Bond Formation Research Articles

Supramolecular Polymerization of Pseudo[2]rotaxanes Formation of per‐Imidazole Pillar[5]arene‐based Host–Guest Complexations and Halogen Bonding Interactions

AbstractIn this study, we reported the construction of 3D supramolecular polymeric networks using per‐imidazole pillar[5]arene (DIMP5) as a host and 1,4‐diiodotetrafluorobenzene (L) as a halogen bond donor in chloroform. The supramolecular polymerization process was characterized by 1H NMR, 19F NMR spectroscopy, and X‐ray single crystal analysis. The C─I⋯N distance (2.78 Å) and C─I⋯N angle (177°) clearly indicated the formation of halogen bonds in the crystal structure. Meanwhile, by introducing adiponitrile (G) as the guest, a supramolecular polymerization of pseudo[2]rotaxanes was also prepared, which was driven by DIMP5‐based host–guest complexations and halogen bonding interactions.

Experimental characterization and dual-temperature molecular dynamics simulation on the intervention of tea saponin in starch chain dynamic behavior

In this work, the typical properties of starchy products were innovatively described as six types of chain dynamic behaviors. Dual-temperature molecular dynamic simulations, alongside multi-experimental methods, were employed to tandemly explore the intervention effect and mechanism of tea saponin (TS, 0 %–40 % w/w) on these behaviors. The findings reveal that the hydrophilic and hydrophobic ends of TS provide numerous sites for hydrogen bonding and steric hindrance, respectively, which hinder the formation of hydrogen bonds between starch chains. This interaction mode facilitated the chain unwinding (pasting temperature: 79.8 → 76.4 °C) and movement (viscosity: 267.67 → 38.92 Pa.s), and also retarded chain short/long-term reassociation (elastic modulus: 0.41 → 0.14 Pa/min; hardening rate: 2.72 → 0.07 gf/d) and rearrangement (hardness: 15.50 → 10.00 gf). Notably, a critical TS content was observed between 10 % and 20 % w/w, beyond which textural collapse (hardness: 15.50 → 10.00 gf) occurred. This research offers a new strategy and relevant theoretical backing for the property regulation of starch products.

Development of polyvinyl alcohol/carboxymethylcellulose-based bio-packaging film with citric acid crosslinking and clove essential oil encapsulated chitosan nanoparticle pickering emulsion

This study developed polyvinyl alcohol (PVA)/carboxymethylcellulose (CMC)-based films, using citric acid (CA) as a non-toxic crosslinking agent, to enhance the shelf life of water-soluble packaging films. Clove essential oil (CEO)-loaded chitosan nanoparticles (CSNPs) were prepared via Pickering emulsion and incorporated into PVA/CMC/CA composite films. The encapsulation of CEO was confirmed by FTIR and optical microscopy. Thermal properties were analyzed using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), revealing improved thermal stability and a decrease in glass transition temperature (Tg) upon crosslinking. The formation of ester bonds was confirmed by ATR-FTIR and 13CNMR. Water contact angle (WCA) measurements showed a decrease in hydrophilicity, enhancing the barrier properties of the films. SEM images demonstrated good dispersion of CSNP/CEO within the matrix, improving mechanical and barrier properties. The films exhibited a 30 % reduction in water vapor permeability and water solubility. Controlled release studies indicated that the composite films sustained CEO release, extending the shelf life of cherry tomatoes. Thus, these PVA/CMC/CA-CSNP/CEO composite films offer strong potential for food preservation applications.

Design, synthesis, and evaluation of some benzimidazole analogs as AMPK agonists

AMP-activated protein kinase is a crucial regulator of cellular metabolism with potential therapeutic implications in various diseases. In this study, the benzimidazole scaffold was chosen for investigation with EX-229 as the lead compound. Modifications were made to the terminal carboxyl group, and the methylindole moiety was replaced with phenylpyrrolidinone to synthesize and assess the AMP-activated protein kinase-activating properties of 13 benzimidazole derivatives. In vitro studies have shown that most of the synthesized compounds have significant excitatory effects on AMP-activated protein kinase. Particularly, A11 demonstrated the most potent activity with an EC50 value of 39 nM. Combining activity data and molecular docking analysis revealed the necessity of end-molecule hydrogen bond donors for LYS29, and the importance of an appropriate torsion angle at the pyrrolidinone position to facilitate the formation of a crucial hydrogen bond with LYS31. These discoveries offer preliminary insights into the interaction of small-molecule drugs with the AMP-activated protein kinase protein and establish a foundation for the future development of AMP-activated protein kinase activators guided by structure–activity relationships.

