2-Anilinonaphthalene-6-sulfonate (2,6-ANS) and 8-anilinonaphthalene-1-sulfonate (8,1-ANS) are polarity-sensitive fluorescent probes that serve as model systems for host–guest interactions with cyclodextrins. Reliable binding free energies with α -, β -, and γ -cyclodextrins are needed to exploit these probes as inexpensive, high-throughput reporters for inclusion complexes. Here, we determine the free energies of association of 2,6-ANS and 8,1-ANS to the three native cyclodextrins using fluorescence spectroscopy, isothermal titration calorimetry (ITC), and molecular simulations from either docking or MM/GBSA. Fluorescence titrations indicate that 2,6-ANS binds most strongly to β -CD, whereas 8,1-ANS binds most strongly to γ -CD, while ITC places the 8,1-ANS γ -CD interaction among the weakest of the complexes studied. Docking simulations qualitatively support the experimental trends, whereas MM/GBSA exhibits systematic deviations, particularly for γ -CD, consistent with limitations of the surface-area-based nonpolar solvation model and parameterization for carbohydrate hosts. Method disagreements are most pronounced for systems with low association constants ( 5 × 10^1 M^-1 ), underscoring the need for cautious interpretation in this weak-binding regime. Molecular dynamics simulations further show that the poor fit of the naphthalene ring in the 2,6-ANS α -CD complex can lead to partial solvent exposure and distorted fluorescence readouts. For 8,1-ANS, its larger size amplifies methodological differences, with γ -CD being the only host, among those examined, that can fully accommodate the naphthalene group within its cavity. Overall, these results illustrate both the utility and the limitations of combining experimental and computational approaches to analyze weak cyclodextrin inclusion complexes.
Derivatives of thiacalix[4]crown-ethers in 1,3-alternate conformation with dodecyloxy and bromopropoxy groups were studied as ionophores for potentiometric sensor materials with plasticized polymeric membranes. The sensitivity of the sensors to alkaline, alkaline earth, and transition metal ions in aqueous solutions was investigated. It was revealed that the size of the crown ether macrocycle plays the main role in the sensitivity of sensors to metal ions, while the type of alkoxy group marginally affects this parameter. Sensors with thiacalix[4]arene-crown-5 exhibit selectivity for K+ ions. The developed sensors have shown high selectivity to Pb2+ ion in the presence of Ni2+, Co2+, Cu2+, Cd2+ ions and can be employed for selective Pb2+ quantification in aqueous media. The pH-sensitivity of sensors with bromopropoxy-substituted thiacalix[4]crown-ethers decreases with an increase in the crown cavity size, while that of dodecyloxy-substituted thiacalix[4]crown-ethers remains low regardless of the size of the crown cavity. Quantum-chemical calculations of the metal ion–thiacalixcrown-ether complex formation indicate ion–π interactions of Pb2+ and Cd2+ with benzene ring of thiacalix[4]arene and ion–dipole interactions with oxygen atoms of crown-ether, whereas alkali metal ion complexes (Na+, K+) are stabilized by ion–dipole interactions. The combined experimental and theoretical data suggest that the potentiometric selectivity of the thiacalix[4]crown-ethers in alkali and transition metal ion series is better interpreted as the interplay of metal ion desolvation and desolvated metal-ion complexation with macrocycle.
In this study, we investigate a pillar[5]arene-based thin film sensor through an integrated experimental and data-driven modelling approach, with the aim of elucidating diffusion-induced swelling behavior. Within this framework, diffusion coefficients were calculated using time-dependent response data for three different volatile organic compounds (VOCs) obtained via Surface Plasmon Resonance (SPR) and Quartz Crystal Microbalance (QCM) measurements. These values were determined using Fick’s early-stage diffusion model. The SPR-derived diffusion coefficients were higher than the QCM values, being approximately 3.3 times higher for dichloromethane and 2.8 times higher for chloroform. To capture the nonlinear and dynamic sensor response, Nonlinear Autoregressive Exogenous Artificial Neural Networks (NARX-ANN) and Gaussian Process Regression (GPR) models were developed and validated using experimental datasets. Both approaches accurately reproduced the temporal response profiles and yielded diffusion coefficients in close agreement with those obtained from physics-based calculations. This study presents a comprehensive framework that combines diffusion-based physical analysis for VOC detection using pillar[5]arene with advanced machine learning techniques. The proposed approaches contribute to the understanding of VOC–sensor interactions and may serve as a useful framework for the design and optimization of chemical sensing systems.
