Host-guest Inclusion Complexes Research Articles

Remdesivir interactions with sulphobutylether-β-cyclodextrins: A case study using selected substitution patterns

Modified cyclodextrins (CDs) consist of a distribution of different structures with different number and location of the substituted groups. Among the most important applications of these molecules is their use as an enabling excipient in pharmaceutical formulations to provide the necessary solubility, stability and bioavailability for a drug to be effectively used. The most typical interaction mechanism of small molecular groups with CDs is the formation of host–guest inclusion complexes. The thermodynamic affinity constant between CDs and drugs should not be too strong, since then the biological activity could be negated by the formation of the complex. In the opposite scenario, if the affinity constant is too weak, the complex is barely formed and the amount of CD required in the formulation may become too great. Thus, a balance between the affinity of the CD and the drug is necessary for an optimal formulation. Additionally in the case of modified CDs and specific drug complexes there are further questions concerning the effect that the locations and number of substitutions plays in complexation. In the present work, this question is explored by using sulphobutylether-β-cyclodextrin and remdesivir, the only antiviral medication currently approved by the United States Food and Drug Administration for treating COVID-19, as a case study. This paper presents results from an orthogonal study using isothermal titration calorimetry measurements and biased molecular dynamics simulations that provide complementary information. Isothermal titration calorimetry delves into the global impact of the species distribution while molecular dynamics simulations deals with specific chemical structures. The goal is to provide useful information to optimize pharmaceutical formulations based on modified CDs, specifically in the case of remdesivir, used to treat SARS-CoV-2 infection, although the main conclusions could be extended to the interaction of other drugs with modified cyclodextrins.

Polyanion and anionic surface monitoring in aqueous medium enabled by an ionic host-guest complex

Detection of polyanions and anionic surfaces/interfaces in aqueous medium remains a challenge for years. Herein, we describe a highly selective sensing strategy for the critical issue via utilization of a new host-guest complex formed from a recently developed fluorescent cationic Cage and the tetrasodium salt of 3, 4, 9, 10-perylene tetracarboxylic acid (PTCA-Na). Binding behavior studies revealed that the cage is a very efficient host for PTCA-Na to form a 1:1 host-guest inclusion complex (PTCA-Na⊂Cage). Surprisingly, the fluorescence of both the host and the guest quenches with the formation of the complex as a result of charge transfer from the guest to the cage. With further increasing the ratio of the guest to the host, the PTCA-Na⊂Cage can bind another PTCA-Na on the outer positive-charged surface of Cage via electrostatic interaction to give a charge-balanced 1:2 host-guest ternary complex. Interestingly, the PTCA-Na⊂Cage is highly sensitive to the presence of polyanions, such as inorganic polyanion salts, anionic surfactants-based micelles, and even bacteria, as a result of competitive binding to the cationic cage or PTCA-Na. We believe our finding not only realizes a universal method for polyanions and anionic surfaces/interfaces monitoring, but also provides an example for exploring the sensing applications of supramolecular systems in different ways.

Host–Guest Inclusion Complexes of Essential Oils with Strong Antibacterial and Antifungal Features in Beta-Cyclodextrin for Solid-State Pharmaceutical Applications

Essential oils are widely recognized as natural alternatives to pharmaceutical antibacterial and antifungal agents. With respect to standard pharmaceutics, the advantages of essential oils are their (i) low production costs, (ii) lack of chemical and biochemical drawbacks that are intrinsic to the synthetic production process and (iii) good tolerance by humans. On the other hand, the liquid nature of essential oils poses concerns about their actual application in different therapeutic issues regarding their persistence and the ability to control or prolong drug release. In this study, two essential oils from oregano and winter savory showing antibacterial and antifungal features were complexed in a solid state with beta-cyclodextrin. Host–guest inclusion complexes were characterized using FT-IR spectroscopy, ESI-MS and GC-MS techniques. Manyfold terpenic and non-terpenic components of the oils could be observed and unambiguously identified as being included inside the carbohydrate hosts. Many of them provided a specific biocidal action. Indeed, essential oil host–guest inclusion products were tested against two Candida species and an S. aureus reference strain, showing that the oils effectively maintained their liquid performances. Solid-state tablets of the essential oil inclusion complexes embedded in polyvinylpyrrolidone could be obtained. These results pave the way for the solid-state application of essential oils in antibacterial and antifungal pharmaceutical treatments.

