Unusual Selectivity Research Articles

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.

General Pyrrolidine Synthesis via Iridium-Catalyzed Reductive Azomethine Ylide Generation from Tertiary Amides and Lactams.

An iridium-catalyzed reductive generation of both stabilized and unstabilized azomethine ylides and their application to functionalized pyrrolidine synthesis via [3 + 2] dipolar cycloaddition reactions is described. Proceeding under mild reaction conditions from both amide and lactam precursors possessing a suitably positioned electron-withdrawing or a trimethylsilyl group, using 1 mol% Vaska’s complex [IrCl(CO)(PPh3)2] and tetramethyldisiloxane (TMDS) as a terminal reductant, a broad range of (un)stabilized azomethine ylides were accessible. Subsequent regio- and diastereoselective, inter- and intramolecular dipolar cycloaddition reactions with variously substituted electron-deficient alkenes enabled ready and efficient access to structurally complex pyrrolidine architectures. Density functional theory (DFT) calculations of the dipolar cycloaddition reactions uncovered an intimate balance between asynchronicity and interaction energies of transition structures, which ultimately control the unusual selectivities observed in certain cases.

Heterotrimetallic Carbon Dioxide Copolymerization and Switchable Catalysts: Sodium is the Key to High Activity and Unusual Selectivity.

A challenge in polymer synthesis using CO2 is to precisely control CO2 placement in the backbone and chain end groups. Here, a new catalyst class delivers unusual selectivity and is self‐switched between different polymerization cycles to construct specific sequences and desirable chain‐end chemistries. The best catalyst is a trinuclear dizinc(II)sodium(I) complex and it functions without additives or co‐catalysts. It shows excellent rates across different ring‐opening (co)polymerization catalytic cycles and allows precise control of CO2 incorporation within polyesters and polyethers, thereby allowing access to new polymer chemistries without requiring esoteric monomers, multi‐reactor processes or complex post‐polymerization procedures. The structures, kinetics and mechanisms of the catalysts are investigated, providing evidence for intermediate speciation and uncovering the factors governing structure and composition and thereby guiding future catalyst design.

Heterotrimetallic Carbon Dioxide Copolymerization and Switchable Catalysts: Sodium is the Key to High Activity and Unusual Selectivity

AbstractA challenge in polymer synthesis using CO2 is to precisely control CO2 placement in the backbone and chain end groups. Here, a new catalyst class delivers unusual selectivity and is self‐switched between different polymerization cycles to construct specific sequences and desirable chain‐end chemistries. The best catalyst is a trinuclear dizinc(II)sodium(I) complex and it functions without additives or co‐catalysts. It shows excellent rates across different ring‐opening (co)polymerization catalytic cycles and allows precise control of CO2 incorporation within polyesters and polyethers, thereby allowing access to new polymer chemistries without requiring esoteric monomers, multi‐reactor processes or complex post‐polymerization procedures. The structures, kinetics and mechanisms of the catalysts are investigated, providing evidence for intermediate speciation and uncovering the factors governing structure and composition and thereby guiding future catalyst design.

Cyclic monoterpenes trapped in a polyaromatic capsule: unusual selectivity, isomerization, and volatility suppression.

Cyclic monoterpenes (CMTs) are intractable natural products with high volatility and strong odors so that there has been no molecular receptor capable of selectively and tightly trapping CMTs in both solution and the solid state. We herein report that a polyaromatic capsule acts as a functional nanoflask for CMTs with the following five features: (i) the capsule can selectively bind menthone from mixtures with other saturated CMTs in water. In contrast, (ii) treatment of the capsule with mixtures of menthone and π-conjugated CMTs gives rise to ternary host–guest complexes with high pair-selectivity. Notably, (iii) the encapsulated menthone displays unusual isomerization from a typical chair conformer to otherwise unstable conformers upon heating. (iv) The selective binding of volatilized CMTs is demonstrated by the capsule even in the solid state at atmospheric pressure. Furthermore, (v) the volatilities of CMTs are significantly suppressed at elevated temperatures by the capsule upon encapsulation in solution as well as in the solid state.

