Unusual Selectivity Research Articles

Halide ion directed templation effect of quadruple-stranded helicates

The allosteric effect, described as biological enzymes’ conformation change to accommodate specific substrates, plays an important role in metabolic regulation. However, well-organized aggregation of synthetic receptors into high-order supramolecular structures with different conformations and functions in response to a variety of external stimuli presents a formidable challenge. Herein, a series of quadruple-stranded helicates are created through the templation effect of halide ions in a library of metallo-macrocycles. Single-crystal X-ray diffraction unambiguously confirms that the four intertwined strands are bridged with halide ions via eight robust C–H···X¯ hydrogen bonds, four anion-π interactions, and two electrostatic contacts. The binding of I¯ results in a D 2 -symmetric helicate, while the Br¯ or Cl¯ adducts display asymmetric infrastructures. Furthermore, the templation effect exhibits non-thermodynamically controlled, high selectivity toward I¯ due to its nucleophilicity toward breaking up partial coordination bonds. • Halide ions create a templation effect, leading to quadruple-stranded helicates • Multiple non-covalent interactions support the quadruple-stranded helicates • The templation effect exhibits unusual nucleophilic selectivity toward halide ions • Over 90% of I¯ ions wereseparated in the presence of other competing halide anions Liu and Jang et al. report halide ion directed (I¯, Br¯, and Cl¯) templation effects, leading from metallo-macrocycles to quadruple-stranded helicates. Multiple non-covalent interactions co-stabilized the assemblies, which is reminiscent of allosteric proteins in nature.

High-resolution crystal structures of ER aminopeptidase 1 with bound antigenic peptide precursor analogues

ER aminopeptidase 1 (ERAP1) in an intracellular enzyme that optimizes the peptide cargo of Major Histocompatibility Class I molecules (MHC-I) and regulates adaptive immune responses thus being an emerging target for immunotherapy applications. It has unusual substrate selectivity, preferring longer peptides to shorter ones and its trimming rates are influenced by sequence, although no clear preference motifs have yet to be identified, hindering efforts to predict the enzyme’s complex effects on the cellular immunopeptidome. To help understand the mechanism of substrate selection by ERAP1 we set out to crystallise the enzyme in complex with substrate analogues. We used x-ray crystallography to solve two structures of ERAP1 at 1.62 Å and 1.68 Å with bound two substrate analogues, one 15mer and one 10mer, designed based on ERAP1-sensitive antigenic peptide precursors. The N-terminus of both peptides is found bound in the catalytic site resembling the transition-state intermediate formed during catalysis. Both peptides extend away from the catalytic site, along the internal cavity of the enzyme, making a series of atomic interactions that can influence selectivity. While both peptides extend along the base of domain II towards the domainII/domainIV junction, the 15mer diverges through the central region of the cavity and has its C-terminus stabilised in a pocket of domain IV by Tyr684, Lys685 and Arg807 in a manner reminiscent of carboxypeptidase recognition, while its middle portion is disordered. Analysis of the crystal structures suggests that the mechanism that underlies the unique specificity of ERAP1 revolves around sequence-dependent opportunistic binding in combination with specific C-terminal recognition for longer peptides. Our results provide a framework for understanding how ERAP1 influences the cellular immunopeptidome and adaptive immunity.

Steering Catalytic Selectivity with Atomically Dispersed Metal Electrocatalysts for Renewable Energy Conversion and Commodity Chemical Production.

