Selectivity tuning of cyclodextrin derivatives by specific substitution

A new, highly enantioselective cyclodextrin derivative combining the properties of heptakis(6‐O‐tert‐butyldimethylsilyl‐2,3‐di‐O‐methyl)‐β‐cyclodextrin and heptakis(2,3‐di‐O‐acetyl‐6‐O‐tert‐butyldimethylsilyl)‐β‐cyclodextrin was prepared by exchanging a methyl group for an acetyl substituent in a single glucose unit of heptakis(6‐O‐tert‐butyldimethylsilyl‐2,3‐di‐O‐methyl)‐β‐cyclodextrin. A comparative evaluation of the separation capabilities showed that the enantioselectivity of both “parent” cyclodextrin derivatives is transferred to the new chiral stationary phase.     

Comparative analysis of the full set of methylated β‐cyclodextrins as chiral selectors in capillary electrophoresis

The chiral separation ability of the full library of methylated‐β‐cyclodextrins towards pharmacologically significant racemic drugs including basic compounds was studied by chiral CE. The syntheses of all the methylated, single isomer β‐cyclodextrins were revised and optimized and the aqueous solubility of the derivatives was unambiguously established. The three most relevant commercially available methylated isomeric mixtures were also included in the screening, so a total of ten various methylated CDs were investigated. The effects of the selector concentration on the enantiorecognition properties at acidic pH were investigated. Among the dimethylated β‐cyclodextrins, the heptakis (2,6‐di‐O‐methyl)‐β‐cyclodextrin isomer (2,6‐DIMEB) resulted to be the most versatile chiral selector. Terbutaline was selected as a model compound for the in‐depth investigation of host‐guest enantiodiscrimination ability. The association constants between the two terbutaline enantiomers and 2,6‐DIMEB were determined in order to support that the enantioseparation is driven by differences is host‐guest binding. The migration order of the enantiomers was confirmed by performing spiking experiments with the pure enantiomers. 1D and 2D NMR spectroscopy was applied to the 2,3‐, and 2,6‐DIMEB/terbutaline systems to rationalize at molecular level the different enantioseparation ability of the dimethylated β‐cyclodextrin selectors.     

Comparative evaluation of a one‐pot strategy for the preparation of β‐cyclodextrin‐functionalized monoliths: Effect of the degree of amino substitution of β‐cyclodextrin on the column performance

To further evaluate the feasibility and applicability of the one‐pot strategy in monolithic column preparation, two novel β‐cyclodextrin‐functionalized organic polymeric monoliths were prepared using two β‐cyclodextrin derivatives, i.e. mono(6‐amino‐6‐deoxy)‐β‐cyclodextrin and heptakis(6‐amino‐6‐deoxy)‐β‐cyclodextrin. In this improved method, mono(6‐amino‐6‐deoxy)‐β‐cyclodextrin or heptakis(6‐amino‐6‐deoxy)‐β‐cyclodextrin reacted with glycidyl methacrylate to generate the corresponding functional monomers and were subsequently copolymerized with ethylene dimethacrylate. The polymerization conditions for both monoliths were carefully optimized to obtain satisfactory column performance with respect to column efficiency, reproducibility, permeability, and stability. The obtained poly(glycidyl methacrylate‐mono(6‐amino‐6‐deoxy)‐β‐cyclodextrin‐co‐ethylene dimethacrylate) and poly(glycidyl methacrylate‐heptakis(6‐amino‐6‐deoxy)‐β‐cyclodextrin‐co‐ethylene dimethacrylate) monoliths exhibited a uniform structure, good permeability, and mechanical stability as indicated by scanning electron microscopy and micro‐high‐performance liquid chromatography experimental results. Because of the probable existence of multi‐glycidyl methacrylate linking spacers on the poly(glycidyl methacrylate‐heptakis(6‐amino‐6‐deoxy)‐β‐cyclodextrin‐co‐ethylene dimethacrylate) monolith, the effect of the ratio of glycidyl methacrylate/heptakis(6‐amino‐6‐deoxy)‐β‐cyclodextrin was especially studied, and satisfactory reproducibility could still be achieved by strictly controlling the composition of the polymerization mixture. To investigate the effect of the degree of amino substitution of β‐cyclodextrin on column performance, a detailed comparison of the two monoliths was also carried out using series of analytes including small peptides and chiral acids. It was found that the β‐cyclodextrin‐functionalized monolith with mono‐glycidyl methacrylate linking spacers demonstrated better chiral separation performance than that with multi‐glycidyl methacrylate linking spacers.     