The effective removal of dyes from polluted water presents an important ecological issue because of their harmful nature and enduring presence. Basic blue 3 (BB3) has considerable health hazards, including possible associations with cancer and genetic abnormalities, alongside established acute toxicity and irritation of the eyes and skin. Nanoporous carbon materials are extensively utilized for dye elimination owing to their extensive surface area and tunable porosity. The present study focuses on the fabrication of Kanak Champa wood nanoporous carbon (KCWNC) by a dual carbonization and KOH activation method intended for the adsorptive removal of BB3. FE-SEM, XRD, FTIR, zeta potential, and BET analyses were utilized to characterize the KCWNC. BET analysis indicates that KCWNC has a surface area of 512.6 m²g⁻¹ and a mean pore diameter of 3.5 nm. FTIR and Boehm titration analyses indicate the presence of –OH, –COOH, C = O, and C-O-C functional groups on the surface of KCWNC. These functional groups facilitate the removal of BB3 dye via electrostatic interactions, hydrogen bonding, and π–π interactions. The adsorption of BB3 on the surface of KCWNC occurs efficiently at an optimum pH of 8.0. KCWNC exhibited the highest adsorption capacity of 244.4 mgg− 1 at 298 K. Adsorption equilibrium efficiently followed the Langmuir isotherm model (R2 = 0.999), and the kinetics of adsorption adhered to the pseudo-second-order approach. The thermodynamic study confirmed the adsorption to be a spontaneous process and exothermic in nature. A ΔH° value of -45.23 kJmol− 1, in conjunction with PSO kinetics, suggests the weak chemisorption of BB3 on the KCWNC surface. The KCWNC obtained in this research was also regenerated, maintaining a retention capacity of 94.1
This study applied computational approached to evaluate β-cyclodextrin (βCD), 2-hydroxypropyl-β-cyclodextrin (HPβCD), and 2,6-dimethyl-β-cyclodextrin (DMβCD) as potential carriers for clausarin (CLA) and dentatin (DEN), coumarin derivatives isolated from the root bark of Clausena excavata. The inclusion behavior and stability of the resulting host-guest complexes were investigated at the molecular level. Molecular docking identified two favorable binding orientations, with either the pyran or pyrone ring of the guests directed toward the primary rim of the CD cavity. Subsequent molecular dynamics simulations confirmed the stability of these complexes, which were mainly stabilized by hydrophobic interactions along with hydrogen bonds at the rim. The MM/PBSA binding free energy calculations showed that HPβCD exhibited the most favorable binding affinity toward both compounds compared to βCD and DMβCD. This trend was further supported by CD-assisted extraction experiments, where HPβCD consistently provided higher extraction efficiency for both CLA and DEN than the native βCD. Taken together, the findings suggest that HPβCD could be a promising carrier among the studied CDs and provide molecular-level insight into CD-coumarin interactions relevant to the development of delivery systems for poorly water-soluble bioactive compounds.