Electrocatalysis is a key driver in promoting the paradigm shift from the current fossil-fuel-based hydrocarbon economy to a renewable-energy-driven hydrogen economy. The success of electrocatalysis hinges primarily on achieving high catalytic selectivity along with maximum activity and sustained longevity. Many electrochemical reactions proceed through multiple pathways, requiring highly selective catalysts.Atomically dispersed metal catalysts have emerged as a new frontier in heterogeneous catalysis. In addition to the widely perceived advantages of maximized active site utilization and substantially reduced metal content, they have shown different catalytic selectivities in some electrocatalytic reactions compared to the traditional nanoparticle (NP)-based catalysts. Although there have been significant advances in their synthesis, the highly energetic nature of a single atomic site has made the preparation of atomically dispersed metal catalysts rely on empiricism rather than rational design. Consequently, the structural comprehension of a single atomic site and the understanding of its unusual electrocatalytic selectivity remain largely elusive.In this Account, we describe our endeavors toward developing general synthetic approaches for atomically dispersed metal catalysts for the discovery of new selective and active electrocatalysts and to understand their catalytic nature. We introduce synthetic approaches to produce a wide range of nonprecious- and precious-metal-based atomically dispersed catalysts and control their coordination environments. Metallomacrocyclic-compound-driven top-down and metal salt/heteroatom layer-based bottom-up strategies, coupled with a SiO2-protective-layer-assisted method, have been developed that can effectively generate single atomic sites while mitigating the formation of metallic NPs. The low-temperature gas-phase ligand exchange method can reversibly tune the coordination structure of the atomically dispersed metal sites. We have used the prepared atomically dispersed metal catalysts as model systems to investigate their electrocatalytic reactivity for renewable energy conversion and commodity chemical production reactions, in which high selectivity is important. The reactions of our interest include the following: (i) the oxygen reduction reaction, where O2 is reduced to either H2O or H2O2 via the four-electron or two electron pathway, respectively; (ii) the CO2 reduction reaction, which should suppress the hydrogen evolution reaction; and (iii) the chlorine evolution reaction, which competes with the oxygen evolution reaction. The type of metal center to which the reactant is directly bound is found to be the most important in determining the selectivity, which originates from the dramatic changes in the binding energy of each metal center with the reactants. The coordination structure surrounding the metal center also has a significant effect on the selectivity; its control can modulate the oxidation state of the metal center, thereby altering the binding strength with the reactants.We envisage that future advances in the synthesis of atomically dispersed metal catalysts, combined with the growing power of computational, spectroscopic, and microscopic methods, will bring their synthesis to the level of rational design. Elaborately designed catalysts can overcome the current limits of catalytic selectivity, which will help establish the field of atomically dispersed metal catalysts as an important branch of catalysis.

N-Heterocyclic Carbene-Based Iridium and Ruthenium/Iridium Nanoparticles for the Hydrogen Isotope Exchange Reaction through C–H Bond Activations

Suppressing aromatic ring reduction in noble-metal-catalyzed H/D exchange reactions remains a challenge. This drawback may be overcome by finding a synergetic effect in bimetallic nanoparticles (NPs). Herein, we report the synthesis of bimetallic lipo- and water-soluble Ru/Ir NPs. They were characterized by state-of-the-art techniques such as transmission electron microscopy (TEM), high-resolution TEM, attenuated total reflection Fourier transform infrared, powder X-ray diffraction, and solid-state nuclear magnetic resonance. These NPs were found to disperse in both organic and aqueous media because of the stabilization and coordination of adequate N-heterocyclic carbene (NHC) ligands to the NP surface. They were tested in the deuteration of 2-phenylpyridine, 2-methyl-naphthylamine, 5,6,7,8-tetrahydro-naphthtylamine, and l-lysine using D2 as the isotopic source. Bimetallic NPs showed an unusual selectivity toward the H/D exchange of 2-phenylpyridine, deuterating not only the expected C–H positions close to the N atom but also remote positions on the heterocycle. Additionally, reduction of the aromatic rings, which is a common undesired side reaction catalyzed by Ru NPs, was not observed. These outcomes, rationalized by a synergetic effect of both metals, are enhanced when NHC ligands are on the surface in comparison to model catalysts stabilized by polyvinylpyrrolidone. With regard to non-aromatic substrates, CH2-α and CH2-ε positions with respect to the amino acid group of l-lysine were fully deuterated, while moderate deuteration of the γ position was observed as the iridium content was increased in the bimetallic system.