Design, Synthesis, Biological and Computational Analysis of Isatin-based bis-Thiourea Analogues as Anti-diabetic and Anti-nematode Agents

A new series of isatin derivatives were synthesized, characterized by 1HNMR, 13CNMR and HREI-MS, and screened for α-glucosidase and alpha amylase inhibition. All the analogues were found to be dual inhibitors and showed good inhibitory potentials with IC50 values ranging from 5.28 ± 0.10 to 38.66 ± 0.30 µM (against alpha-amylase), and 5.45 ± 0.10 to 39.25 ± 0.50 µM (against alpha-glucosidase), as compared to the standard drug acarbose (IC50 = 11.12 ± 0.15 and 11.29 ± 0.07 µM, respectively). The most potent inhibitor among the series was analogue 24 (IC50 = 5.28 ± 0.10 for alpha-amylase and IC50 = 5.46 ± 0.10 µM for alpha-glucosidase), which has a nitro group attached at the meta-position of the phenyl ring A and the para position of phenyl ring B. Structure-activity relationship has been established mainly based on the position, nature and number of the substituent(s) attached to the phenyl ring. To investigate the binding interaction of the potent analog with the active site of an enzyme, molecular docking studies were carried out. To study the drug-likeness properties, the ADME study was also carried out. The most active compounds engage most of the amino acids composing the active site and display maximum interactions. These interactions majorly include formation of strong hydrogen bonds, which might be due to the presence of highly electronegative heteroatoms on aromatic rings. All the analogues were also tested for in vivo anti-nematodal activity against C. elegans to assess their cytotoxicity in comparison to the reference Levamisole. The cytotoxicity profile demonstrated that analogues 2, 7, 20 and 22 displayed minimum cytotoxicity at every concentration.

Preparation of high temperature proton exchange membrane through covalent organic framework doped polyvinylidene fluoride nanofibers

Covalent organic framework (COF) exhibits the great potential to promote proton conduction under low relative humidity for proton exchange membranes (PEMs). In this research, quick and stable proton conduction has been achieved since the prepared COF and polyvinylidene fluoride (PVDF) nanofibers are believed to constitute successive proton conduction channels. The PVDF-COF nanofibers membrane is prepared through the in-situ growth of COF along PVDF nanofibers. The fine compatibility can drive the stable combination of COF with the PVDF nanofibers in PVDF-COF nanofibers. Most importantly, the fibrous PVDF nanofibers accelerate proton conduction through confining the proton conduction pathways. Additionally, ionic liquids of 1-butyl-3-methylimidazolium chloride (BmimCl) and 1-butyl-3-methylimidazole hexafluorophosphate (BmimPF6) as proton conduction carriers have been introduced to accelerate proton conduction in the prepared PVDF-COF/BmimCl/PA and PVDF-COF/BmimPF6/PA membranes. Phosphoric acid (PA) molecules are combined by COF and ionic liquid cations with the formation of intermolecular hydrogen bonds. As a result, the PVDF-COF/BmimPF6/PA membrane exhibits the proton conductivity of (1.81 ± 0.07) × 10−1 S/cm at 160 °C. The long-term proton conductivity stability is determined, deriving from the proton conductivities of 1.77×10−2 S/cm at 80 °C and 1.42×10−2 S/cm at 110 °C in the 400 h non-stop measurement. The single fuel cell equipped with the PVDF-COF/BmimPF6/PA membrane represents the open circuit voltage of 0.927 V and the peak power density of 178.8 mW/cm2 at 100 °C, 0.907 V and 326.5 mW/cm2 at 120 °C.

Towards highly efficient and stable perovskite solar cells: suppressing ion migration by inorganic boric acid stabilizer

The poor stability of organic-inorganic perovskite solar cells is commonly ascribed to elevated ion migration, stemming from the low electronegativity of iodine. To address this issue, boric acid was chosen as a stabilizer for perovskite thin films. As a Lewis acid, the boric acid has a sp2 hybridized boron atom, which can readily accept a pair of electrons from iodine ion into their vacant unhybridized p orbital, and the formation of the Pb-O bond further increases the iodide migration barrier. The significantly increased barrier of the iodine ion migration was demonstrated by the improved phase stability of the perovskite film under an electric field and the obviously enhanced stability of the perovskite films under strong ultraviolet light. PSCs that included the BA stabilizer were able to achieve an enhanced PCE of 25.52%. The initial efficiency of BA-modified devices remained at 80% even after being aged for 1000hours at 85 ℃ under around 30% relative humidity (RH). When subjected to maximum power point tracking and 20-25% RH, the PCE of BA-modified devices maintained an initial efficiency of 80% after 1500hours.