Colorimetric discrimination of nucleoside phosphates based on catalytic signal amplification strategy and its application to related enzyme assays.

Selective detection of adenosine monophosphate (AMP) and adenosine diphosphate (ADP) which are less charged molecules than adenosine triphosphate (ATP) or pyrophosphate (PPi) in aqueous solution has been considered challenging because AMP and ADP have relatively low binding affinity for phosphate receptors. In this study, colorimetric discrimination of nucleoside phosphates was achieved based on catalytic signal amplification through the activation of artificial peroxidase. This method showed high selectivity for AMP and ADP over ATP and PPi, unlike previous phosphate sensors that use Zn2+-dipicolylamine-based receptors. High selectivity of the suggested method allowed discrimination of AMP in aqueous solution by the naked eye, and the detection limit was estimated to be 0.5 μM. Mechanism analysis revealed AMP acted as activators in the peroxidation cycle of the Mn2(bpmp)/ABTS/H2O2 system despite having relatively low binding affinity. Additionally, high selectivity and quantitative signal amplification allowed for the development of colorimetric phosphodiesterase and a small molecule kinase assay method. The newly proposed method offers direct, real-time, and quantitative analysis of enzyme activities and inhibition, and is expected to be further applied to high-throughput screening of inhibitors.

Delineating Heme-Mediated versus Direct Protein Oxidation in Peroxidase-Activated Cytochrome c by Top-Down Mass Spectrometry.

Oxidation of key residues in cytochrome c (cyt c) by chloramine T (CT) converts the protein from an electron transporter to a peroxidase. This peroxidase-activated state represents an important model system for exploring the early steps of apoptosis. CT-induced transformations include oxidation of the distal heme ligand Met80 (MetO, +16 Da) and carbonylation (LysCHO, -1 Da) in the range of Lys53/55/72/73. Remarkably, the 15 remaining Lys residues in cyt c are not susceptible to carbonylation. The cause of this unusual selectivity is unknown. Here we applied top-down mass spectrometry (MS) to examine whether CT-induced oxidation is catalyzed by heme. To this end, we compared the behavior of cyt c with (holo-cyt c) and without heme (apoSS-cyt c). CT caused MetO formation at Met80 for both holo- and apoSS-cyt c, implying that this transformation can proceed independently of heme. The aldehyde-specific label Girard's reagent T (GRT) reacted with oxidized holo-cyt c, consistent with the presence of several LysCHO. In contrast, oxidized apo-cyt c did not react with GRT, revealing that LysCHO forms only in the presence of heme. The heme dependence of LysCHO formation was further confirmed using microperoxidase-11 (MP11). CT exposure of apoSS-cyt c in the presence of MP11 caused extensive nonselective LysCHO formation. Our results imply that the selectivity of LysCHO formation at Lys53/55/72/73 in holo-cyt c is caused by the spatial proximity of these sites to the reactive (distal) heme face. Overall, this work highlights the utility of top-down MS for unravelling complex oxidative modifications.

Visible-Light-Driven Anti-Markovnikov Hydrocarboxylation of Acrylates and Styrenes with CO 2

Light-driven carbon dioxide (CO2) capture and utilization is one of the most fundamental reactions in Nature. Herein, we report the first visible-light-driven photocatalyst-free hydrocarboxylation ...

Photocontrolled Cobalt Catalysis for Selective Hydroboration of α,β‐Unsaturated Ketones

AbstractSelectivity between 1,2 and 1,4 addition of a nucleophile to an α,β‐unsaturated carbonyl compound has classically been modified by the addition of stoichiometric additives to the substrate or reagent to increase their “hard” or “soft” character. Here, we demonstrate a conceptually distinct approach that instead relies on controlling the coordination sphere of a catalyst with visible light. In this way, we bias the reaction down two divergent pathways, giving contrasting products in the catalytic hydroboration of α,β‐unsaturated ketones. This includes direct access to previously elusive cyclic enolborates, via 1,4‐selective hydroboration, providing a straightforward and stereoselective route to rare syn‐aldol products in one‐pot. DFT calculations and mechanistic experiments confirm two different mechanisms are operative, underpinning this unusual photocontrolled selectivity switch.

