Dual-ligand Approach Research Articles

Transforming waste into valuables: Preparation and evaluation of dual-ligand hydrophobic charge-induction chromatography using two poor performing ligands

In conventional chromatographic ligand screening, underperforming ligands are often dismissed. However, this practice may inadvertently overlook potential opportunities. This study aims to investigate whether these underperforming ligands can be repurposed as valuable assets. Hydrophobic charge-induction chromatography (HCIC) is chosen as the validation target for its potential as an innovative chromatographic mode. A novel dual-ligand approach is employed, combining two suboptimal ligands (5-Aminobenzimidazole and Tryptamine) to explore enhanced performance and optimization prospects. Various dual-ligand HCIC resins with different ligand densities were synthesized by adjusting the ligand ratio and concentration. The resins were characterized to assess appearance, functional groups, and pore features using SEM, FTIR, and ISEC techniques. Performance assessments were conducted using single-ligand mode resins as controls, evaluating the selectivity against human immunoglobulin G and human serum albumin. Static adsorption experiments were performed to understand pH and salt influence on adsorption. Breakthrough experiments were conducted to assess dynamic adsorption capacity of the novel resin. Finally, chromatographic separation using human serum was performed to evaluate the purity and yield of the resin. Results indicated that the dual-ligand HCIC resin designed for human antibodies demonstrates exceptional selectivity, surpassing not only single ligand states but also outperforming certain high-performing ligand types, particularly under specific salt and pH conditions. Ultimately, a high yield of 83.9 % and purity of 96.7 % were achieved in the separation of hIgG from human serum with the dual-ligand HCIC, significantly superior to the single-ligand resins. In conclusion, through rational design and proper operational conditions, the dual-ligand mode can revitalize underutilized ligands, potentially introducing novel and promising chromatographic modes.

Long-range order enabled stability in quantum dot light-emitting diodes.

Light-emitting diodes (LEDs) based on perovskite quantum dots (QDs) have produced external quantum efficiencies (EQEs) of more than 25% with narrowband emission1,2, but these LEDs have limited operating lifetimes. We posit that poor long-range ordering in perovskite QD films-variations in dot size, surface ligand density and dot-to-dot stacking-inhibits carrier injection, resulting in inferior operating stability because of the large bias required to produce emission in these LEDs. Here we report a chemical treatment to improve the long-range order of perovskite QD films: the diffraction intensity from the repeating QD units increases three-fold compared with that of controls. We achieve this using a synergistic dual-ligand approach: an iodide-rich agent (aniline hydroiodide) for anion exchange and a chemically reactive agent (bromotrimethylsilane) that produces a strong acid that in situ dissolves smaller QDs to regulate size and more effectively removes less conductive ligands to enable compact, uniform and defect-free films. These films exhibit high conductivity (4 × 10-4 S m-1), which is 2.5-fold higher than that of the control, and represents the highest conductivity recorded so far among perovskite QDs. The high conductivity ensures efficient charge transportation, enabling red perovskite QD-LEDs that generate a luminance of 1,000 cd m-2 at a record-low voltage of 2.8 V. The EQE at this luminance is more than 20%. Furthermore, the stability of the operating device is 100 times better than previous red perovskite LEDs at EQEs of more than 20%.

Syntheses and photochemically antibiotic degradation of two Co(II)-based coordination polymers

Two new Co(II)-based coordination polymers (CPs), designated as [Co2(bbp)4(1,3-bdc)4]n(1) and [Co(bbp)3(NO3)2(H2O)]n(2) (bbp = 3,5-bis(benzoimidazo-1-ly) pyridine; 1,3-H2bdc = 1,3-benzenedicarboxy acid), were synthesized using a dual ligand approach. The characterization of these CPs involved single- crystal -XRD, UV–visible, FT-IR, and TGA analysis. Both CPs 1 and 2 exhibit a distorted octahedral geometry. Both 1 and 2 show a 1D ladder chain, and this chain-like structure undergoes further development into a more intricate two-dimensional (2D) supramolecular network. The thermal stability analysis revealed that 1 and 2 are stable at temperatures of 119 °C and 286 °C, respectively, with no significant mass loss. Notably, both CPs displayed semiconducting properties. The photocatalytic degradation capabilities of CPs 1 and 2 were investigated against antibiotics such as metronidazole (MDZ), Tinidazole (TDZ), ornidazole (ODZ), and furazolidone (FZD). CP 1 exhibits exceptional photocatalytic activity against FZD. A dosage of 5 mg/L of CP 1 resulted in a remarkable degradation efficiency of 92.2 % for 40 ppm FZD. Additionally, a proposed photodegradation mechanism was investigated through radical trapping experiments.

