Configuration Of Ligand Research Articles

Structure-based pose prediction: Non-cognate docking extended to macrocyclic ligands

So-called “cross-docking” is the prediction of the bound configuration of small-molecule ligands that differ from the cognate ligand of a protein co-crystal structure. This is a much more challenging problem than re-docking the cognate ligand, particularly when the new ligand is structurally dissimilar from prior known ones. We have updated the previously introduced PINC (“PINC Is Not Cognate”) benchmark which introduced the idea of temporal segregation to measure cross-docking performance. The temporal set encompasses 846 future ligands for ten targets based on information from the earliest 25% of X-ray co-crystal structures known for each target. Here, we extend the benchmark to include thirteen targets where the bound poses of 128 macrocyclic ligands are to be predicted based on knowledge from structures of bound non-macrocyclic ligands. Performance was roughly equivalent for both the temporally-split non-macrocyclic ligand set and the macrocycle prediction set. Using standard and fully automatic protocols for the Surflex-Dock and ForceGen methods, across the combined 974 non-macrocyclic and macrocyclic ligands, the top-scoring pose family was correct 68% of the time, with the top-two pose families achieving a 79% success rate. Correct poses among all those predicted were identified 92% of the time. These success rates far exceeded those observed for the alternative methods AutoDock Vina and Gnina on both sets.

Chemical assessment of three octahedral Ni(II) complexes with heterocyclic acylpyrazolone ligand: Crystal structure, DFT-NBO analysis, Hirshfeld and Magnetic study

We have synthesized three novel mononuclear Nickel(II) coordination complexes [Ni(DMBPTMP)2(EtOH)2], [Ni(PCBPMP)2(DMF)(H2O)] and [Ni(PCBPTMP)2(DMSO)2] with σ-donating acylpyarazolone ligands. All the complexes have been comprehensively characterized via FTIR, UV–Vis, TGA, and Magnetic study. Additionally, single crystal X-ray diffraction analysis was successfully used to characterize the three complexes. The findings showed that the geometry around Ni(II) is slightly distorted octahedral in [Ni(DMBPTMP)2(EtOH)2], [Ni(PCBPMP)2(DMF)(H2O)] complexes and also in the centrosymmetric [Ni(PCBPTMP)2(DMSO)2] complex. In all the complexes the metal is bischelated by two pyrazolone molecules via carbonyl and benzoyl carbonyl oxygen donors, but with a different configuration of ligands. In addition to the experimental studies and spectroscopic characteristics, DFT computational analysis and Natural bonding orbital (NBO) analysis have been performed using a B3LYP/LANL2DZ basis set for the optimization. All three Ni(II) complexes give three distinct absorption transitions which has been proved by Electronic spectral analysis. A paramagnetic nature of the complex is confirmed through magnetic study. Utilising Hirshfeld surface analysis, intermolecular interactions of complexes were evaluated.

Using Er/Cd-Codoped Bi4O5Br2 Microspheres to Enhance Antibiotic Degradation under Visible Illumination: A Combined Experimental and DFT Investigation.

High levels of antibiotic accumulation and the difficulty of degradation can have serious consequences for the environment and, therefore, require urgent attention. To solve this problem, a synergistic Er and Cd ion-codoped Bi4O5Br2 photocatalyst was proposed. The degradation rate of sulfamethoxazole (SMX) by Er/Cd-Bi4O5Br2 was eight times higher than that of pure Bi4O5Br2, exceeding that of single Er-doped or Cd-doped Bi4O5Br2, which was attributed to the ability of Er/Cd-Bi4O5Br2 to generate a variety of free radicals. Experimental results and theoretical calculations suggested a possible mechanism for the improved photocatalytic degradation rate. The reduction of the band gap can facilitate the production of electron-hole pairs, which play a significant role in the production of reactive radicals. Furthermore, an optimal stabilized structure of the ErCd-Bi4O5Br2 dopant system was identified based on the formation energy formulas of different ligand configurations. These findings offer promising potential for the degradation of broad-spectrum antibiotics and provide valuable insights for the design and modification of photocatalytic materials.