Structure, Function and Engineering of the Nonribosomal Peptide Synthetase Condensation Domain.

The nonribosomal peptide synthetase (NRPS) is a highly precise molecular assembly machinery for synthesizing structurally diverse peptides, which have broad medicinal applications. Withinthe NRPS, the condensation (C) domain is a core catalytic domain responsible for the formation of amide bonds between individual monomer residues during peptide elongation. This review summarizes various aspects of the C domain, including its structural characteristics, catalytic mechanisms, substrate specificity, substrate gating function, and auxiliary functions. Moreover, through case analyses of the NRPS engineering targeting the C domains, the vast potential of the C domain in the combinatorial biosynthesis of peptide natural product derivatives is demonstrated.

Development of Reactivity for Organobismuth (III, V) Toward Sulfur-Containing Compounds

Organobismuth compounds have been used in various areas of science, like biology and organic synthesis, because they are normally nontoxic and exhibit unique properties. Bismuth induces metallothionein production and is known to exhibit thiophilicity. However, few reports on the reactions between bismuth and sulfur compounds exist. This article reviews studies on the reactivity of bismuth (III and V) with sulfur compounds. A simple approach for the reaction of azole-2-thiones, which contains a heterocyclic ring, with triaryl bismuthines in the presence of a copper catalyst affords the S-arylated coupling product. When a palladium catalyst is used instead of a copper catalyst, desulfinative C-C bond formation occurs. These reactions indicate that trivalent bismuth compounds can be used as novel aryl sources. Triphenylbismuth dichloride, an organobismuth (V) reagent, successfully promotes the cyclodesulfurization of thioureas within short reaction times under mild conditions. The reaction affords N-substituted benzoxazol-2-amines in excellent yields. Tafamidis, a drug used to treat transthyretin amyloidosis, can be synthesized using this reaction.

Structuring chicken breast analogs via high moisture extrusion of dairy-plant proteins blends

Chicken analogs were structured using binary blends of soy protein isolate (SPI) and wheat gluten (WG) or whey protein concentrate (WPC), as well as trinary blends of SPI-WG-WPC via high moisture extrusion. Chicken analogs with anisotropic structures were achieved (anisotropic index >1). Although adding WPC increased hardness, by varying the ratio of SPI to WG in the trinary blends, comparable texture profile properties as cooked chicken breast were achieved. The drivers of the fiber structure formation were non-covalent protein-protein interactions like hydrogen bonds and hydrophobic interactions, and to a lesser extent, inter-protein disulfide bonds formation. β-sheets were the dominant secondary structure, and adding WPC increased the proportion of α-helix while adding WG increased the proportion of β-turns in the meat analog (MA). This study offered strategies on structuring extruded chicken analogs with WPC, a high-quality protein source, and provided insights into mechanisms underlying the formation of fiber structures.

Computational Analysis of Interactions Between Drugs and Human Serum Albumin.

