively deliver a radiation payload to cancer cells. However, their clinical success is highly dependent on finding a suitable ligand for stable chelation and conjugation to a disease-targeting vector. Currently, the commercially available chelates exploited in the radiopharmaceutical design do not fulfill all of the requirements for nuclear medicine applications, and there is a need to further explore their chemistry to rationally design highly specific chelates. Herein, we describe the rational design and chemical development of a novel decadentate acyclic chelate containing five 1,2-hydroxypyridinones, 3,4,3,3-(LI-1,2-HOPO), referred to herein as HOPO-O10, based on the well-known octadentate ligand 3,4,3-(LI-1,2-HOPO), referred to herein as HOPO-O8, a highly efficient chelator for 89Zr[Zr4+]. Analysis by 1H NMR spectroscopy and mass spectrometry of the La3+ and Tb3+ complexes revealed that HOPO-O10 forms bimetallic complexes compared to HOPO-O8, which only forms monometallic species. The radiolabeling properties of both chelates were screened with [135La]La3+, [155/161Tb]Tb3+, [225Ac]Ac3+ and, [227Th]Th4+. Comparable high specific activity was observed for the [155/161Tb]Tb3+ complexes, outperforming the gold-standard 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, yet HOPO-O10 surpassed HOPO-O8 with higher [227Th]Th4+ affinity and improved complex stability in a human serum challenge assay. A comprehensive analysis of the decadentate and octadentate chelates was performed with density functional theory for the La3+, Ac3+, Eu3+, Tb3+, Lu3+, and Th4+ complexes. The computational simulations demonstrated the enhanced stability of Th4+-HOPO-O10 over Th4+-HOPO-O8. This investigation reveals the potential of HOPO-O10 for the stable chelation of large tetravalent radioactinides for nuclear medicine applications and provides insight for further chelate development.

Rigid H4OCTAPA derivatives as model chelators for the development of Bi(III)-based radiopharmaceuticals.

Octadentate ligands containing ethyl (H4OCTAPA), cyclohexyl (H4CHXOCTAPA) or cyclopentyl (H4CpOCTAPA) spacers were assessed as chelators for Bi(III)-based radiopharmaceuticals. The H4CHXOCTAPA chelator displays excellent properties, including 205/206Bi-nuclide radiolabelling under mild conditions, excellent stability in serum and in the presence of competing cations or H5DTPA. The poor performance of H4CpOCTAPA appears to be related to the stereochemical activity of the Bi(III) lone pair.

Co(II) complexes of tetraazamacrocycles appended with amide or hydroxypropyl groups as paraCEST agents.

Co(II) complexes of 1,4,7,10-tetraazacyclododecane (CYCLEN) or 1,4,8,11-tetraazacyclotetradecane (CYCLAM) with 2-hydroxypropyl or carbamoylmethyl (amide) pendants are studied with the goal of developing paramagnetic chemical exchange saturation transfer (paraCEST) agents. Single-crystal X-ray diffraction studies show that two of the coordination cations with hexadentate ligands, [Co(DHP)]2+ and [Co(BABC)]2+, form six-coordinate complexes; whereas two CYCLEN-based complexes with potentially octadentate ligands, [Co(THP)]2+ and [Co(HPAC)]2+, are seven-coordinate with only three of the four pendant groups bound to the metal center. 1H NMR spectra of these complexes suggest that the six-coordinate complexes are present as a single isomer in aqueous solution. For the complexes which are seven-coordinate in the solid state, one is highly fluxional in aqueous solution on the NMR time scale ([Co(HPAC)]2+), whereas the NMR spectrum of [Co(THP)]2+ is consistent with an eight-coordinate complex with all pendants bound. Co(II) complexes of CYCLEN derivatives show CEST effects of low intensity that are assigned to NH or OH groups of the pendants. One complex, [Co(DHP)]2+, shows a highly-shifted CEST peak at 113 ppm versus bulk water, attributed to OH protons. However, the CEST effect is largest for two Co(II) CYCLAM-based complexes with coordinated amide groups that undergo NH proton exchange. All five complexes are inert towards dissociation in buffered solutions containing carbonate and phosphate and towards trans-metalation by excess Zn(II). These data give insight into the production of an intense CEST effect for tetraazamacrocyclic complexes with pendant groups containing NH or OH exchangeable protons. The intense and highly shifted CEST peak(s) of the CYCLAM-based complexes suggest that they are promising for further development as paraCEST agents.