Inclusion Complexes of Gold(I)-Dithiocarbamates with β-Cyclodextrin: A Journey from Drug Repurposing towards Drug Discovery.

The gold(I)‐dithiocarbamate (dtc) complex [Au(N,N‐diethyl)dtc]2 was identified as the active cytotoxic agent in the combination treatment of sodium aurothiomalate and disulfiram on a panel of cancer cell lines. In addition to demonstrating pronounced differential cytotoxicity to these cell lines, the gold complex showed no cross‐resistance in therapy‐surviving cancer cells. In the course of a medicinal chemistry campaign on this class of poorly soluble gold(I)‐dtc complexes, >35 derivatives were synthesized and X‐ray crystallography was used to examine structural aspects of the dtc moiety. A group of hydroxy‐substituted complexes has an improved solubility profile, and it was found that these complexes form 2 : 1 host–guest inclusion complexes with β‐cyclodextrin (CD), exhibiting a rarely observed “tail‐to‐tail” arrangement of the CD cones. Formulation of a hydroxy‐substituted gold(I)‐dtc complex with excess sulfobutylether‐β‐CD prevents the induction of mitochondrial reactive oxygen species, which is a major burden in the development of metallodrugs.

Targeting hypoxia for sensitization of tumors to apoptosis enhancement through supramolecular biohybrid bacteria

Bacteria-driven drug-delivery systems have drawn considerable interests for their highly selective hypoxia-targeting and efficacy in tumor inhibition. For the first time, a supramolecular biohybrid bacterium (SA@HU) is constructed by coating attenuated Salmonella typhimurium (S. typhimurium ΔppGpp/Lux) with nanoassemblies. In addition, the host–guest inclusion complexes based on hydroxypropyl-β-cyclodextrin (HPCD) and amantadine (AMA) was developed to encapsulate the natural antineoplastic product, ursolic acid (UA). It is found that the drug-carried coating layer has no significant impact on the antitumor activity or tumor-targeting capacity of bacteria. Significant restraint of tumor progression is achieved by SA@HU due to the synergy of cellular immune activation and apoptosis enhancement. Most importantly, intravenous delivery of UA by this biohybrid vector can cause tumor lysis, as the bacteria-attracting nutrients beneficial for preferential accumulation of bacteria in tumor. The mutual promotion of bacteria and UA may also contribute to a superior anticancer effect. Hence, the SA@HU-based biotic/abiotic supramolecular therapeutic system represents a novel strategy for combined chemo-bacterial therapy.

Methyl Hexadecyl Viologen Inclusion in Cucurbit[8]uril: Coexistence of Three Host–Guest Complexes with Different Stoichiometry in a Highly Hydrated Crystal

The host–guest inclusion complexes of cucurbiturils with alkyl viologen have interesting architectures, chemical properties, and potential applications in sensors and nanotechnology. A highly hydrated triclinic crystal of cucurbit[8]uril (CB[8]) complexed by methyl hexadecyl viologen (MVC16) is characterized by the unprecedented coexistence in the crystal of three host–guest complexes with 3:2, 2:2, and 1:1 stoichiometries. In all these complexes, the hook-shaped alkyl chain of the MVC16 is hosted in the CB[8] macrocycles, while the methyl viologen moieties have various environments. In the Z-shaped 3:2 complex, a central CB[8] unit hosts two viologen heads in the cavity, while the 2:2 complex is held together by π-stacking interactions between two viologen units. In the square 2D tiling crystal packing of CB[8] macrocycles, the same site which favors the dimerization observed in the 2:2 complex is also statistically occupied by a single methyl viologen moiety of the 1:1 complex. The rational interpretation of the crystal structure represented an intriguing challenge, due to the complicated statistical disorder in the alkyl chains hosted in CB[8] units and in the methyl viologen moieties of 2:2 and 1:1 complexes. In contrast with the solution behavior dominated by the 2:1 complex, the coexistence of three host–guest complexes with 3:2, 2:2, and 1:1 ratios highlights the fundamental importance of packing effects in the crystallized supramolecular complexes. Therefore, the crystallization process has permitted us to capture different host–guest systems in a single crystal, revealing a supramolecular landscape in a single photo.