Drug molecules exist as complexed with serum proteins such as human serum albumin (HSA) and/or unbound free form in the blood circulation. Drugs can be effective only when they are free. Thus, it is important to understand aspects that are important for interaction between drugs and interacting proteins. In this study, interactions among 2990 FDA approved drugs and HSA were computational analyzed to unravel principles that are critical for drug-HSA interactions. Docking results showed that drugs have higher affinity toward cavity-1 (C1) than cavity-2 (C2). A total of 1131 drug molecules have docking score greater than 60 while 768 molecules have docking score greater than 60 when they are docked in C2. In addition, three solvent channels have potential to direct solvent to C1 cavity while C2 does not have any effective channel. The post MD analyses demonstrated that drugs are making polar interactions with basic amino acids in the binding cavities. Verbscoside and ceftazidime both have stable low RMSD values throughout MD simulation with 2 Å on average in C1 cavity. The ligand RMSD shows less stability for verbscoside, which is around 4 Å when it is in complex with HSA in C1. The individual contribution of the residues K192, K196, R215, and R254 to ceftazidime are -1.92 ± 0.18, -3.09 ± 0.09, -2.17 ± 0.17, and - 2.32 ± 0.098, respectively. These residues contribute the binding energy of the verbscoside by -6.06 ± 0.08, -2.10 ± 0.06, and - 1.57 ± 0.03 kcal/mol individually in C1 cavity. C2 is making polar interactions with drug via R469, K472, and K488 residues and their contribution to the two drugs are -3.13 ± 0.21 kcal/mol for R469, -1.94 ± 0.18 kcal/mol for K472, and -1.96 ± 0.11 kcal/mol for K488 to total binding energy of ceftazidime. The binding energy of verbscoside is 57.17 ± 7.00 kcal/mol and Arg-407 has the highest contribution this bind energy individually with -4.29 ± 0.12 kcal/mol. Drugs with hydrogen bond donor/acceptor chemical adducts such as verbscoside involve higher hydrogen bond formation in C1 pocket. Ceftazidime makes interaction with HSA toward hydrophobic residues, L384, L404, L487, and L488 in the C2 cavity.

High-yield production of recombinant human myelin oligodendrocyte glycoprotein in SHuffle bacteria without a refolding step

Experimental autoimmune encephalomyelitis (EAE) is a model for central nervous system (CNS) autoimmune demyelinating diseases such as multiple sclerosis (MS) and MOG antibody-associated disease (MOGAD). Immunization with the extracellular domain of recombinant human MOG (rhMOG), which contains pathogenic antibody and T cell epitopes, induces B cell-dependent EAE for studies in mice. However, these studies have been hampered by rhMOG availability due to its insolubility when overexpressed in bacterial cells, and the requirement for inefficient denaturation and refolding. Here, we describe a new protocol for the high-yield production of soluble rhMOG in SHuffle cells, a commercially available E. coli strain engineered to facilitate disulfide bond formation in the cytoplasm. SHuffle cells can produce a soluble fraction of rhMOG yielding >100 mg/L. Analytical size exclusion chromatography multi-angle light scattering (SEC-MALS) and differential scanning fluorimetry of purified rhMOG reveals a homogeneous monomer with a high melting temperature, indicative of a well-folded protein. An in vitro proliferation assay establishes that purified rhMOG can be processed and recognized by T cells expressing a T cell receptor (TCR) specific for the immunodominant MOG35–55 peptide epitope. Lastly, immunization of wild-type, but not B cell deficient, mice with rhMOG resulted in robust induction of EAE, indicating a B cell-dependent induction. Our SHuffle cell method greatly simplifies rhMOG production by combining the high yield and speed of bacterial cell expression with enhanced disulfide bond formation and folding, which will enable further investigation of B cell-dependent EAE and expand human research of MOG in CNS demyelinating diseases.

Extraction of rare earth elements from ion adsorption clay using bio-based ionic liquid via COSMO-RS: computational and experimental validation

The study introduces eco-friendly leaching agents as alternatives to traditional rare earth element (REE) extraction solvents, addressing environmental concerns associated with ammonium sulfate. Bio-based ionic liquids (ILs), known for their non-toxic and biodegradable properties, were screened using the COSMO-RS software. Initially, 105 ILs involving 7 cations and 15 anions were computationally screened to find the best ILs for REE extraction. The chosen criteria were based on hydrogen bond formation, affinity screening, hydrophobicity, viscosity, and eco-toxicity test. Based on the COSMO-RS screening, choline oleate, choline decanoate, and choline hexanoate exhibit high solubility for REEs, with a chemical potential of 17.60, 17.01, and 18.37 kcal/mol at REE oxidation state +2. Choline glycinate, choline oleate, choline decanoate, choline hexanoate, choline lysinate, and choline leucinate were selected for their strong affinity to extract REE dissociate ions. Experimental results show slightly higher REE extraction from ammonium sulfate (3.17 ppm) compared to choline glycinate (3.15 ppm). For long-term applications, choline glycinate offers a promising eco-friendly and cost-effective alternative to traditional leaching agents, promoting economic feasibility and environmental friendliness.