Metallomacrocycle-Derived Atomically Dispersed Metal Electrocatalysts with Controlled Selectivity for Small Molecule Conversion Reactions

Atomically dispersed metal catalysts or single-atom catalysts have recently emerged as a new frontier in the field of catalysis. They exhibit extreme atom efficiency and unusual catalytic activity and selectivity, which are hard to be attained with nanoparticle-based concentional catalysts. In this talk, we present metallomacrocyclic compound-driven syntheses of carbon supported atomically dispersed metal (M–N/C) catalysts toward selective small molecule conversion reactions, including oxygen reduction reaction reaction (ORR), CO2 reduction reaction (CO2RR), and chlorine evolution reaction (CER) [1-5]. The M–N/C catalysts provide unique catalytic selectivity in these reactions. For the ORR, tuning of metal type can direct the reaction pathway with Fe–N/C catalyzing the ORR via the four-electron (4e–) reduction to generate water (H2O) [1,2] whereas Co–N/C exhibiting preferred 2e– pathway to produce hydrogen peroxide (H2O2) [3,4]. In the CO2RR, Ni–N/C selectively reduces CO2 to CO while suppressing parasitic hydrogen evolution reaction [5]. For the CER, Pt–N/C catalyst is capable of catalyzing the CER with very high selectivity approaching 100% without competitive oxygen evolution reaction, even under low concentration of Cl– and neutral electrolyte, where OER is favored [6,7]. In contrast, traditional mixed metal oxide catalysts show substantially low CER selectivity. For the selective ORR and CER, in situ X-ray absorption spectroscopy combined with other spectroscopic techniques and density functional theory calculations have played a pivotal role in identifying the active sites and uncovering reaction kinetics and mechanisms.References J. Sa et al., J. Am. Chem. Soc. 138, 15046 (2016).Woo et al., Chem. Mater. 30, 6684 (2018).Ko et al., Nature Commun. 10, 5123 (2019).Ko et al., Nature Catal. Accepted for Publication (2021).J. Sa et al., ACS Catal. 10, 10920 (2020).Lim et al., Nature Commun. 11, 412 (2020).Lim et al., ACS Catal. 11, 12232 (2021).

Confinement‐Induced Selectivities in Gold(I) Catalysis—The Benefit of Using Bulky Tri‐(ortho‐biaryl)phosphine Ligands

The confinement of a catalytic site is an efficient strategy to control a reaction and modulate its selectivity. In the present work, a new class of structurally simple and easily accessible bulky tri-(ortho-biaryl)phosphine ligands were accessed, and their gold(I) complexes synthesized. Their X-ray diffraction analysis and the comparative evaluation of their VBur % and G steric parameters against a series of gold complexes commonly employed in catalysis demonstrated their confined nature. Despite their notable steric congestion, these complexes exhibited remarkable catalytic activities and unusual selectivities, both in nature and level, that make them unique in the field of synthetic homogeneous gold catalysis.

Confinement‐Induced Selectivities in Gold(I) Catalysis—The Benefit of Using Bulky Tri‐(ortho‐biaryl)phosphine Ligands

AbstractThe confinement of a catalytic site is an efficient strategy to control a reaction and modulate its selectivity. In the present work, a new class of structurally simple and easily accessible bulky tri‐(ortho‐biaryl)phosphine ligands were accessed, and their gold(I) complexes synthesized. Their X‐ray diffraction analysis and the comparative evaluation of their VBur% and G steric parameters against a series of gold complexes commonly employed in catalysis demonstrated their confined nature. Despite their notable steric congestion, these complexes exhibited remarkable catalytic activities and unusual selectivities, both in nature and level, that make them unique in the field of synthetic homogeneous gold catalysis.

Improving and stabilizing fluorinated aryl borane catalysts for epoxide ring-opening

Epoxide ring-opening is a key reaction in organic chemistry. We have previously shown that B(C6F5)3, a strongly Lewis acidic arylborane, exhibited high rates and unusual selectivities for catalyzing the ring-opening of aliphatic epoxides with alcohols. Here we compare catalysts of the form B(C6H5−XFX)3 (x = 5, 4, 3, and 0) and determine that moderately Lewis acidic arylboranes have higher regioselectivity, but slower rates in this reaction. At high temperatures, these arylboranes can also hydrolyze into inactive species. However, deactivation is suppressed in the presence of co-catalytic amounts of 1,2-propanediol, and DFT calculations suggest a role for arylborane-H2O-diol complexes. Thermal stabilization and regioselectivity enhancement by diol are both more pronounced for B(C6F5)3 than for less Lewis acidic B(C6HF4)3 and B(C6H2F3)3 catalysts. These results further demonstrate the catalytic relevance of H-bound networks of arylboranes and diols and enable their use at higher temperatures and greatly increased rates.

