Stability Of Inclusion Complexes Research Articles

Structure, stability, and dynamics of inclusion complexes formed from auranofin derivatives and hydroxypropyl-β-cyclodextrin

Structure, stability, and dynamics of inclusion complexes formed from auranofin derivatives and hydroxypropyl-β-cyclodextrin

A Review of Machine Learning and QSAR/QSPR Predictions for Complexes of Organic Molecules with Cyclodextrins.

Cyclodextrins are macrocyclic rings composed of glucose residues. Due to their remarkable structural properties, they can form host-guest inclusion complexes, which is why they are frequently used in the pharmaceutical, cosmetic, and food industries, as well as in environmental and analytical chemistry. This review presents the reports from 2011 to 2023 on the quantitative structure-activity/property relationship (QSAR/QSPR) approach, which is primarily employed to predict the thermodynamic stability of inclusion complexes. This article extensively discusses the significant developments related to the size of available experimental data, the available sets of descriptors, and the machine learning (ML) algorithms used, such as support vector machines, random forests, artificial neural networks, and gradient boosting. As QSAR/QPR analysis only requires molecular structures of guests and experimental values of stability constants, this approach may be particularly useful for predicting these values for complexes with randomly substituted cyclodextrins, as well as for estimating their dependence on pH. This work proposes solutions on how to effectively use this knowledge, which is especially important for researchers who will deal with this topic in the future. This review also presents other applications of ML in relation to CD complexes, including the prediction of physicochemical properties of CD complexes, the development of analytical methods based on complexation with CDs, and the optimisation of experimental conditions for the preparation of the complexes.

Exploring the enhanced stability and therapeutic efficacy of Sorafenib-Cyclodextrin inclusion complex

Sorafenib (Soraf) is a second-generation tyrosine kinase inhibitor repurposed against different cancers by working on various molecular pathways, playing a vital role in cancer cell proliferation. Sorafenib is a BCS class II drug, and its low solubility further hinders its bioavailability and results in reduced therapeutic efficacy. Therefore, in this study, we aim to explore the potential of β-cyclodextrins (β-CD) derivatives to form an inclusion complex with sorafenib to enhance sorafenib's solubility, stability, and therapeutic efficacy. Our findings suggest that HP-β-CD portrayed a higher affinity towards sorafenib than SBE-β-CD and significantly improved the solubility of sorafenib. Additionally, spectroscopic analysis and solid-state studies provided valuable information regarding the intermolecular interaction between sorafenib and HP-β-CD.Furthermore, the stability of sorafenib in biological fluids and under physiological conditions was maintained under the influence of the inclusion complex, whereas plain sorafenib degraded quickly. In addition, β-CD complexation significantly improved sorafenib's intestinal permeability, as shown in physiologically relevant EpiIntestinal® models. Lastly, the sorafenib inclusion complex demonstrated increased cytotoxicity in NSCLC and HCC cell lines. This study shows the potential of HP-β-CD to improve the solubility and therapeutic efficacy of sorafenib, thus extending its clinical application.

Cyclodextrins: Establishing building blocks for AI-driven drug design by determining affinity constants in silico

Cyclodextrins (CDs) are cyclic carbohydrate polymers that hold significant promise for drug delivery and industrial applications. Their effectiveness depends on their ability to encapsulate target molecules with strong affinity and specificity, but quantifying affinities in these systems accurately is challenging for a variety of reasons. Computational methods represent an exceptional complement to in vitro assays because they can be employed for existing and hypothetical molecules, providing high resolution structures in addition to a mechanistic, dynamic, kinetic, and thermodynamic characterization. Here, we employ potential of mean force (PMF) calculations obtained from guided metadynamics simulations to characterize the 1:1 inclusion complexes between four different modified βCDs, with different type, number, and location of substitutions, and two sterol molecules (cholesterol and 7-ketocholesterol). Our methods, validated for reproducibility through four independent repeated simulations per system and different post processing techniques, offer new insights into the formation and stability of CD-sterol inclusion complexes. A systematic distinct orientation preference where the sterol tail projects from the CD's larger face and significant impacts of CD substitutions on binding are observed. Notably, sampling only the CD cavity's wide face during simulations yielded comparable binding energies to full-cavity sampling, but in less time and with reduced statistical uncertainty, suggesting a more efficient approach. Bridging computational methods with complex molecular interactions, our research enables predictive CD designs for diverse applications. Moreover, the high reproducibility, sensitivity, and cost-effectiveness of the studied methods pave the way for extensive studies of massive CD-ligand combinations, enabling AI algorithm training and automated molecular design.

