Metal-mediated DNA base pairing of easily prepared 2-oxo-imidazole-4-carboxylate nucleotides

Metal-mediated DNA base pairs, which consist of two ligand-type artificial nucleobases and a bridging metal ion, have attracted increasing attention in recent years as a different base pairing mode from natural base pairing. Metal-mediated base pairing has been extensively studied, not only for metal-dependent thermal stabilisation of duplexes, but also for metal assembly by DNA templates and construction of functional DNAs that can be controlled by metals. Here, we report the metal-mediated base paring properties of a novel 2-oxo-imidazole-4-carboxylate (Im^OC) nucleobase and a previously reported 2-oxo-imidazole-4-carboxamide (Im^OA) nucleobase, both of which can be easily derived from a commercially available uridine analogue. The Im^OC nucleobases were found to form stable Im^OC–Cu^II–Im^OC and Im^OC–Hg^II–Im^OC base pairs in the presence of the corresponding metal ions, leading to an increase in the duplex melting temperature by +20 °C and +11 °C, respectively. The Im^OC bases did not react with other divalent metal ions and showed superior metal selectivity compared to similar nucleobase design reported so far. The Im^OC–Cu^II–Im^OC base pair was much more stable than mismatch pairs with other natural nucleobases, confirming the base pair specificity in the presence of Cu^II. Furthermore, we demonstrated the quantitative assembly of three Cu^II ions inside a DNA duplex with three consecutive Im^OC–Im^OC pairs, showing great potential of DNA-template based Cu^II nanoarray construction. The study of easily-prepared Im^OC base pairs will provide a new design strategy for metal-responsive DNA materials.

A novel 2-oxo-imidazole-4-carboxylate (Im^OC) nucleobase, which can be easily derived from a commercially available uridine analogue, was found to form stable Cu^II- and Hg^II-mediated base pairs in DNA duplexes.     

Reversible OH-bond activation and amphoterism by metal–ligand cooperativity of calix[4]pyrrolato aluminate

Most p-block metal amides irreversibly react with metal alkoxides when subjected to alcohols, making reversible transformations with OH-substrates a challenging task. Herein, we describe how the combination of a Lewis acidic square-planar-coordinated aluminum(iii) center with metal–ligand cooperativity leverages unconventional reactivity toward protic substrates. Calix[4]pyrrolato aluminate performs OH-bond activation of primary, secondary, and tertiary aliphatic and aromatic alcohols, which can be fully reversed under reduced pressure. The products exhibit a new form of metal–ligand cooperative amphoterism and undergo counterintuitive substitution reactions of a polar covalent Al–O bond by a dative Al–N bond. A comprehensive mechanistic picture of all processes is buttressed by isolation of intermediates, spectroscopy, and computation. This study delineates how structural constraints can invert thermodynamics for seemingly simple addition reactions and invert common trends in bond energies.

The combination of structural constraint and metal–ligand cooperativity in calix[4]pyrrolato aluminate inverts common trends of bond energies and enables reversible OH-bond activation.     

Platinum(ii) non-covalent crosslinkers for supramolecular DNA hydrogels

Manipulation of non-covalent metal–metal interactions allows the fabrication of functional metallosupramolecular structures with diverse supramolecular behaviors. The majority of reported studies are mostly designed and governed by thermodynamics, with very few examples of metallosupramolecular systems exhibiting intriguing kinetics. Here we report a serendipitous finding of platinum(ii) complexes serving as non-covalent crosslinkers for the fabrication of supramolecular DNA hydrogels. Upon mixing the alkynylplatinum(ii) terpyridine complex with double-stranded DNA in aqueous solution, the platinum(ii) complex molecules are found to first stack into columnar phases by metal–metal and π–π interactions, and then the columnar phases that carry multiple positive charges crosslink the negatively charged DNA strands to form supramolecular hydrogels with luminescence properties and excellent processability. Subsequent platinum(ii) intercalation into DNA competes with the metal–metal and π–π interactions at the crosslinking points, switching on the spontaneous gel-to-sol transition. In the case of a chloro (2,6-bis(benzimidazol-2′-yl)pyridine)platinum(ii) complex, with [Pt(bzimpy)Cl]⁺ serving as a non-covalent crosslinker where the metal–metal and π–π interactions outcompete platinum(ii) intercalation, the intercalation-driven gel-to-sol transition pathway is blocked since the gel state is energetically more favorable than the sol state. Interestingly, the ligand exchange reaction of the chloro ligand in [Pt(bzimpy)Cl]⁺ with glutathione (GSH) has endowed the complexes with enhanced hydrophilicity, decreasing the planarity of the complexes, and turning off the metal–metal and π–π interactions at the crosslinking points, leading to GSH-triggered hydrogel dissociation.