Inclusion complex of thymol and hydroxypropyl-β-cyclodextrin (HP-β-CD) in polymeric hydrogel for topical application: Physicochemical characterization, molecular docking, and stability evaluation

The current investigation aimed to prepare and characterize the inclusion complex of thymol with hydroxypropyl-β-cyclodextrin (HP-β-CD) to uniformly incorporate in hydrogel system for its topical application. An inclusion complex of thymol with HP-β-CD was formulated through different methods viz. physical mixture, kneading, and co-precipitation. Phase solubility study was carried out to find the stability constant of complex. Further, the inclusion complex of thymol with HP-β-CD was characterized by DSC, FT-IR, and 1H NMR spectroscopy. The molecular docking studies were also performed to understand the molecular interactions of stable supra-molecular host-guest inclusion complex of thymol with HP-β-CD. After that inclusion complex was incorporated in carbopol 940 hydrogel and evaluated for its drug content, pH, homogeneity, rheological behavior, and in-vitro release. The phase solubility graph demonstrated AL type correlation with apparent stability constant (K1:1) of 370 M−1. The inclusion complex formulated by the co-precipitation technique exhibited the highest dissolution rate (98.73%) of thymol as compared to kneading and physical methods. The DSC, FT-IR and 1H NMR spectroscopic analysis confirmed the formation of inclusion complex between thymol and HP-β-CD. The molecular docking study has confirmed that the binding affinity of thymol with the HP-β-CD was −9.6 kcal/mol, indicating desirable stability of the prepared inclusion complex. The diffusion flux of thymol in a form of inclusion complex was found to be approximately 4.4 folds higher as compared to that of thymol in the hydrogel system for topical administration. The in vitro release of thymol from carbopol 940 hydrogel system exhibited a sustained release profile with thixotropic behaviour. The thymol in a form of inclusion complex was found to be stable in the developed hydrogel system according to ICH guidelines. Therefore, incorporation of thymol in form of inclusion complex in hydrogel system is an effective approach to improve its biopharmaceutical performance for topical administration.

Formononetin/methyl-β-cyclodextrin inclusion complex incorporated into electrospun polyvinyl-alcohol nanofibers: Enhanced water solubility and oral fast-dissolving property

Improving solubility and administration route of isoflavone formononetin (FMN) are critical factors to improve its bioavailability in the oral cavity. This study fabricated fast-dissolving nanofibers containing FMN/methyl-β-cyclodextrin (FMN/Me-β-CD) inclusion complex. The solubility of FMN could be increased by approximately 50 times at 20 mM aqueous Me-β-CD. Interactions and thermodynamic parameters of the host-guest inclusion complex were studied by a fluorescence quenching method. The structure and mechanisms of the complex were further studied by molecular docking and molecular dynamics. Finally, polyvinyl-alcohol (PVA) nanofibrous webs containing the FMN/Me-β-CD inclusion complex were fabricated by electrospinning. The dissolution test demonstrated that the FMN/Me-β-CD/PVA nanofibers can be dissolved in artificial saliva within approximately 2 s. This study shows the potential of Me-β-CD inclusion and electrospinning to improve solubility and administration route of isoflavones.