Chlorpropamide-cyclodextrin inclusion complexes, theoretical basis of stability

A study of the stability of inclusion complexes of chlorpropamide and α, β, γ, and HP-β cyclodextrin, has been carried out using molecular dynamics simulations. The contribution of weak interactions to the stability of the complexes through DFT has been analyzed. The conventional molecular dynamics analysis suggests stable complexes for the inclusion of chlorpropamide. As expected, the complex stabilization is driven by hydrophobic interactions between cyclodextrin and chlorpropamide aromatic ring; similar mobility of chlorpropamide in the cyclodextrin cavities was observed. Molecular dynamics results indicate that intermolecular hydrogen bonds appeared between 17.70 and 22.52 % of the simulation time; consequently, the crucial complex stabilizing interactions encompass more than just hydrogen bonds, revealing a more intricate network of stabilizing forces at play. For the first time, based on quantum chemistry, a correlation between the electron density contributions to weak interactions and the glucopyranose units in each CD is presented. The most relevant stabilizing interactions are of the van der Waals type, followed by small contributions from hydrogen bonds. Non-covalent interactions are more intense in the chlorpropamide/HP-β cyclodextrin complex than in other systems. The inclusion complexes formed with β-type cyclodextrins are the most stable (due to the number and intensity of the contributions), in agreement with the molecular dynamics simulation results. In addition, MMPBSA and QM energies predict CPD/αCD as unstable and least stable complex, respectively. These results highlight the importance of β-type cyclodextrins in the formation of creating reliable inclusion complexes, which could be potentially applied to molecular encapsulation and drug delivery systems.

Highly robust quantum mechanics and umbrella sampling studies on inclusion complexes of curcumin and β-cyclodextrin

The poor aqueous solubility of curcumin (CUR) obstructs its wide utilization in nutraceuticals, cosmetics, and pharmaceutical companies. This study is dedicated to investigate the stability of CUR inside the hydrophobic pocket of β-cyclodextrin (β-CD), hydroxypropyl-β-CD (HP-β-CD), and 2,6-Di-O-methyl-β-CD (DM-β-CD). Initially, molecular mechanics (MM) calculations and subsequently quantum mechanical (QM) calculations were performed on inclusion complexes to strengthen the MM results. We performed microsecond timescale MD simulations to observe the structural dynamics of CUR inside the cavity of CDs. We elucidated the most stable binding orientations of CUR inside the cavity of CDs based on binding free energy obtained from the Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) and umbrella sampling simulations. Furthermore, the two-layered ONIOM (B3LYP/6-311+G(2d,p):PM7) method with CPCM implicit water model was used to derive the complete energetics and thermodynamics of inclusion complexes at 1:1 stoichiometry. Each inclusion reaction was exothermic and spontaneous. The chemical reactivity and kinetic stability of inclusion complexes were described by HOMO-LUMO molecular orbital energies. In conclusion, our studies revealed that HP-β-CD had the highest binding affinity for CUR with the most negative complexation energy (−6520.69 kJ/mol) and Gibb's free energy change (−6448.20 kJ/mol). The atomic-level investigation of noncovalent interactions between CUR and the hydroxypropyl groups in HP-β-CD/CUR complex may be helpful to drive new derivatives of HP-β-CD with better host capacity. The computational strategy adopted here might serve as a benchmark for increasing the solubility of numerous clinically significant molecules.

Dispersion-corrected DFT calculations and umbrella sampling simulations to investigate stability of Chrysin-cyclodextrin inclusion complexes