Triggering of Valence Tautomeric Transitions in Dioxolene-Based Cobalt Complexes Influenced by Ligand Substituents, Co-ligands, and Anions

We report the multistep synthesis of the 1,1′-(piperazine-1,4-diyl)bis(N,N-bis(pyridin-2-ylmethyl)methanamine)(Ltpbap) octadentate ligand, which, in combination with the known 3,5-di-tert-butylcatechol (3,5-dbcat), allowed the preparation of two di-nuclear cobalt complexes [Co2(Ltpbap)(3,5-dbcat)2](SO4)·5.5MeOH·2H2O (3a) and [Co2(Ltpbap)(3,5-dbcat)2 ](ClO4)2·1.5H2O (3b). We also report the synthesis of two mono-nuclear cobalt complexes [Co(3,5-dbsq)(3,5-dbcat)(4-Mepip)2] (1) with 4-Mepip being 4-methylpiperidine and (Hpip)[Co(tbcat)2(pip)2]·CH3CN (2) where Hpip denotes a piperidinium cation and tbcat is the tetra-bromocatechol ligand. The obtained complexes were characterized by single-crystal X-ray crystallography, SQUID magnetometry, and IR spectroscopy. The structure of the crystalline material in all the cases was determined at 173 K. The magnetic properties of all complexes were measured between 2 and 380 K. The magnetic data clearly show that mono-nuclear complex 1 and di-nuclear complex 3a exhibit valence tautomerism with onset around 300 K and 370 K, respectively, whereas the other two complexes 2 and 3b remain unchanged over the measured temperature range.

Thermodynamic Stability of Mn(II) Complexes with Aminocarboxylate Ligands Analyzed Using Structural Descriptors.

We present a quantitative analysis of the thermodynamic stabilities of Mn(II) complexes, defined by the equilibrium constants (log KMnL values) and the values of pMn obtained as −log[Mn]free for total metal and ligand concentrations of 1 and 10 μM, respectively. We used structural descriptors to analyze the contributions to complex stability of different structural motifs in a quantitative way. The experimental log KMnL and pMn values can be predicted to a good accuracy by adding the contributions of the different motifs present in the ligand structure. This allowed for the identification of features that provide larger contributions to complex stability, which will be very helpful for the design of efficient chelators for Mn(II) complexation. This issue is particularly important to develop Mn(II) complexes for medical applications, for instance, as magnetic resonance imaging (MRI) contrast agents. The analysis performed here also indicates that coordination number eight is more common for Mn(II) than is generally assumed, with the highest log KMnL values generally observed for hepta- and octadentate ligands. The X-ray crystal structure of [Mn2(DOTA)(H2O)2], in which eight-coordinate [Mn(DOTA)]2– units are bridged by six-coordinate exocyclic Mn(II) ions, is also reported.

Rigidified Derivative of the Non-macrocyclic Ligand H4OCTAPA for Stable Lanthanide(III) Complexation.

