Journal of Inclusion Phenomena and Macrocyclic Chemistry最新文献

Oseltamivir (OST) phosphate is a prodrug, metabolized by hepatic carboxylesterase to its active metabolite (oseltamivir carboxylate). OST is efficient in treatment of influenza, in both children and adults. The protein bonding of the prodrug and its active metabolite is low (42% and 3%, respectively). It has a short half-life 1–3 h but its active metabolite has a half-life of 6–10 h, permitting twice daily administration. The most common side effect is gastrointestinal disturbances that are usually nausea and vomiting and can be reduced when taken simultaneously with food. OST phosphate is a white powder with bitter taste and the marketed oral suspension uses sorbitol for masking it. Cross-linked cyclodextrin polymers are known for their ability to increase the dissolution rate, solubility, stability, and permeability of insoluble drugs and provide prolonged release. Therefore, they are promising drug delivery systems that could improve its pharmacokinetic properties and patient adherence. In this study we focused on developing a therapeutic system of OST using cyclodextrin polymer crosslinked with pyromellitic dianhydride (PMDA CD) to enhance its pharmacokinetic properties and to improve its compliance. PMDA CD polymer and PMDA CD polymer complex with OST were prepared. Physicochemical characterization by FTIR spectra, thermal analysis, DLS, SEM and EDX confirmed the existence of interaction between the two components. The prepared complex has a different pharmaceutical profile compared to OST, with higher stability and a controlled dissolution profile. Toxicity studies showed that the polymer complex has lower toxicity than OST, suggesting the protective effect of the polymer.

Here we report on the host behaviour of compounds N, N’-bis(9-phenyl-9-xanthenyl)propane-1,3-diamine (H1) and N, N’-bis(9-phenyl-9-xanthenyl)butane-1,4-diamine (H2) in the presence of potential guest species cyclohexanone (CYC) and 2-, 3- and 4-methylcyclohexanone (2MeCYC, 3MeCYC and 4MeCYC). H1 only formed a complex with CYC, whilst all four guest solvents were enclathrated by H2. Thermal analyses in conjunction with SCXRD experiments revealed that more energy was required to remove guest species from the crystals of their complexes when they were housed in discrete cavities compared with guest molecules retained in channels. Only in H1·CYC was identified an intramolecular (host)N‒H···N(host) hydrogen bond, while complexes H2·2(CYC), H2·2(3MeCYC) and H2·4MeCYC all experienced strong (host)N‒H···O(guest) hydrogen bonds which assisted in retention of the guests in the complexes; this interaction type was absent in both H1·CYC and H2·2(2MeCYC). Hirshfeld surface analyses demonstrated that the amounts of (guest)O···H(host) interatomic interactions were comparable and ranged between 11.1 and 13.9%. Guest competition experiments showed that H2 possessed an affinity for, more usually, 3MeCYC, despite the complex H2·2(3MeCYC) being the least thermally stable one. Finally, it was established that H1 and H2 would not be appropriate host compounds for separations of mixed cyclohexanones through supramolecular chemistry strategies.

As a booming research theme, heterogeneous catalysts have demonstrated significant advantages over homogeneous catalysts in terms of stability, recyclability, and separability from the reactant mixture. In this study, a supramolecular coordinated polymer (P[5]-SCP) was synthesized by complexing thiazole-derived pillar[5]arene (P[5]) with Pd(II), which was obtained by nucleophilic substitution between 1,4-bis(2-Bromoethoxy) pillar[5]arene and 4-methyl-5-(β-hydroxyethyl) thiazole. The chemical component and structure of the P[5]-SCP were confirmed by NMR, EA, FI-IR, XPS, XRD, SEM, TEM, HR MS. In the Suzuki–Miyaura coupling reaction, the catalytic activity, stability, and recyclability were thoroughly evaluated. The P[5]-SCP had excellent catalytic activity in mild reaction conditions (up to 81% yield) and exhibited little loss of activity after at least five recycles. Furthermore, catalyst P[5]-SCP was easily synthesized from simple raw materials and low-cost, thereby a novel pillar[5]arene based-NHC catalyst was developed in green heterogeneous catalysis.