Advancing Chelation Strategies for Large Metal Ions for Nuclear Medicine Applications

Nuclear medicine leverages radioisotopes of a wide range of elements, a significant portion of which are metals, for the diagnosis and treatment of disease. To optimally use radioisotopes of the metal ions, or radiometals, for these applications, a chelator that efficiently forms thermodynamically and kinetically stable complexes with them is required. The chelator also needs to attach to a biological targeting vector that locates pathological tissues. Numerous chelators suitable for small radiometals have been established to date, but chelators that work well for large radiometals are significantly less common. In this Account, we describe recent progress by us and others in the advancement of ligands for large radiometal chelation with emerging applications in nuclear medicine.First, we discuss and analyze the coordination chemistry of the chelator macropa, a macrocyclic ligand that contains the 18-crown-6 backbone and two picolinate pendent arms, with large metal ions in the context of nuclear medicine. This ligand is known for its unusual reverse size selectivity, the preference for binding large over small metal ions. The radiolabeling properties of macropa with large radiometals 225Ac3+, 132/135La3+, 131Ba2+, 223Ra2+, 213Bi3+, and related in vivo investigations are described. The development of macropa derivatives containing different pendent donors or rigidifying groups in the macrocyclic core is also briefly reviewed.Next, efforts to transform macropa into a radiopharmaceutical agent via covalent conjugation to biological targeting vectors are summarized. In this discussion, two types of bifunctional analogues of macropa reported in the literature, macropa-NCS and mcp-click, are presented. Their implementation in different radiopharmaceutical agents is discussed. Bioconjugates containing macropa attached to small-molecule targeting vectors or macromolecular antibodies are presented. The in vitro and in vivo evaluations of these constructs are also discussed.Lastly, chelators with dual size selectivity are described. This class of ligands exhibits good affinities for both large and small metal ions. This property is valuable for nuclear medicine applications that require the simultaneous chelation of both large and small radiometals with complementary therapeutic and diagnostic properties. Recently, we reported an 18-membered macrocyclic ligand called macrodipa that attains this selectivity pattern. This chelator, its second-generation analogue py-macrodipa, and their applications for chelating the medicinally relevant large 135La3+, 225Ac3+, 213Bi3+, and small 44Sc3+ ions are also presented. Studies with these radiometals show that py-macrodipa can effectively radiolabel and stably retain both large and small radiometals. Overall, this Account makes the case for innovative ligand design approaches for novel emerging radiometal ions with unusual coordination chemistry properties.

Pyridine diglycolamide: A novel ligand for plutonium extraction from nitric acid medium

A novel ligand N, N, N’, N’ tetra-isobutyl pyridine diglycolamide (PDGA) was synthesized and tested for extraction of actinides and fission products present in high level liquid waste (HLLW). The ligand was studied in presence of two different diluents- nitrobenzene (NB), a molecular diluent and 3-methyl-1-octyl immidazolium bis[(trifluoromethyl)sulfonyl] imide, an Ionic Liquid (IL). Unusual selectivity towards tetravalent plutonium over minor actinides and alkali & alkaline metal ions present in nuclear waste was showed by PDGA in presence of NB as diluent. The trend in kinetics of extraction as well as dependency of DPu(IV) values with nitric acid concentration was found to be different for two diluents studied. Mechanism of extraction was also varied for the two diluents studied. It followed solvation mechanism for NB whereas for IL it was a combination of solvation and ion-exchange mechanism. The calculated Gibbs free energy of extraction, ΔGext for Pu(IV) using density functional theory was found to be higher than that of other competitive metal ions corroborating the results from solvent extraction experiment. Further, ΔGext was found to be highly negative for metal and ionic liquid cations thus complimenting the experimental findings of ion exchange mechanism for a metal cation with cation of the ionic liquid.