The stability constants of lanthanide complexes with the potentially octadentate ligand CHXOCTAPA4–, which contains a rigid 1,2-diaminocyclohexane scaffold functionalized with two acetate and two picolinate pendant arms, reveal the formation of stable complexes [log KLaL = 17.82(1) and log KYbL = 19.65(1)]. Luminescence studies on the Eu3+ and Tb3+ analogues evidenced rather high emission quantum yields of 3.4 and 11%, respectively. The emission lifetimes recorded in H2O and D2O solutions indicate the presence of a water molecule coordinated to the metal ion. 1H nuclear magnetic relaxation dispersion profiles and 17O NMR chemical shift and relaxation measurements point to a rather low water exchange rate of the coordinated water molecule (kex298 = 1.58 × 106 s–1) and relatively high relaxivities of 5.6 and 4.5 mM–1 s–1 at 20 MHz and 25 and 37 °C, respectively. Density functional theory calculations and analysis of the paramagnetic shifts induced by Yb3+ indicate that the complexes adopt an unprecedented cis geometry with the two picolinate groups situated on the same side of the coordination sphere. Dissociation kinetics experiments were conducted by investigating the exchange reactions of LuL occurring with Cu2+. The results confirmed the beneficial effect of the rigid cyclohexyl group on the inertness of the Lu3+ complex. Complex dissociation occurs following proton- and metal-assisted pathways. The latter is relatively efficient at neutral pH, thanks to the formation of a heterodinuclear hydroxo complex.

Pyridine-containing octadentate ligand NE3TA-PY for formation of neutral complex with 177Lu(III) and 90Y(III) for radiopharmaceutical applications: Synthesis, DFT calculation, radiolabeling, and in vitro complex stability

Targeted radionuclide therapy is a developing therapeutic modality for cancer and employs a cytotoxic radionuclide bound to a chelating agent and a bioactive molecule with high binding affinity for a specific biomarker in tumors. An optimal chelator is one of the critical components to control therapeutic efficacy and toxicity of targeted radionuclide therapy. We designed a new octadentate ligand NE3TA-PY (7-[2-[(carboxymethyl)(2-pyridylmethyl)amino]ethyl]-1,4,7-triazacyclononane-1,4-diacetic acid) for β-particle-emitting 177Lu and 90Y with targeted radionuclide therapy applications. The pyridine-containing polyaminocarboxylate ligand was proposed to form a neutral complex with Lu(III) and Y(III). The new chelator NE3TA-PY was synthesized and experimentally and theorectically studied for complexation with 177Lu(III) and 90Y(III). DFT-optimized structures of Y(III)-NE3TA-PY and Lu(III)-NE3TA-PY complexes were predicted. NE3TA-PY displayed excellent radiolabeling efficiency with both 177Lu and 90Y. The new chelator (NE3TA-PY) bound to 177Lu was more stable in human serum and better tolerated when challenged by EDTA than 90Y-labeled NE3TA-PY. Our findings suggest that the new chelator (NE3TA-PY) produced excellent Lu-177 radiolabeling and in vitro complex stability profiles.

Reduced quenching effect of pyridine ligands in highly luminescent Ln(III) complexes: the role of tertiary amide linkers.

Luminescent Eu(III) and Tb(III) complexes were synthesised from octadentate ligands carrying various carbostyril sensitizing antennae and two bidentate picolinate donors. Antennae were connected to the metal binding site via tertiary amide linkers. Antennae and donors were assembled on a 1,4,7-triazacyclononane (tacn) platform. Solution- and solid-state structures were comparable to those of previously reported complexes with tacn architectures, with nine-coordinate distorted tricapped trigonal prismatic Ln(III) centres, and distinct from those based on 1,4,7,10-tetraazacyclododecane (cyclen) macrocycles. In contrast, the photophysical properties of these tertiary amide tacn-based complexes were more comparable to those of previously reported systems with cyclen ligands, showing efficient Eu(III) and Tb(III) luminescence. This represents an improvement over secondary amide-linked analogues, and is due to a greatly increased sensitization efficiency in the tertiary amide-linked complexes. Tertiary amide-linked Eu(III) and Tb(III) emitters were more photostable than their secondary amide-linked analogues due to the suppression of photoinduced electron transfer and back energy transfer.