We report a serendipitous finding of platinum(ii) complexes serving as non-covalent crosslinkers for the fabrication of supramolecular DNA hydrogels.     

Experimental evidence for a general model of modulated MOF nanoparticle growth

Nanoparticles of metal–organic frameworks (nanoMOFs) boast superior properties compared to their bulk analogs, yet little is known about how common synthetic parameters dictate particle sizes. Here, we provide experimental evidence for the “seesaw” model of nanoMOF growth. Solution acidity, ligand excess, and reactant concentrations are decoupled and shown to form the key independent determinants of nanoMOF sizes, thereby validating the proposal that nanoMOFs arise from coupled equilibria involving ligand deprotonation and metal–ligand complexation. By achieving the first demonstration of a seesaw relationship between nanoMOF sizes and ligand excess, these results provide further proof of the model, as they required deliberate manipulation of relationships outlined by the model. Exploring the relative impacts of these parameters reveals that ligand excess has the greatest ability to decrease sizes, although low acidity and high concentrations can exhibit similar effects. As a complement to existing models of polymer formation and crystal growth, the seesaw model therefore offers a powerful tool for reliable control over nanoMOF sizes.

Nanoparticles of metal–organic frameworks (nanoMOFs) boast superior properties compared to their bulk analogs, yet little is known about how common synthetic parameters dictate particle sizes.     

Hg(II) ion specifically binds with T:T mismatched base pair in duplex DNA

Metal-mediated base pair formation, resulting from the interaction between metal ions and artificial bases in oligonucleotides, has been developed for its potential application in nanotechnology. We have recently found that the T:T mismatched base pair binds with Hg(II) ions to generate a novel metal-mediated base pair in duplex DNA. The thermal stability of the duplex with the T-Hg-T base pair was comparable to that of the corresponding T:A or A:T. The novel T-Hg-T base pair involving the natural base thymine is more convenient than the metal-mediated base pairs involving artificial bases due to the lack of time-consuming synthesis. Here, we examine the specificity and thermodynamic properties of the binding between Hg(II) ions and the T:T mismatched base pair. Only the melting temperature of the duplex with T:T and not of the perfectly matched or other mismatched base pairs was found to specifically increase in the presence of Hg(II) ions. Hg(II) specifically bound with the T:T mismatched base pair at a molar ratio of 1:1 with a binding constant of 10(6) M(-1), which is significantly higher than that for nonspecific metal ion-DNA interactions. Furthermore, the higher-order structure of the duplex was not significantly distorted by the Hg(II) ion binding. Our results support the idea that the T-Hg-T base pair could eventually lead to progress in potential applications of metal-mediated base pairs in nanotechnology.     

Remote toehold: a mechanism for flexible control of DNA hybridization kinetics

Hybridization of DNA strands can be used to build molecular devices, and control of the kinetics of DNA hybridization is a crucial element in the design and construction of functional and autonomous devices. Toehold-mediated strand displacement has proved to be a powerful mechanism that allows programmable control of DNA hybridization. So far, attempts to control hybridization kinetics have mainly focused on the length and binding strength of toehold sequences. Here we show that insertion of a spacer between the toehold and displacement domains provides additional control: modulation of the nature and length of the spacer can be used to control strand-displacement rates over at least 3 orders of magnitude. We apply this mechanism to operate displacement reactions in potentially useful kinetic regimes: the kinetic proofreading and concentration-robust regimes.     

