Hydrophilic Ligands Research Articles

Versatile Dehydration-Assisted Functionalization of Quantum Dots and Rods.

Functionalization of quantum dots (QDs) and quantum rods (QRs) with ligands is essential for their further practical application across various domains. Dehydration-assisted functionalization (DAF) is a versatile method applicable to a wide range of hydrophilic ligands with an affinity to the surface of QDs and QRs. This approach facilitates rapid one-pot ligand exchange and dense modification by efficiently transferring these ligands onto the surface of QDs and QRs. This study demonstrates the efficacy of DAF in preparing chiral QRs, engineering the surface charge of QDs, utilizing QR aggregates, and conjugating dense DNA onto cadmium-free InP/ZnS QDs. DAF therefore offers a versatile solution for hydrophilic ligand functionalization of QDs and QRs applicable to diverse applications.

Synthesis and study of bistriazolyl-pyrazines as new ligands for An/Ln separations

Herein, we present new hydrophilic tridentate ligands, bistriazolyl pyrazines. Their design was inspired by structurally similar and promising bis-triazolyl-pyridines (PyTri) ligands as well as theoretically derived criteria for the design of tridentate ligands for An/Ln separations suggested by theoretical studies. These ligands have been synthesised, characterised and tested as possible extractants for An/Ln nuclear separations. In addition, UV and fluorescence studies, pKa determination, and crystallographic and theoretical studies have been performed to explain their observed behaviour. Although the results of the solvent extraction studies have shown that these ligands do not possess sufficient selectivity for the extraction of Am vs Eu in i-SANEX conditions, this study presents a valuable test of the criteria for the design of tridentate heterocyclic N-donor ligands for advanced nuclear separation as postulated by theoretical studies a decade ago. Our experimental observations and theoretical studies have found that these criteria might not be the best guidance for designing novel hydrophilic ligands for An/Ln separations in i-SANEX conditions.

Amino Acid Decorated Phenanthroline Diimide as Sustainable Hydrophilic Am(III) Masking Agent with High Acid Resistance.

Hydrophilic actinide masking agents are believed to be efficient alternatives to circumvent the extensive hazardous organic solvents/diluents typically employed in the liquid-liquid extraction for nuclear waste management. However, the practical application of hydrophilic ligands faces significant challenges in both synthetic/purification procedures and, more importantly, the acid resistance of the ligands themselves. Herein, we have demonstrated the combination of phenanthroline diimide framework with a biomotif of histidine flanking parts could achieve efficient separation of trivalent lanthanides/actinides (also actinides/actinides) under high acidity of over 1 M HNO3. This approach leverages the soft-hard coordination properties of N, O-hybrid ligands, as well as the energetically favored imides for metal coordination and the multiple protonation of histidine. These factors collectively contribute to the synthesis of an easily accessible, highly water-soluble, superior selective, and acid-resistant Am(III) masking agent. Thus, we have shown in this paper, by proper combination of synthetic N, O-hybrid ligand with amino acid, trivalent lanthanide and actinide separation could be efficiently fulfilled in a more sustainable manner.

Ubiquitous Role of Phosphine-Based Water-Soluble Ligand in Promoting Catalytic Reactions in Water.

Catalysis has been at the forefront of the developments that has revolutionised synthesis and provided the impetus in the discovery of platform technologies for efficient C-C or C-X bond formation. Current environmental situation however, demands a change in strategy with catalysis being promoted more in solvents that are benign (Water) and for that the development of hydrophilic ligands (especially phosphines) is a necessity which could promote catalytic reactions in water, allow recyclability of the catalytic solutions and make it possible to isolate products using column-free techniques that involve lesser usage of hazardous organic solvents. In this review, we therefore critically analyse such catalytic processes providing examples that do follow the above-mentioned parameter.

Amine-Terminated Phenanthroline Diimides as Aqueous Masking Agents for Am(III)/Eu(III) Separation: An Alternative Ligand Design Strategy for Water-Soluble Lanthanide/Actinide Chelating Ligands.