The basic area of research is the recognition of metal ions that have an imperative role in the biological and environmental world. Among these metal ions, Copper and Mercury are two key metal ions whose selective and sensitive detection is still the topic of current research. In the present study, we have developed a new hydrazone with a fluorescein moiety as the ideal photophysical partner. This new hydrazone was synthesised via one-step condensation of fluorescein hydrazide with 5-Allyl-3-methoxy salicylaldehyde (FP1). FP1 was fully characterised by employing different physicochemical techniques, and its single-crystal X-ray studies have been carried out. In mixture of ethanol and water (9:1 v/v) FP1 showed colorimetric response for Cu2+, Co2+ and Zn2+. Interestingly, FP1 demonstrated selective behaviour with Cu2+ ions exclusively on changing the solvent combination to acetonitrile and water (8:2 v/v), enabling FP1 to act as a sensor for Cu2+ ions only. Hg2+ ions depicted turn on response in fluorescence in a solution of acetonitrile and water (8:2 v/v) via chelation-enhanced fluorescence. The sensing mechanism favours the spirolactum ring remaining closed on the interaction of FP1 with the metal ions. The limit of detection (LOD) and binding constant are 0.11 ppm, 2.74 × 103 M− 1 and 3.03 ppm, 6.5 × 106 M− 1 for Cu2+ and Hg2+ ions, respectively. Cu2+ and Hg2+ ions binding with FP1 have been confirmed using FT-IR, NMR and HRMS data. FP1 displayed reversible response with EDTA2− ions (4 cycle). A thorough investigation of FP1 was conducted using Hirshfeld surface analysis and two-dimensional fingerprint plots to identify and quantify intermolecular contacts. Complementary topological evaluations involving NCI (Non-Covalent Interaction), QTAIM (Quantum Theory of Atoms in Molecules), ELF (Electron Localization Function) and LOL (Localized Orbital Locator methods) were utilized to dissect the electronic characteristics and non-covalent framework of the molecule. TD-DFT computations further revealed that coordination with transition metals such as Cu2+ and Hg2+ induces notable spectral shifts, particularly toward lower energies, reflecting stronger charge-transfer effects. Alamar blue assay of FP1 on HEK-293(Human embryonic kidney − 293) cell lines exhibited biocompatibility with minimal cytotoxicity and applied for live cell imaging for intracellular sensing of Cu2+ and Hg2+. In a study focusing on latent fingerprint detection with the help of three variants of FP1, researchers observed that the three variants of the compounds exhibited strong adhesion to fingerprint ridges, resulting in well-defined patterns without any unwanted background staining.
Cyclodextrins (CDs) are widely deployed to improve the performance of poorly water soluble drugs, yet their role is still often framed narrowly as empirical “solubilizers.” This review reframes CDs as predictable stabilizers by connecting host–guest thermodynamics, stability constants (K1:1), complexation efficiency (CE), and ΔGbind, to quantitative kinetic outcomes that control exposure: supersaturation trajectories, induction time (tind), and intrinsic dissolution rate (IDR). We synthesize evidence across native and derivative CDs (HP-β-CD, SBE-β-CD, RM-β-CD, γ-CD) and across hybrid architectures (nanosponges, polymer- and lipid based systems). A practitioner-oriented framework maps drug motifs and speciation at intestinal pH to derivative choice, then prescribes when to add polymers/surfactants to secure recrystallization resistance. Templates for measurement (phase solubility, tind, IDR, XRPD/DSC) and a computational toolbox (docking → MD → ΔG estimation; QSPR/ML) translate ΔG/K/CE into effect sizes in log(S/S0) and tind. We codify reporting standards (raw points, CE with CI, buffer/pH/ionic strength, DS/vendor) and common pitfalls (misreading AN/BS curvature, filter adsorption, confusing complex precipitation with drug recrystallization). The review culminates in decision trees and design rules that elevate CDs from trial and error excipients to mechanistically rational stabilizers, supporting robust and reproducible formulation design in oral delivery.