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Steroid hormones play a crucial role in the body by acting as chemical messengers. They are, however, poorly soluble in water, and cyclodextrins can increase their solubility thus leading to increased bioavailability when used in drug formulations. Accuracy in the prediction of the free energy of binding of cyclodextrin/steroid inclusion complexes with simulation is important because of the potential value it brings by providing low-cost predictions of the real-life behavior of the cyclodextrin/steroid inclusion complex and the potential for high-through-put screening. Many computational methods exist, and it is therefore important to understand the ability of current theoretical models to accurately predict the free energy of binding for these inclusion complexes. We focused specifically on the estimation of the free energy of binding of inclusion complexes of four steroids: Hydrocortisone, dexamethasone, prednisolone, and 6α-methylprednisolone with native α-CD, β-CD, γ-CD, (2-hydroxy)propyl-β-CD, and sulfobutylether-β-CD by phase solubility as well as with α, β, and γ-CD by simulations. The simulations were assessed with both docking and the molecular mechanics combined with the generalized Born and surface area (MM/GBSA) continuum solvation approach. Considering the phase solubility diagram, (2-hydroxy)propyl-β-CD and sulfobutylether-β-CD dissolved more steroids in the higher concentration range as expected. The assessment of the free energy of binding obtained from the phase solubility and theory showed that the MM/GBSA method has shown promise in reliably generating accurate predictions in the field of calculating the free energy of binding of steroids/cyclodextrins with a correlation coefficient (R²) = 0.94.

The aim of this review is to compile important results of single-crystal X-ray diffraction method, vibrational and NMR studies conducted on alkali metal ion complexes of some small ring benzo-crown ethers namely benzo-15-crown-5, dibenzo-15-crown-5 and benzo-12-crown-4 to determine their structure, stoichiometry and conformation in the solid-state. This review focuses on solid-state architectural diversity of alkali metal ion complexes studied by single-crystal X-ray diffraction method. Investigations of these complexes are significant as the interactions of alkali metal ions with these crown ethers mimic those present in nature between univalent ions and several bioligands. The benzo group in the macrocycle allows to monitor the complexation event by fluorescence studies and extends the applications of these crown ethers to fluorescent ion sensors. The selected small ring benzo oxa-crown ethers have cavities that match the size of the alkali metal ions and give stable complexes with them. The review presents results related to variation in infrared and Raman spectra of the ligands with changes in their crystal structure and conformation on complexation with alkali salts. Single-crystal X-ray diffraction studies of these complexes help to confirm the chemical structure, stoichiometry, stable conformation and presence of associated solvent molecules in the solid state. As noncovalent interactions are involved in the formation of these complexes, they are capable of forming supramolecular assemblies for building smart functional materials.

Graphical Abstract

The inclusion compounds of auranofin (AF) and its iodide derivative (AF-I) with HP-β-CD were recently identified and characterized experimentally. In the present work, classical molecular dynamics and the quantum computational GFN2-xTB method were applied to investigate the inclusion processes. As a result, both approaches identified AF-I@HP-β-CD as the most favourable system, as observed experimentally. The higher stability of AF-I@HP-β-CD was explained by entropy and solvation factors, with the GFN2-xTB method providing a stability constant (logK_1:1) in good agreement with the experimental results: 0.21–1.21 for AF@HP-β-CD and 1.31–2.33 for AF-I@HP-β-CD (the experimental values are 1.48 and 2.52, respectively). The preferred inclusion mode for AF-I@HP-β-CD has a triethylphosphine (-PEt₃) group pointed towards the head portion of the HP-β-CD where the HP groups are attached (labelled P2). The P2 mode showed short contacts between -CH₂CH₃ groups (-PEt₃) and -H-3 only (inside the CD cavity), which is also supported by ROESY experiments.