Photocontrolled Cobalt Catalysis for Selective Hydroboration of α,β-Unsaturated Ketones.

Selectivity between 1,2 and 1,4 addition of a nucleophile to an α,β‐unsaturated carbonyl compound has classically been modified by the addition of stoichiometric additives to the substrate or reagent to increase their “hard” or “soft” character. Here, we demonstrate a conceptually distinct approach that instead relies on controlling the coordination sphere of a catalyst with visible light. In this way, we bias the reaction down two divergent pathways, giving contrasting products in the catalytic hydroboration of α,β‐unsaturated ketones. This includes direct access to previously elusive cyclic enolborates, via 1,4‐selective hydroboration, providing a straightforward and stereoselective route to rare syn‐aldol products in one‐pot. DFT calculations and mechanistic experiments confirm two different mechanisms are operative, underpinning this unusual photocontrolled selectivity switch.

Fluorescence and Metal-Binding Properties of the Highly Preorganized Tetradentate Ligand 2,2'-Bi-1,10-phenanthroline and Its Remarkable Affinity for Cadmium(II).

The metal-ion-complexing properties of the tetradentate ligand 2,2'-bi-1,10-phenanthroline (BIPHEN) in 50% CH3OH/H2O are reported for a variety of metal ions. BIPHEN (with two reinforcing benzo groups in the backbone) was compared to other tetrapyridyls, 2,9-di(pyrid-2-yl)-1,10-phenanthroline (DPP; with one benzo group) and 2,2':6',2″:6″,2‴- quaterpyridine (QPY; with no benzo groups), with levels of preorganization BIPHEN > DPP > QPY. Formation constants were determined by following the variation of the intense π → π* transitions in the absorbance spectra of BIPHEN in the presence of metal ion as a function of the pH. The log K1 values show that the increased level of preorganization produced by the two benzo groups, reinforcing the backbone of the BIPHEN ligand, leads to increased complex stability with large metal ions (an ionic radius greater than 0.9 Å) compared to the less preorganized tetrapyridines DPP and QPY. In particular, the large CdII ion [log K1(BIPHEN) = 12.7] shows unusual selectivity over the small ZnII ion [log K1(BIPHEN) = 7.78]. The order of levels of preorganization BIPHEN > DPP > QPY leads to enhanced selectivity for SmIII over GdIII with increased preorganization, which is of interest in relation to separating AmIII from GdIII in the treatment of radioactive waste. AmIII is very close in ionic radius to SmIII, so that the size-based selectivity produced by the enhanced preorganization of BIPHEN should translate into enhanced AmIII/GdIII selectivity. The chelation-enhanced fluorescence (CHEF) effect in BIPHEN complexes is discussed. The CHEF effect in the ZnII complex is somewhat smaller than that for CdII, which is discussed in terms of decreased overlap in the Zn-N bonds formed by the too small ZnII, leading to a partial photoinduced-electron-transfer quenching of fluorescence. The structure of the complex [Cd(BIPHEN)2](ClO4)2 is reported and shows that the Cd-N bonds are largely normal for the unusual 8-coordination observed, except that steric clashes between the terminal pyridyl groups of each of the BIPHEN ligands, and the rest of the orthogonal BIPHEN ligand, lead to some stretching of the outer Cd-N bonds.