Selective actinide coordination (from lanthanides) is critical for both nuclear waste management and sustainable development of nuclear power. Hydrophilic ligands used as masking agents to withhold actinides in the aqueous phase are currently highly pursued, while synthetic accessibility, water solubility, acid resistance, and extraction capability are the remaining problems. Most reported hydrophilic ligands are only effective at low acidity. We recently proved that the phenanthroline diimide skeleton was an efficient building block for the construction of highly efficient acid-resistant hydrophilic lanthanide/actinide separation agents, while the limited water solubility hindered the loading capability of the ligand. Herein, amine was introduced as the terminal solubilizing group onto the phenanthroline diimide backbone, which after protonation in acid showed high water solubility. The positively charged terminal amines enhanced the ligand water solubility to a large extent, which, on the other side, was believed to be detrimental for the coordination and complexation of the metal cations. We showed that by delicately adjusting the alkyl chain spacing, this intuitive disadvantage could be relieved and superior extraction performances could be achieved. This work holds significance for both hydrophilic lanthanide/actinide separation ligand design and, concurrently, offers insights into the development of water-soluble lanthanide/actinide complexes for biomedical and bioimaging applications.

Self-assembly of nanocrystal checkerboard patterns via non-specific interactions

Checkerboard lattices—where the resulting structure is open, porous, and highly symmetric—are difficult to create by self-assembly. Synthetic systems that adopt such structures typically rely on shape complementarity and site-specific chemical interactions that are only available to biomolecular systems (e.g., protein, DNA). Here we show the assembly of checkerboard lattices from colloidal nanocrystals that harness the effects of multiple, coupled physical forces at disparate length scales (interfacial, interparticle, and intermolecular) and that do not rely on chemical binding. Colloidal Ag nanocubes were bi-functionalized with mixtures of hydrophilic and hydrophobic surface ligands and subsequently assembled at an air–water interface. Using feedback between molecular dynamics simulations and interfacial assembly experiments, we achieve a periodic checkerboard mesostructure that represents a tiny fraction of the phase space associated with the polymer-grafted nanocrystals used in these experiments. In a broader context, this work expands our knowledge of non-specific nanocrystal interactions and presents a computation-guided strategy for designing self-assembling materials.

Abstract 4167: Selective imaging of cancer-associated fibroblasts in the breast cancer microenvironment with near-infrared fluorescent probes

Abstract Tumors consist of a complex mixture of resident and infiltrating cells that can support their survival and evasion of treatment. Selective detection of genetically stable cells in the tumor microenvironment (TME) offers insight into tumor biology beyond the malignant cells, which are the focus of most molecular imaging approaches to cancer detection. Motivated by the goal of non-invasively understanding the primary breast TME, we have developed fluorescent molecular probes that target cancer-associated fibroblasts (CAFs), a major component of the stromal compartment of many tumors, and emit light in the near-infrared (NIR) spectral window, providing access to deeper tissues than visible probes. We synthesized and characterized a series of CAF-targeted antibody- and small molecule-based fluorescent imaging agents utilizing a highly hydrophilic NIR dye and ligands that target Fibroblast Activation Protein (FAP). FAP is a key cell-surface marker of breast cancer CAFs with an S1 phenotype, which are modulators of immunosuppression, metastatic spread, and are associated with worse outcomes, especially in HER2+ and triple-negative breast cancer. Modifications to the chemical structure of the linker and targeting ligands allowed us to alter the specificity and brightness of the CAF-probes in cellulo. Imaging of a co-implanted tumor model of SKBR3 human breast cancer cells and FAP expressing fibroblasts after administering our lead small-molecule CAF imaging agent revealed selective tumor targeting of CAF-rich tumors compared to cancer cell predominant tumors with favorable pharmacokinetics and tumor-to-background ratio (TBR) greater than 2. Similar imaging studies with MMTV-PyMT transgenic mice, an established murine model of breast cancer, showed analogous enhanced uptake in mammary tumors (TBR > 2) and clearance over 24 hours. NIR fluorescence also correlated with CAFs isolated from PyMT tumor tissue via flow cytometry, consistent with our hypothesis that this agent can specifically detect endogenous CAFs. This study identified a novel, bright, and water-soluble FAP-specific NIR agent for in vivo imaging, setting the stage for simultaneous optical imaging of malignant cells and activated fibroblasts in the TME to elucidate cancer-host interactions. Citation Format: Megan S. Michie, Junwei Du, Jiayu (Jennifer) Ye, Kathleen Duncan, Mikhail Y. Berezin, Samuel Achilefu. Selective imaging of cancer-associated fibroblasts in the breast cancer microenvironment with near-infrared fluorescent probes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4167.

