Ligand Modification Research Articles

Modulation of Phenolate-Functionalized Donor-Flexible PYE Ligands for Iridium-Catalyzed Formic Acid Dehydrogenation

Modulation of Phenolate-Functionalized Donor-Flexible PYE Ligands for Iridium-Catalyzed Formic Acid Dehydrogenation

Symmetry breaking of fluorophore binding to a G-quadruplex generates an RNA aptamer with picomolar KD.

Fluorogenic RNA aptamer tags with high affinity enable RNA purification and imaging. The G-quadruplex (G4) based Mango (M) series of aptamers were selected to bind a thiazole orange based (TO1-Biotin) ligand. Using a chemical biology and reselection approach, we have produced a MII.2 aptamer-ligand complex with a remarkable set of properties: Its unprecedented KD of 45 pM, formaldehyde resistance (8% v/v), temperature stability and ligand photo-recycling properties are all unusual to find simultaneously within a small RNA tag. Crystal structures demonstrate how MII.2, which differs from MII by a single A23U mutation, and modification of the TO1-Biotin ligand to TO1-6A-Biotin achieves these results. MII binds TO1-Biotin heterogeneously via a G4 surface that is surrounded by a stadium of five adenosines. Breaking this pseudo-rotational symmetry results in a highly cooperative and homogeneous ligand binding pocket: A22 of the G4 stadium stacks on the G4 binding surface while the TO1-6A-Biotin ligand completely fills the remaining three quadrants of the G4 ligand binding face. Similar optimization attempts with MIII.1, which already binds TO1-Biotin in a homogeneous manner, did not produce such marked improvements. We use the novel features of the MII.2 complex to demonstrate a powerful optically-based RNA purification system.

Enhancing CO2 adsorption capacity and selectivity of UiO-67 through external ligand modification

To address the escalating issue of CO2 pollution, the development of innovative CO2 adsorbents has been necessitated, leading to the exploration of UiO-67-based materials. In this study, UiO-67 was synthesized with meticulous selection of the appropriate modulators in optimal ratios. Subsequently, 4-iodopyrazole, a ligand distinguished by its local electric fields and polar sites, was incorporated to fabricate UiO-67-I. This novel material underwent examination employing techniques such as transmission electron microscopy (TEM), X-ray diffraction (XRD), and Brunauer-Emmett-Teller (BET) analysis. The adsorption rates of gases including CO2, CH4, and N2 were measured at various temperatures. Utilizing the ideal adsorbed solution theory (IAST) and the Clausius-Clapeyron equation, the selectivity of CO2 against CH4 and N2 was calculated, along with the CO2 adsorption isotherms. Remarkably, UiO-67-I(50) demonstrated a CO2 adsorption capacity of 1.84 mmol/g at 298 K and 1 bar, representing a significant enhancement attributable to the ligand's enhanced local electric fields and polar sites. The selectivities for CO2 over CH4 and CO2 over N2 were determined to be 14.2 and 84.6, respectively, under these conditions. Moreover, UiO-67-I(50) proved effective in the separation of CO2 from N2 under dynamic flow conditions, showcasing its potential for practical application in gas separation.

Rational design of red iridophosphors based on 1-(6-methoxynaphthalene-2-yl)isoquinoline ligand for solution‐processed OLEDs

Phosphorescent metal complexes find widespread application in organic light-emitting diodes (OLEDs), with iridium(III) complexes being particularly favored for their superior performance. Owing to the flexible modifications of both main and auxiliary ligands, the photophysical properties of iridium(III) complexes can be finely tuned. In this study, two red neutral iridium(III) complexes, designated as Ir1 and Ir2, are successfully synthesized and characterized. Various auxiliary ligands including acetylacetone and 2-picolinic acid are employed in combination with 1-(6-methoxynaphthalene-2-yl)isoquinoline as the cyclometalating ligand. Both complexes exhibit red emission, with Ir1 emitting at 631 nm and Ir2 at 615 nm. Furthermore, they demonstrated good solubility in common organic solvents, facilitating device fabrication via solution methods. Electroluminescent (EL) devices based on complexes Ir1 and Ir2 are further prepared using spin-coating method, achieving maximum external quantum efficiencies (EQEs) of 3.30 % and 4.52 %, respectively, and both devices exhibited bright red EL with CIE coordinates of (0.68, 0.32) and (0.66, 0.34), which were very close to the standard red coordinates of (0.67, 0.33).