Photophysics of a cyanine dye within cyclodextrin cavity

The modulated photophysical and dynamical behavior of a potent anti-tumor photosensitizer 3,3/-diethyloxadicarbocyanine iodide (DODCI) following host-guest inclusion complex formation with α-, β- and γ-Cyclodextrins (CDs) has been studied using steady-state and time-resolved spectroscopic methods. The cavity size of the CDs (α-CD <β-CD <γ-CD) is argued to play an instrumental role underlying the formation of the host-guest inclusion complex. While negligible interaction with α-CD is found to be succeeded by prominent quenching of monomeric fluorescence of the dye within β-CD and γ-CD with the degree of quenching being greater within γ-CD. The most appealing fact attained from the experimental results is the anticipation of dimer formation of DODCI within the large cavity of γ-CD which can entrap more than one molecule of DODCI. The steady-state results are found to be adequately corroborated by time-resolved fluorescence decay studies. Such encapsulation of the cyanine dye within the carrier cargo can be designed for targeted delivery inside biological systems.

Ultrasonication-assisted host–guest inclusion complexes of β-cyclodextrins and 5-hydroxytryptophan: Enhancement of water solubility, thermal stability, and in vitro anticancer activity

The use of ultrasonic waves for the preparation of inclusion complexes in pharmaceutical industries has increased, owing to their versatility, promising nondestructive capability, and short reaction time. 5-Hydroxytryptophan (5-HTP), a precursor of serotonin, is used therapeutically, in the clinical setting, for psychiatric disorders such as anxiety and depression. In this study, 5-HTP is used as a guest molecule to prepare β-cyclodextrins (CDs; β-CD, HPβ-CD, and SBEβ-CD) inclusion complexes with the assistance of the ultrasonic method. The solubility of 5-HTP increases linearly as the concentration of CDs increased, confirming the 1:1 stoichiometry of the complex, obtained using UV–visible and fluorescence spectroscopy. The structural characteristics of the solid inclusion complexes are analyzed using various spectroscopic and microscopic techniques such as FTIR spectroscopy, PXRD, TGA, and FE-SEM. Molecular modeling elucidates the most stable inclusion model and phase solubility studies indicate that 5-HTP and SBEβ-CD form a 1:1 inclusion complex with an apparent stability constant of 1592.5 M−1. Furthermore, in vitro cytotoxicity studies show that the CDs:5-HTP complex has a better antitumor efficacy than pure 5-HTP. Thus, ultrasonication can be utilized as an advanced, time-saving, and cost-effective method for the generation of CDs:5-HTP inclusion complexes, resulting in the potential development of anticancer drugs.

Fluorescence-based investigations of the host–guest inclusion of anilinonaphthalene sulfonic acids (1,8- and 2,6-ANS) by dimethoxypillar[5]arene in nonaqueous solvents

Pillar[n]arenes are a relatively new class of macrocyclic host molecules which have not been extensively studied for their ability to form inclusion complexes. The properties and host–guest inclusion complexes of dimethoxypillar[5]arene (DMPill[5]) hosts with the polarity-sensitive fluorescent probes 8-anilinonaphthalene-1-sulfonic acid (1,8-ANS) and 2-anilinonaphthalene-6-sulfonic acid (2,6-ANS) as guests were investigated in nonaqueous solvents via fluorescence spectroscopy. The binding properties of DMPill[5] were found to depend significantly on the shape of the guest molecule, as well as on the properties of the solvent. Formation of host–guest inclusion complexes of DMPill[5] with these two fluorescent ANS guests occurred in the polar aprotic solvents acetonitrile, acetone, and tetrahydrofuran. Fluorescence titration experiments were performed to determine the nature and strength of the complexation. In the case of 1,8-ANS, 1:1 host–guest complexation was observed in all three solvents, with average binding constant K values of 408, 1000 and 5500 M−1 in acetone, acetonitrile, and tetrahydrofuran, respectively. This large dependence of the binding constant on solvent provides insight into the nature of the binding in these complexes. In the case of 2,6-ANS, 2:1 host–guest complexation was observed; this difference with 1,8-ANS was explained in terms of the shape and size of these two isomeric guests. These results show that DMPill[5] is an excellent host for these neutral aromatic guests, and shows strong binding abilities even in these nonaqueous solvents. The strength (or lack) of binding in different solvents was found to be dependent on a range of factors beyond solvent polarity, including guest and solvent shape and size, and most importantly, specific solvent–solute interactions.