QbD-driven development and characterization of superparamagnetic iron oxide nanoparticles (SPIONS) of a bone-targeting peptide for early detection of osteoporosis

Osteoporosis is a metabolic disorder that leads to deterioration of bones. The major challenges confronting osteoporosis therapy include early-stage detection and regular disease monitoring. The present studies employed D-aspartic acid octapeptide (-D-Asp-)8 as bone-targeting peptide for evaluating osteoporosis manifestation, and superparamagnetic iron oxide nanoparticles (SPIONs) as nanocarriers for MRI-aided diagnosis. Thermal decomposition technique was employed to synthesize SPIONs, followed by surface-functionalization with hydrophilic ligands. Failure mode effect analysis and factor screening studies were performed to identify concentrations of SPIONs and ligand as critical material attributes, and systematic optimization was subsequently conducted employing face-centered cubic design. The optimum formulation was delineated using desirability function, and design space demarcated with 178.70 nm as hydrodynamic particle size, –24.40 mV as zeta potential, and 99.89 % as hydrophilic iron content as critical quality attributes. XRD patterns ratified lattice structure and SQUID studies corroborated superparamagnetic properties of hydrophilic SPIONs. Bioconjugation of (-D-Asp-)8 with SPIONs (1:1) was confirmed using UV spectroscopy, FTIR and NMR studies. Cell line studies indicated successful targeting of SPIONs to MG-63 human osteoblasts, ratifying enormous bone-targeting and safety potential of peptide-tethered SPIONs as MRI probes. In vivo MRI imaging studies in rats showcased promising contrast ability and safety of peptide-conjugated SPIONs.

Oligomeric Zinc Thiolates Tethering Multidentate Carboxylates for Nondestructive Aqueous Phase Transfer of Quantum Dots.

Functionalization of quantum dots (QDs) via ligand exchange is prone to debase their photoluminescence quantum yield (PL QY) owing to the unavoidable surface damage by excess reactants, and even worse in aqueous medium. Herein, the oligomeric zinc thiolate as the multidentate hydrophilic ligand featuring facile synthetic protocol is proposed. A simple reaction between ZnCl2 and 3-mercaptopropionic acid produces oligomeric ligands containing 3-6 zinc thiolate units, where the terminal moieties provide multidentate anchoring to the surface as well as hydrophilicity. 2D proton nuclear Overhauser effect spectroscopy (2D 1H NOESY) and X-ray photoelectron spectroscopy (XPS) reveal that the oligomeric zinc thiolate ligands adsorb on the surface via multidentate metal carboxylate bindings without destruction of molecular structure, regardless of partial dissociation of thiolate branches in aqueous phase. Enhanced binding affinity granted by the multidentate nature allows for the effective exchange of original surface ligands without considerable surface deterioration. The zinc thiolate-capped Cd-free aqueous QDs exhibit a high photoluminescence quantum yield of ≈90% and extended stability against long-term storage and photochemical stress.

Cross Coupling of Aryl Iodides with Terminal Alkynes, Catalyzed by a PdCl2–Hydrophilic Arylphosphine Ligand System

Cross Coupling of Aryl Iodides with Terminal Alkynes, Catalyzed by a PdCl2–Hydrophilic Arylphosphine Ligand System

Hydrophilic Ligand Exchange Induces Improved Upconversion Nanoparticle Incorporation in Dye-Sensitized Solar Cells with Efficiency Exceeding 8% in a Low-Temperature Fabrication Process

Hydrophilic Ligand Exchange Induces Improved Upconversion Nanoparticle Incorporation in Dye-Sensitized Solar Cells with Efficiency Exceeding 8% in a Low-Temperature Fabrication Process

Design, synthesis and catalytic application of water-soluble 1,1′-bis(diphenylphosphino)ferrocene ligands