Evaluation of AlphaFold3 for the fatty acids docking to human fatty acid-binding proteins

Human fatty acid-binding proteins (FABPs) are involved in many aspects of lipid metabolism, such as the uptake, transport, and storage of lipophilic molecules, as well as cellular functions. Understanding how FABPs recognize fatty acids (FAs) is crucial for identifying FABP function and applications, such as in inhibitor design or biomarker development. The recently developed AlphaFold3 (AF3) demonstrates significantly higher accuracy than other prediction tools, particularly in predicting protein–ligand interactions with state-of-the-art docking tools. Studies on whether AF3 can be used to identify the FAs of FABP are lacking. To assess the accuracy of FA docking to FABPs using AF3, models of FA docked into FABP generated using AF3 were compared with experimentally determined FA-bound FABP structures. FA ligands in AF3 structures docked reliably into the FA-binding pocket of FABPs; however, the detailed binding configuration of most FA ligands docked into FABPs and the interaction between FA and FABP determined using AF3 and experimentally differed. These results will aid in understanding FA docking to FABPs and other FA-binding proteins using AF3.

Sulfur Modified Carbon-Based Single-Atom Catalysts for Electrocatalytic Reactions.

Efficient and sustainable energy development is a powerful tool for addressing the energy and environmental crises. Single-atom catalysts (SACs) have received high attention for their extremely high atom utilization efficiency and excellent catalytic activity, and have broad application prospects in energy development and chemical production. M-N4 is an active center model with clear catalytic activity, but its catalytic properties such as catalytic activity, selectivity, and durability need to be further improved. Adjustment of the coordination environment of the central metal by incorporating heteroatoms (e.g., sulfur) is an effective and feasible modification method. This paper describes the precise synthetic methods for introducing sulfur atoms into M-N4 and controlling whether they are directly coordinated with the central metal to form a specific coordination configuration, the application of sulfur-doped carbon-based single-atom catalysts in electrocatalytic reactions such as ORR, CO2RR, HER, OER, and other electrocatalytic reaction are systematically reviewed. Meanwhile, the effect of the tuning of the electronic structure and ligand configuration parameters of the active center due to doped sulfur atoms with the improvement of catalytic performance is introduced by combining different characterization and testing methods. Finally, several opinions on development of sulfur-doped carbon-based SACs are put forward.

(Invited) Carbon Phase Adjustment by Multi-Configuration Ligand in Endohedral Metallofullerene Derivatives Gd@C82(morpholine)7 Under High Pressure

Metallofullerenes present an ideal research object for developing new carbon structures with improved properties under high pressure. In this presentation, high pressure investigation is realized on metallofullerene derivatives (Gd@C82(morpholine)7) by applying in situ synchrotron XRD, Raman, and IR spectroscopy, combined with high pressure density functional theory (DFT) calculations. The regulations of multi-configuration morpholine ligands avoid the direct collapse of the carbon cages commonly happened to fullerenes, making the fine structure transformation possible for the first time, including ligand configuration exchange, anisotropic shrinkage of cage, new constructed bonds, and even the encaged metal’s movement with increasing pressure. The charge-transfer principle as the beneath driving force of structural transition is found. These findings demonstrate that multi-configuration ligand maps an innovative strategy for phase transition control of metallofullerenes under high pressure, thus providing deep insight, step by step, into the phase transition mechanism of these hybrid molecular systems on molecular level.

Ligand-Induced Size-Dependent Circular Dichroism in Quantum Dots.

Recent experiments have probed the chiral properties of semiconductor nanocrystal (NC) quantum dots (QDs), but understanding the circular dichroism line shape, excitonic features, and chirality induction mechanism remains a challenge. We propose an atomistic pseudopotential method to model chiral ligand passivated QDs, computing circular dichroism (CD) spectra for CdSe QDs (2.6-3.8 nm). We find strong agreement between calculated and measured line shapes, predicting consistent bisignate line shapes with decreasing CD magnitude as size increases. Our analysis reveals the origin of bisignate line shapes, arising from nondegenerate excitons with opposing angular momenta. We also explore the impact of chiral ligand orientation on QD surfaces, observing changes in the optical activity magnitude and sign. This orientation sensitivity offers the means to distinguish ordered from disordered ligand configurations, facilitating the study of order-disorder transitions at ligand-QD interfaces.

Structure and magnetism of DyIII2 based triple-stranded helicates derived from dinucleating Schiff base ligands

We report herein the synthesis of three dinuclear DyIII helicates, [DyIII2(H2LR)3](NO3)3·xH2O (1–3, R = Me, Cl, Br), by reacting Dy(NO3)3·5H2O and three closely related Schiff bases derived from 3-Hydroxy-2-naphthohydrazide and three different 2,6-diformylphenols. Single crystal X-ray structural characterization revealed that all these complexes are isostructural and composed of complex cations of general formula [DyIII2(H2LR)3]3+, in which three monoanionic Schiff base ligands are wrapped around two DyIII centers, leading to triple-stranded helical structures. Notably, the configuration of monoanionic H2LR ligands imparts a coordination-induced chirality on individual complex cation, and the presence of equivalent amounts of enantiopure Λ and Δ complex cations made the solid products as racemic mixtures, crystalizing in the centrosymmetrical space groups. Variable-temperature magnetic susceptibility measurements have been performed in the temperature range 2 − 300 K for a representative complex 2, and AC susceptibility studies further disclose the slow relaxation of magnetization in 2, characteristics for single-molecule magnets.