The study of inclusion complexes of Chrysin (ChR) with three forms of cyclodextrins (CDs) α-, β-, and γ-CD was accomplished to examine the stability of ChR inside the central cavities of CDs. The aim of study was to identify the most suitable form of CD to improve the hydro-solubility of poorly soluble ChR bioactive molecule. Microsecond timescale molecular dynamics (MD) simulations were performed on four inclusion complexes (α-CD/ChR, β-CD/ChR, and two conformations of γ-CD/ChR) to examine the dynamics of ChR inside the cavity of CDs. The first conformation of γ-CD/ChR inclusion complex (γ-CD1/ChR) was identified to possess the highest affinity between host and guest molecule on the basis of binding energy calculated by employing Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) and umbrella sampling simulations. To further strengthen the claims of classical and biased MD studies, Our own N-layered Integrated molecular Orbital and Molecular mechanics (ONIOM) (wB97XD/6–311+g(d,p):pm7) calculations were performed on the selected inclusion complexes. The ONIOM based complexation energy reaffirmed that ChR had highest affinity for the γ-CD1 host molecule. Further, the non-covalent interaction analysis was conducted using Multiwfn software on QM-optimized inclusion complexes with wB97XD/6–311+G(d,p) model chemistry, revealing non-covalent interactions between ChR and CDs. This atomic level information helped us to gain better insights into critical atoms of ChR and CD that participated in intermolecular interactions and identify γ-CD as a suitable host molecule for improving the hydro-solubulity of ChR. The structural insights would help to derive new derivatives of γ-CD with better host capacity.

Solubility and Antioxidant Activity of 1,2-Dihydro-2-Methyl-2-Phenyl-3H-Indole-3-One-1-Oxyl Hosted at Randomly Methylated-Βétacyclodextrin: A Computational Investigation

In this work, the mechanism of the formation of a radical from 1,2-dihydro-2-methyl-2-phenyl-3H-indole-3-one-1-oxyl has been studied theoretically by the B3LYP/6-31G(d) method as well as the global descriptors of its reactivity have been calculated. The formation of an inclusion complex (stoichiometry 1:1) between the radical form of 1,2-dihydro-2-methyl-2-phenyl-3H-indole-3-one-1-oxyl and the randomly methylated β-cyclodextrin was also studied by B3LYP-D3/6-31G(d) method. The results obtained show that the formation of the radical is ensured by the HAT mechanism according to the BDE energies obtained in vacuum and in water. Formation of the inclusion complex according to the two models C1 and C2 leads to an increase in solubility and improve antioxidant activity of 1,2-dihydro-2-methyl-2-phenyl-3H-indole-3-one-1-oxyl radical which is agreed well with experimental results. Finally, intermolecular interaction such us H-bonds and van Der Waals interactions are the major contribution of inclusion complex stability.

Conductometric Studies of Formation the Inclusion Complexes of Phenolic Acids with β-Cyclodextrin and 2-HP-β-Cyclodextrin in Aqueous Solutions.

An attempt was made to evaluate the possibility of creating and assessing the stability of inclusion complexes of selected phenolic acids [trans-4-hydroxycinnamic acid (trans-p-coumaric acid), trans-3,4-dihydroxycinnamic acid (trans-caffeic acid), trans-4-hydroxy-3-methoxycinnamic acid, (trans-ferulic acid) and trans-3-phenylacrylic acid (trans-cinnamic acid)] with β-cyclodextrin and 2-HP-β-cyclodextrin in aqueous solutions in a wide temperature range 283.15 K-313.15 K. On the basis of the values of the limiting molar conductivity (ΛCDNaDod), calculated from the experimental data, the values of the formation constants and the thermodynamic functions of formation (standard enthalpy, entropy, and Gibs standard enthalpy) of the studied complexes were determined. It has been found that the stability of the studied complexes increases with lowering of the molar mass of cyclodextrin and lowering of the temperature.

Association Complexes of Calix[6]arenes with Amino Acids Explained by Energy-Partitioning Methods.

Intermolecular complexes with calixarenes are intriguing because of multiple possibilities of noncovalent binding for both polar and nonpolar molecules, including docking in the calixarene cavity. In this contribution calix[6]arenes interacting with amino acids are studied with an additional aim to show that tools such as symmetry-adapted perturbation theory (SAPT), functional-group SAPT (F-SAPT), and systematic molecular fragmentation (SMF) methods may provide explanations for different numbers of noncovalent bonds and of their varying strength for various calixarene conformers and guest molecules. The partitioning of the interaction energy provides an easy way to identify hydrogen bonds, including those with unconventional hydrogen acceptors, as well as other noncovalent bonds, and to find repulsive destabilizing interactions between functional groups. Various other features can be explained by energy partitioning, such as the red shift of an IR stretching frequency for some hydroxy groups, which arises from their attraction to the phenyl ring of calixarene. Pairs of hydrogen bonds and other noncovalent bonds of similar magnitude found by F-SAPT explain an increase in the stability of both inclusion and outer complexes.