Hydrophilic phosphine ligands have proven indispensable for the translation of metal-catalyzed reactions into aqueous solvent systems and thus for the implementation of safe as well as sustainable chemical processes. Despite numerous reports on water-soluble variants of several renowned ligands, the dppf ligand family has been neglected thus far. Herein, we disclose synthetic strategies towards the first hydrophilic dppf derivatives overcoming issues typically encountered due to their intrinsic oxidizability. Core-sulfonated dppf ligands (meso‑2,2′- or 2,5-disubstituted) were prepared by a directed metalation strategy starting from diisopropyl ferrocene-1,1′-disulfonate. Alternatively, hydrophilic sulfonate or ammonium groups were introduced at the phenyl substituents of dppf. The novel ligands were spectroscopically characterized and showed their catalytic potential in the Pd-catalyzed Tsuji-Trost allylation of amines in water furnishing pharmaceutically relevant N-allylated products (e.g., naftifine, cinnarizine) through a scalable, safe and environmentally benign process.

Selective Separation of Americium(III), Curium(III), and Lanthanide(III) by Aqueous and Organic Competitive Extraction.

Adding hydrophilic ligands into aqueous solutions for the selective binding of actinides(III) is acknowledged as an advanced strategy in Ln(III)/An(III) separation. In view of the recycling and radioactive waste disposal of the minor actinide, there remains an urgent need to design and develop the appropriate ligand for selective separation of An(III) from Ln(III). Herein, four novel hydrophilic ligands with hard-soft hybrid donors, derived from the pyridine and phenanthroline skeletons, were designed and synthesized as masking agents for selective complexation of An(III) in the aqueous phase. The known N,N,N',N'-tetraoctyl diglycolamide (TODGA) was used as lipophilic extractant in the organic phase for extraction of Ln(III), and a new strategy for the competitive extraction of An(III) and Ln(III) was developed based on TODGA and the above hydrophilic ligands. The optimal hydrophilic ligand of N,N'-bis(2-hydroxyethyl)-2,9-dicarboxamide-1,10-phenanthroline (2OH-DAPhen) displayed exceptional selectivity toward Am(III) over Ln(III), with the concentrations of HNO3 ranging from 0.05 to 3.0 M. The maximum separation factors were up to 1365 for Eu/Am, 417.66 for Eu/Cm, and 42.38 for La/Am. The coordination mode and bonding property of 2OH-DAPhen with Ln(III) were investigated by 1H NMR titration, UV-vis spectrophotometric titration, luminescence titration, FT-IR, ESI-HRMS analysis, and DFT calculations. The results revealed that the predominant species formed in the aqueous phase was a 1:1 ligand/metal complex. DFT calculations also confirmed that the affinity of 2OH-DAPhen for Am(III) was better than that for Eu(III). The present work using a competitive extraction strategy developed a feasible alternative method for the selective separation of trivalent actinides from lanthanides.

Pickering high internal phase emulsions stabilized by metal-organic framework nanoribbons

Pickering high internal phase emulsions (HIPEs) stabilized by colloidal particles are of great practical significance in the formulation of food, pharmaceutical, cosmetic, paint products and the chemical oil flooding. Herein, we report that a manganese-based metal–organic framework (MOF) (Mn3(BTC)2 (BTC = 1,3,5-benzenetricarboxylate)) nanoribbons synthesized by a simple solution method can stabilize water-in-oil (W/O) high-viscosity Pickering HIPEs with crude oil as oil phase for more than one month at 43 °C. The Mn3(BTC)2 nanoribbons assemble at the oil/water interface of HIPE, owing to its advantageous structural features with the size of several micrometers, thickness of about 100 nm and amphiphilicity originated from the hydrophilic metal ions and hydrophobic organic ligands. The phase behavior and properties of the as-prepared HIPEs strongly depend on the MOF concentration (CMOF) and internal phase volume fraction of water (Fw) of emulsion. The MOF dispersions and crude oil are miscible into stable W/O HIPEs at Fw = 75 % when the CMOF ranges from 50 ppm to 5000 ppm. More interestingly, the viscosity of W/O emulsions greatly increases as the Fw varying from 50 % to 80 % and a viscosity of 4.5 Pa·s is obtained at CMOF = 2000 ppm and Fw = 80 %, which is nearly 400 times higher than that of crude oil. Moreover, the pressure generated by HIPEs flowing in core is about 40 times more than that of water injection and can remain the highest stable value substantially. These results show that the MOF dispersions are favorable to form stable W/O emulsions with high internal phase volume fraction, which has a great potential in improving oil displacement efficiency of chemical flooding.