Furfural Adsorption and Hydrogenation at the Oxide‐Metal Interface: Evidence of the Support Influence on the Selectivity of Iridium‐Based Catalysts

AbstractHere, tetrakis(hydroxymethyl)phosphonium chloride‐protected colloidal iridium nanoparticles were deposited by sol‐immobilisation on three different supports (CeO2, NiO and TiO2) and were investigated for the liquid‐phase direct hydrogenation (H2 atmosphere) and catalytic transfer hydrogenation – CTH (N2 atmosphere) of furfural to study the effect of the H donor. The occurrence of strong‐metal support interactions in 1 wt % Ir/CeO2 catalyst, as disclosed by XPS, was revealed to be responsible for the high activity observed in the direct hydrogenation (81 % conversion after 6 h) and for the unusual selectivity to 2‐methylfuran (70 %) under CTH conditions. On the other hand, Ir/NiO showed peculiar selectivity to tetrahydrofurfuryl alcohol in both H2 and N2 atmospheres (71 % and 70 %, respectively). The density functional theory calculations further showed that the unique selectivity of Ir/NiO may be ascribed to the adsorption properties of furfural on the support, which activates a dual‐site hydrogenation mechanism.

Rare-Earth-Metal Complexes Bearing an Iminodibenzyl-PNP Pincer Ligand: Synthesis and Reactivity toward 3,4-Selective Polymerization of 1,3-Dienes.

A PNP-pincer ligand provides a versatile ligation framework, which is highly useful in organometallic chemistry and catalytic chemistry. In this work, by a de novo strategy, a simple and efficient synthetic pathway, has been developed to prepare the new iminodibenzyl-based PNP pincer proligand imin-RPNP(Li or H) (R = isopropyl, phenyl). By employing salt metathesis or direct alkyl elimination, we successfully synthesized a series of iminodibenzyl-PNP rare-earth-metal (Ln = Sc, Y, Dy, Ho, Er, Tm, Lu) complexes and characterized them by NMR and X-ray diffraction analyses. Upon addition of a borate and triisobutylaluminum (TIBA), the rare-earth-metal complexes 2-Y, 2-Dy, 2-Ho, 2-Er, and 2-Tm bearing the imin-PhPNP ligand exhibited unexpectedly high 3,4-selectivity (up to 95%) for the polymerization of 1,3-dienes (isoprene and myrcene); in particular, the chosen yttrium complex 2-Y promoted the 1,3-diene polymerization in a living manner. A computational study suggested that the sterically congested configuration around the metal center imposed by the imin-RPNP ligand might be the main reason for this unusual selectivity.

Mechanism, reactivity, and selectivity in a palladium-catalyzed organosilicon-based cross coupling reaction

A thermodynamic control mechanism unravels the unusual chemical selectivity in Pd-catalyzed cross-coupling reaction of silacycles.

Local Charge Distributions, Electric Dipole Moments, and Local Electric Fields Influence Reactivity Patterns and Guide Regioselectivities in α-Ketoglutarate-Dependent Non-heme Iron Dioxygenases.