Recent advances and applications of cyclodextrins in magnetic solid phase extraction

Cyclodextrins (CDs) as a family of cyclic oligosaccharides are toroidal with a hydrophobic interior and a hydrophilic exterior. They are well-known for their ability to form host-guest inclusion complexes with different compounds. They are used as chiral stationary phases in high performance liquid chromatography (HPLC) and gas chromatography (GC) or as chiral reagents in the background electrolyte of capillary electrophoresis (CE). In recent years, they have been used for modification of sorbents or as sorbents in solid phase extraction (SPE) procedures. Magnetic solid-phase extraction (MSPE), as a new type of SPE procedure, has received considerable attention due to its rapid phase separation process as compared to traditional extraction mode. This review covers the synthesis of CD-based magnetic sorbents (such as immobilization of CDs onto the different supports, production of nanosponges, and making hybrid substances with nanomaterials) and the use of these compounds in MSPE of different analytes from biological, environmental, and food samples. Also, prospects of CD-based sorbents for sample pre-treatment are also proposed.

Redox-responsive poly(ionic liquid) microgels explored as the building blocks for supramolecular assembly

In this study, poly(ionic liquid) (PIL) microgel functionalized by ferrocene (Fc) was fabricated via a facile one-step cross-linking copolymerization in selective solvent. The results demonstrated that the sizes of PIL microgels could be well-tuned through the feeding ratio of IL monomers to the cross-linker. The presence of Fc groups in PIL microgel was confirmed through ultraviolet–visible (UV–vis), inductively coupled plasma optical emission spectrometer (ICP-OES) and Fourier transform infrared (FT-IR) measurements, as well as cyclic voltammetry (CV) technique. In addition, Fc-anchored PIL microgels were found to be electrochemically active and could respond reversibly to the redox stimulus. As a prototype application, Fc-anchored PIL microgels were explored as the building blocks for the supramolecular self-assembly. Through the host-guest inclusion complexation interaction of Fc group with β-cyclodextrin (β-CD) dimer, PIL microgels could undergo a reversible association and dissociation. Importantly, an enhanced peak current could be achieved when PIL microgel-supported Fc groups were complexed with β-CD dimer. The founding thus pave a way toward fabricating supramolecular systems using nanoparticles as the building blocks, which will find wide applications in smart material, drug delivery and electrochemistry.

Comparative chemical examination of inclusion complexes formed with β-cyclodextrin derivatives and basic amino acids

In this study, we have investigated the host-guest inclusion complexes between β-cyclodextrin (βCD), 2-hydroxypropyl-β-cyclodextrin (2-HPβCD), and mono-6-tosyl-β-cyclodextrin (TS-βCD) excipients and two amino acids, such as L-arginine (L-Arg) and L-lysine (L-Lys). The formation of inclusion complexes was detected, and a comparative study was conducted at different pH, density, and viscosity. A physical mixture, comprising equal amount of amino acids was used to prepare the complex in a solid-state form. The experimental parameters, such as apparent molar volume, limiting apparent molar volume, partial molar volume were analyzed by measuring density at infinite dilution. The other quantities, such as dynamic viscosity, kinematic viscosity, relative viscosity, intrinsic viscosity, spatial viscosity, activation energy were determined for amino acid/βCD complexes at various mass fractions of βCDs and different temperatures. Finally, we found moderate (R2 > 0.5) and strong (R2 > 0.7) linear relationships (p-value < 0.0001) between the dynamic viscosity and the temperature: the temperature evaluation promotes the decrease in dynamic viscosity for amnio acid-βCD (its derivatives) complexes. The results of this study emphasize important properties of analyzed complexes that can be utilized in the development of controlled drug delivery vectors.