Cooperative defect engineering and ligand modification in UiO-66 to achieve high proton conductivity.

D-UiO-66-NIM with high proton conductivity has been synthesized through the dual strategy of defect engineering and ligand modification. Moreover, D-UiO-66-NIM exhibits good temperature cycling stability and durability in proton conductivity. This work has developed a new method to obtain efficient MOF-based proton conductors.

In vitro screening of chemically synthesized dipeptide-antisense oligonucleotide conjugates to identify ligand molecules enhancing their activity

Oligonucleotide therapeutics, particularly antisense oligonucleotides (ASOs), have emerged as promising candidates in drug discovery. However, their effective delivery to the target tissues and cells remains a challenge, necessitating the development of suitable drug delivery technologies for ASOs to enable their practical application. In this study, we synthesized a library of chemically modified dipeptide-ASO conjugates using a recent synthetic method based on the Ugi reaction. We then conducted in vitro screening of this library using luciferase-expressing cell lines to identify ligands capable of enhancing ASO activity. Our findings suggest that N-(4-nitrophenoxycarbonyl)glycine may interact with the thiophosphate moiety of the phosphorothioate-modification in ASO. Through our screening efforts, we identified two ligands that modestly reduced luciferase luminescence in a cell type-selective manner. Furthermore, quantification of luciferase mRNA levels revealed that one of these promising dipeptide-ASO conjugates markedly suppressed luciferase RNA levels through its antisense effect in prostate-derived DU-145 cells compared to the ASOs without ligand modification.

Engineering the Active Sites of MOF‐derived Catalysts: From Oxygen Activation to Activate Metal‐Air Batteries†

Comprehensive SummaryThe electrochemical processes of oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) play a crucial role in various energy storage and conversion systems. However, the inherently slow kinetics of reversible oxygen reactions present an urgent demand for the development of efficient oxygen electrocatalysts. Recently, metal‐organic framework (MOF) derivatives have attracted extensive attention in electrocatalysis research due to their unique porous structure, abundant active sites, and tunable structural properties. Especially, the optimization of the electronic structure of active sites in MOF derivatives has been proven as an effective strategy to enhance the catalytic activity. In this review, we provide an overview of the electronic structure optimization strategies for active sites in MOF derivatives as advanced catalysts in various O—O bond activation reactions, including the construction of synergistic effects between multiple sites, the development of heterogeneous interfaces, the utilization of metal support interactions, and the precise modulation of organic ligands surrounding catalytic active sites at the atomic level. Furthermore, this review offers theoretical insights into the oxygen activation and catalytic mechanisms of MOF derivatives, as well as the identification of active sites. Finally, the potential challenges and prospects of MOF derivatives in electrocatalysis are discussed. This review contributes to the understanding and advancement of efficient oxygen electrocatalysis in energy systems. Key Scientists

Extraction of uranyl from spent nuclear fuel wastewater via complexation—a local vibrational mode study

ContextThe efficient extraction of uranyl from spent nuclear fuel wastewater for subsequent reprocessing and reuse is an essential effort toward minimization of long-lived radioactive waste. N-substituted amides and Schiff base ligands are propitious candidates, where extraction occurs via complexation with the uranyl moiety. In this study, we extensively probed chemical bonding in various uranyl complexes, utilizing the local vibrational modes theory alongside QTAIM and NBO analyses. We focused on (i) the assessment of the equatorial O-U and N-U bonding, including the question of chelation, and (ii) how the strength of the axial U=\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$=$$\\end{document}O bonds of the uranyl moiety changes upon complexation. Our results reveal that the strength of the equatorial uranium-ligand interactions correlates with their covalent character and with charge donation from O and N lone pairs into the vacant uranium orbitals. We also found an inverse relationship between the covalent character of the equatorial ligand bonds and the strength of the axial uranium-oxygen bond. In summary, our study provides valuable data for a strategic modulation of N-substituted amide and Schiff base ligands towards the maximization of uranyl extraction.MethodQuantum chemistry calculations were performed under the PBE0 level of theory, paired with the relativistic NESCau Hamiltonian, currently implemented in Cologne2020 (interfaced with Gaussian16). Wave functions were expanded in the cc-pwCVTZ-X2C basis set for uranium and Dunning’s cc-pVTZ for the remaining atoms. For the bonding properties, we utilized the package LModeA in the local modes analyses, AIMALL in the QTAIM calculations, and NBO 7.0 for the NBO analyses.Graphical abstract