Correlating Microstructural and Rheological Variations in Acrylonitrile-Butadiene-Styrene (ABS) with Interlayer Bond Formation in Material Extrusion Additive Manufacturing

Correlating Microstructural and Rheological Variations in Acrylonitrile-Butadiene-Styrene (ABS) with Interlayer Bond Formation in Material Extrusion Additive Manufacturing

Efficient synthesis of novel phenanthroline-dimedone derivatives using Pd@HQBI-SPION as a versatile palladium-immobilized catalyst

This paper presents the synthesis and application of a novel catalyst for carbon–carbon bond formations, comprising palladium immobilized on 2-(5-hydroxyquinolin-8-yl)-1H-benzo[d]imidazole-5-carboxylic acid modified superparamagnetic iron oxide nanoparticles (Pd@HQBI-SPION). The synthesis involved the attachment of HQBI ligands to SPION using APTES, followed by the immobilization of palladium. Characterization techniques, including FTIR, TEM, and magnetic measurements, confirmed the successful synthesis and structural integrity of Pd@HQBI-SPION. The catalytic activity of Pd@HQBI-SPION was evaluated in various carbon–carbon bond formation reactions, demonstrating high efficiency and reusability. 8 different derivatives bearing several electron withdrawing and electron donating functionalities were used as starting materials and the products were obtained in high isolated yields (75–97%). The catalyst exhibited excellent performance in one-pot synthesis of phenanthroline-dimedone polycyclic derivatives via C-alkylation followed by intramolecular O-alkylation of phenanthroline with dimedone. The products are obtained in high to excellent yields is described. This protocol presents a highly selective synthetic method for the construction of polycyclic aromatic compounds containing nitrogen and oxygen atoms.

Comprehensive Investigation of Ti-Doped Sr3CoSb2O9 Triple Perovskite: Structural, Morphological, Optical, and Dielectric Characteristics

We report a comprehensive investigation of the doped Ti4+ and the pristine Sr3CoSb2O9 triple perovskite material. By conducting a solid-state reaction in the air at room pressure, a stabilized single orthorhombic Immm (SG 71) phase is obtained. For series samples Sr3CoSb2−xTixO9 (x = 0.0, 0.1, 0.3, 0.5), using Rietveld refinements of powdered x-ray patterns, we reach to the conclusion that the Ti4+ doping at B-site has considerable impact on its structural parameters. The microstructure of the series samples was studied using FESEM and associated with EDS mapping for compositional analysis. The optical characteristics studied via optical absorbance measurements indicate that with an increasing doping concentration of Ti4+, the optical bandgap increases for 0.1 sample and then decreases up to 1.50 eV for 0.5 sample. As a result, they can be considered potential candidates for technological applications like photocatalytic systems and solar cells due to their suitable bandgap values and optical absorption-related applications. The FTIR analysis aimed to examine the bond forms and vibrational modes of the synthesized samples. Moreover, the space charge polarization mechanism explains a detailed analysis of temperature-dependent dielectric properties in the 1 KHz-2 MHz frequency range. The dielectric loss behavior is described by the thermally activated relaxation process tailored by the Arrhenius law and characterized by doping Ti4+ ions into the material’s structure. The existence of Co in Co2+ and Co3+ oxidation states, while Sb3+ state is stabilized with doping confirmed by X-ray photoelectron spectroscopy research. The current study thereby advances our knowledge of how these materials’ structural, morphological, optical, and dielectric characteristics are related.

Emotion coupling across socialization contexts in adolescence: Differences in parent-child and peer interactions.

People spontaneously adjust their emotions to others when they interact. This temporal coupling of emotions is an adaptive process facilitating social bonding. The present study examined differences in coupling patterns during parent-child versus peer interactions in adolescence, a developmental period marked by evolving parent-child dynamics and bond formation with peers. Because adolescents prioritize peer bonding while gradually asserting their autonomy from parental influence, we hypothesized that peer dyads showed stronger coupling than parent-adolescent dyads. Adolescents (age 16) with diverse ethnic backgrounds (N = 615; 50.2% female; 46.8% European American, 31.2% African American, 5.0% Hispanic, 3.0% Asian or Pacific Islander, 2.0% Native American, and 12.0% multiple ethnic backgrounds) participated in two videotaped interaction tasks: one with a parent and one with a self-nominated peer. Parent and peer interactions included discussions on positive and negative topics. Both dyad members' emotions were coded in real time. Cross-recurrence quantification analyses and growth-curve modeling revealed concurrent emotion coupling patterns, with peer dyads showing stronger coupling than parent-adolescent dyads. Moreover, peer dyads showed the most pronounced coupling patterns when they discussed personal problems, while parent-adolescent dyads showed the most pronounced coupling patterns when they discussed the planning of a fun activity. Our findings emphasize the importance of microlevel emotion dynamics in understanding larger scale developmental shifts in relationships during adolescence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Optimizing solvothermal synthesis of aluminum-loaded pomelo peel for enhanced fluoride adsorption using response surface methodology