Chelating ligand-bridged IO-Gd nanoparticles with enhanced contrast performance for dual-mode MRI

Magnetic resonance imaging (MRI) is a non-invasive medical imaging technique that has been widely applied in the clinical diagnosis of diseases across various fields. Currently, there is a dearth of high-performance dual-mode contrast agents that provide precise diagnostic information for complex diseases. In this study, iron oxide-gadolinium nanoparticles (IO-Gd NPs) bridged by hydrophilic ligand ethylenediamine tetramethylenephosphonic acid (EDTMP) are designed inspired by Solomon-Bloembergen–Morgan (SBM) theory, where T1 and T2 relaxivity increase with a reduction in Gd content. In particular, the NPs with minimum Gd content exhibit excellent dual-mode contrast performance (r1 = 94.42 mM−1 s−1, r2 = 343.62 mM−1 s−1). The underlying mechanism is that the bridged EDTMP coordinate limits Gd tumbling and forces Gd3+ to expose itself to the surface of the NPs. This provides more opportunities for water molecules to coordinate with Gd3+ and significantly enhances proton relaxivity. Moreover, the hydrophilicity of the ligand enhances the water dispersion stability of the NPs and increases the exchange rate of water protons near the NPs, further enhancing the dual-mode contrast effect. Finally, the biocompatibility and in vitro/vivo imaging performances of the IO@EDTMP-Gd NPs are systematically evaluated, and the results demonstrate their potential as dual-mode contrast agents. This study provides a new strategy for developing dual-mode MRI contrast agents that can further improve the accuracy of MRI in the diagnosis of complex diseases.

Coupling of augmented PAN membranes by surface immobilization of pincer ligands with an activated sludge to treat a real wastewater

In the present study, industrial estate wastewater was subjected to treat with a conventional activated sludge (CAS) bioreactor and then purified using a highly efficient surface-modified PAN ultrafiltration membrane. Response surface methodology (RSM) has been employed to analytically design, carry out, and optimize biological experiments using two independent operating variables, MLSS (6,000–14,000 mg/L) and HRT (5–15 h). This resulted in an effluent that was optimally stabilized before ultrafiltration due to the consequent responses of COD removal (90 %), effluent turbidity (1 NTU), and SVI (82 mL/g). To rationally tailor the antifouling PAN UF membranes for this intended purpose, novel hydrophilic pincer ligands were formed by covalent binding of cyanuric chloride (CC) activated membrane surfaces with various loadings of (1.0, 3.0, and 5.0 wt%) 5-amino-1, 3, 4-thiadiazol-2-thiol (AMT). In terms of hydrophilicity, surface roughness, antifouling characteristics, and permeate flux, the optimum membrane surface-modified with 3.0 wt% pincer ligand loading outperformed the others, leading to a low WCA of 42.75°, smoother surface (Sa = 14.77 nm), FRR of 97.1 %, and PWF of 56.07 kg/m2.h. The operated CAS followed by surface-modified Pincer/PAN membranes is therefore an appealing proposal for generating high-quality effluent from industrial wastewaters.

Chitobiose exhibited a lipid-lowering effect in ob/ob−/− mice via butyric acid enrolled liver–gut crosstalk

Chitobiose (COS2) efficiently lowers lipids in vivo and facilitates butyric acid enrichment during human fecal fermentation. However, whether COS2 can interact with butyric acid to generate a hypolipidemic effect remains unclear. This study examined the hypolipidemic mechanism of COS2 involving butyric acid, which could alleviate non-alcoholic fatty liver disease (NAFLD). The results revealed that COS2 administration modulated the β-oxidation pathway in the liver and restructured the short chain fatty acids in the fecal of ob/ob−/− mice. Moreover, the hypolipidemic effect of COS2 and its specific accumulated metabolite butyric acid was verified in sodium oleate-induced HepG2 cells. Butyric acid was more effective to reverse lipid accumulation and up-regulate β-oxidation pathway at lower concentrations. Furthermore, structural analysis suggested that butyric acid formed hydrogen bonds with key residues in hydrophilic ligand binding domains (LBDs) of PPARα and activated the transcriptional activity of the receptor. Therefore, the potential mechanism behind the lipid-lowering effect of COS2 in vivo involved restoring hepatic lipid disorders via butyric acid accumulation and liver–gut axis signaling.Graphical

Ligand Sulfur Oxidation State Progressively Alters Galectin-3-Ligand Complex Conformations To Induce Affinity-Influencing Hydrogen Bonds.