Controlling Reactivity and Selectivity in the Nondirected C-H Activation of Arenes with Palladium.

ConspectusAromatic structures are widespread motifs throughout organic chemistry, and C-H activation has been recognized as a major tool for enabling their sustainable and efficient functionalization. Through C-H activation, arenes can be modified without the need for prefunctionalization, leading to inherent atom- and step-economic advantages over traditional methods. However, for the development of synthetically useful methods, several hurdles have to be overcome. The strength of C-H bonds necessitates the development of sufficiently reactive catalysts, while the presence of multiple C-H bonds within a substrate poses challenges in terms of site-selectivity. Traditionally these challenges have been addressed by substrate control. By attaching different directing groups (DGs), the reactivity of the respective arene was significantly enhanced and the DG guided the metal in close proximity to specific C-H bonds, resulting in high site-selectivity. However, the introduction and removal of the DG add additional steps to the synthetic sequence, and the scope of the reaction is limited to a specific substrate class. The development of complementary nondirected methods that can be applied to a broad range of arenes without the necessity to carry a specific functional group that coordinates to Pd (referred to as simple arenes) is therefore highly desirable. However, the intrinsically lower reactivity of such substrates and the absence of a selectivity-determining DG pose significant challenges that can be solved only by the development of highly efficient catalysts. Consequently, the field of nondirected C-H activation, especially with respect to Pd-catalyzed methods, remained comparatively underdeveloped when we initiated our research program in 2017. At that time, state-of-the-art methods required the arene to be used in large excess, precluding its use in late-stage functionalization. Since organopalladium species are among the most versatile synthetic intermediates, we realized that developing a system, which can effectively and selectively activate C-H bonds in simple arenes with the arene as the limiting reagent, would be a powerful tool in synthetic organic chemistry. This account summarizes our groups' research toward the development and application of catalytic systems offering this desired reactivity and focuses explicitly on Pd-catalyzed nondirected C-H functionalization reactions of arenes, where the arene is employed as a limiting reagent. After an introduction that summarizes the state of Pd-catalyzed C-H activation of arenes before 2017 and the associated challenges, experimental and mechanistic details about the development of the first arene-limited, nondirected C-H functionalization of simple arenes with palladium will be discussed. This reactivity was enabled by the identification and combination of two complementary ligands, an N-heterocycle and an amino acid-derived ligand. Afterward we will discuss the expansion of this dual-ligand approach to further arene-limited transformations. Finally, we describe two methodologies that originated from the observations we made during our studies, namely, the late-stage deuteration of simple arenes and a highly selective olefination method that uses noncovalent interactions to induce meta selectivity.

Dual-ligand lanthanide metal-organic framework probe for ratiometric fluorescence detection of mercury ions in wastewater.

Byserving dipyridylic acid (DPA) and 2,5-dihydroxyterephthalic acid (DHTA) as the biligands, a novel lanthanide (Eu3+) metal-organic framework (MOF) namely Eu-DHTA/DPA was prepared for specific Hg2+ fluorescence determination. The dual-ligand approach can endows the resultingluminescent MOF with dual emission of ratiometric fluorescence and uniform size. Eu3+ produces intense red fluorescence when activated by the ligand DPA, while the other ligand DHTA produces yellow fluorescence. Under 273nm excitation, thepresence of Hg2+ in the monitoring environment causes an increase in the intensity of the DHTA fluorescence peak at 559nm and a decrease in the intensity of the Eu3+ fluorescence peak at 616nm. Hg2+ effectively quenches the fluorescence emission of the central metal Eu3+ in Eu-DHTA/DPA at 616nm through a dynamic quenching effect. This recognition process occurs due to the coordination of Hg2+ with ligands such as benzene rings, carboxyl groups, and pyridine N in three-dimensional space. Hg2+ was detected by measuring the ratio between two fluorescence peaks (I559 nm/I616 nm) within the range 2-20μM, achieving a remarkably low detection limit of 40nM. The established ratiometric fluorescence method hasbeen successfully applied to the determination of Hg2+ in industrial wastewater ofcomplex composition. The methodplays a crucial role in the rapid and sensitive monitoring of Hg2+ in real environmental samples. The recoveries ranged from 92.82% to 112.67% (n = 3) with relative standard deviations (RSD) below 4.8%. This study offers a convenient and effective method for constructing probes for Hg2+ monitoring, with practical applications in environmental monitoring.