Variable Peripheral Ligand Donation Tunes Electronic Structure and NIR II Emission in Tetrathiafulvalene Tetrathiolate Diradicaloids.

Near-infrared (NIR) lumiphores are promising candidates for numerous imaging, communication, and sensing applications, but they typically require large, conjugated scaffolds to achieve emission in this low-energy region. Due to the extended conjugation and synthetic complexity required, it is extremely difficult to tune the photophysical properties of these systems for desired applications. Here, we report facile tuning of deep NIR-emitting diradicaloid complexes through simple modification of peripheral ligands. These new lumiphores are rare examples of air-, acid-, and water-stable emissive diradicaloids. We apply a simple Hammett parameter-based strategy to tune the electron donation of the capping ligand across a series of commercially available triarylphosphines. This minor peripheral modification significantly alters the electronic structure, and consequently, the electrochemical, photophysical, and magnetic properties of the tetrathiafulvalene tetrathiolate (TTFtt)-based lumiphores. The resultant ∼100 nm absorption and emission range spans common laser lines and the desirable telecom region (ca. 1260-1550 nm). Furthermore, these lumiphores are sensitive to local dielectrics, distinguishing them as promising candidates for ratiometric imaging and/or barcoding in the deep NIR region.

CHARMM-GUI QM/MM Interfacer for a Quantum Mechanical and Molecular Mechanical (QM/MM) Simulation Setup: 1. Semiempirical Methods.

Quantum mechanical (QM) treatments, when combined with molecular mechanical (MM) force fields, can effectively handle enzyme-catalyzed reactions without significantly increasing the computational cost. In this context, we present CHARMM-GUI QM/MM Interfacer, a web-based cyberinfrastructure designed to streamline the preparation of various QM/MM simulation inputs with ligand modification. The development of QM/MM Interfacer has been achieved through integration with existing CHARMM-GUI modules, such as PDB Reader and Manipulator, Solution Builder, and Membrane Builder. In addition, new functionalities have been developed to facilitate the one-stop preparation of QM/MM systems and enable interactive and intuitive ligand modifications and QM atom selections. QM/MM Interfacer offers support for a range of semiempirical QM methods, including AM1(+/d), PM3(+/PDDG), MNDO(+/d, +/PDDG), PM6, RM1, and SCC-DFTB, tailored for both AMBER and CHARMM. A nontrivial setup related to ligand modification, link-atom insertion, and charge distribution is automatized through intuitive user interfaces. To illustrate the robustness of QM/MM Interfacer, we conducted QM/MM simulations of three enzyme-substrate systems: dihydrofolate reductase, insulin receptor kinase, and oligosaccharyltransferase. In addition, we have created three tutorial videos about building these systems, which can be found at https://www.charmm-gui.org/demo/qmi. QM/MM Interfacer is expected to be a valuable and accessible web-based tool that simplifies and accelerates the setup process for hybrid QM/MM simulations.