Light-assisted cyclohexane oxidation catalysis by a manganese(III) porphyrin immobilized onto zinc hydroxide salt and zinc oxide obtained by zinc hydroxide salt hydrothermal decomposition

Two manganese(III) porphyrin complexes prepared with the tetra anionic free base porphyrin (Na4[H2(TDFSPP)]) and two different manganese(II) salts (manganese(II) acetate - MnP(OAc) complex and manganese(II) chloride - MnP(Cl) complex) were immobilized onto zinc hydroxide nitrate (ZHN), a layered hydroxide salt, and also into zinc oxide (ZnO), obtained via hydrothermal decomposition of the ZHN. The resulting solids, MnP(OAc)-ZHN, MnP(Cl)-ZHN, MnP(OAc)-ZnO and MnP(Cl)-ZnO, were characterized by X-ray powder diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), electronic paramagnetic resonance (EPR) and ultraviolet-visible spectroscopy (UV–vis) (solid samples). Manganese and consequently the immobilized manganese porphyrin complexes were quantified by ICP-OES. The materials were applied as catalysts for the oxidation of cyclohexane, using iodosylbenzene as the oxygen donor, under conventional conditions (absence of light) as well as using light assisted conditions. Good catalytic results were obtained and, in absence of light, an unusual selectivity for the ketone was observed when using MnP(OAc)-ZHN as catalyst different from what can be observed when the catalyst is the solid MnP(Cl)-ZHN, that present selectivity to alcohol, suggesting an influence of both axial ligand and support in the catalytic activity.

Main-Group Metal Complexes in Selective Bond Formations Through Radical Pathways.

Recent years have witnessed remarkable advances in radical reactions involving main‐group metal complexes. This includes the isolation and detailed characterization of main‐group metal radical compounds, but also the generation of highly reactive persistent or transient radical species. A rich arsenal of methods has been established that allows control over and exploitation of their unusual reactivity patterns. Thus, main‐group metal compounds have entered the field of selective bond formations in controlled radical reactions. Transformations that used to be the domain of late transition‐metal compounds have been realized, and unusual selectivities, high activities, as well as remarkable functional‐group tolerances have been reported. Recent findings demonstrate the potential of main‐group metal compounds to become standard tools of synthetic chemistry, catalysis, and materials science, when operating through radical pathways.

Chemical Bath Deposition of Copper Sulfide on Functionalized SAMs: An Unusual Selectivity Mechanism.

We have investigated the chemical bath deposition (CBD) of CuS using thioacetamide on functionalized self-assembled monolayers (SAMs) using scanning electron and optical microscopies, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry. For all SAMs studied, the amount of CuS deposited is strongly dependent on the bath pH and can be attributed to the interaction of the SAM terminal groups with the chalcogenide ions present in solution. For -CH3-terminated SAMs, there is a steady increase in the amount of CuS deposited with an increase in the bath pH because there is an increase in the concentration of chalcogenide ion. However, for -OH- and -COOH-terminated SAMs, we observe that the maximum amount of CuS is deposited at pH 10. We attribute this behavior to a competition between the repulsion of the chalcogenide ions by the negatively charged SAM terminal groups and an increase in the chalcogenide ion concentration with an increase in the bath pH. Using the interaction of the chalcogenide ions with the different SAM terminal functional groups, we demonstrate that CuS can be selectively deposited on the -CH3-terminated areas of patterned -OH/-CH3- and -COOH/-CH3-terminated SAMs.

Transmembrane anion transport mediated by halogen bonding and hydrogen bonding triazole anionophores.

Transmembrane ion transport by synthetic anionophores is typically achieved using polar hydrogen bonding anion receptors. Here we show that readily accessible halogen and hydrogen bonding 1,2,3-triazole derivatives can efficiently mediate anion transport across lipid bilayer membranes with unusual anti-Hofmeister selectivity. Importantly, the results demonstrate that the iodo-triazole systems exhibit the highest reported activity to date for halogen bonding anionophores, and enhanced transport efficiency relative to the hydrogen bonding analogues. In contrast, the analogous fluoro-triazole systems, which are unable to form intermolecular interactions with anions, are inactive. The halogen bonding anionophores also exhibit a remarkable intrinsic chloride over hydroxide selectivity, which is usually observed only in more complex anionophore designs, in contrast to the readily accessible acyclic systems reported here. This highlights the potential of iodo-triazoles as synthetically accessible and versatile motifs for developing more efficient anion transport systems. Computational studies provide further insight into the nature of the anion-triazole intermolecular interactions, examining the origins of the observed transport activity and selectivity of the systems, and revealing the role of enhanced charge delocalisation in the halogen bonding anion complexes.