The first application of the Claisen rearrangement of resorcinarene derivatives is described. Optimisation of this reaction allowed the preparation of gram-quantities of the Claisen-rearranged product in yields greater than 80
Examples of calix[4]arene ligands binding fluorescent organic dye molecules are very limited and usually focused on complexations at the calixarene upper rim, governed mostly by non-specific hydrophobic interactions. Herein, we report a spectrophotometric study of complexation of three selected dyes, namely, auramine O, rhodamine B, and fluorescein, by two disubstituted and one tetrasubstituted phenanthridine calix[4]arene derivative. The experimental investigation is accompanied by an exhaustive theoretical study of the structural features controlling the complexation, as well as optical properties of the formed complexes. It was shown that the studied ligands had high affinity towards the binding of the dyes and that π-π stacking interactions had an important role in the “sandwich” complex stabilization. The binding affinity of the tetrasubstituted ligand was particularly strong. Even more, upon binding the first dye molecule, this ligand proceeded to bind a sequential one, forming a stable complex with 2:1 stoichiometry with two sandwich complexes within a single calixarene host. Aside from the extent of the π -system and resulting strength of π-π interactions, additional factors like charge distribution and the presence of electron-withdrawing groups and sterically hindering groups, contributed to the overall stability of the complexes. The understanding of the structure-binding affinity relationship given by this study provides a solid foundation for further development of lower rim substituted calixarenes for molecular recognition.
Azamacrocyclic Schiff bases have a high affinity for coordinating with transition metals, making them valuable for various advanced scientific and technological applications. Despite extensive studies on Schiff base macrocycles from aromatic diamines and dicarbonyls, research on those involving aliphatic carbonyl compounds and triethylenetetramine remains limited; however, its integration into Schiff base macrocycles opens new avenues for material and biological applications. In this article, a novel 15-membered tetraazamacrocyclic Schiff base, (1E, 10E)1,4,7,10-tetraazacyclopentadeca-10,15-diene (GTETA) was synthesized through microwave-assisted condensation of pentane-1,5-dial and triethylenetetramine. The structural and electronic properties of GTETA were analyzed using Density Functional Theory (DFT/B3LYP) calculations, providing insights into its molecular geometry, vibrational and NMR properties. Global reactivity descriptors, molecular electrostatic potential (MEP) mapping, FMO and NBO analysis were employed to understand its chemical behavior. Additionally, first-order hyperpolarizability calculations and second harmonic generation (SHG) measurements confirmed its nonlinear optical activity. Molecular docking revealed that GTETA binds effectively to the target protein 6GGD via hydrogen-bond interactions, and in vitro biological assays further supported its biological potential.
Cavity size plays a decisive role in governing host–guest interactions in cyclodextrin-based inclusion systems. In this study, the encapsulation behavior of 4-aminopyridine (4-AP) with α- and β-cyclodextrins (α-CD and β-CD) was systematically investigated to elucidate the relationship between cavity dimensions, binding thermodynamics, and functional performance. Inclusion complex formation was confirmed by ^1H NMR, UV–visible, FTIR, fluorescence spectroscopy, and ESI–MS analyses, revealing distinct cavity-dependent binding modes. Pronounced upfield shifts of inner cavity protons (H3 and H5), along with guest proton perturbations, indicated deeper inclusion and stronger stabilization of 4-AP within the β-CD cavity compared to α-CD. Thermodynamic parameters demonstrated enhanced binding affinity and stability for the β-CD complex, consistent with its optimal cavity size. Density functional theory (DFT) calculations further corroborated the experimental findings, providing insights into inclusion geometry, interaction energies, and non-covalent stabilization, while reduced density gradient (RDG) analysis confirmed the dominance of van der Waals and hydrogen bonding interactions. In vitro release studies revealed a cavity size–dependent modulation of drug release, with β-CD complexes exhibiting more sustained release profiles relative to α-CD and free 4-AP, indicating improved encapsulation efficiency and controlled delivery behavior. Importantly, biological evaluations demonstrated that cyclodextrin inclusion significantly influences functional activity. Antioxidant and antimicrobial assays showed enhanced activity for the inclusion complexes, particularly for β-CD, compared to the free drug, highlighting the role of improved stability and molecular dispersion. Furthermore, in vitro cytotoxicity studies using A549 human lung adenocarcinoma cells confirmed that β-CD encapsulation leads to superior biological response, attributable to optimized release and stronger host–guest interactions. Overall, this study establishes a direct correlation between cyclodextrin cavity size, binding energetics, release behavior, and biological function, demonstrating that cavity size–dependent control of host–guest interactions can be strategically exploited to enhance drug performance.
