Β-cyclodextrin Host Research Articles

In situ self-assembly of artesunate-β-cyclodextrin supramolecular nanomedicine as potential anti-cancer prodrug

Supramolecular nanomedicines have drawn great interest in cancer therapy, but their potential immunotoxicities restrict application in clinical translation. Herein, we constructed a supramolecular nanomedicine CD-Artesunate (CD-ATS) in situ by supramolecular polymerization and orthogonal self-assembly. The nanostructure was meticulously characterized using 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy, Mass spectrometry, Transmission Electron Microscopy (TEM), and particle size distribution analysis. β-cyclodextrin (β-CD) hosts are conjugated with artesunate (ATS) by click chemistry to improve the solubility and antitumor activity of ATS. Supramolecular nanomedicine was prepared through orthogonal self-assembly driven by host−guest complexation and hydrogen bonds. The results showed that the aqueous solubility of CD-ATS was 30 times better than that of free ATS. Furthermore, CD-ATS displayed a superior antitumor effect against HCT116 tumor cells compared to the first-line drug Taxol. This enhanced effect was attributed to the induction of excessive reactive oxygen species (ROS) generation, which subsequently triggered apoptosis.

Structural and antibacterial assessment of two distinct dihydroxy biphenyls encapsulated with β-cyclodextrin supramolecular complex

β-Cyclodextrin plays a vital role in biological application because it can enhance the stability and solubility of the guest molecules in the supramolecular inclusion complexes. Moreover, the β-Cyclodextrin inclusion complex has control-releasing behavior and lower toxicity than bare guest molecules. To improve the solubility and stability properties of two structurally different fluorescent guest molecules, namely 2,2′-dihydroxy biphenyl and 3,3′-dihydroxy biphenyls, they involve the β-Cyclodextrin inclusion complex process. Optical measurements clearly described the efficient binding through the changes in the absorbance and emission intensities of guest molecules in the presence of β-Cyclodextrin. The Job's plot from absorbance measurements reveals the 1:1 stochiometric ratio of binding of guests and the β-Cyclodextrin host. The FT-IR spectra of the solid complex show the characteristic stretching and bending vibrations from both the guests and the host molecule. The 1HNMR spectra of the inclusion complex promote downfield shifting of guest molecule protons upon binding with the β-Cyclodextrin host. The solid complex prepared using the solution method exhibits superior antibacterial activity against both gram-positive and gram-negative bacteria compared to the kneading and physical mixing methods.

Influence of Surface Chemistry on Host/Guest Interactions: A Model Study on Redox-Sensitive β-Cyclodextrin/Ferrocene Complexes.

While host/guest interactions are widely used to control molecular assembly on surfaces, quantitative information on the effect of surface chemistry on their efficiency is lacking. To address this question, we combined electrochemical characterization with quartz crystal microbalance with dissipation monitoring to study host/guest interactions between surface-attached ferrocene (Fc) guests and soluble β-cyclodextrin (β-CD) hosts. We identified several parameters that influence the redox response, β-CD complexation ability, and repellent properties of Fc monolayers, including the method of Fc grafting, the linker connecting Fc with the surface, and the diluting molecule used to tune Fc surface density. The study on monovalent β-CD/Fc complexation was completed by the characterization of multivalent interactions between Fc monolayers and β-CD-functionalized polymers, with new insights being obtained on the interplay between the surface chemistry, binding efficiency, and reversibility under electrochemical stimulus. These results should facilitate the design of well-defined functional interfaces and their implementation in stimuli-responsive materials and sensing devices.

Synthesis of supramolecular polymers with calix[4]arene and β-cyclodextrin and their application in heavy metal ion absorption.

Two categories of supramolecular polymer monomers were produced by introducing the ureidopyrimidone quadruple-hydrogen bonding assemblies on the calix[4]arene and the β-cyclodextrin host units. The adsorption capacity of these supramolecular polymers for different metal ions was investigated by static adsorption. The results showed that at pH = 6 and when the adsorption equilibrium was reached, the supramolecular polymer with calixarene and β-cyclodextrin as the main body adsorbed up to 99% of Pb2+ and Cd2+, respectively. Also, the supramolecular polymer connected with six carbon chains on β-cyclodextrin had better recognition of Cd2+ and Pb2+, and the highest adsorption rate reached 99%. Industrial adsorbent materials from such supramolecular polymers will provide more options for water pollution control, especially for heavy metal ions.