Dual ligand approach increases functional group tolerance in the Pd-catalysed C-H arylation of N-heterocyclic pharmaceuticals.

The excellent functional group tolerance of the Suzuki-Miyaura cross-coupling reactions has been decisive for their success in the pharmaceutical industry. Highly diversified (hetero)aromatic scaffolds can be effectively coupled in the final step(s) of a convergent synthetic route. In contrast, electrophilic Pd catalysts for non-directed C-H activation are particularly sensitive to inhibition by coordinating groups in pharmaceutical precursors. While C-H arylation enables the direct conversion of (hetero)aromatics without preinstalled functional or directing groups, its functional group tolerance should be increased to be viable in late-stage cross-couplings. In this work, we report on a dual ligand approach that combines a strongly coordinating phosphine ligand with a chelating 2-hydroxypyridine for the highly robust C-H coupling of bicyclic N-heteroaromatics with aryl bromide scaffolds. The catalyst speciation was studied via in situ XAS measurements, confirming the coordination of both ligands under the reaction conditions. The C-H activation catalyst was shown to be tolerant to a wide range of pharmaceutically relevant scaffolds, including examples of late-stage functionalization of known drug molecules.

Constructing MOFs-derived Co3O4 microsphere with atomic p-n homojunction as an efficient photothermal catalyst for boosting ethyl acetate oxidation under light irradiation

A synthetic strategy for Co-MOF-74-derived Co3O4-based materials (polyhedral prism, hexagonal-prism spindle and prism-assembly 3D microspheres with different surface dense degrees) with atomic p-n homojunctions were proposed by introducing a dual-ligand (2,5-dihydroxyterephthalic acid and 2-methylimidazole) approach in the hydrothermal process. Among these Co3O4-based catalysts, the Co3O4-M-3 catalyst with 3D prism-assembly microsphere exhibited the greatest photothermal catalytic activity for ethyl acetate oxidation (around 92%) under the visible-IR light intensity of 480 mW/cm2 (λ > 420nm). The smart modulation of dual-ligand approach could effectively improve the oxygen storage capacity, abundant oxygen vacancies and outstanding reductive ability over the Co3O4-M-3 catalyst. In addition, Mott-Schottky plot characterization verified the formation of p-n homojunction over the Co3O4-M-3, and its suitable energy band level and Z-scheme charge transfer pathway effectively improved visible-light absorption capacity, accelerated charge pairs transportation and restrained photogenerated electron-hole recombination. Finally, in situ DRIFTS results demonstrated that the adsorbed oxygen and lattice oxygen would participate in the photothermal catalytic reaction. Ethanol and acetic acid were considered as a main reaction pathway, whereas methyl ethyl ketone as no-critical intermediate was generated in the strict condition with exclusive active lattice oxygen of catalyst and light irradiation.

Dual Ligand Enabled Nondirected C-H Chalcogenation of Arenes and Heteroarenes.

Chalcogenide motifs are present as principal moieties in a vast array of natural products and complex molecules. Till date, the construction of these chalcogen motifs has been restricted to either the use of directing groups or the employment of a large excess of electronically activated arenes, typically employed as a cosolvent. Despite being highly effective, these methods have their own limitations in the step economy and the deployment of an excess amount of arenes. Herein, we report the evolution of a catalytic system employing arene-limited, nondirected thioarylation of arenes and heteroarenes using a complimentary dual-ligand approach. The reaction is controlled by a combination of steric and electronic factors, and the utilization of a suitable ligand enables the generation of products on a complimentary spectrum to that generated by classical methods. The combination of ligands remains imperative in the reaction protocol with theoretical calculations pointing towards a monoprotected amino acid ligand being crucial in the concerted metalation deprotonation (CMD) mechanism by a characteristic [5,6]-palladacyclic transition state, while the pyridine moiety assists in the active catalyst species formation and product release. Combined experimental and computational mechanistic investigations point toward the C-H activation step being both regio- and rate-determining. Interestingly, oxidative addition of the diphenyl disulfide substrate is found to be unlikely, and an alternative transmetalation-like mechanism involving the Pd-Ag heterometallic complex is proposed to be operative.