Non-heme iron dioxygenases catalyze vital processes for human health related to the biosynthesis of essential products and the biodegradation of toxic metabolites. Often the natural product biosyntheses by these non-heme iron dioxygenases is highly regio- and chemoselective, which are commonly assigned to tight substrate-binding and positioning. However, recent high-level computational modeling has shown that substrate-binding and positioning is only part of the story and long-range electrostatic interactions can play a major additional role.In this Account, we review and summarize computational viewpoints on the high regio- and chemoselectivity of α-ketoglutarate-dependent non-heme iron dioxygenases and how external perturbations affect the catalysis. In particular, studies from our groups have shown that often a regioselectivity in enzymes can be accomplished by stabilization of the rate-determining transition state for the reaction through external charges, electric dipole moments, or local electric field effects. Furthermore, bond dissociation energies in molecules are shown to be influenced by an electric field effect, and through targeting a specific bond in an electric field, this can lead to an unusually specific reaction. For instance, in the carbon-induced starvation protein, we studied two substrate-bound conformations and showed that regardless of what C-H bond of the substrate is closest to the iron(IV)-oxo oxidant, the lowest hydrogen atom abstraction barrier is always for the pro-S C2-H abstraction due to an induced dipole moment of the protein that weakens this bond. In another example of the hygromycin biosynthesis enzyme, an oxidative ring-closure reaction in the substrate forms an ortho-δ-ester ring. Calculations on this enzyme show that the selectivity is guided by a protonated lysine residue in the active site that, through its positive charge, triggers a low energy hydrogen atom abstraction barrier. A final set of examples in this Account discuss the viomycin biosynthesis enzyme and the 2-(trimethylammonio)ethylphosphonate dioxygenase (TmpA) enzyme. Both of these enzymes are shown to possess a significant local dipole moment and local electric field effect due to charged residues surrounding the substrate and oxidant binding pockets. The protein dipole moment and local electric field strength changes the C-H bond strengths of the substrate as compared to the gas-phase triggers the regioselectivity of substrate activation. In particular, we show that in the gas phase and in a protein environment C-H bond strengths are different due to local electric dipole moments and electric field strengths. These examples show that enzymes have an intricately designed structure that enables a chemical reaction under ambient conditions through the positioning of positively and negatively charged residues that influence and enhance reaction mechanisms. These computational insights create huge possibilities in bioengineering to apply local electric field and dipole moments in proteins to achieve an unusual selectivity and specificity and trigger a fit-for-purpose biocatalyst for unique biotransformations.

Hydrodenitrogenation of Quinoline with high selectivity to aromatics over α-MoC1-x

The hydrodenitrogenation (HDN) with a low hydrogen consumption in the hydroprocessing of crude oils derived from carbon resources is still a challenge. Here, a molybdenum carbide (α-MoC1-x) catalyst with a high selectivity to aromatic compounds was reported, using the HDN of quinoline as a model reaction. This process was characterized by low hydrogen consumption. The prepared α-MoC1-x had a much larger specific surface area (107.6 m2•g−1) than β-Mo2C (6.8 m2•g−1). Under the catalysis of α-MoC1-x, the conversion and the denitrification rate of quinoline could both reach 99%, and the highest selectivity of the total aromatics reached 48.5% at 360 °C, which was 10.7% higher than that on β-Mo2C. The cleavage of CC bonds of side chain of Propylbenzene (PB) and Propylcyclohexane (PCH) occurred, producing several unexpected products with unusual high selectivity. A new possible reaction network of quinoline hydrodenitrogenation was drawn, and the reaction mechanism was discussed based on the experiments and DFT (density functional theory) calculations.

Spain’s Repsol adding electrolytic hydrogen production at Petronor refinery

SAPO-34 molecular sieve was hydrothermally synthesized by using organosilane phenylaminopropyl-trimethoxysilane (PHAPTMS) as a part of silicon source and tetraethylammonium hydroxide as microporous template at 160 °C. The XRD, SEM and N2 adsorption/desorption characterizations revealed the hierarchical SAPO-34 is a nanocrystal assembly of 50 nm particles prepared in the system. The catalyst showed improved stability and unusual selectivity of propylene and butylene in methanol to olefins reaction by introducing the mesoporous structure and changing the surface acid sites distribution. The yield of light olefins in hydrocarbons was up to 86%, the selectivity of C3= and C4= reached more than 40% and 10%.