Mechanism for antigenic peptide selection by endoplasmic reticulum aminopeptidase 1

Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an intracellular enzyme that optimizes the peptide cargo of major histocompatibility class I (MHC-I) molecules and regulates adaptive immunity. It has unusual substrate selectivity for length and sequence, resulting in poorly understood effects on the cellular immunopeptidome. To understand substrate selection by ERAP1, we solved 2 crystal structures of the enzyme with bound transition-state pseudopeptide analogs at 1.68 Å and 1.72 Å. Both peptides have their N terminus bound at the active site and extend away along a large internal cavity, interacting with shallow pockets that can influence selectivity. The longer peptide is disordered through the central region of the cavity and has its C terminus bound in an allosteric pocket of domain IV that features a carboxypeptidase-like structural motif. These structures, along with enzymatic and computational analyses, explain how ERAP1 can select peptides based on length while retaining the broad sequence-specificity necessary for its biological function.

A Mechanistic Analysis of the Palladium‐Catalyzed Formation of Branched Allylic Amines Reveals the Origin of the Regio‐ and Enantioselectivity through a Unique Inner‐Sphere Pathway

AbstractA recently reported palladium‐catalyzed allylic substitution of vinyl‐substituted cyclic carbonates (VCCs) with aryl amines represents a rare example of a regio‐ and enantioselective synthesis of α,α‐disubstituted allylic N‐aryl amines. However, the underlying reasons for this unusual selectivity profile remain elusive. In the present work, density functional theory (DFT) calculations in combination with mechanistic control experiments were performed to elucidate in detail this allylic amination manifold and the origin of the regio‐ and enantioselectivity. The combined data show that after oxidative addition of the VCC to Pd0, the nucleophilic attack via an originally proposed outer‐sphere pathway gives, however, the opposite regioisomer compared to the experimental results. Instead, nucleophilic attack of the amine reagent via a unique type of chelation‐assisted, inner‐sphere pathway accounts for the experimentally observed “branched” regioselectivity and high enantio‐control.

A Mechanistic Analysis of the Palladium-Catalyzed Formation of Branched Allylic Amines Reveals the Origin of the Regio- and Enantioselectivity through a Unique Inner-Sphere Pathway.

A recently reported palladium-catalyzed allylic substitution of vinyl-substituted cyclic carbonates (VCCs) with aryl amines represents a rare example of a regio- and enantioselective synthesis of α,α-disubstituted allylic N-aryl amines. However, the underlying reasons for this unusual selectivity profile remain elusive. In the present work, density functional theory (DFT) calculations in combination with mechanistic control experiments were performed to elucidate in detail this allylic amination manifold and the origin of the regio- and enantioselectivity. The combined data show that after oxidative addition of the VCC to Pd0 , the nucleophilic attack via an originally proposed outer-sphere pathway gives, however, the opposite regioisomer compared to the experimental results. Instead, nucleophilic attack of the amine reagent via a unique type of chelation-assisted, inner-sphere pathway accounts for the experimentally observed "branched" regioselectivity and high enantio-control.

Nickel-Catalyzed Hydroarylation of Alkynes under Reductive Conditions with Aryl Bromides and Water.

An operationally simple nickel-catalyzed hydroarylation reaction for alkynes is described. This three-component coupling reaction utilizes commercially available alkynes and aryl bromides, along with water and Zn. An air-stable and easily synthesized Ni(II) precatalyst is the only entity used in the reaction that is not commercially available. This reductive cross-coupling reaction displays a fairly unusual anti selectivity when aryl bromides with ortho substituents are used. In addition to optimization data and a preliminary substrate scope, complementary experiments including deuterium labeling studies are used to provide a tentative catalytic mechanism. We believe this report should inspire and inform other Ni-catalyzed carbofunctionalization reactions.