Gas Chromatographic Enantiomer Separation of Atropisomeric PCBs Using Modified Cyclodextrins as Chiral Phases

Columns containing different types of cyclodextrin derivatives have been evaluated for chiral gas chromatographic separation of atropisomeric PCBs, o,p´‐DDT and o,p´‐DDD. Separation was attempted on columns containing mixed chiral selectors, and the performance of two closely related selectors was also examined. The cyclodextrins were: permethylated‐β‐CD (PM‐β‐CD), heptakis(2,3‐di‐O‐methyl‐6‐O‐tert‐butyldimethylsilyl)‐β‐CD (2,3‐M‐6‐TBDMS‐β‐CD), heptakis(2,3‐di‐O‐methyl‐6‐O‐tert‐hexyldimethylsilyl)‐β‐CD (2,3‐M‐6‐THDMS‐β‐CD), and heptakis(2,3‐di‐O‐ethyl‐6‐O‐tert‐hexyldimethylsilyl)‐β‐cyclodextrin (2,3‐E‐6‐THDMS‐β‐CD). The cyclodextrins were dissolved in OV‐1701 or in a dimethylsiloxane/silarylene copolymer containing 5% phenyl in the backbone. The application of mixed chiral selectors led to improved separations, however; at most eleven PCB congeners were separated on a single column. Chiral resolution of o,p´‐DDD was achieved. The use of a dimethylsiloxane/silarylene copolymer as a matrix for the cyclodextrins is a promising approach. With such a matrix, blocking of the CD cavities by silicone substituent groups can be avoided, and a reasonable CD solubility can be provided. The selectivity of heptakis(2,3‐di‐O‐ethyl‐6‐O‐tert‐hexyldimethylsilyl)‐β‐CD and heptakis(2,3‐di‐O‐methyl‐6‐O‐tert‐hexyldimethylsilyl)‐β‐CD was quite different, the former selector could separate four congeners, while the latter separated ten congeners.     

Supramolecular Complexation in Biological Media: NMR Study on Inclusion of an Anionic Tetraarylporphyrin into a Per‐O‐Methylated β‐Cyclodextrin Cavity in Serum,Blood, and Urine

The supramolecular complexation of 5,10,15,20‐tetrakis(4‐sulfonatophenyl)porphyrin (TPPS) with heptakis(2,3,6‐tri‐O‐methyl)‐β‐cyclodextrin (TMCD) has been known to be highly specific in aqueous media. In this study, we have used NMR spectroscopy to reveal that this supramolecular system also works even in biologically crowded media such as serum, blood, and urine. A ¹³C‐labeled heptakis(2,3,6‐tri‐O‐methyl‐¹³C)‐β‐cyclodextrin (¹³C‐TMCD) was synthesized and studied using one‐dimensional (1D) HMQC spectroscopy in serum and blood. The 1D HMQC spectrum of ¹³C‐TMCD showed clear signals due to the 2‐, 3‐, and 6‐O¹³CH₃ groups, whose chemical shifts changed upon addition of TPPS due to quantitative formation of the ¹³C‐TMCD/TPPS=2/1 inclusion complex in such biological media. The ¹H NMR signals of non‐isotope‐labeled TPPS included by ¹³C‐TMCD were detected using the ¹³C‐filtered ROESY technique. A pharmacokinetic study of ¹³C‐TMCD and its complex with TPPS was carried out in mice using the 1D HMQC method. The results indicated that (1) 1D HMQC is an effective technique for monitoring the inclusion phenomena of ¹³C‐labeled cyclodextrin in biological media and (2) the intermolecular interaction between ¹³C‐TMCD and TPPS is highly selective even in contaminated media like blood, serum, and urine.     