A bipolar Electrode-Electrochemiluminescence sensor for Salmonella typhimurium detection based on β-cyclodextrin Host-Guest recognition

A bipolar electrode electrochemiluminescence (BPE-ECL) with β-cyclodextrin (β-CD) host–guest recognition was constructed for the rapid detection of Salmonella typhimurium (S. typhimurium). Firstly, the sulfhydryl β-CD (SH-β-CD, with inner diameter size: 6.0–6.5 Å) was assembled on the gold-plated cathode of BPE. Ferrocene (Fc, length: 3.5 Å; width: 4.4 Å) labelled signal probe and parts Fc-aptamer complement each other to form a double-stranded DNA (dsDNA). Due to its large size, the dsDNA with a double Fc (width > 8.8 Å) could not be embedded into the cavities of β-CD. In the presence of S. typhimurium, Fc-aptamer bond specifically to S. typhimurium, and the signal probe was shed from the dsDNA. Then, the signal probe (guest) was captured by the SH-β-CD (host) on the surface of the BPE. Due to the principle of spatial matching between Fc and SH-β-CD, a stable inclusion complex could be formed, which made Fc close to the cathode surface of the BPE. When a certain driving voltage was applied, Fc was oxidized to Fc+. The cathode surface of Fc+ would promote electron transfer, causing the [Ru(bpy)3]2+ at the anode emit light, and effectively convert the electrochemical signal into an ECL signal. 101-105 CFU mL−1S. typhimurium was positively correlated with Fc+ and ECL intensity, with a detection limit of 101 CFU mL−1. Therefore, S. typhimurium can be quantitatively detected by the electron transfer rate of the BPE.

Ultralong Room-Temperature Phosphorescence with Second-level Lifetime in Water Based on Cyclodextrin Supramolecular Assembly.

Organic solid-state materials with long-lived room-temperature phosphorescence (RTP) emission have been widely developed and applied in many fields, while works in developing solution-phase phosphorescence materials were rarely reported owing to the ultrafast nonradiative relaxation and quenchers from the liquid medium. Herein, we report an ultralong RTP system in water through assembly based on a β-cyclodextrin host and p-biphenylboronic acid guest with a lifetime of 1.03 s under ambient conditions. It is worth noting that the long-lived phosphorescence depends on the host-guest inclusion as well as intermolecular hydrogen bonding interactions, which suppress nonradiative relaxation and avoid quenchers effectively. Furthermore, the addition of fluorescent dyes to the assembly system achieved the tuning of the afterglow color through radiative energy transfer of reabsorption.

Composite hydrogels with host–guest interaction using cellulose nanocrystal as supramolecular filler

The functional nanocomposite hydrogels are of great interest in the research field of materials science because of their improved mechanical performances and their ability to be used in a wider range of applications. Herein, the supramolecular composite hydrogels were developed and studied using a cellulose nanocrystal (CNC) as bio-based filler. The hydrogels were designed by introducing supramolecular bonding between host β-cyclodextrin (β-CD) and guest adamantane (Ad) groups at the interface between the highly dispersed CNC and the polymer matrix. For this purpose, the CNC surface was successfully modified with Ad to act not only as a reinforcing filler in the polymer network but also as a supramolecular cross-linker with the β-CD-modified polymer. Importantly, CNC exhibited the ability of preserving their good dispersibility in aqueous media, even after modification with the hydrophobic Ad group, owing to electrostatic repulsion among negative charges incorporated onto CNC surface. Furthermore, the modification of CNC with Ad contributed to the greater interfacial compatibility between the filler and the matrix. The present study therefore highlights that the toughness of a hydrogel can be improved by the incorporation of supramolecular bonding as reversible bonding at the filler/matrix interface, which sacrificially depletes the mechanical energy upon deformation of the gels.

Injectable Hydrogels Based on Cyclodextrin/Cholesterol Inclusion Complexation and Loaded with 5-Fluorouracil/Methotrexate for Breast Cancer Treatment