Interaction mechanism of cholesterol/β-cyclodextrin complexation by combined experimental and computational approaches

It is crucial to accurately describe non-covalent weak interactions between the components of cholesterol/β-cyclodextrin inclusion complex in the modulation of its stability. Experimental and theoretical infrared spectra confirmed that the inclusion complex was successfully prepared. Phase solubility studies suggested the formation of 1:1 stoichiometric inclusion complex of cholesterol with β-CD. The inclusion complex showed higher decomposed temperature (327.3 °C) than physical mixture (321.6 °C), indicating improved thermal stability of inclusion complex. Conformational search and density functional theory calculations were performed to find the most stable conformation with the lowest complexation energy (−129.66 kJ/mol). Dispersion energy from van der Waals (−283.31 kJ/mol) contributed greatly on total bonding energy (−204.72 kJ/mol). The bond lengths of hydrogen bonds (O127⋅⋅⋅H221 and O220⋅⋅⋅H107) were 1.77 and 1.62 Å, respectively. Van der Waals and hydrogen bonds were necessary to drive spontaneous formation and maintain the stability of inclusion complex. This study revealed a deep insight into the formation mechanism of cholesterol/β-CD inclusion complex using computational and experimental approaches, providing theoretical basis for the removal of cholesterol from hydrocolloid-containing systems. • Mechanism of β-CD complexation with cholesterol was illustrated through experimental and computational methods. • The thermal stability of cholesterol/β-CD inclusion complex was significantly improved. • Weak interactions of the complex were shown by means of images and data. • The inclusion complex was mainly stabilized by hydrogen bonds and van der Waals forces.

Preparation, binding behaviours and thermal stability of inclusion complexes between (Z)‐jasmone and acyclic cucurbit[n]urils

Abstract(Z)‐jasmone is the most important contribution to the scents of perfumes and cosmetics. However, (Z)‐jasmone is water insoluble and highly volatile, which limits its development and application. Inclusion technology has become a promising strategy to improve the solubility and stability of hydrophobic small molecules. Here, we used saturated aqueous solution and freeze‐drying method to prepare solid inclusion complexes of (Z)‐jasmone and three acyclic cucurbit[n]urils (ACBs, M1‐M3), and studied their binding behaviours by fluorescence spectroscopy, NMR, XRD, FT‐IR, TG and DSC, confirming the formation of the host‐guest inclusion complexes. The stoichiometry of inclusion complexes was 1:1 by Job's plot. The inclusion complexes exhibited better water solubility, higher thermal stability and heat‐controlled release comparing with that of native (Z)‐jasmone. This work uncloses a new strategy to enhance the performance of essential oil and flavours/fragrances and further application in the field of cosmetic and food industry.

Both alkyl chain length and V-amylose structure affect the structural and digestive stability of amylose-alkylresorcinols inclusion complexes

Alkylresorcinols (ARs) are a group of bioactive phenolic lipids and mostly concentrated in the bran of whole grains. In this study, the influences of alkyl chain length of ARs and V-amylose structure on the stability of V-amylose-ARs inclusion complexes were characterized. On the one hand, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and in vitro digestion studies of complexes showed that the crystallinity, thermo-stability, and digestion resistance of V-amylose-ARs inclusion complexes increased with increasing alkyl chain length of ARs. On the other hand, V6-amylose-ARs inclusion complexes displayed the strongest thermostability, the highest crystallinity, and the lowest digestibility compared to V7-amylose-ARs inclusion complexes and V8-amylose-ARs inclusion complexes. It could be concluded that both the helical structure of hydrated V6-amylose and ARs with longer alkyl chain stabilized the structure and stability of the inclusion complexes. This work could pave a way to develop bioactive cereal foods with high bioaccessibility of ARs.