Hosts, a key component of inclusion complexes, are cyclic oligomeric compounds containing a cavity in which another component of the complex is bound by non-covalent forces. Chiral hosts are particularly important and interesting because they allow the study of specific intermolecular interactions and molecular recognition. The most important classes of chiral hosts and their physicochemical properties are briefly reviewed. An important part of this Review is the description of selected concepts necessary to understand the properties and behavior of inclusion complexes studied by the most suitable analytical method for studying inclusion complexes—nuclear magnetic resonance.

The geometrical structures of cucurbit[n]uril (CB[n], n = 5–8 and their complexes with molnupiravir (MLP) drug have been investigated using the DFT computations. The complexation energies and electronic properties of CB[n]/MLP complexes were also computed. The host–guest interactions in the complexation are occurred through the of dipole–dipole interactions which are the hydrogen bonds between the O−H or N−H of molnupiravir and oxygen atoms of CB[n]s. The CB[n]/MLP host–guest complexation in both gas and water are found to be an exothermic reaction with negative complexation energy values. By means of the NBO analysis and MEP contours, the partial charge transfers from CB[n]s to molnupiravir are displayed. After drug complexation, the electronics properties of CB[n]s are significantly changed. This means that CB[n]s can act as a host for appropriately molnupiravir guest, even in aqueous solution.

The effective binding of Rhodamine B (RhB), a xanthene dye, in solutions of amphiphilic sulfobetaine tetrapentylcalix[4]resorcinarene (C₅-SB) at millimolar concentrations has been found. Using the FT-PGSE NMR technique, it was determined that the binding fraction (P_b) of RhB in the solution with a С(RhB)/С(С₅-SB) ratio of 3.75 mM/5 mM was 0.57, whereas in a solution with an order of magnitude lower concentration, the P_b was only 0.12. This significant difference in interaction is also supported by 2D NOESY and ¹H NMR spectra. Based on fluorimetry data, it appears that the influence of C₅-SB on the spectral properties of RhB increases as the C₅-SB/RhB molar ratio increases, but decreases as the concentration of C₅-SB and RhB decreases. By comparing the spectral properties of RhB in the presence of C₅-SB and tetrapentylcalix[4]resorcinarene with carboxylic (C₅-COO⁻) and trimethylammonium (C5-N⁺Me₃) peripheral groups, an assumption about the driving forces behind RhB, which led to an enhancement of the emission properties of the dye, was made. The study demonstrates the possibility of controlling the emissive properties of a xanthene dye by binding it to a supramolecular associate with amphiphilic calix [4] resorcinarene.

Physical manipulation can be carried out on molecules and cells through the utilization of nanomachines which are machines with nano dimensions. There are different types of nanomachines. Among them, rotaxanes stand out as the most well-known. The term of rotaxane originates from the combination of the Latin words wheel and axis. The application of nanomachines is identifying and measuring the concentration of toxic substances in the environment, targeted drug delivery and cancer diagnosis. The objective of this study is to synthesize and identify several new nanomachines in the form of rotaxanes (internally locked molecules) with nanopharmaceutical properties from the corresponding crown compounds. In the first step, 2,2-dimethylphenol was converted into bisphenol compound (1) in reaction with thionyl chloride. Bisphenol compound (1) was converted into methyl diester compound (2) in reaction with methyl chloroacetate. The methyl diester compound (2) reacts with the appropriate diamine to form the diamide macrocycle compound (3). Rod (4) is prepared from the reaction of diethylene glycol ditosylate, 4,4-bipyridine and a bulk phenol such as 4-tert-butylphenol in DMF. Each of the rings in the presence of the prepared rod leads to the corresponding rotaxane compound (5). Chemical structure of the obtained compounds were established by ¹HNMR, ¹³CNMR, FT-IR and SEM spectroscopic methods.