Synthesis, characterization, reactivity, and catalytic studies of heterobimetallic vanadium(V) complexes containing hydrazone ligands

Six heterobimetallic alkali metal dioxidovanadium(V) coordination polymer complexes {[M6{VO(μ-O)}2(μ-OH)4(μ4-slox/nph)].n DMF}∞ where M = Na, K, and Cs; n = 1 for (1), 0 for (2)-(6) of two dihydrazone ligands, disalicylaldehydeoxaloyldihydrazone (H4slox) and bis(2-hydroxy-1-naphthaldehyde)oxaloyldihydrazone (H4nph) are reported. All the complexes have been characterized by various physicochemical techniques such as elemental analyses, molar conductance, IR, NMR, UV–vis, and cyclic voltammetry. The IR, 1HNMR, and 13CNMR spectral data suggest that the dihydrazones are coordinated through phenolate/naphtholate oxygen, enolate oxygen, and azine nitrogen atoms to the metal centres. The structure of complex {[Na6{VO(μ-O)}2(μ-OH)4(μ4-slox)].DMF}∞ (1) is also determined by single-crystal X-ray data, which revealed that the H4slox coordinated via all possible dative sites to metal centres as tetrabasic octadentate ligand. The vanadium metal centres adopted distorted square-pyramidal coordination geometries, and the sodium atoms are also in five coordination atmospheres. The electronic spectra of the complexes showed LMCT bands in addition to intra-ligand π → π* and n → π* transitions. As evident from the cyclic voltammetry, the complexes showed two metal-centred electron transfer reactions {[(VVVV(slox)2−/VVVIV(slox)3−] and [(VVVIV(slox)3−/VVVIV(slox)4−]}, in addition to the ligand centred electron transfer reactions. Further, bovine serum albumin (BSA interaction studies of the complexes {[Na6{VO(μ-O)}2(μ-OH)4(μ4-slox)].DMF}∞ (1) and [Na6{VO(μ-O)}2(μ-OH)4(μ4-nph)]∞ (4) revealed strong binding affinity. Moreover, the catalytic studies of the complexes (1) and (4) were found to be effective for the oxidation of alcohols into their corresponding aldehydes and ketones and bromination of some organic substrates in the presence of H2O2 as an oxidizing agent.

HOCl Responsive Lanthanide Complexes Using Hydroquinone Caging Units.

Redox biology is still looking for tools to monitor redox potential in cellular biology and, despite a large and sustained effort, reliable molecular probes have yet to emerge. In contrast, molecular probes for reactive oxygen and nitrogen have been widely explored. In this manuscript, three kinetically inert lanthanide complexes that selectively react with hypochlorous acid are prepared and characterized. The design is based on 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) and 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) ligands appended with one or two redox active hydroquinone derived arms, thereby forming octadentate ligands ideally suited to complex trivalent lanthanide ions. The three complexes are found to react selectively with hypochlorous acid to form highly symmetric lanthanide(III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacedic acid (DOTA) complexes. The conversion of the probe to [Ln.DOTA]− is followed by luminescence, absorption, and NMR spectroscopy in a model system comprised of a Triton-X modified HEPES buffer. It was concluded that the design principle works, and that simple caging units like hydroquinones can work well in conjugation with lanthanide(III) complexes.

An octadentate bis(semicarbazone) macrocycle: a potential chelator for lead and bismuth radiopharmaceuticals.

A variant of 1,4,7,10-tetraazacyclododecane (cyclen) bearing two semicarbazone pendant groups has been prepared. The octadentate ligand forms complexes with Bi3+ and Pb2+. X-ray crystallography showed that the neutral ligand provides an eight-coordinate environment for both metal ions and intermolecular hydrogen bond interactions have influenced the coordination environments of both complexes in the solid state. NMR spectroscopy revealed a fluxional environment for both complexes. The ligand was radiolabeled with the α-emitting radioactive isotope 213Bi3+, which is used in systemic targeted radiotherapy. The resulting complex was stable in serum for at least 90 min (two decay half-lives). The Pb2+ complex has reasonably fast kinetics of formation (t1/2 = 20 min) at 25 °C and pH 7.4. The Bi3+ and Pb2+ complexes show kinetic stability in 1.2 M HCl (half-lives of 214 min and 47 min, respectively). This is the first description of a macrocycle bearing semicarbazone pendant groups and its utility in coordinating main group metals, specifically those with radiotherapeutic potential.