Efficient tuning of the selectivity of Cu-based interface for electrocatalytic CO2 reduction by ligand modification

The development of efficient strategies to tune the CO2RR selectivity of Cu-based catalytic interfaces, especially on specific domains, such as Cu (200) facets with high activity toward competitive hydrogenation evolution reaction (HER), remains a challenging task. In this work, Cu-based catalytic layers with thiocyanate (-SCN), cyanide (-CN), or ethylenediamine (-NH2R) coordination linkages are prepared on Cu nanocolumns arrays (Cu NCAs) with predominant (200) exposed facets. The coordination of these ligands induces more Cu+ species and inhibits the adsorption of H∗ on the Cu (200) facet, leading to enhanced CO2RR performance and substantially suppressing the competitive HER. The faradaic efficiency (FE) of Cu–SCN, Cu–CN, and Cu–NH2R NWAs for producing HCOOH, C2H4, and C1 mixture products (HCOOH and CO) reach to 66.5%, 21.1%, and 57.1%, respectively. In situ spectroscopic studies reveal Cu–SCN, Cu–CN, and Cu–NH2R exhibit more reasonable adsorption energy toward ∗OCHO, ∗CO, and ∗COOH intermediates, promoting the HCOOH, C2H4, and C1 mixture generation, respectively. This study might provide a new perspective for the development of high-performance Cu-based CO2RR catalytic electrodes based on the combination of various commercial free-standing Cu substrates and organic/inorganic ligands.

Sensitive detection of bilirubin using highly luminescent benzylamine capped CH3NH3PbBr3 perovskite quantum dots

Luminescent organic–inorganic metal halide hybrid perovskite quantum dots (PQDs) as a new class of fluorophores are finding increasing attention towards chemical and biological sensing due to their exceptional photophysical properties. Herein, we synthesized highly fluorescent CH3NH3PbBr3 perovskite quantum dots (B-PQDs) through the ligand assisted reprecipitation method (LARP), using benzylamine as the surface capping ligand. Morphological and opto-structural properties of the as-synthesized B-PQDs were thoroughly investigated using high resolution transmission electron microscopy (HR-TEM), X-Ray diffraction (XRD), Fourier transform infra-red spectroscopy (FT-IR), UV–Vis absorption, and fluorescence spectroscopy. The as-synthesized electron-rich amine-capped B-PQDs were employed to study their sensing response towards bilirubin (BL). The aromatic amine capped B-PQDs enhance the sensory response towards BL due to the π-π interaction with BL’s conjugated system. The B-PQDs were found to be highly sensitive towards BL with a stern–volmer constant value ≈ 4.3 × 104 M−1 and limit of detection of 0.42 μM. A panel of characterizations were carried out to investigate the detailed sensing mechanism where resonance energy transfer was found to be the dominant quenching mechanism for BL detection. Our results demonstrated the potential for utilizing organic–inorganic halide perovskite quantum dots for sensing applications, through surface ligand modification tailored for detecting specific analytes.

Pushing Patterning Limits of Drop‐On‐Demand Inkjet Printing with Cspbbr3/PDMS Nanoparticles

AbstractPatterning is crucial for advancing perovskite materials into color conversion micro‐display applications, but achieving inkjet‐printed patterns with high performance and precision remains challenging. Here, novel CsPbBr3/PDMS nanoparticles as a promising candidate is proposed for achieving precise and perfect inkjet printing patterns. The as‐prepared nanoparticles ensure exceeding brightness, exceptional stability, uniform fluorescence emission, and high resolution reaching the highest performance of drop‐on‐demand inkjet printing. Specifically, the performance and stability of CsPbBr3/PDMS nanoparticles are enhanced through a two‐step optimization involving dodecyl benzene sulfonic acid (DBSA) ligand modification and polydimethylsiloxane (PDMS) in situ coating, resulting in the highest photoluminescence quantum yield (PLQY) of 92% among CsPbBr3/polymer core‐shell composites so far. The branched structure of DBSA and the PDMS shell provide steric hindrance and effectively prevent agglomeration during storage or patterning. The viscous PDMS coating inhibits the coffee ring effect, not only leading to excellent near‐unity uniform emission but also promoting the formation of smaller and more elaborate droplets, increasing the printing resolution by up to surprisingly 300%. Importantly, the impeccably displayed, high‐resolution patterns formed by versatile CsPbBr3/PDMS nanoparticles have demonstrated significant potential for high pixel density Micro‐LED displays, enabling efficient and stable color conversion.