Self-healing and shape memory functions exhibited by supramolecular liquid-crystalline networks formed by combination of hydrogen bonding interactions and coordination bonding

We here report a new approach to develop self-healing shape memory supramolecular liquid-crystalline (LC) networks through self-assembly of molecular building blocks via combination of hydrogen bonding and coordination bonding. We have designed and synthesized supramolecular LC polymers and networks based on the complexation of a forklike mesogenic ligand with Ag⁺ ions and carboxylic acids. Unidirectionally aligned fibers and free-standing films forming layered LC nanostructures have been obtained for the supramolecular LC networks. We have found that hybrid supramolecular LC networks formed through metal–ligand interactions and hydrogen bonding exhibit both self-healing properties and shape memory functions, while hydrogen-bonded LC networks only show self-healing properties. The combination of hydrogen bonds and metal–ligand interactions allows the tuning of intermolecular interactions and self-assembled structures, leading to the formation of the dynamic supramolecular LC materials. The new material design presented here has potential for the development of smart LC materials and functional LC membranes with tunable responsiveness.

New supramolecular hybrid liquid-crystalline networks exhibiting self-healing and shape memory properties are developed by self-assembly of small components through hydrogen bonding interactions and coordination bonding.     

Soft metal-mediated base pairing with novel synthetic nucleosides possessing an O,S-donor ligand

Metal-mediated base pairing with artificial ligand-bearing nucleosides allows site-selective metal incorporation inside DNA duplexes. In particular, this strategy has provided a general way of discrete, heterogeneous metal arrays in a programmable manner. To increase the kind of metallo-building blocks, we have newly synthesized two artificial nucleosides which have an O, S-donor ligand as the nucleobase moiety, mercaptopyridone ( M) and hydroxypyridinethione ( S). These nucleosides were found to efficiently form metal-mediated base pairs with soft transition metal ions such as Pd (2+) and Pt (2+).     

Chimeric GNA/DNA metal-mediated base pairs

DNA double helices comprising chimeric GNA/DNA metal-mediated base pairs have been synthesized and characterized (GNA = glycol nucleic acid). The possibility to combine different nucleic acid backbones within one metal-mediated base pair expands the applicability of metal-functionalized nucleic acids.     

Light-Induced Formation of Thymine-Containing Mercury(II)-Mediated Base Pairs

By applying caged thymidine residues, DNA duplexes were created in which Hg^II-mediated base pair formation can be triggered by irradiation with light. When a bidentate ligand was used as the complementary nucleobase, an unprecedented stepwise formation of different metal-mediated base pairs was achieved.     

Impact of sphingosine and acetylsphingosines on the aggregation and toxicity of metal-free and metal-treated amyloid-β

Pathophysiological shifts in the cerebral levels of sphingolipids in Alzheimer''s disease (AD) patients suggest a link between sphingolipid metabolism and the disease pathology. Sphingosine (SP), a structural backbone of sphingolipids, is an amphiphilic molecule that is able to undergo aggregation into micelles and micellar aggregates. Considering its structural properties and cellular localization, we hypothesized that SP potentially interacts with amyloid-β (Aβ) and metal ions that are found as pathological components in AD-affected brains, with manifesting its reactivity towards metal-free Aβ and metal-bound Aβ (metal–Aβ). Herein, we report, for the first time, that SP is capable of interacting with both Aβ and metal ions and consequently affects the aggregation of metal-free Aβ and metal–Aβ. Moreover, incubation of SP with Aβ in the absence and presence of metal ions results in the aggravation of toxicity induced by metal-free Aβ and metal–Aβ in living cells. As the simplest acyl derivatives of SP, N-acetylsphingosine and 3-O-acetylsphingosine also influence metal-free Aβ and metal–Aβ aggregation to different degrees, compared to SP. Such slight structural modifications of SP neutralize its ability to exacerbate the cytotoxicity triggered by metal-free Aβ and metal–Aβ. Notably, the reactivity of SP and the acetylsphingosines towards metal-free Aβ and metal–Aβ is determined to be dependent on their formation of micelles and micellar aggregates. Our overall studies demonstrate that SP and its derivatives could directly interact with pathological factors in AD and modify their pathogenic properties at concentrations below and above critical aggregation concentrations.