Studies of thermal, spectral and antibacterial activities of some inclusion complexes of 4-Thiazolidinone derivatives with β-Cyclodextrin

2-Hydrazinobezothiazole is taken as starting material for the preparation of some compounds of 4-thazolidinone derivative. 4-Thiazolidinone and its analogous are very good pharamacophores performing wide range of biological activities. But the compounds being poor solubility in aqueous medium may be a limiting factor for decreasing their bio-accessibility. To removes the difficulties, its inclusion complexes can be prepared with β-cyclodextrin which is non-toxic oligosaccharide. The nature of inclusion complexes along with the compounds characters such as physical, spectral and thermal are discussed. The stoichiometry ratio of 1:1 between the compound and β-cyclodextrin confirmed from their aqueous phase solubility study. The existence of weak intermolecular force between 4-thiazolidinone derivatives and β-cyclodextrin can be ascertained from their thermodynamic stability constants. The antibacterial activity against the microbes like E.coli and S.aureus are susceptible to compounds of 4-thiazolidinone, and it enhances in their corresponding inclusion complexes. The stability of inclusion complex and host–guest relation can be ascertained from thermodynamic parameters along with the free energy change. Besides this, there is alternation in physical and spectral properties of compounds after formation of inclusion complexes.

Studies of the Formation and Stability of Ezetimibe-Cyclodextrin Inclusion Complexes.

In the presented studies, the interactions between ezetimibe (EZE) and selected cyclodextrins were investigated. α-Cyclodextrin (αCD), β-cyclodextrin (βCD) and its modified derivatives, hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD), were selected for the research. Measurements were carried out using calorimetric and spectroscopic methods. Additionally, the Hirshfeld surface and biochemical analysis were achieved. As a result of the study, the inclusion complexes with 1:1 stoichiometry were obtained. The most stable are the complexes of β-cyclodextrin and its derivatives. The comparison of βCD with its derivatives shows that the modifications have an affect on the formation of more durable and stable complexes.

Effect of the pH on the thermodynamic stability of inclusion complexes of thymol and carvacrol in β-cyclodextrin in water

Thymol and carvacrol are terpenes which have great potential to be used as preservatives in food and antimicrobial agents in medicinal herbs. As they present low water solubility and display acid-basic properties, inclusion in cyclodextrins and pH variations may enhance their properties. Here, the inclusion of thymol and carvacrol in β-cyclodextrin, at neutral and basic pH at 25 °C, is reported. The pKa for free thymol and carvacrol, and the pKa’ for the complexes HThy−βCD and HCar−βCD are determined by UV–Visible spectrophotometry. Inclusion in βCD has a stronger effect on ionization of thymol than on ionization of carvacrol. At neutral pH, the inclusion thermodynamic constants of the complexes HThy−βCD and HCar−βCD, reported as log βTer', are also determined by UV–Vis spectrophotometry. For the pHs 7.0, 8.0, 10.1 and 11.5, the log βTer' are obtained by isothermal titration calorimetry. Quantum chemistry molecular modeling is employed to reveal non-covalent interactions between terpenes and βCD molecules. Equations to calculate the inclusion constant βTer' at any pH value are derived. Furthermore, the Higuchi and Connors method is used to evaluate the increase of neutral terpenes solubility as result of the inclusion in βCD. Finally, using the experimental S0, pKa, pKa’ and βHTer, the terpenes solubility (S) are obtained in terms of pH and βCD total concentration.

Exploiting Food-Grade Mesoporous Silica to Preserve the Antioxidant Properties of Fresh Olive Mill Wastewaters Phenolic Extracts.

Fresh olive mill wastewaters phenolic extracts are of great interest as preservatives or fortifying ingredients but are characterized by limited stability. The purpose of this study was to use mesoporous silica to enhance their stability and preserve their antioxidant properties. The phenolic extracts were characterized for their composition by HPLC-DAD and included in a mesoporous matrix with or without a lipid coating. The inclusion complexes were characterized in terms of total phenolic content, radical scavenging capacity and in vitro antioxidative activity and cell compatibility. Besides, inclusion complex stability under different storage conditions (22 and 37 °C, 75% relative humidity, 1 month) was evaluated. The inclusion process was nearly quantitative and modified neither the total phenolic content nor the total antioxidant capacity. None of the inclusion complex concentrations assayed on the HT29 cell line showed toxicity. Moreover, HT29 cells treated with the inclusion complex exhibited a significant antioxidant effect, while the lipid coating impaired the antioxidant activity. The complexes without lipid were stable under all the investigated conditions, while the lipid-coated products were less stable under the more drastic conditions. Overall, inclusion complexes in mesoporous silica have suitable characteristics to be used for different applications, including food supplementation.