Fluoride ion (F⁻) exhibits a dual role in environmental and biological systems, being beneficial at trace levels but toxic at elevated concentrations, necessitating reliable detection methods. Small-molecule optical probes, particularly colorimetric and fluorescent chemosensors, have emerged as efficient tools due to their simplicity, high sensitivity, and real-time response. This review summarizes the sources, industrial applications, and toxicological impacts of fluoride, and highlights key sensing mechanisms including hydrogen bonding, π-conjugation modulation, Lewis acid–base coordination, desilylation, and fluoride-induced deprotonation. Recent developments in heterocycle-based probes derived from imidazole, coumarin, thiazole, naphthalimide, and Schiff base frameworks are discussed, emphasizing structure–activity relationships, selectivity, and practical sensing applications.
Enantiopure [2 + 3] covalent organic cages deriving from the 3,3’-diformyl-2,2’-BINOL building block are produced through a dynamic covalent chemistry approach. These architectures are formed with different triamino caps, 1,3,5-tris(aminomethyl)-2,4,6-triethylbenzene (2a), 1,3,5-tris(aminomethyl)-2,4,6-trimethylbenzene (2b), and 2,7,14-triaminotriptycene (3). For the synthesis of the cage 6b containing 3, a less direct synthetic route regarding the formation of the amine cages (4a and 4b) generated from the spacers 2a and 2b was followed. Instead of being directly synthesized from 3,3’-diformyl-2,2’-BINOL, the targeted compound 6b required a protected BINOL derivative. The ability of the three cages to host the 1-phenylethylammonium cation (8+) as a guest was evaluated through UV–vis titration, CD, and DOSY NMR studies. while the formation of the supramolecular complex 8+ with cage 6b was not possible, cages 4a and 4b were able to bind 8+ with the same enantiopreference, higher association constants being obtained for cage 4a. The association constants determined for the host–guest complexes are discussed in relation with the cavity size calculated for the host cages.
The requirements for high thermal energy in conventional nanocellulose extraction methods remain a major limitation for the sustainable valorization of lignocellulosic residues. In this study, a chemical route operating entirely at room-temperature ( 25 °C) is proposed for converting residual carpentry wood chips (WC) into cellulose nanocrystals (CNCs) via sequential alkalization, bleaching, and sulfuric acid hydrolysis. The process achieved a 56
The water vapor sorption and desorption kinetics of the cucurbit[n]uril (CB[n]) homologues (n = 5–8) were investigated. Kinetic analysis revealed that the water uptake capacity varies as a function of cavity size with CB[5], CB[6], CB[7] and CB[8] exhibiting sorption of 8, 12, 18 and 17 mol H2O per mol of host, respectively. The corresponding sorption equilibria were attained over 270, 320, 210 and 300 min, while complete desorption required 270, 390, 450 and 400 min, respectively. Experimentally derived rate constants for sorption (ksorp) and desorption (kdes) were determined as follows: CB[5] ksorp = 0.0172 min− 1, kdes = 0.0101 min− 1; CB[6] ksorp = 0.013 min− 1, kdes = 0.0047 min− 1; CB[7] ksorp = 0.0195 min− 1, kdes = 0.039 min− 1; CB[8] ksorp = 0.0129 min− 1, kdes = 0.0063 min− 1. Notably, the highest sorption rate constants were observed for CB [5] and CB [7], which also demonstrate comparatively greater aqueous solubility, suggesting a possible correlation between hydration affinity and solubility behavior.