Computational Estimation of Residues Involving Resistance to the SARS-CoV-2 Main Protease Inhibitor Ensitrelvir Based on Virtual Alanine Scan of the Active Site.

Ensitrelvir is a noncovalent inhibitor of the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2. Acquisition of drug resistance in virus-derived proteins is a serious therapeutic concern, and drug resistance occurs due to amino acid mutations. In this study, we computationally constructed 24 mutants, in which one residue around the active site was replaced with alanine and performed molecular dynamics simulations to the complex of Mpro and ensitrelvir to predict the residues involved in drug resistance. We evaluated the changes in the entire protein structure and ligand configuration in each of these mutants and estimated which residues were involved in ensitrelvir recognition. This method is called a virtual alanine scan. In nine mutants (S1A, T26A, H41A, M49A, L141A, H163A, E166A, V186A, and R188A), although the entire protein structure and catalytic dyad (cysteine (Cys)145 and histidine (His)41) were not significantly moved, the ensitrelvir configuration changed. Thus, it is considered that these mutants did not recognize ensitrelvir while maintaining Mpro enzymatic activities, and Ser1, Thr26, His41, Met49, Leu141, His163, Glu166, Val186, and Arg188 may be related to ensitrelvir resistance. The ligand shift noted in M49A was similar to that observed in M49I, which has been shown to be experimentally ensitrelvir resistant. These findings suggest that our research approach can predict mutations that incite drug resistance.

Distinct photochemistry of adsorbed and coprecipitated dicarboxylates with ferrihydrite: Implications for iron reductive dissolution and carbon stabilization

Although ligand-promoted photodissolution of ferrihydrite (FH) has long been known for low molecular weight organic acids (LMWOAs), such as oxalate (Oxa) and malonate (Mal), photochemistry of coprecipitated FH with Oxa and Mal remains unknown, despite the importance of these mineral-organic associations in carbon retention has been acknowledged recently. In this study, ferrihydrite-LMWOAs associations (FLAs) were synthesized under circumneutral conditions. Photo-dissolution kinetics of FLAs were compared with those of adsorbed LMWOAs on FH surface and dissolved Fe-LMWOAs complexes through monitoring Fe(II) formation and organic carbon decay. For aqueous Fe(III)-LMWOAs complexes, Fe(II) yield was controlled by the initial concentration of LMWOAs and nature of photochemically generated carbon-centered radicals. Inner-sphere mononuclear bidentate (MB) configuration dominated while LMWOAs were adsorbed on the FH surface. MB complex of FH-Oxa was more photoreactive, leading to the rapid depletion of Oxa. Oxa can be readsorbed but in the form of binuclear bidentate and outer-sphere complexation, with much lower photoreactivity. While LMWOAs was coprecipitated with FH, the combination mode of LMWOAs with FH includes surface adsorption with a mononuclear bidentate structure and internal physical inclusion. Higher content of LMWOAs in the FLAs promoted the photo-production of Fe(II) as compared to pure FH, while it was not the case for FLAs containing moderate amounts of LMWOAs. The distinct photochemistry of adsorbed and coprecipitated Fe-LMWOAs complexes is attributed to ligand availability and configuration patterns of LMWOAs on the surface or entrapped in the interior structure. The present findings have significant implications for understanding the photochemical redox cycling of iron across the interface of Fe-organic mineral associates.

Understanding the Effects of Ligand Configuration on Protoporphyrinogen IX Oxidase with Rationally Designed 3-(N-Phenyluracil)but-2-enoates.

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is a promising target for green herbicide discovery. However, the ligand configuration effects on PPO activity were still poorly understood. Herein, we designed 3-(N-phenyluracil)but-2-enoates using our previously developed active fragments exchange and link (AFEL) approach and synthesized a series of novel compounds with nanomolar ranges of Nicotiana tabacum PPO (NtPPO) inhibitory potency and promising herbicidal potency. Our systematic structure-activity relationship investigations showed that the E isomers of 3-(N-phenyluracil)but-2-enoates displayed improved bioactivity than their corresponding Z isomers. Using molecular simulation studies, we found that the E isomers showed a relatively lower entropy change and could sample more stable binding conformation to the receptor than the Z isomers. Our density functional theory (DFT) calculations showed that the E isomers showed higher chemical reactivity and lower electronic chemical potential than their corresponding Z isomers. Compound E-Ic emerged as the optimal compound with a Ki value of 3.0 nM against NtPPO, exhibiting a broader spectrum of weed control than saflufenacil at 37.5-75 g ai/ha and also safe to maize at 75 g ai/ha, which could be considered as a promising lead herbicide for further development.