Efficient and Highly Selective CO2 Capture, Separation, and Chemical Conversion under Ambient Conditions by a Polar-Group-Appended Copper(II) Metal–Organic Framework

A polar sulfone-appended copper(II) metal-organic framework (MOF; 1) has been synthesized from the dual-ligand approach comprised of tetrakis(4-pyridyloxymethylene)methane and dibenzothiophene-5,5'-dioxide-3,7-dicarboxylic acid under solvothermal conditions. This has been studied by different techniques that included single-crystal X-ray diffractometry, based on which the presence of Lewis acidic open-metal sites as well as polar sulfone groups aligned on the pore walls is identified. MOF 1 displays a high uptake of CO2 over N2 and CH4 with an excellent selectivity (S = 883) for CO2/N2 (15:85) at 298 K under flue gas combustion conditions. Additionally, the presence of Lewis acidic metal centers facilitates an efficient size-selective catalytic performance at ambient conditions for the conversion of CO2 into industrially valuable cyclic carbonates. The experimental investigations for this functional solvent-free heterogeneous catalyst are also found to be in good correlation with the computational studies provided by configurational bias Monte Carlo simulation for both CO2 capture and its conversion.

Dual-ligand approach for the solvent-free synthesis of indium-based coordination polymers

Three indium-based coordination polymers, formulated as In2(glu)3(2,2′-bpy)2 (1), In(glu)(Hglu)(phen) (2), and In(glu)(Hglu)(4,4′-bpy) (3), were prepared under solvent-free conditions, where H2glu = glutaric acid, 2,2′-bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, and 4,4′-bpy = 4,4′-bipyridine. Structural analyses reveal that these compounds have ribbonlike, chainlike, and layered architectures, respectively. The fluorescent property of compound 2 was also investigated.

Two New Nonlinear Optical and Ferroelectric Zn(II) Compounds Based on Nicotinic Acid and Tetrazole Derivative Ligands

Two new zinc compounds, [Zn2(mtz)(nic)2(OH)]n·0.5nH2O (1) and [Zn(phtz)(nic)]2n (2) (Hmtz = 5-methyltetrazole, Hphtz = 5-phenyltetrazole, Hnic = nicotinic acid), have been synthesized by a dual-ligand approach under solvothermal conditions. The compounds were characterized by single-crystal X-ray diffraction, elemental analysis, and infrared spectroscopy, respectively. The X-ray diffraction analysis reveals that both compounds exhibit a noncentrosymmetric polar packing arrangement. Compound 1 is a 3D framework constructed from the zigzag chain subunits of [Zn(nic)]+ with a 4-connected “irl” topology. Compound 2 possesses a 2D 4-connected ‘“sql” topology constructed from the linear chain subunit of [Zn(nic)]+, which are linked together with phtz– ligands. Impressively, both of the two compounds display second-harmonic generation response and ferroelectric behaviors. Furthermore, the photoluminescence of the compounds was also investigated.

Dual-ligand approach to synthesize a new 3-D heterometallic framework consisting of dysprosium–carboxyl belt and inorganic copper–iodine chain

A novel three-dimensional (3-D) Dy(III)–Cu(I) heterometallic polymer, [Dy 2 (pca) 2 (npa) 2 (H 2 O) 3 ](Cu 2 I 2 ) ( 1 , pca = 2-pyrazinecarboxylic acid, npa = 1,8- naphthalenedicarboxylic acid), has been synthesized by hydrothermal reactions of Dy 2 O 3 , CuI, 2-pyrazinecarboxylic acid, 1,8-naphthalene anhydride in water in the presence of HClO 4 . Compound 1 has been characterized by elemental analysis, infrared spectroscopy, powder X-ray diffraction and single-crystal X-ray diffraction analysis, respectively. The thermal stability and luminescence property of compound 1 have also been studied. Single crystal X-ray diffraction analysis reveals that compound 1 contains two distinct units of 1-D Dy–carboxyl belt and Cu–I chain. The two types of 1-D units are further linked via pca ligands to give a heterometallic Dy–Cu framework. A novel three-dimensional (3-D) Dy–Cu heterometallic polymer 1 contains two distinct units of 1-D Dy–carboxyl belt and Cu–I chain. The two types of 1-D units are further linked via pca ligands to give a heterometallic Dy–Cu framework. The two different types of 1-D building units are rarely observed in the reported heterometallic framework. • Compound 1 is a 3-D Dy–Cu heterometallic framework. • Compound 1 contains two distinct units of 1-D Dy–carboxyl belt and Cu–I chain. • Compound 1 is synthesized by dual-ligand approach.

New Semiconducting Coordination Polymers from Zinc Sulfide Clusters and Chains

Two new semiconducting zinc coordination polymers, Zn(8)S(SPh)(14)(bpy) (1) and Zn(2)(SPh)(4)(bpy) (2), have been synthesized by a dual-ligand approach. Single-crystal structural analyses indicate that compound 1 has a helical-chain structure with P1 clusters bridging with bipyridyl (bpy) ligands and compound 2 possesses a layered structure with zinc sulfide chains cross-linked with bpy ligands. The diffuse-reflectance spectra reveal that the band gaps of the two compounds are 2.41 eV for 1 and 2.56 eV for 2.