Breast cancer is the second most common cancer in women worldwide. Long-term treatment with conventional chemotherapy may result in severe systemic side effects. Therefore, the localized delivery of chemotherapy helps to overcome such a problem. In this article, self-assembling hydrogels were constructed via inclusion complexation between host β-cyclodextrin polymers (8armPEG20k-CD and pβ-CD) and the guest polymers 8-armed poly(ethylene glycol) capped either with cholesterol (8armPEG20k-chol) or adamantane (8armPEG20k-Ad) and were loaded with 5-fluorouracil (5-FU) and methotrexate (MTX). The prepared hydrogels were characterized by SEM and rheological behaviors. The in vitro release of 5-FU and MTX was studied. The cytotoxicity of our modified systems was investigated against breast tumor cells (MCF-7) using an MTT assay. Additionally, the histopathological changes in breast tissues were monitored before and after their intratumor injection. The results of rheological characterization indicated the viscoelastic behavior in all cases except for 8armPEG-Ad. In vitro release results showed a variable range of release profiles from 6 to 21 days, depending on the hydrogel composition. MTT findings indicated the inhibition ability of our systems against the viability of cancer cells depending on the kind and concentration of the hydrogel and the incubation period. Moreover, the results of histopathology showed the improvement of cancer manifestation (swelling and inflammation) after intratumor injection of loaded hydrogel systems. In conclusion, the obtained results indicated the applicability of the modified hydrogels as injectable vehicles for both loading and controlled release of anticancer therapies.

Supramolecular Theranostic Nanomedicine for In Situ Self-Boosting Cancer Photochemotherapy.

Although traditional nanomedicines have enhanced the therapeutic efficacy and improved the survival quality of cancer patients, random drug release and drug resistance are deep-rooted problems hindering their clinical application. A precise nanoplatform combing chemotherapy and photodynamic therapy (PDT) is developing as a new therapeutic strategy to overcome the above challenges. Herein, a novel supramolecular nanomedicine is ingeniously constructed for in situ self-boosting cancer photochemotherapy. Hydrophilic polyethylene glycol (PEG) chains or β-cyclodextrin (β-CD) hosts are first conjugated onto tetraphenyl porphyrin (TCPP) to improve the solubility of TCPP and decrease their π-π stacking interactions, guaranteeing a high-efficiency PDT. Then, two camptothecin (CPT) molecules are linked together via a reactive oxygen species (ROS)-responsive thioketal bond, which averts the premature burst release of CPT and realizes in situ drug release at the tumor site where PDT is performed, resulting in an enhanced chemotherapy. Benefiting from the collaboration of host-guest complexation between β-CD and CPT, multiple intermolecular hydrogen bonds of β-CD, π-π stacking interactions among CPT and TCPP as well as PEG shell protection, a prolonged blood circulation time, and a selective tumor accumulation are acquired, which facilitate the synergistic photochemotherapy and bring a pre-eminent antitumor response with a low systemic toxicity.

Taming multiple binding poses in alchemical binding free energy prediction: the β-cyclodextrin host-guest SAMPL9 blinded challenge.

We apply the Alchemical Transfer Method (ATM) and a bespoke fixed partial charge force field to the SAMPL9 bCD host-guest binding free energy prediction challenge that comprises a combination of complexes formed between five phenothiazine guests and two cyclodextrin hosts. Multiple chemical forms, competing binding poses, and computational modeling challenges pose significant obstacles to obtaining reliable computational predictions for these systems. The phenothiazine guests exist in solution as racemic mixtures of enantiomers related by nitrogen inversions that bind the hosts in various binding poses, each requiring an individual free energy analysis. Due to the large size of the guests and the conformational reorganization of the hosts, which prevent a direct absolute binding free energy route, binding free energies are obtained by a series of absolute and relative binding alchemical steps for each chemical species in each binding pose. Metadynamics-accelerated conformational sampling was found to be necessary to address the poor convergence of some numerical estimates affected by conformational trapping. Despite these challenges, our blinded predictions quantitatively reproduced the experimental affinities for the β-cyclodextrin host and, to a lesser extent, those with a methylated derivative. The work illustrates the challenges of obtaining reliable free energy data in in silico drug design for even seemingly simple systems and introduces some of the technologies available to tackle them.

2-Hydroxychalcone-β-Cyclodextrin Conjugate with pH-Modulated Photoresponsive Binding Properties.

Stimuli-responsive supramolecular receptors are important building blocks for the construction of self-assembled functional materials. We report the design and synthesis of a pH- and light-responsive 2-hydroxychalcone-β-cyclodextrin conjugate (1-Ct) and its characterization by spectroscopic and computational methods. 1-Ct follows the typical reaction network of trans-chalcone-flavylium photoswitches. Upon light irradiation, 1-Ct can be photochemically converted into the cis-chalcone/hemiketal forms (1-Cc/1-B) under neutral pH conditions or to the flavylium cation (1-AH+) at acidic pH values. This stimuli-responsive β-cyclodextrin host, 1-Ct, was found to form stronger intramolecular self-inclusion complexes (Kintra = 14) than 1-AH+ (Kintra = 3) and weaker than 1-Cc/1-B (overall Kintra = 179), allowing control over their stability and binding properties by combinations of pH and light stimuli.