Addressing fluoride contamination in water remains a critical challenge, particularly when seeking cost-effective solutions. In this study, we present a novel aluminum-loaded pomelo peel adsorbent (PPA-Al), synthesized via a one-step solvothermal method, with parameters optimized through response surface methodology. The ideal conditions were established at 2.96 g of pomelo peel, 2 g of NaAlO₂, a reaction temperature of 168.62 °C, and a duration of 140.78 minutes. Characterization of PPA-Al revealed an abundance of hydroxyl and carbon functional groups, enhancing its reactivity with coordination unsaturated aluminum sites. Adsorption isotherms conformed to both Langmuir and Freundlich models, achieving a maximum adsorption capacity of 88.81 mg·g⁻¹, outperforming many existing biomass-based adsorbents. Kinetic analysis indicated that fluoride adsorption followed a pseudo-second-order model, with thermodynamic evaluations suggesting that this process is a spontaneous endothermic reaction. Characterization techniques, including Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS), confirmed interactions between fluoride ions and -OH and -CH groups, as well as the formation of Al-F bonds. Notably, the use of PPA-Al reduces groundwater treatment costs by approximately 74.33∼83.24 % compared to activated alumina, and it can be reused multiple times without reagent regeneration. These findings highlight PPA-Al as a promising, efficient material for fluoride removal, while also demonstrating innovative applications for agricultural waste.

Sulfadimethylpyrimidine degradation by non-radical dominated peroxomonosulfate activated with geopolymer-loaded cobalt catalysts

Geopolymers are frequently employed as adsorbent materials to treat heavy metals in wastewater due to their special structure analogous to that of zeolites. Nevertheless, their utilization as catalyst supports has not been extensively employed. In this study, geopolymers were modified using carboxymethyl chitosan and subsequently converted into zeolite through the hydrothermal method. Following calcination with Co loading, Co@MGA was obtained. The results indicated that as-prepared Co@MGA exhibited an excellent performance in activating PMS to degrade SMT. Moreover, the mineralization rate of SMT reached 76 %. Quenching experiments and electron paramagnetic resonance analyses had demonstrated that the non-radical pathway predominated in the degradation process of SMT, and 1O2 was the primary reactive oxygen species. The formation of surface bond was further elucidated through in-situ Raman spectroscopy and electrochemical tests. The potential mechanism and pathways of SMT degradation within the Co@MGA/PMS system were proposed. The system exhibited adaptability to different pH levels and robust resistance to inorganic ions and humic acid. Co@MGA demonstrated excellent reusability and stability, suggesting that Co@MGA is a highly promising catalyst for the activation of PMS.

Tuning the Protonation Sensitivity of Weak Acidic Groups on a Zwitterionic Dendrimer for Selectively Targeting GD2-Overexpressed Tumor Cells in an Acidic Tumor Microenvironment.

Disialoganglioside (GD2) is one of the most popular overexpressed antigens for tumor cell targeting. However, GD2-specific antibodies often show unintended targeting to GD2-expressing health-maintaining cells due to the comparable binding affinities both at physiological pH and in a slightly acidic tumor microenvironment (TME). In this work, an affinity-switchable zwitterionic PAMAM G5 dendrimer (G5-3S) is developed for selective binding to GD2 only in a slightly acidic TME. It has 3 sulfonic groups, 128 carboxylic groups, and 125 amino groups on the surface. This affinity switch is realized by multiple hydrogen bond (H-bond) formation between protonated carboxylic groups surrounding a sulfonic group and overexpressed GD2 clusters on the tumor cell membrane in the slightly acidic TME, whereas there is no stable H-bond formation at physiological pH. Thus, G5-3S shows superior selectivity to GD2-overexpressed tumor cells over anti-GD2 antibodies by avoiding targeting GD2-expressing health-maintaining cells at physiological pH. This suggests that G5-3S is a promising candidate for GD2-overexpressed cancer treatment.