Dual-ligand approach to the synthesis of new luminescent cadmium(II) coordination polymers with one- and two-dimensional homochiral structures

Two new homochiral cadmium(II) coordination polymers, Cd 2(bipy) 2(H 2O) 2 (cam) 2 ( 1) and Cd 2(phen) 2(cam) 2·eg ( 2), where bipy = 2,2′-bipyridine, phen = 1,10-phenanthroline, H 2cam = (1R, 3S)-(+)-camphoric acid, and eg = ethylene glycol, have been synthesized by a dual-ligand approach. Compound 1 possesses a chain-like architecture and compound 2 has a layered structure with a (4,4) grid topology. Both compounds crystallize in the space group C2 and exhibit intense photoluminescence upon photoexcitation at 280 and 300 nm, respectively.

Streptavidin Binding and Endothelial Cell Adhesion to Biotinylated Fibronectin

A dual ligand (DL) system that combines high affinity streptavidin-biotin binding with lower affinity fibronectin-integrin ligand binding was developed to augment endothelial cell adhesion to polymers. In this study, we examined the utility of biotinylated fibronectin (bFN) as an enhancement to the previously developed DL approach. The goal was to make the system more amenable to clinical studies by eliminating xenogenic bovine serum albumin (bBSA). Fibronectin (FN) biotinylation was achieved with Sulfo-NHS-LC-Biotin. The affinity of conjugated biotin for wild-type streptavidin (WT-SA) and a mutant strain streptavidin (RGD-SA) was measured using surface plasmon resonance (SPR) spectroscopy. Enzyme-Linked ImmunoSorbent Assay (ELISA) absorbance values confirmed the accessibility of the cell binding domain on mildly biotinylated bFN when compared to unmodified native protein. SPR binding analysis confirmed similar binding behavior to bFN with WT-SA and RGD-SA. Kinetic analysis, however, showed no increase in affinity due to increased biotins per FN, an indication of the absence of positive cooperativity in the system. We verified the essential utility of bFN in affinity binding by SPR and confirmed the potential for integrin-FN linkages by ELISA. Finally, Vinculin immunostaining was used to determine focal adhesion formation using bFN in the DL system. Significantly greater focal adhesion density was achieved with the bFN in the DL system than with FN alone.

A dual-ligand approach for enhancing targeting selectivity of therapeutic nanocarriers

Conjugation of ligands to nano-scale drug carriers targeting over-expressed cell surface receptors is a promising approach for delivery of therapeutic agents to tumor cells. However, most commonly utilized ligands are directed at receptors expressed not only on target cells but also on other cells in the body, leading to unintended uptake in these off-target cells. In this study, a novel, dual-ligand approach is reported, which targets tumor cells while sparing off-target cells by exploiting the fact that tumor cells typically over-express multiple types of surface receptors. This approach was tested in the human KB cell line, which over-expresses both folate receptor (FR) and the epidermal growth factor receptor (EGFR). Liposomal nanocarriers loaded with doxorubicin and bearing controlled numbers of both folic acid and a monoclonal antibody against the EGFR were designed. Cytotoxicity was used to determine targeting selectivity of the designed carriers in vitro by utilizing KB cells expressing both FR and EGFR and off-target control cells in which one or both receptors were blocked. The data demonstrates that nanocarriers can be designed to achieve toxicity only when all targeted receptors are available, providing an approach to improve selectivity over current single-ligand approaches.

Investigations of carbon-supported CoPd 3 catalysts as oxygen cathodes in PEM fuel cells

The oxygen reduction reaction (ORR) has been studied on platinum free, palladium-based electrocatalysts in acid media. Polycrystalline electrodes were prepared by electrodeposition on a polycrystalline gold substrate using a dual ligand approach at room temperature. The surface morphology and approximate surface composition of the electrodeposits were confirmed by scanning electron microscopy and energy dispersive X-ray spectroscopy. The electrodeposits showed performance for the ORR similar to polycrystalline platinum under identical conditions, despite an observed 50 mV cathodic shift in the peak potential. Carbon supported CoPd 3 electrocatalysts also showed high catalytic activity for oxygen reduction in a 5 cm 2 fuel cell.

SPECT quantification of benzodiazepine receptor concentration and ligand affinity using a dual-ligand approach

SPECT quantification of benzodiazepine receptor concentration and ligand affinity using a dual-ligand approach