Evaluation of the Tetrakis(3-Hydroxy-4-Pyridinone) Ligand THPN with Zirconium(IV): Thermodynamic Solution Studies, Bifunctionalization, and in Vivo Assessment of Macromolecular 89Zr-THPN-Conjugates.

Zirconium-89 (89Zr) is a suitable radionuclide for positron-emission tomography (PET) of long-circulating targeting vectors such as monoclonal antibodies (mAbs). Due to stability concerns for the most widely used 89Zr-chelating agent desferrioxamine B (DFO) in preclinical studies, alternative 89Zr-chelators are currently being developed. We recently reported on the first tetrakis(3-hydroxy-4-pyridinone) (3,4-HOPO) ligand THPN, which was identified as a promising 89Zr-chelator. In this study, we aimed to further explore this octadentate chelate in vitro and in vivo. The [ZrIV(THPN)] thermodynamic stability was quantified in solution titration studies, which revealed one of the highest formation constants reported for a zirconium chelate (log βML 50.3(1), pM = 42.8). Solution stabilities with iron(III) were also exceptionally high and can compete with some of the strongest FeIII-chelates. A first bifunctional derivative of the octadentate ligand, p-SCN-Bn-THPN, was then produced in a multistep synthesis. To assess and compare the long-term 89Zr complex stability, bifunctional THPN, as well as the literature chelators p-SCN-Phe-DFO and p-SCN-Phe-DFO*, were conjugated to the high-molecular weight (800 kDa) polymeric carrier hyperbranched polyglycerol (HPG). The functionalized HPGs were radiolabeled with 89ZrIV, and the integrity of the radioconjugates was assessed over several days in vitro and in vivo. While all three radioconjugates remained >95% intact over 5 days in human plasma, the in vivo study in healthy mice revealed higher physiologic stability of the DFO and DFO* radiochelates over bifunctional THPN conjugates. This was evidenced by increased bone uptake of osteophilic 89ZrIV for THPN. This finding contrasts with the exceptionally high thermodynamic stability of the chelate and suggests either a kinetic or metabolic lability, or may stem from coordinative changes due to the covalent conjugation of the 89Zr-THPN radiochelate as suggested by density functional theory (DFT) calculations. These important findings inform the design of next generation 3,4-HOPO chelates with the aim of improving the physiologic stability. This study furthermore demonstrates how HPG can be used as a robust carrier tool to assess and compare the long-term in vivo stability of radiochelates.

Two new supramolecular compounds with reversible skeleton structure changes during dehydration and rehydration: Synthesis and characterization

Two novel supramolecular compounds of Keggin-type polyoxometalate (POM), [Cr(apca)2(H2O)2]4[KBW12O40]·9H2O (1), [Al(apca)2(H2O)2]8[SiW12O40]2·13H2O (2); apca = 3-aminopyrazine-2-carboxylic acid), were synthesized in aqueous solution and characterized by single-crystal X-ray diffraction technique, elemental analysis, TG analyses, IR, X-ray powder diffraction and fluorescence spectroscopy. In compound 1 [BW12O40]5− anion acting as octadentate ligand coordinates to two K ions through weak interaction, forming an infinite anionic chain extending along c–axis. The chains locate in the channels formed by stacking of the complex cations [M(apca)2(H2O)2]+. Hydrogen bonds combine the chains, cations and lattice water molecules forming a 3D framework. Besides the hydrogen bonds there exists π-π interaction between the complex cations. Compound 2 has a similar structure except without the K+ ion. They show a high proton conductivity of 1.70 × 10−3 S cm−1 and 9.30 × 10−3 S cm−1 at 77° C under 97% RH, respectively. Compound 1-2 showed reversible skeleton structure changes upon dehydration and rehydration, which had been established and monitored by X-ray powder diffraction.