Supramolecular modulation in photophysical features of berberine and its application towards ATP sensing

In this study we report supramolecular interaction of the cationic dye berberine (BBR) with the highly substituted polyanionic cyclodextrin derivative, sulfobutylether beta cyclodextrin (SBE10βCD). Though interaction of BBR with parent β-cyclodextrin (βCD) host is very weak, its interaction with SBE10βCD host is significantly strong with an association constant Ka as large as ∼2.67 × 105 M−1. Strong binding of BBR with SBE10βCD is governed by cooperative effect of electrostatic attraction and enhanced hydrophobic interaction caused by extended SBE10βCD cavity for bound BBR dye. In the BBR-SBE10βCD complex, lower micropolarity and rigid microenvironment of host cavity cause a large decrease both in structural agility and intramolecular charge transfer (ICT) state formation of bound BBR. Accordingly, the non-radiative de-excitation of excited BBR in the dye-host complex is reduced significantly, causing its emission intensity to increase quite largely. The BBR-SBE10βCD complex is found to be highly sensitive towards ionic strength of the medium. This property is further explored to form a ternary complex, BBR-SBE10βCD-Cd2+, with largely reduced fluorescence intensity. Interestingly, this ternary complex exhibits selective fluorescence turn-on in response to an important bio-analyte, adenosine triphosphate (ATP). Present study, thus, demonstrates a very strong supramolecular complex, BBR-SBE10βCD, which is found to be very useful in the ATP detection in the presence of Cd2+, involving the ATP responsive fluorescence.

Comparative study of inclusion complex formation between β-cyclodextrin (host) and aromatic diamines (guests) by mixing in hot water, co-precipitation, and solid-state grinding methods

Aromatic diamines are essential components of polyimide and many other thermosetting polymers. Recent attention has been growing on the threading of cyclodextrins (CDs) onto diamine monomers intended to improve the solubility in water and thermal stability of resultant polymers. The co-precipitation method is often used to isolate inclusion complexes (ICs) of aromatic diamines and other sparingly water-soluble aromatic guest molecules with β-CD. To find the viability of other methods, we studied IC formation between β-CD and some aromatic diamines by mixing in hot water, co-precipitation, and solid-state grinding. ICs formation in water was carried out by solid guest dispersion into the β-CD aqueous solution at 80 °C with high-speed magnetic stirring. In contrast, solid-state grinding was employed by adding a small amount of water to promote IC formation. Thus, ICs prepared by mixing in hot water and solid-state grinding methods were crystallized from water by cooling to 4 °C. Structures of the ICs in solution were confirmed by chemical shifts changes of cavity protons of β-CD in 1H NMR and the cross-peaks between aromatic protons and cavity protons in 1H-1H ROESY NMR. Job’s plot and NMR titration experiments were used to determine the stoichiometric ratio of host and guest in solution.

Theoretical Investigation on Inclusion Complex of (s)-2-Isopropyl-1-(o-nitrophenyl) Sulfonyl) Aziridine with β-Cyclodextrin

The present work aims to study the theoretical chemistry applied to organic systems such as host / guest inclusion complexes. In literature different molecular modeling computation methods have been used to study the complexation of the host β-cyclodextrin molecule, with the guest (S) -2-Isopropyl-1- (o-nitrophenyl) sulfonyl) aziridine molecule, as semi-empirical PM3 and DFT (Density Functional Theory) calculations in gas and aqueous phases. The present paper focus on complexation, interaction and deformation energies determination, besides geometries, electronic structure, and chemical reactivity in order to describe the changes that AZ during encapsulation in two phases and two orientations. The results obtained with the Long-range corrected hybrid functional (WB97X-D / Base 6-31G (d))clearly indicate that the formed complex is energetically preferred in both phases, and the inclusion complex in the orientation A is more favorable than in the orientation B and shows good compatibility with the experimental results. NBO and NCI analysis were performed on the β - CD / AZ complex to understand the different interactions. The 1H nuclear magnetic resonance (NMR) of the complex was studied using the Gauge-Including Atomic Orbital (GIAO).