Fabrication of Self‐Expanding Metal–Organic Cages Using a Ring‐Openable Ligand

AbstractMetal–organic cages (MOCs), which are formed via coordination‐driven assembly, are being extensively developed for various applications owing to the utility of their accessible molecular‐sized cavity. While MOC structures are uniquely and precisely predetermined by the metal coordination number and ligand configuration, tailoring MOCs to further modulate the size, shape, and chemical environment of the cavities has become intensively studied for a more efficient and adaptive molecular binding. Herein, we report self‐expanding MOCs that exhibit remarkable structural variations in cage size and flexibility while maintaining their topology. A cyclic ligand with an oligomeric chain tethering the two benzene rings of stilbene was designed and mixed with RhII ions to obtain the parent MOCs. These MOCs were successfully transformed into expanded MOCs via the selective cleavage of the double bond in stilbene. The expanded MOCs could effectively trap multidentate N‐donor molecules in their enlarged cavity, in contrast to the original MOCs with a narrow cavity. As the direct synthesis of expanded MOCs is impractical because of the entropically disfavored structures, self‐expansion using ring‐openable ligands is a promising approach that allows precision engineering and the production of functional MOCs that would otherwise be inaccessible.

Fabrication of Self-Expanding Metal-Organic Cages Using a Ring-Openable Ligand.

Metal-organic cages (MOCs), which are formed via coordination-driven assembly, are being extensively developed for various applications owing to the utility of their accessible molecular-sized cavity. While MOC structures are uniquely and precisely predetermined by the metal coordination number and ligand configuration, tailoring MOCs to further modulate the size, shape, and chemical environment of the cavities has become intensively studied for a more efficient and adaptive molecular binding. Herein, we report self-expanding MOCs that exhibit remarkable structural variations in cage size and flexibility while maintaining their topology. A cyclic ligand with an oligomeric chain tethering the two benzene rings of stilbene was designed and mixed with RhII ions to obtain the parent MOCs. These MOCs were successfully transformed into expanded MOCs via the selective cleavage of the double bond in stilbene. The expanded MOCs could effectively trap multidentate N-donor molecules in their enlarged cavity, in contrast to the original MOCs with a narrow cavity. As the direct synthesis of expanded MOCs is impractical because of the entropically disfavored structures, self-expansion using ring-openable ligands is a promising approach that allows precision engineering and the production of functional MOCs that would otherwise be inaccessible.

CW or Pulsed laser – That is the Question: Comparative Steady‐state Photocrystallographic Analysis of Metal Nitrosyl Linkage Isomers

AbstractThe investigation of photo‐induced effects is profoundly influenced by the characteristics of photo‐excitation sources. In this study, we present a comprehensive analysis of the structures of two photoinduced linkage isomers (PLI) in a ruthenium nitrosyl complex, trans‐[Ru(py)4F(NO)](ClO4)2, following irradiation with both pulsed and continuous wave (CW) light sources under low temperature conditions. The X‐ray (photo)diffraction analysis shows that the resulting PLI generated from the two types of irradiation sources, an isonitrosyl configuration of the nitrosyl ligand in the so‐called metastable state MS1, and a side‐on configuration of the nitrosyl ligand in the metastable state MS2, are identical. In‐situ optical absorption spectroscopy was employed during CW and pulsed irradiation, enabling the monitoring of the population process of these PLI. The results obtained from the infrared spectroscopic analysis after pulsed irradiation give insight into the population mechanism illustrating that the generation of the isonitrosyl MS1 occurs through a two‐step process, via the second PLI, the side‐on configuration MS2.

Cinchona-Alkaloid-Derived NNP Ligand for Iridium-Catalyzed Asymmetric Hydrogenation of β-Keto Ester.

The Ir-catalyzed asymmetric hydrogenation of β-keto esters with Cinchona-alkaloid-derived NNP ligands has been developed. β-Hydroxy esters of opposite configuration were afforded smoothly with 91.5-99.1 and 81.6-99.3% ee, respectively, using NNP L2 and L7 derived from quinidine and quinine separately even on the gram scale. The protocol for the preparation of β-hydroxy esters of opposite configuration by the simple conversion of ligand configurations offered further opportunities for the synthesis of biologically active molecules and drugs.