The reactivity of sphingosine and acetylsphingosines towards both metal-free and metal-treated amyloid-β is demonstrated showing a correlation of their micellization properties.     

Pressure-induced phosphorescence enhancement and piezochromism of a carbazole-based cyclic trinuclear Cu(i) complex

Interest in piezochromic luminescence has increased in recent decades, even though it is mostly limited to pure organic compounds and fluorescence. In this work, a Cu₃Pz₃ (Cu3, Pz: pyrazolate) cyclic trinuclear complex (CTC) with two different crystalline polymorphs, namely 1a and 1b, was synthesized. The CTC consists of two functional moieties: carbazole (Cz) chromophore and Cu3 units. In crystals of 1a, discrete Cz–Cu3–Cu3–Cz stacking was found, showing abnormal pressure-induced phosphorescence enhancement (PIPE), which was 12 times stronger at 2.23 GPa compared to under ambient conditions. This novel observation is ascribed to cooperation between heavy-atom effects (i.e., from Cu atoms) and metal–ligand charge-transfer promotion. The infinite π–π stacking of Cz motifs was observed in 1b and it exhibited good piezochromism as the pressure increased. This work demonstrates a new concept in the design of piezochromic materials to achieve PIPE via combining organic chromophores and metal–organic phosphorescence emitters.

One molecule, two response mechanisms: a pair of newly-designed cyclic trinuclear Cu(i) complex crystalline polymorphs are engineered, which show excellent luminescent piezochromism and pressure-induced phosphorescence enhancement, respectively.     

Lattice oxygen self-spillover on reducible oxide supported metal cluster: the water–gas shift reaction on Cu/CeO2 catalyst

In this work we have tackled one of the most challenging problems in nanocatalysis namely understanding the role of reducible oxide supports in metal catalyzed reactions. As a prototypical example, the very well-studied water gas shift reaction catalyzed by CeO₂ supported Cu nanoclusters is chosen to probe how the reducible oxide support modifies the catalyst structures, catalytically active sites and even the reaction mechanisms. By employing density functional theory calculations in conjunction with a genetic algorithm and ab initio molecular dynamics simulations, we have identified an unprecedented spillover of the surface lattice oxygen from the ceria support to the Cu cluster, which is rarely considered previously but may widely exist in oxide supported metal catalysts under realistic conditions. The oxygen spillover causes a highly energetic preference of the monolayered configuration of the supported Cu nanocluster, compared to multilayered configurations. Due to the strong metal–oxide interaction, after the O spillover the monolayered cluster is highly oxidized by transferring electrons to the Ce 4f orbitals. The water–gas-shift reaction is further found to more favorably take place on the supported copper monolayer than the copper-ceria periphery, where the on-site oxygen and the adjacent oxidized Cu sites account for the catalytically active sites, synergistically facilitating the water dissociation and the carboxyl formation. The present work provides mechanistic insights into the strong metal–support interaction and its role in catalytic reactions, which may pave a way towards the rational design of metal–oxide catalysts with promising stability, dispersion and catalytic activity.

The lattice oxygen on the reducible CeO₂ support could self-spillover to surface of Cu cluster, generating the on-site oxygen to promote the catalytic water–gas shift reaction.     