Optimizing Photochirogenic Performance by Solvent-Driven Conformational Fixation in Enantiodifferentiating Photoisomerization of (Z)-Cyclooctene Mediated by Sensitizing β-Cyclodextrin Hosts.

Catalytic enantiodifferentiating photoisomerization of cyclooctene (1Z) included and sensitized by regioisomeric 6-O-(o-, m-, and p-methoxybenzoyl)-β-cyclodextrins (CDs) was performed under a variety of solvent conditions for higher enantioselectivities. The enantiomeric excess (ee) of chiral (E)-isomer (1E) produced was a critical function of all the internal and external factors examined, in particular, the sensitizer structure and the solvent conditions, to afford (R)-1E in record-high ee's of up to 67% upon sensitization with the meta-substituted β-CD host in water and salt solutions but neither in 50% aqueous ethanol nor with the ortho- and para-substituted hosts. The mechanistic origin of the sudden ee enhancement achieved under the specific conditions is discussed on the basis of the circular dichroism spectral behaviors upon substrate inclusion and the compensatory enthalpy-entropy relationship of the activation parameters for the enantiodifferentiating photoisomerization.

Adamantane Functionalized Poly(2-oxazoline)s with Broadly Tunable LCST-Behavior by Molecular Recognition.

Smart or adaptive materials often utilize stimuli-responsive polymers, which undergo a phase transition in response to a given stimulus. So far, various stimuli have been used to enable the modulation of drug release profiles, cell-interactive behavior, and optical and mechanical properties. In this respect, molecular recognition is a powerful tool to fine-tune the stimuli-responsive behavior due to its high specificity. Within this contribution, a poly(2-oxazoline) copolymer bearing adamantane side chains was synthesized via triazabicyclodecene-catalyzed amidation of the ester side chains of a poly(2-ethyl-2-oxazoline-stat-2-methoxycarbonylpropyl-2-oxazoline) statistical copolymer. Subsequent complexation of the pendant adamantane groups with sub-stoichiometric amounts (0–1 equivalents) of hydroxypropyl β-cyclodextrin or β-cyclodextrin enabled accurate tuning of its lower critical solution temperature (LCST) over an exceptionally wide temperature range, spanning from 30 °C to 56 °C. Furthermore, the sharp thermal transitions display minimal hysteresis, suggesting a reversible phase transition of the complexed polymer chains (i.e., the β-cyclodextrin host collapses together with the polymers) and a minimal influence by the temperature on the supramolecular association. Analysis of the association constant of the polymer with hydroxypropyl β-cyclodextrin via 1H NMR spectroscopy suggests that the selection of the macrocyclic host and rational polymer design can have a profound influence on the observed thermal transitions.

Glutathione sensitive vesicles prepared from supramolecular amphiphiles.

Glutathione (GSH) sensitive vesicles were prepared by the self-assembly of amphiphilic inclusion complexes. These novel chemically sensitive supramolecular amphiphiles are anticipated to have applications in drug delivery; the nanocarriers can protect the encapsulated cargo and release it via triggered degradation in high concentrations of GSH. Additionally, the sensitivity of the vesicles to GSH indicates that the dynamic covalent disulfide bond at the vesicle surface can be used for post-modification of the nanocarrier via a thiol-disulfide exchange, a strategy that can be exploited to introduce targeting moieties to increase treatment specificity. Supramolecular amphiphiles containing a dynamic covalent disulfide bond were prepared via the host-guest inclusion complexes between alkylated β-cyclodextrin (β-CD) hosts and adamantane terminated polyethylene glycol derivatives. The significant difference between the critical micelle concentrations of the supramolecular amphiphiles and the individual host and guest components confirmed that a unique supramolecular amphiphile was formed. Fluorescence experiments and dynamic light scattering (DLS) revealed that the supramolecular amphiphiles self-assembled into vesicles of 130 nm diameter which were stable for 8 months. Degradation of the vesicles after incubation with GSH was monitored using DLS and by the release of encapsulated 5,6-carboxyfluorescein (CF), observed by an increase in fluorescence intensity. Degradation of the nanocarrier was faster at intracellular GSH concentrations than at extracellular GSH concentrations.