Galectins play biological roles in immune regulation and tumor progression. Ligands with high affinity for the shallow, hydrophilic galectin-3 ligand binding site rely primarily on a galactose core with appended aryltriazole moieties, making hydrophobic interactions and π-stacking. We designed and synthesized phenyl sulfone, sulfoxide, and sulfide-triazolyl thiogalactoside derivatives to create affinity-enhancing hydrogen bonds, hydrophobic and π-interactions. Crystal structures and thermodynamic analyses revealed that the sulfoxide and sulfone ligands form hydrogen bonds while retaining π-interactions, resulting in improved affinities and unique binding poses. The sulfoxide, bearing one hydrogen bond acceptor, leads to an affinity decrease compared to the sulfide, whereas the corresponding sulfone forms three hydrogen bonds, two directly with Asn and Arg side chains and one water-mediated to an Asp side chain, respectively, which alters the complex structure and increases affinity. These findings highlight that the sulfur oxidation state influences both the interaction thermodynamics and structure.

Hydroxyl-group functionalized phenanthroline diimides as efficient masking agents for Am(III)/Eu(III) separation under harsh conditions

The separation of Lns(III) from radioactive Ans(III) in high-level liquid waste remains a formidable hydrometallurgical challenge. Water-soluble ligands are believed to be new frontiers in the search of efficient Lns/Ans separation ligands to close the nuclear fuel cycles and dealing with current existing nuclear waste. Currently, the development of hydrophilic ligands far lags behind their lipophilic counterparts due to their complicated synthetic procedures, inferior extraction performances, and acid tolerances. In this paper, we have showed a series of hydroxyl-group functionalized phenanthroline diimides were efficient masking agents for Am(III)/Eu(III) separation under high acidity (˃ 1 M HNO3). Record high SFEu(III)/Am(III) of 162 and 264 were observed for Phen-2DIC2OH and Phen-2DIC4OH in 1.25 M HNO3 which represents the best Eu(III)/Am(III) separation performance at this acidity. UV–vis absorption, NMR and TRLFS titrations were conducted to elucidate the predominant of 1:1 ligand/metal species under extraction conditions. X-ray data of both the ligand and Eu(III) complex together with DFT calculations revealed the superior extraction performances and selectivities. The current reported hydrophilic ligands were easy to prepare and readily to scale-up, acid tolerant and highly efficient, together with their CHON-compatible nature make them promising candidates in the development of advanced separation processes.

Polyhedral Colloidal Clusters Assembled from Amphiphilic Nanoparticles in Deformable Droplets.

Polyhedral colloidal clusters assembled from functional inorganic nanoparticles have attracted great interest in both scientific research and applications. However, the spontaneous assembly of colloidal nanoparticles into polyhedral clusters with regular shape and tunable structures remains a grand challenges. Here, we successfully construct Mackay icosahedral and regular tetrahedral colloidal clusters assembled from gold nanoparticles grafted with a mixture of polystyrene (PS) and poly(2-vinylpyridine) (P2VP) homopolymers by precisely tuning the interfacial interaction between the nanoparticles and the oil/water interface. By increasing the proportion of hydrophilic P2VP ligands on the surface of gold nanoparticles, the Mackay icosahedral clusters can transform into regular tetrahedral clusters in order to maximize the surface area of the polyhedral assembly. Furthermore, we reveal the formation mechanism of these regular polyhedral colloidal clusters. The formation of polyhedral colloidal clusters is not only dependent on the entropy but also determined by the interfacial free energy. This finding demonstrates an effective approach to organize nanoparticles into polyhedral colloidal clusters with potential applications in various fields.