Uncovering Heavy Actinide Covalency: Implications for Minor Actinide Partitioning.

Across the actinide period, the stability of the trivalent oxidation state predominates in the heavy actinides, making their chemical nature close to that of rare earth elements. The resemblance in their chemistry poses difficulties in separating heavy actinides from lanthanides, which is a vital separation in the minor actinide partitioning process. Actinide contraction has conventionally implied electrostatic actinide-ligand interactions among the heavy actinides. The present study challenges this conventional understanding and reveals increasing covalency in the actinide-ligand bond across Am to Cf. Complexes of Am, Cm, Bk, and Cf have been examined for their electronic structure with a focus on the nature of their interactions with different ligands within the framework of density functional theory, where the relativistic effects have been incorporated by using zero-order regular approximation and spin-orbit coupling. The choice of ligands selected for this study facilitates the effect of the donor atom as well as denticity to be accounted for. Hence, heavy actinide complexes of the N- and O-donor ligand dipicolinic acid, S and O mixed donor ligands of the Cyanex type, and an octadentate ligand N, N, N' N'-tetrakis[(6-carboxypyridin-2-yl)methyl]ethylenediamine have been optimized and evaluated. In each case energy decomposition analysis has been used to explicitly decompose the metal-ligand interaction energy into components which have then been analyzed. Irrespective of the hard-soft characteristics of donor atoms or the denticity of the ligands, steadily increased covalency has been observed across Am to Cf. Inspection of the ligand highest energy occupied molecular orbitals and metal orbitals sheds light on the origin of the unexpected covalency. An overall increase in bonding and also the orbital contribution along the Am-Cf series is clearly due to the enhancement in covalency, which is complementary to the orbital degeneracy induced covalency proposed very recently by Batista and co-workers.

Assembly of two hybrid organic-inorganic hexatantalate

Two neutral polyoxotantalates {[CuL]2[Cu(L)2]2[Ta6O19]}·nH2O have been synthesized by conventional reaction conditions, and characterized via different physical methods. Single-crystal X-ray analyses were carried out on {[CuL]2[CuL2]2[Ta6O19]}‧21H2O (L = 1,10-phen, denoted as 1) and the isostructural {[CuL]2[CuL2]2[Ta6O19]}‧20H2O (L′ = 2,2′-bipy, denoted as 2). Both complexes comprise a Lindqvist [Ta6O19]8− hexatantalate which acts as an octadentate ligand to coordinate two [CuL] units and two [CuL2] fragments through six bridging and two terminal oxygen atoms. In addition, the solid-state magnetic susceptibility of 1 and 2 are investigated briefly.

Methoxy-substituted tetrakisquinoline analogs of EGTA and BAPTA for fluorescence detection of Cd2+ .