β-Cyclodextrin modified Pt(II) metallacycle-based supramolecular hyperbranched polymer assemblies for DOX delivery to liver cancer cells

Despite the widespread clinical application of chemotherapeutic anticancer drugs, their adverse side effects and inefficient performances remain ongoing issues. A drug delivery system (DDS) designed for a specific cancer may therefore overcome the drawbacks of single chemotherapeutic drugs and provide precise and synergistical cancer treatment by introducing exclusive stimulus responsiveness and combined chemotherapy properties. Herein, we report the design and synthesis of a supramolecular drug delivery assembly 1 constructed by orthogonal self-assembly technique in aqueous media specifically for application in liver cancer therapy. Complex 1 incorporates the β-cyclodextrin host molecule-functionalized organoplatinum(II) metallacycle 2 with two specific stimulus-responsive motifs to the signaling molecule nitric oxide (NO), in addition to the three-armed polyethylene glycol (PEG) functionalized ferrocene 3 with redox responsiveness. With this molecular design, the particularly low critical aggregation concentration (CAC) of assembly 1 allowed encapsulation of the commercial anticancer drug doxorubicin (DOX). Controlled drug release was also achieved by morphological transfer via a sensitive response to the endogenous redox and NO stimuli, which are specifically related to the microenvironment of liver tumor cells. Upon combination of these properties with the anticancer ability from the platinum acceptor, in vitro studies demonstrated that DOX-loaded 1 is able to codeliver anticancer drugs and exhibit therapeutic effectiveness to liver tumor sites via a synergistic effect, thereby revealing a potential DDS platform for precise liver cancer therapeutics.

Ligand Gaussian Accelerated Molecular Dynamics (LiGaMD): Characterization of Ligand Binding Thermodynamics and Kinetics.

Calculations of ligand binding free energies and kinetic rates are important for drug design. However, such tasks have proven challenging in computational chemistry and biophysics. To address this challenge, we have developed a new computational method, ligand Gaussian accelerated molecular dynamics (LiGaMD), which selectively boosts the ligand nonbonded interaction potential energy based on the Gaussian accelerated molecular dynamics (GaMD) enhanced sampling technique. Another boost potential could be applied to the remaining potential energy of the entire system in a dual-boost algorithm (LiGaMD_Dual) to facilitate ligand binding. LiGaMD has been demonstrated on host-guest and protein-ligand binding model systems. Repetitive guest binding and unbinding in the β-cyclodextrin host were observed in hundreds-of-nanosecond LiGaMD_Dual simulations. The calculated guest binding free energies agreed excellently with experimental data with <1.0 kcal/mol errors. Compared with converged microsecond-time scale conventional molecular dynamics simulations, the sampling errors of LiGaMD_Dual simulations were also <1.0 kcal/mol. Accelerations of ligand kinetic rate constants in LiGaMD simulations were properly estimated using Kramers' rate theory. Furthermore, LiGaMD allowed us to capture repetitive dissociation and binding of the benzamidine inhibitor in trypsin within 1 μs simulations. The calculated ligand binding free energy and kinetic rate constants compared well with the experimental data. In summary, LiGaMD provides a powerful enhanced sampling approach for characterizing ligand binding thermodynamics and kinetics simultaneously, which is expected to facilitate computer-aided drug design.

Enhanced Characterization of Pyrene Binding in Mixed Cyclodextrin Systems via Fluorescence Spectroscopy.

Although significant effort has been expended to analyze the binding of pyrene in β-cyclodextrin and γ-cyclodextrin, little has been published on the binding of this guest in β-cyclodextrin derivatives (methyl-β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin) or in mixtures of such derivatives, despite the fact that these derivatives are known to have different supramolecular properties that facilitate unique modes of complexation. Reported herein is a detailed spectroscopic investigation of the binding of pyrene in β-cyclodextrin derivatives and in binary mixtures of cyclodextrins. Py values, defined as the ratio of representative vibronic bands in the fluorescence emission of pyrene, were used to measure changes in the pyrene microenvironment in the presence of the cyclodextrin hosts, and indicated that unmodified β-cyclodextrin is unique in providing a fully hydrophobic environment for pyrene through the use of two cyclodextrins to bind a single pyrene guest. By comparison, both γ-cyclodextrin and modified β-cyclodextrin analogues bind pyrene in a less hydrophobic environment through 1:1 binding stoichiometries that allow for continued interactions between the incompletely encapsulated pyrene guest and the aqueous solvent system. Binary mixtures of cyclodextrins were also explored and reinforce the unique properties of the unmodified β-cyclodextrin host. Graphical Abstract The unique binding geometries of pyrene in beta-cyclodextrin and its derivatives leads to measurable fluorescence emission signals, whose information can be used to elucidate the highly structurally dependent binding geometries and stoichiometries.