A Self-Consistent Framework for Tailored Single-Atom Catalysts in Electrocatalytic Nitrogen Reduction.

The catalytic activity of single-atom catalysts (SACs) is crucially affected by the actual ligand configurations under the reaction condition; thus, carefully considering the reaction condition is crucial for the theoretical design of SACs. With single metal atoms supported by g-C3N4 as a model system, a self-consistent screening framework is proposed for the theoretical design of SACs with respect to the nitrogen reduction reaction (NRR). Pourbaix diagrams are constructed on the basis of various co-adsorption configurations of N2, H, and OH. Possible stable configurations containing N2 under the expected reaction condition are considered to obtain the limiting potential of NRR, and the stability of the configuration at the calculated UL is rechecked. With this framework, AC stacking of double-layer g-C3N4-supported Nb and AA stacking and AB stacking of double-layer g-C3N4-supported W are predicted to exhibit superior NRR activity with UL values of -0.36, -0.45, and -0.52 V, respectively. This procedure can be widely applied to the screening of SACs for electrocatalytic reactions.

Stereodivergent 1,5-Conjugate Addition with Iminoesters via Pd/Cu Dual Catalysis

AbstractThe first stereodivergent umpolung 1,5-conjugate addition reaction via synergistic Pd/Cu catalysts is reported. By dictating the absolute configuration of each chiral ligand ligated to corresponding metals, all four stereoisomers of the products are easily achieved. A series of amino acid moieties are introduced to the γ-position of the conjugated esters in high yields with excellent diastereoselectivities and enantioselectivities. The downstream transformations highlight the synthetic value of the method.

A stabilization rule for metal carbido cluster bearing μ3-carbido single-atom-ligand encapsulated in carbon cage

Metal carbido complexes bearing single-carbon-atom ligand such as nitrogenase provide ideal models of adsorbed carbon atoms in heterogeneous catalysis. Trimetallic μ3-carbido clusterfullerenes found recently represent the simplest metal carbido complexes with the ligands being only carbon atoms, but only few are crystallographically characterized, and its formation prerequisite is unclear. Herein, we synthesize and isolate three vanadium-based μ3-CCFs featuring V = C double bonds and high valence state of V (+4), including VSc2C@Ih(7)-C80, VSc2C@D5h(6)-C80 and VSc2C@D3h(5)-C78. Based on a systematic theoretical study of all reported μ3-carbido clusterfullerenes, we further propose a supplemental Octet Rule, i.e., an eight-electron configuration of the μ3-carbido ligand is needed for stabilization of metal carbido clusters within μ3-carbido clusterfullerenes. Distinct from the classic Effective Atomic Number rule based on valence electron count of metal proposed in the 1920s, this rule counts the valence electrons of the single-carbon-atom ligand, and offers a general rule governing the stabilities of μ3-carbido clusterfullerenes.

Metal dimer nanojunction-magnetic material composites for magnetic field sensing.

Noble metal nanocrystals are used as high sensitivity optoelectronic sensors, such as surface-enhanced Raman scattering, SERS. The sensing performance of metal nanocrystals can be further improved by forming dimer nanojunctions with strong "plasmonic coupling". Since the strength of "plasmonic coupling" is highly sensitive to the sub-nanoscale spacing between plasmonic nanocrystals in nanojunctions, nanojunctions can be used to detect external stimuli that can change the spacing of nanocrystals in the nanojunction and thus change the sensitivity of the Raman scattering spectrum. Here, we utilize this principle to detect the direction and strength of an external magnetic field (MF) using dimer nanojunctions surrounded by magnetic materials as a sensing platform. The results reveal that the changes in nanocrystal spacing in the nanojunction are caused by the rearrangement of the magnetic material under an external MF, which strongly depends on the interaction between the magnetic material and the ligands on the nanocrystal surface and the steric repulsion generated by the ligand configuration on the nanocrystal surface. Compared with the Raman spectrum without an external MF, the enhancement factors of the Raman scattering spectrum under an external MF can reach up to ∼900%, which makes dimer nanojunctions with magnetic materials suitable for "magnetic field" sensing applications.

Ultralong Room Temperature Phosphorescence in Cd-MOFs Regulated by the Multimode Coordination Configuration of Niacin Ligand

Long persistent luminescence (LPL) materials have attracted significant attention due to their potential applications in the fields of bioimaging, anti-counterfeiting and chemosensors. It is well known that the aggregation manner...