Journal of Inclusion Phenomena and Macrocyclic Chemistry最新文献

Novel derivatives of diazadioxocalix[2]arene[2]triazine were synthesized and evaluated for their catalytic effects on direct asymmetric Aldol reactions in organic solvents. Chiral groups were attached to the heteroatom-bridged calix[2]triazine scaffold through reactions involving (R)/(S)-1,2,3,4-tetrahydro-1-naphthylamine with diazadioxocalix[2]arene[2]triazine. Diazadioxocalix[2]arene[2]triazine derivatives were found to be effective catalysts for the reaction of acetone with aromatic aldehydes. According to the obtained results, it has been determined that the moiety of the catalyst affects the configuration of the Aldol product. The Aldol adducts were obtained in excellent yields (93%) and enantioselectivities (96%).

The wheel-and-axle host compounds 9,9′-(1,4-phenylene)bis(fluoren-9-ol) (H1), 9,9′-(ethyne-1,2-diyl)bis(fluoren-9-ol) (H2) and 9,9′-(biphenyl-4,4′-diyl)bis(fluoren-9-ol) (H3) each formed complexes with tetramethylurea (TMU), a polar aprotic organic solvent, with host: guest ratios of 1:2. Single crystal X-ray diffraction revealed that these complexes crystallized in the monoclinic space group P2₁/c, their analyses being performed in P2₁/c for H1⋅2(TMU) and in the alternative setting P2₁/n for both H2·2(TMU) and H3·2(TMU). Furthermore, these inclusion compounds are stabilized by both classical and non-classical hydrogen bonds between the host and guest molecules. Hirshfeld surface analyses demonstrated that the percentage of interatomic (host)H···O(guest) interactions ranged between 7.8 and 10.3%, while thermal analyses showed that the relative thermal stabilities of these complexes were high, with the onset temperatures for the guest release event, T_on, being 83.1 (H1·2(TMU)), 81.1 (H2·2(TMU)) and 90.3 °C (H3·2(TMU)). Moreover, the calculated mass loss percentages, after heating each complex in a controlled manner to release the guest species, correlated closely with those expected for these 1:2 host: guest inclusion complexes. Finally, determination of the activation energies for complex desolvation yielded 148.7 ± 5.4, 128.6 ± 10.8 and 149.4 ± 0.8 kJ·mol^‒1 for H1·2(TMU), H2·2(TMU) and H3·2(TMU) respectively. A single guest desolvation mechanism was at work in the first and last of these complexes, while this mechanism in H2·2(TMU) changed during this process. The H1·2(TMU) inclusion complex has been reported previously, and the results obtained in that work are also compared with those from the present investigation.

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.