Impact of Ligand Modification on the Hydrogen Evolution Reaction of Highly Active Silver(I)- and Ruthenium(II)-N-Heterocyclic Carbene-Based Electrocatalysts: Comprehension from the Hydrogen Oxidation Reaction

Impact of Ligand Modification on the Hydrogen Evolution Reaction of Highly Active Silver(I)- and Ruthenium(II)-N-Heterocyclic Carbene-Based Electrocatalysts: Comprehension from the Hydrogen Oxidation Reaction

Exciton polaron formation and hot-carrier relaxation in rigid Dion-Jacobson-type two-dimensional perovskites.

The efficiency of two-dimensional Dion-Jacobson-type materials relies on the complex interplay between electronic and lattice dynamics; however, questions remain about the functional role of exciton-phonon interactions. Here we establish the robust polaronic nature of the excitons in these materials at room temperature by combining ultrafast spectroscopy and electronic structure calculations. We show that polaronic distortion is associated with low-frequency (30-60 cm-1) lead iodide octahedral lattice motions. More importantly, we discover how targeted ligand modification of this two-dimensional perovskite structure manipulates exciton-phonon coupling, exciton polaron population and carrier cooling. At high excitation density, stronger exciton-phonon coupling increases the hot-carrier lifetime, forming a hot-phonon bottleneck. Our study provides detailed insight into the exciton-phonon coupling and its role in carrier cooling in two-dimensional perovskites relevant for developing emerging hybrid semiconductor materials with tailored properties.

Physiological temperature drives TRPM4 ligand recognition and gating

Temperature profoundly affects macromolecular function, particularly in proteins with temperature sensitivity1,2. However, its impact is often overlooked in biophysical studies that are typically performed at non-physiological temperatures, potentially leading to inaccurate mechanistic and pharmacological insights. Here we demonstrate temperature-dependent changes in the structure and function of TRPM4, a temperature-sensitive Ca2+-activated ion channel3–7. By studying TRPM4 prepared at physiological temperature using single-particle cryo-electron microscopy, we identified a ‘warm’ conformation that is distinct from those observed at lower temperatures. This conformation is driven by a temperature-dependent Ca2+-binding site in the intracellular domain, and is essential for TRPM4 function in physiological contexts. We demonstrated that ligands, exemplified by decavanadate (a positive modulator)8 and ATP (an inhibitor)9, bind to different locations of TRPM4 at physiological temperatures than at lower temperatures10,11, and that these sites have bona fide functional relevance. We elucidated the TRPM4 gating mechanism by capturing structural snapshots of its different functional states at physiological temperatures, revealing the channel opening that is not observed at lower temperatures. Our study provides an example of temperature-dependent ligand recognition and modulation of an ion channel, underscoring the importance of studying macromolecules at physiological temperatures. It also provides a potential molecular framework for deciphering how thermosensitive TRPM channels perceive temperature changes.

Tuning the Thermochemistry and Reactivity of a Series of Cu-Based 4H+/4e- Electron-Coupled-Proton Buffers.

Electron-coupled-proton buffers (ECPBs) store and deliver protons and electrons in a reversible fashion. We have recently reported an ECPB based on Cu and a redox-active ligand that promoted 4H+/4e- reversible transformations (J. Am. Chem. Soc. 2022, 144, 16905). Herein, we report a series of Cu-based ECPBs in which the ability of these to accept and/or donate H• equivalents can be tuned via ligand modification. The thermochemistry of the 4H+/4e- ECPB equilibrium was determined using open-circuit potential measurements. The reactivity of the ECPBs against proton-coupled electron transfer (PCET) reagents was also analyzed, and the results obtained were rationalized based on the thermochemical parameters. Experimental and computational analysis of the thermochemistry of the H+/e- transfers involved in the 4H+/4e- ECPB transformations found substantial differences between the stepwise (namely, BDFE1, BDFE2, BDFE3, and BDFE4) and average bond dissociation free energy values (BDFEavg.). Our analysis suggests that this "redox unleveling" is critical to promoting the disproportionation and ligand-exchange reactions involved in the 4H+/4e- ECPB equilibria. The difference in BDFEavg. within the series of Cu-based ECPBs was found to arise from a substantial change in the redox potential (E1/2) upon modification of the ligand scaffold, which is not fully compensated for by a change in the acidity/basicity (pKa), suggesting "thermochemical decompensation".