Inclusion complexes of tea polyphenols with HP-β-cyclodextrin:Preparation, characterization, molecular docking, and antioxidant activity.

The purpose of this study was to prepare and characterize inclusion complexes between tea polyphenol (TP) and hydroxypropyl-β-cyclodextrin (HP-β-CD), and to evaluate their antioxidant properties. Freeze-drying was used to prepare the inclusion complex of TP/HP-β-CD at different component ratios (1:0.5, 1:1, and 1:2). The supermolecular structure of the TP/HP-β-CD complex was characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). Molecular docking was used to simulate the positions and interactions of the binding sites of TP/HP-β-CD inclusion complexes and target protein receptors. In addition, the effects of TP/HP-β-CD inclusion complexes on myofibrillar protein (MP) from lamb tripe were observed under oxidative conditions. Results showed that TP was encapsulated in the cavity of HP-β-CD to form an optimal complex with 1:2 molar ratio of stoichiometry, while the FTIR, TGA, and SEM studies also support the inclusion process. Molecular modeling results were systematically analyzed to determine the stability of inclusion complexes and protein. Furthermore, the addition of an appropriate concentration (5 to 105µmol/g) of TP/HP-β-CD inclusion complex decreased the carbonyl content, hydrophobicity, and protein aggregation of MP from lamb tripe, whereas it increased the sulfhydryl content. This improved antioxidant activity and bioavailability of the inclusion complexes will be beneficial for its potential applications in food. PRACTICAL APPLICATION: Tea polyphenol was an antioxidant with potential for the field of food. In this study, the unstable properties of tea polyphenols were evaluated and were improved by inclusion of HP-β-cyclodextrin. The binding mode of the inclusion complex with protein was revealed via the molecular docking method, and the application of inclusion complex to control protein oxidation was studied. Results showed that the inclusion complex could effectively inhibit protein oxidation, which can provide a reference for the application of polyphenols in meat products and the improvement of protein properties.

Molecular dynamics studies on the aggregating behaviors of cellulose molecules in NaOH/urea aqueous solution

Aggregating behaviors of cellulose molecules in NaOH/urea aqueous solution were investigated using a molecular dynamics (MD) simulation method. All the components, including cellulose, NaOH, urea and H2O were combined into the simulation. By monitoring the transformation of cellulose aggregates, we quantitatively revealed the solvent aggregating behaviors around cellulose molecules in the whole simulation process. And the aggregation evolution of solvent components around cellulose molecules, distributions of the solvent components in cellulose ICs, and the impacts of urea and NaOH in the dissolving process were discussed. In the simulation, the aggregated structure of cellulose molecules was dramatically changed and went through a dispersion process, equilibrium process and reaggregation process. The dramatic transformation of the cellulose aggregated structure indicates that the solvent components prefer to penetrate into the cellulose molecular sheets from the direction perpendicular to the molecular sheet. In the dispersion process, sodium ions around O6 and hydroxide ions around O3 and O2 play crucial roles in the dissolution of cellulose. In the reaggregation process, the sodium ions near O6 and the urea around acetalic oxygen atoms impact the stability of cellulose inclusion complexes, and obvious decrements in these solvent components were observed.

In silico prediction of binding capacity and interaction forces of organic compounds with α- and β-cyclodextrins

As commonly-used cyclic oligomers, cyclodextrins are usually composed of 6 and 7 glucopyranose units (α-cyclodextrin and β-cyclodextrin). The binding constant is a significant parameter to estimate the association stability of inclusion complexes and evaluate the influence of cyclodextrins on guest compounds. In order to cover the shortage of experimental methods, we intended to predict the binding constants and interaction forces of cyclodextrin inclusion complexes by developing consensus models and calculating energy changes. 418 cyclodextrin inclusion complexes were collected with their experimental binding constants. By combining 6 description methods and 5 machine learning methods, we built 60 single models, which were selected to develop 104 consensus models. The coefficients of determination of the test sets in the best α-cyclodextrin consensus model and the best β-cyclodextrin consensus model were 0.84 and 0.89, respectively. The applicability domains of models were defined. After performing molecular docking and calculating energy changes, we could observe the binding poses, identify the interaction forces, and select the dominant forces. The consensus models and the calculation of energy changes can be applied to explore the binding capacity and interaction forces of inclusion complexes.