A new anthraquinone-based tetra-benzimidazolium salt 1,8-bis2’-[2’’-(N-picoly-benzimidazoliumyl)ethyl]benzimidazoliumylethoxy-9,10-anthraquinone hexafluorophosphate (1) was prepared and characterized. Particularly, the recognition performance of H2PO4− using of compound 1 as a chemical sensor was investigated through fluorescence spectra, ultraviolet spectra, HRMS, 1H NMR titrations and IR spectra. The experimental results showed compound 1 has a good recognition ability for H2PO4−. One tetra-benzimidazolium salt 1 was prepared and characterized. The recognition of H2PO4− using 1 as a chemosensor was studied.
Macrocyclic compounds have advanced the molecular recognition of many organic and inorganic guest molecules, utilizing in particular their high degree of pre-organization. This has led to a number of attractive applications, for example in sensor technology, selective separation processes, and the manufacture of advanced materials, right through to the development of artificial enzymes. Liquid-liquid extraction has accompanied these developments from the outset and has contributed, on the one hand, to a better understanding of the fundamentals of molecular recognition processes and, on the other hand, to the development of practical methods for the effective and selective separation of different guest molecules using macrocyclic compounds. Extraction offers the possibility to investigate host-guest systems where the reaction partners have very different solubility properties. The use of the radiotracer method in particular provides very reliable data with a high degree of accuracy. This approach yields highly accurate separation and selectivity factors, as well as information on the lipophilicity of host compounds and even thermodynamic parameters, which provide insight into the enthalpic and entropic contributions of the molecular recognition process.
Tetraacetic acid and crossed carboxylic acid derivatives of calix[4]arene were prepared and investigated for extraction of various metal ions in the absence and presence of sodium ion. The extraction equilibrium constants and separation factors of Cu(II), Zn(II), and Co(II) with three carboxylic acid derivatives of calix[4]arene were determined, both in the absence and presence of sodium ion, to evaluate the effect of allosteric coextraction of sodium and the other metal ions. Extraction in the presence of sodium ion was enhanced by an allosteric effect compared with that in its absence. The extent of enhancement depended on the extraction reagents, as the crossed carboxylic acid derivatives of calix[4]arene possess longer carboxylic acid groups that relieve steric repulsion between two metal cations. The extent of enhancement also depended on the concentration of coexisting sodium ion.
A novel hydroxypyranone-based tripodal chelator, NHPY (tris((5-hydroxy-4-oxo-4H-pyran-2-yl)methyl)2,2’,2’’-nitrilotriactate was synthesized and the binding interactions with trivalent metal ions were studied meticulously using computational and experimental approaches. The chelator was designed to utilize the hydroxyl and carbonyl groups of the pyranone ring to successfully coordinate with metal ions, and it was synthesized via a condensation reaction that produced a highly chelating tripodal chelator. The coordination properties were analysed via solution studies, including potentiometric titrations, and spectrophotometric titrations. The chelator displayed selectivity and strong binding affinity for trivalent metal ions, such as Fe(III), Cr(III), Al(III), and Ga(III) with stability constants determined for each complex. For various complexes involved in this research, the complexation studies demonstrated high formation constants with the formation of species ML, MLH, MLH2, and MLH− 1. Spectral shifts caused by the addition of metal ions and corresponding modifications to the solution properties indicated that stable metal-ligand complexes were formed. DFT studies were performed to understand the molecular features of the electronic structure and the binding interactions between the two species. As a result of the DFT data collected, geometries, electronic distributions, and binding strengths were evaluated to further substantiate the experimental results. Additionally, NHPY had been identified through in-vitro testing as a highly potent Cathepsin B inhibitor. Experimental validation of its therapeutic application was conducted via molecular docking studies demonstrating the compounds’ ability to inhibit inflammatory responses, cancer progression, and Alzheimer’s disease. Thus, the collection of data through these approaches indicates that hydroxypyranone-derived chelators may represent future applications for the detection of metal ions, to facilitate environmental clean-up, and as therapeutic agents to treat metal dysregulation in living systems.