Combining metal–metal cooperativity,metal–ligand cooperativity and chemical non-innocence in diiron carbonyl complexes

Several metalloenzymes, including [FeFe]-hydrogenase, employ cofactors wherein multiple metal atoms work together with surrounding ligands that mediate heterolytic and concerted proton–electron transfer (CPET) bond activation steps. Herein, we report a new dinucleating PNNP expanded pincer ligand, which can bind two low-valent iron atoms in close proximity to enable metal–metal cooperativity (MMC). In addition, reversible partial dearomatization of the ligand''s naphthyridine core enables both heterolytic metal–ligand cooperativity (MLC) and chemical non-innocence through CPET steps. Thermochemical and computational studies show how a change in ligand binding mode can lower the bond dissociation free energy of ligand C(sp³)–H bonds by ∼25 kcal mol⁻¹. H-atom abstraction enabled trapping of an unstable intermediate, which undergoes facile loss of two carbonyl ligands to form an unusual paramagnetic (S = ) complex containing a mixed-valent iron(0)–iron(i) core bound within a partially dearomatized PNNP ligand. Finally, cyclic voltammetry experiments showed that these diiron complexes show catalytic activity for the electrochemical hydrogen evolution reaction. This work presents the first example of a ligand system that enables MMC, heterolytic MLC and chemical non-innocence, thereby providing important insights and opportunities for the development of bimetallic systems that exploit these features to enable new (catalytic) reactivity.

The PNNP expanded pincer ligand can bind two iron centers in close proximity and display heterolytic and homolytic metal–ligand cooperativity.     

Engineering plasticization resistant gas separation membranes using metal–organic nanocapsules

Membrane technologies hold great potential for industrial gas separation. Nevertheless, plasticization, a common phenomenon that is responsible for the loss of gas pair selectivity and the decrease of membrane lifespan, is one of the top challenges withholding the deployment of advanced membrane materials in realistic applications. Here, we report a highly generalizable approach, that utilizes PgC₅Cu, a copper metal–organic nanocapsule (MONC) containing 24 open metal sites (OMSs) as a multi-dentate node to coordinatively crosslink polymers. By adding merely 1–3 wt% of PgC₅Cu, a wide range of carbonyl group-containing polymers can be effectively crosslinked. Through rigorous dissolution tests, molecular dynamic simulations, and in situ FT-IR spectroscopy, we qualitatively and quantitatively unveiled the coordinative binding nature at the polymer–MONC interface. As a result, we produced a series of composite membranes showing near complete plasticization resistance to CO₂, C₂H₄, and C₂H₆ under high pressure with no loss of mechanical and gas transport properties.

Ultra-small metal–organic nanocapsules (MONCs) with open metal sites (OMSs) are used as multi-dentate nodes to form coordinative crosslinking networks with polymers.     

Unveiling ultrafast dynamics in bridged bimetallic complexes using optical and X-ray transient absorption spectroscopies

In photosynthetic systems employing multiple transition metal centers, the properties of charge-transfer states are tuned by the coupling between metal centers. Here, we use ultrafast optical and X-ray spectroscopies to elucidate the effects of metal–metal interactions in a bimetallic tetrapyridophenazine-bridged Os(ii)/Cu(i) complex. Despite having an appropriate driving force for Os-to-Cu hole transfer in the Os(ii) moiety excited state, no such charge transfer was observed. However, excited-state coupling between the metal centers is present, evidenced by variations in the Os MLCT lifetime depending on the identity of the opposite metal center. This coupling results in concerted coherent vibrations appearing in the relaxation kinetics of the MLCT states for both Cu and Os centers. These vibrations are dominated by metal–ligand contraction at the Cu/Os centers, which are in-phase and linked through the conjugated bridging ligand. This study shows how vibronic coupling between transition metal centers affects the ultrafast dynamics in bridged, multi-metallic systems from the earliest times after photoexcitation to excited-state decay, presenting avenues for tuning charge-transfer states through judicious choice of metal/ligand groups.

In photosynthetic systems employing multiple transition metal centers, the properties of charge-transfer states are tuned by the coupling between metal centers.     