EGTA (ethylene glycol bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid) and BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid) are well-known Ca2+ chelators that have four carboxylates, two nitrogen atoms and two ether oxygen atoms. In the present study, we prepared EGTQ (N,N,N',N'-tetrakis(2-quinolylmethyl)-1,2-bis(2-aminoethoxy)ethane) and BAPTQ (N,N,N',N'-tetrakis(2-quinolylmethyl)-1,2-bis(2-aminophenoxy)ethane) as quinoline alternatives of EGTA and BAPTA, respectively. In methanol-HEPES buffer solution (9 : 1, 50 mM HEPES, 0.1 M KCl, pH = 7.5), EGTQ exhibits fluorescence enhancement induced by Zn2+ and Cd2+ with poor selectivity, but BAPTQ did not exhibit a fluorescence response to either metal ion. Introduction of three methoxy substituents at the 5,6,7-positions of each quinoline moiety in BAPTQ specifically enhanced the fluorescence intensity of the Cd2+ complex, establishing the Cd2+-specific probe TriMeOBAPTQ (N,N,N',N'-tetrakis(5,6,7-trimethoxy-2-quinolylmethyl)-1,2-bis(2-aminophenoxy)ethane). In contrast, TriMeOEGTQ (N,N,N',N'-tetrakis(5,6,7-trimethoxy-2-quinolylmethyl)-1,2-bis(2-aminoethoxy)ethane) maintains a poor Cd2+/Zn2+ selectivity in its fluorescence response. Although the crystal structures of Cd2+/Zn2+ complexes with EGTQ and BAPTQ derivatives reveal the formation of multiple components including mononuclear and dinuclear complexes, the dinuclear Cd2+ and Zn2+ complexes with a linearly extended structure are regarded as possible fluorescent species in the solution. The conformational restriction of BAPTQ due to the orthophenylene moieties in the molecular skeleton is responsible for the formation of the weakly fluorescent, OH-bridged dizinc complex, which is critical to the strict Cd2+-specificity in the fluorescence response of TriMeOBAPTQ.

Solution Thermodynamics and Kinetics of Metal Complexation with a Hydroxypyridinone Chelator Designed for Thorium-227 Targeted Alpha Therapy.

The solution chemistry of a chelator developed for 227Th targeted alpha therapy was probed. The compound of interest is an octadentate ligand comprising four N-methyl-3-hydroxy-pyridine-2-one metal-binding units, two tertiary amine groups, and one carboxylate arm appended for bioconjugation. The seven p Ka values of the ligand and the stability constants of complexes formed with Th(IV), Hf(IV), Zr(IV), Gd(III), Eu(III), Al(III), and Fe(III) were determined. The ligand exhibits extreme thermodynamic selectivity toward tetravalent metal ions with a ca. 20 orders of magnitude difference between the formation constant of the Th(IV) species formed at physiological pH, namely [ThL]-, and that of its Eu(III) analogue. Likewise, log β110 values of 41.7 ± 0.3 and 26.9 ± 0.3 (T = 25 °C) were measured for [ThL]- and [FeIIIL]2-, respectively, highlighting the high affinity and selectivity of the ligand for Th ions over potentially competing endogenous metals. Single crystal X-ray analysis of the Fe(III) complex revealed a dinuclear 2:2 metal:chelator complex crystallizing in the space group P1̅. The formation of this dimeric species is likely favored by several intramolecular hydrogen bonds and the protonation state of the chelator in acidic media. LIII edge EXAFS data on the Th(IV) complexes of both the ligand and a monoclonal antibody conjugate revealed the expected mononuclear 1:1 metal:chelator coordination environment. This was also confirmed by high resolution mass spectrometry. Finally, kinetic experiments demonstrated that labeling the bioconjugated ligand with Th(IV) could be achieved and completed after 1 h at room temperature, reinforcing the high suitability of this chelator for 227Th targeted alpha therapy.

A Potassium Metal-Organic Framework based on Perylene-3,4,9,10-tetracarboxylate as Sensing Layer for Humidity Actuators

We have synthesized a novel three-dimensional metal-organic-framework (MOF) based on the perylene-3,4,9,10-tetracarboxylate linker and potassium as metallic centre. We report the formation of this K-based MOF using conventional routes with water as solvent. This material displays intense green photoluminescence at room temperature, and displays an aggregation dependent quenching. Correlation of the optical properties with the crystalline packing was confirmed by DFT calculations. We also demonstrate its potential to build humidity actuators with a reversible and reproducible response, with a change of 5 orders of magnitudes in its impedance at about 40% relative humidity (RH). This 3D-MOF is based on an interesting perylene derivative octadentate ligand, a moiety with interesting fluorescent properties and known component in organic semiconductors. To the best of our knowledge, this is the first time to build such a printed and flexible actuator towards humidity with a reversible response, enabling precise humidity threshold monitoring.