Cucurbit[7]uril as a matrix solid-phase dispersion for the extraction of quaternary ammonium pesticides from vegetables and their determination using HPLC–UV

Cucurbit[7]uril (Q[7]) was first used as a dispersant sorbent material in a matrix solid-phase dispersion for the simultaneous extraction of four quaternary ammonium pesticides from vegetables before analysis using high-performance liquid chromatography with UV detection. Q[7] exhibited a better selectivity and adsorption capability for these compounds, which is due to its ability to bind selectively organic molecules into its hydrophobic cavity and to form stable host–guest inclusion complexes. Various parameters affecting the extraction were investigated and optimized, such as sorbent/sample mass ratio, grinding time, rinsing and eluting conditions. Under optimized conditions, the proposed method exhibited a linear response in the concentration range of 1–100 μg·kg−1, satisfactory recoveries for eight types of vegetable samples (>70%), and high repeatability (RSD < 9.0%). The limits of quantification were between 0.43 μg·kg−1 and 0.99 μg·kg−1, which is nearly 50 times lower than the maximum residue limits established by the European Council.

Cyclodextrin-derivatized hybrid nanocomposites as novel magnetic solid-phase extraction adsorbent for preconcentration of trace fluoroquinolones from water samples coupled with HPLC-MS/MS determination

A novel cyclodextrin-derivatized hybrid magnetic nanocomposite, denoted as Fe3O4@SiO2@CD, was fabricated and employed as the adsorbent of magnetic solid-phase extraction (MSPE) for preconcentration of elven fluoroquinolones (FQs) from water samples. The prepared nanoparticles exhibited excellent magnetic responsiveness (56.7 emu g−1), uniform size distribution (about 300 nm), good thermal and chemical stability, excellent reusability and superior chemical affinities to the target FQs via hydrogen bond, host–guest inclusion complexation and π–π interactions. Under the optimized conditions, the MSPE was coupled with HPLC-MS/MS to sensitively quantify trance levels of FQs in environmental water. The developed method revealed satisfactory precision with RSDs lower than 4%, good linearity (R2 ≥ 0.9981), low limits of detection (0.0014–0.023 µg L−1) and satisfactory recoveries (93.2–105%). Furthermore, the proposed approach was validated by analyzing the Certified Reference Material of GBW 10152 and GBW 10153 chicken meat powder. These results demonstrated that the Fe3O4@SiO2@CD nanoparticles are a promising magnetic adsorbent for FQs, and the established MSPE-HPLC-MS/MS approach is suitable for simultaneous analysis of trace levels of FQs in actual samples.

Emulsion stabilization of cyclodextrin polymer inclusion amphiphilic polymers with different hydrophobic chain

In order to investigate the effect of host-guest inclusion on the stability of emulsion, two host-guest inclusion complexes (CDP-APC16 and CDP-APP4 respectively) were constructed by using cyclodextrin polymer (CDP) and amphiphilic polymers(named APC16, APP4). The optimal inclusion ratios of APP4 and APC16 with CDP were explored and the O/W emulsion were prepared by APC16, APP4, CDP-APC16 and CDP-APP4. The stability of these four types of emulsion were analyzed by laser particle size analyzer and rheometer etc. The mechanism of inclusion complex emulsion stability was discussed by interfacial viscosity and interfacial viscoelasticity. The CDP including hydrophobic chain can form a more stable network structure and the free hydrophobic chain of CDP-APC16 easily insert into oil phase to emulsify the oil. The longer hydrophobic chain length of APC16 is easier to be included by CDP than that of APP4.Therefore, the CDP-APC16 inclusion complex emulsion show better stability. The inclusion complex shows a prospect application in tertiary oil recovery.