Metal–ligand–Lewis acid multi-cooperative catalysis: a step forward in the Conia-ene reaction

An original multi-cooperative catalytic approach was developed by combining metal–ligand cooperation and Lewis acid activation. The [(SCS)Pd]₂ complex featuring a non-innocent indenediide-based ligand was found to be a very efficient and versatile catalyst for the Conia-ene reaction, when associated with Mg(OTf)₂. The reaction operates at low catalytic loadings under mild conditions with HFIP as a co-solvent. It works with a variety of substrates, including those bearing internal alkynes. It displays complete 5-exo vs. 6-endo regio-selectivity. In addition, except for the highly congested ^tBu-substituent, the reaction occurs with high Z vs. E stereo-selectivity, making it synthetically useful and complementary to known catalysts.

An original multi-cooperative catalytic approach was developed by combining metal–ligand cooperation and Lewis acid activation.     

Ligand field-actuated redox-activity of acetylacetonate

The quest for simple ligands that enable multi-electron metal–ligand redox chemistry is driven by a desire to replace noble metals in catalysis and to discover novel chemical reactivity. The vast majority of simple ligand systems display electrochemical potentials impractical for catalytic cycles, illustrating the importance of creating new strategies towards energetically aligned ligand frontier and transition metal d orbitals. We herein demonstrate the ability to chemically control the redox-activity of the ubiquitous acetylacetonate (acac) ligand. By employing the ligand field of high-spin Cr(ii) as a switch, we were able to chemically tailor the occurrence of metal–ligand redox events via simple coordination or decoordination of the labile auxiliary ligands. The mechanism of ligand field actuation can be viewed as a destabilization of the d_z² orbital relative to the π* LUMO of acac, which proffers a generalizable strategy to synthetically engineer redox-activity with seemingly redox-inactive ligands.

Tailoring the chemical surroundings of chromium(ii) allows reversible electron-transfer to the ubiquitous, purportedly redox-inactive acetylacetonate.     

A DNA nanopillar as a scaffold to regulate the ratio and distance of mimic enzymes for an efficient cascade catalytic platform

Herein, a rigid 3D DNA nanopillar was used to investigate the influence of spatial organization on the cascade activity in multienzyme systems, realizing controllable regulation of the mimic enzyme ratio and spacing for acquiring a high-efficiency enzyme cascade catalytic platform. Initially, the ratio of mimic enzyme AuNPs (glucose oxidase-like activity) and hemin/G-quadruplex DNAzyme (peroxidase-like activity) fixed at the designed position was adjusted by changing the number of edges in a DNA polyhedron, resulting in an optimal mimic enzyme ratio of 1 : 4 with a quadrangular prism as the scaffold. Notably, the DNA nanopillar formed by quadrangular prism layer-by-layer assembly acted as a track for directional and controllable movement of a bipedal DNA walker based on the toehold mediated strand displacement reaction (TSDR), which endowed the assay system with continuous enzyme spacing regulation compared with previous enzyme cascade systems that induced inflexible operation. Furthermore, enzyme mimetics in this work circumvented the drawbacks of natural enzymes, such as time-consuming purification processes and poor thermal stability. As a proof of concept, the proposed dual regulation strategy of cascade enzymes was applied in the ultrasensitive electrochemical detection of Pb²⁺, which provided a new route to fabrication of high-performance artificial enzyme cascade platforms for ultimate application in bioanalysis and biodiagnostics.

A rigid 3D DNA nanopillar was used to investigate the influence of spatial organization on the cascade activity in multienzyme systems, realizing controllable regulation of the mimic enzyme ratio and spacing for efficient cascade catalytic platform.     

Switchable electrical conductivity in a three-dimensional metal–organic framework via reversible ligand n-doping

Redox-active metal–organic frameworks (MOFs) are promising materials for a number of next-generation technologies, and recent work has shown that redox manipulation can dramatically enhance electrical conductivity in MOFs. However, ligand-based strategies for controlling conductivity remain under-developed, particularly those that make use of reversible redox processes. Here we report the first use of ligand n-doping to engender electrical conductivity in a porous 3D MOF, leading to tunable conductivity values that span over six orders of magnitude. Moreover, this work represents the first example of redox switching leading to reversible conductivity changes in a 3D MOF.

Redox-active ligands are used to reversibly tune electrical conductivity in a porous 3D metal–organic framework (MOF).