Unusual Ion-exchange Selectivity in Crystalline Coordination Polymers Accompanied by Structural Change of the Framework

Unusual Ion-exchange Selectivity in Crystalline Coordination Polymers Accompanied by Structural Change of the Framework

Bottom-Up Approach for the Rational Loading of Linear Oligomers and Polymers with Lanthanides

The adducts between luminescent lanthanide tris(β-diketonate)s and diimine or triimine ligands have been explored exhaustively for their exceptional photophysical properties. Their formation, stability, and structures in solution, together with the design of extended metallopolymers exploiting these building blocks, remain, however, elusive. The systematic peripheral substitution of tridentate 2,6-bis(benzimidazol-2-yl)pyridine binding units (Lk = L1-L5), taken as building blocks for linear oligomers and polymers, allows a fine-tuning of their affinity toward neutral [Ln(hfa)3] (hfa = hexafluoroacetylacetonate) lanthanide containers in the [LkLn(hfa)3] adducts. Two trends emerge with (i) an unusual pronounced thermodynamic selectivity for midrange lanthanides (Ln = Eu) and (ii) an intriguing influence of remote peripheral substitutions of the benzimidazole rings on the affinity of the tridentate unit for [Ln(hfa)3]. These trends are amplified upon the connection of several tridentate binding units via their benzimidazole rings to give linear segmental dimers (L6) and trimers (L7), which are considered as models for programming linear Wolf-Type II metallopollymers. Modulation of the affinity between the terminal and central binding units in the linear multitridentate ligands deciphers the global decrease of metal-ligand binding strengths with an increase in the length of the receptors (monomer → dimer → trimer → polymer). Application of the site binding model shed light onto the origin of the variation of the thermodynamic affinities: a prerequisite for the programmed loading of a polymer backbone with luminescent lanthanide β-diketonates. Analysis of the crystal structures for these adducts reveals delicate correlations between the chemical bond lengths measured in the solid state (or bond valence parameters) and the metal-ligand affinities operating in solution.

Alkali Metal Ion-exchange in a Metal-Organic Framework Based on Lanthanum and 1,4-Phenylenebis(methylidyne)tetrakis(phosphonic acid).

The ion-exchange selectivity of four metal-organic frameworks (denoted as MLaL), formed by alkali metal ions (M+), La3+, and 1,4-phenylenebis(methylidyne)tetrakis(phosphonic acid) (L), was examined. Unusual selectivity for the alkali metal ions was observed, which did not follow the previously proposed mechanism that was explained based on the ion-size similarity in the framework. The changes in the crystal structures after ion-exchange reactions were observed by powder X-ray diffraction analysis. The change in the lattice energy in a mixed-metal framework is likely to be one of the significant parameters to affect ion-exchange selectivity.

Py-Macrodipa: A Janus Chelator Capable of Binding Medicinally Relevant Rare-Earth Radiometals of Disparate Sizes.

Nuclear medicine leverages different types of radiometals for disease diagnosis and treatment, but these applications usually require them to be stably chelated. Given the often-disparate chemical properties of these radionuclides, it is challenging to find a single chelator that binds all of them effectively. Toward addressing this problem, we recently reported a macrocyclic chelator macrodipa with an unprecedented "dual-size-selectivity" pattern for lanthanide (Ln3+) ions, characterized by its high affinity for both the large and the small Ln3+ ( J. Am. Chem. Soc, 2020, 142, 13500). Here, we describe a second-generation "macrodipa-type" ligand, py-macrodipa. Its coordination chemistry with Ln3+ was thoroughly investigated experimentally and computationally. These studies reveal that the Ln3+-py-macrodipa complexes exhibit enhanced thermodynamic and kinetic stabilities compared to Ln3+-macrodipa, while retaining the unusual dual-size selectivity. Nuclear medicine applications of py-macrodipa for chelating radiometals with disparate chemical properties were assessed using the therapeutic 135La3+ and diagnostic 44Sc3+ radiometals representing the two size extremes within the rare-earth series. Radiolabeling and stability studies demonstrate that the rapidly formed complexes of these radionuclides with py-macrodipa are highly stable in human serum. Thus, in contrast to gold standard chelators like DOTA and macropa, py-macrodipa can be harnessed for the simultaneous, efficient binding of radiometals with disparate ionic radii like La3+ and Sc3+, signifying a substantial achievement in nuclear medicine. This concept could enable the facile incorporation of a breadth of medicinally relevant radiometals into chemically identical radiopharmaceutical agents. The fundamental coordination chemistry learned from py-macrodipa provides valuable insight for future chelator development.