Host-guest molecular encapsulation of cucurbit[7]uril with dillapiole congeners using docking simulation and density functional theory approaches

Binding affinity and intermolecular interactions are essential characteristics that could be used to comprehend molecular recognition between molecules in supramolecular host-guest systems. This work presented a molecular docking simulation and density functional theory (DFT) calculation at the B3LYP-631g(d) level of theory on dillapiole and its derivatives (guest compounds) complexation with cucurbit[7]uril (host compound). The supramolecular host-guest inclusion complex binding energies, − 4.46 to − 5.47 kcal mol−1 and − 0.53 to − 15.38 kcal mol−1 for docking and DFT calculation, respectively, were calculated, and the intermolecular interactions such as the hydrogen bonding, electrostatic, dispersion, and pi-alkyl formation involved were observed. The negative binding energies of D1-CB [7], D2-CB [7], D3-CB [7], D4-CB [7], D5-CB [7], D6-CB [7], and D-CB [7], computed from both the theoretical approaches, suggested the possible inclusion of the guests inside the cucurbit[7]uril cavity, enabling the formation of stable inclusion compounds. However, the significant difference in the binding energy values from the DFT calculation demonstrated a clustered preference in terms of the complex stabilisation, with D2-CB [7], D3-CB [7], D5-CB [7], and D6-CB [7] dominantly favourable, while D1-CB [7], D4-CB [7], and D were inclusion complexes with the least favourable. Encapsulation of the guests’ structural frame as a whole or a part and steric constraint associated with the guests’ substituents positioning in addition to the intermolecular interactions were also noted to induce stabilisation in the binding energy, thus reflecting a preferable inclusion complex. Besides, the theoretical calculations on the rationalisation of the selected guests’ energy barrier were found to correlate well with experimental works of hydroboration oxidation synthesis to produce alcohol derivatives of dillapiole.

In situ reversible tuning of chemical interface damping in single gold nanorod-based recyclable platforms through manipulation of supramolecular host-guest interactions.

Recently, chemical interface damping (CID) has been proposed as a new plasmon damping pathway based on interfacial hot-electron transfer from metal to adsorbate molecules. It has been considered essential, owing to its potential implications in efficient photochemical processes and sensing experiments. However, thus far, studies focusing on controlling CID in single gold nanoparticles have been very limited, and in situ reversible tuning has remained a considerable challenge. In these scanning electron microscopy-correlated dark-field spectroscopic measurements and density functional theory calculations, cucurbit[7]uril (CB[7])-based host–guest supramolecular interactions were employed to examine and control the CID process using monoamine-functionalized CB[7] (CB[7]-NH2) attached to single gold nanorods (AuNRs). In situ tuning of CID through the CB[7]–oxaliplatin complexation, which can result in the variation of the chemical nature and electronic properties of adsorbates, was presented. In addition, in situ tuning of CID was demonstrated through the competitive release of the oxaliplatin guest from the oxaliplatin@CB[7] complex, which was then replaced by a competitor guest of spermine in sufficient amounts. Furthermore, nuclear magnetic resonance experiments confirmed that the release of the guest is the consequence of adding salt (NaCl). Thus, in situ reversible tuning of CID in single AuNRs was achieved through successive steps of encapsulation and release of the guest on the same AuNR in a flow cell. Finally, single CB[7]-NH2@AuNRs were presented as a recyclable platform for CID investigations after the complete release of guest molecules from their host–guest inclusion complexes. Therefore, this study has paved a new route to achieve in situ reversible tuning of CID in the same AuNR and to investigate the CID process using CB-based host–guest chemistry with various guest molecules in single AuNRs for efficient hot-electron photochemistry and biosensing applications.

Pillar[5]arene-based supramolecular photosensitizer for enhanced hypoxic-tumor therapeutic effectiveness.

A galactose-targeting supramolecular photosensitizer system DOX@GP5⊃NBSPD was constructed based on a host-guest inclusion complex. The supramolecular system could achieve efficient delivery of DOX/NBS and selective release under GSH stimulation. In vitro studies revealed that this supramolecular DOX/NBS co-delivery system exhibited high ROS production and excellent cancer cell damage capability in a hypoxic environment. This strategy can therefore achieve enhanced hypoxic-tumor therapeutic effectiveness by chemo-photodynamic combination.