The Effect of Ligand Field on Enhanced Electrocatalytic Performance of NO Reduction Under Applied Potential

We employed density functional theory to investigate Co-N4/Gra single-atom catalysts, focusing on the modification of axial ligand (X=-F, -CN and -C3H4N2) and examined the influence of ligand field and electric potential on eNORR. Our results demonstrate that Co-N4[X]/Gra exhibit favorable thermodynamic adsorption (ΔG *NO < 0) and remarkable activation activity toward NO molecules. Co-N4/Gra demonstrates a limiting potential of −0.13 V with the potential-determining step (PDS) of *NH3 → * + NH3(g). Notably, under the introduction of ligands, Co-N4[F]/Gra achieves the most favorable overpotential of −0.07 V, superior to most of NORR electrocatalysts, and meanwhile shows an exceptional selectivity of 99.99% for eNORR compared to competitive hydrogen evolution reaction. Under the solvent environment, Co-N4/Gra features the triggering potentials of −0.33 V for a pH of 1, −0.71 V for a pH of 7, and −1.10 V vs RHE for a pH of 13, respectively. Additionally, the potential reduces the desorption energy and adsorption energy of NH3, facilitating the accessibility of the NH3 desorption step (PDS) and promoting NO reduction. Thus, under realistic conditions, the Co ion’s active site displays variable valence electrons and forms a dynamic interplay with the ligand field effect, rendering a crucial effect on the adsorption of reaction species during the eNORR.

Therapeutic modulation of KIT ligand in melanocytic disorders with implications for mast cell diseases.

KIT ligand and its associated receptor KIT serve as a master regulatory system for both melanocytes and mast cells controlling survival, migration, proliferation and activation. Blockade of this pathway results in cell depletion, while overactivation leads to mastocytosis or melanoma. Expression defects are associated with pigmentary and mast cell disorders. KIT ligand regulation is complex but efficient targeting of this system would be of significant benefit to those suffering from melanocytic or mast cell disorders. Herein, we review the known associations of this pathway with cutaneous diseases and the regulators of this system both in skin and in the more well-studied germ cell system. Exogenous agents modulating this pathway will also be presented. Ultimately, we will review potential therapeutic opportunities to help our patients with melanocytic and mast cell disease processes potentially including vitiligo, hair greying, melasma, urticaria, mastocytosis and melanoma.

To Explore Potential Inhibitors Against Various Enzymatic Targets of Human African Trypanosomiasis.

Synthetic drugs currently prescribed for the treatment of Human African Trypanosomiasis (HAT) are non-specific, toxic, demand extended therapeutic regimes and are of varying efficacy. Along with the challenging demographic and socio-economic hurdles, the everincreasing risk of drug resistance is another major problem to be addressed. Cysteine protease, Heat shock proteins (HSP-90), Trypanothione reductase (TR), Farnesyl diphosphate synthase, Glucose-6-phosphate dehydrogenase, UP-4-galactose epimerase, and Cytidine triphosphate synthetase are potential enzymatic targets for the development of novel inhibitors against HAT which are the main focus of this review. The potential enzymatic targets of Trypanosoma brucei, especially small molecules like cysteine proteases and heat shock proteins are identified as major candidates for the sustenance of the parasite, their proliferation, infection, and spread of the disease. The development of new compounds to combat the disease by thorough ligand modification has been explored in the current review. Extracting these compounds and studying their efficacy, toxicity, and target mechanism extensively, this review has proposed a list of different compounds, including some synthetic and natural compounds along with multi-target inhibitors such as acoziborole, fexinidazole, etc. Potential inhibitors against these enzymatic targets of the T. brucei are important candidates for designing novel therapeutics against HAT. Multi-target inhibitors have also been identified as crucial molecules because of their potential advantage against the development of drug resistance.