Gas phase isomeric differentiation of oleanolic and ursolic acids associated with heptakis‐(2,6‐di‐O‐methyl)‐β‐cyclodextrin by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

Oleanolic acid (OA) and ursolic acid (UA) are isomeric triterpenoid compounds with similar pharmaceutical properties. Usually, modern chromatographic and electrophoretic methods are widely utilized to differentiate these two compounds. Compared with mass spectrometric (MS) methods, these modern separation methods are both time‐ and sample‐consuming. Herein, we present a new method for structural differentiation of OA and UA by Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR MS) with the association of heptakis‐(2,6‐di‐O‐methyl)‐β‐cyclodextrin (DM‐β‐CD). Exact MS and tandem MS (MS/MS) data showed that there is no perceptible difference between OA and UA, as well as their β‐cyclodextrin and γ‐cyclodextrin complexes. However, there is a remarkable difference in MS/MS spectra of DM‐β‐CD complexes of OA and UA. The peak corresponding to the neutral loss of a formic acid and a water molecule could only be observed in the MS/MS spectrum of the complex of DM‐β‐CD : OA. Molecular modeling calculations were also employed to further investigate the structural differences of DM‐β‐CD : OA and DM‐β‐CD : UA complexes. Therefore, by employing DM‐β‐CD as a reference reagent, OA and UA could be differentiated with purely MS method. Copyright © 2010 John Wiley & Sons, Ltd.     

A mixed cyclodextrin‐biphenyl thermotropic liquid crystal: Synthesis,liquid‐crystalline properties,and supramolecular organization

A well‐defined structure liquid crystal heptakis [6‐deoxy‐6‐(1‐H‐1,2,3‐triazol‐4‐yl)(methyl)6‐(4‐methoxybiphenyl‐4′‐yloxy) hexanoyl]‐β‐cyclodextrin (H6B‐β‐CD) was synthesized from propargyl 6‐(4‐methoxybiphenyl‐4′‐yloxy) hexanoate (P6B) and heptakis (6‐deoxy‐6‐azido)‐β‐cyclodextrin ((N₃)₇‐β‐CD) by click reaction. The chemical structure of H6B‐β‐CD was confirmed by ¹H NMR, FTIR, and MALDI‐TOF MS. The thermal stability of the compound was investigated by thermogravimetric analysis (TGA). The liquid crystalline behavior was studied by differential scanning calorimetry (DSC), polarizing optical microcopy (POM), and wide‐angle X‐ray diffraction (WAXD) measurement. These investigations have shown that the supramolecular structure of H6B‐β‐CD are consisted of a large scale ordered lamellar structure and a small scale ordered structure (SmE) at low temperature region. As the temperature increases, the small scale structure becomes disordered relatively in the first instance, from smectic E to smectic A. Then, the lamellar structure collapses and nematic phase and isotropic phase are observed in sequence. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2838–2845, 2010     

Dramatic decrease of the cis content and molecular weight of cis‐transoidal polyphenylacetylene at 23 °C in solutions prepared in air

The thermal cis–trans isomerization of cis‐transoidal polyphenylacetylene (PPA) synthesized with Noyori's catalyst [Rh(C?CPh)(norbornadiene)(PPh₃)₂] has been investigated under both ambient and inert atmospheres in solution and in bulk. In all cases, an intramolecular cyclization results in cis–trans isomerization, and subsequent chain cleavage produces 1,3,5‐triphenylbenzene. This reaction is accelerated by the presence of air, particularly when the reaction takes place in solution. Decreases in the cis content and molecular weight show that the intramolecular cyclization process takes place at 23 °C in solution. The mechanism of this reaction is identical to that reported previously for cis‐cisoidal and cis‐transoidal PPA synthesized with Ziegler–Natta catalysts. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3212–3220, 2002     

6‐TIPS‐β‐Cyclodextrin‐Modified Fe3O4 for Facile Enantioseparation of 1‐(1‐Naphthyl)ethylamine

A new type of chiral magnetic nanoparticle was prepared from covalently linked magnetic nanoparticles (Fe₃O₄) and heptakis‐(6‐O‐triisopropylsilyl)‐β‐cyclodextrin (6‐TIPS‐β‐CD). The resulting selectors (TIPS‐β‐CD‐MNPs) combined the good magnetic properties Fe₃O₄ and efficient chiral recognition ability of 6‐TIPS‐β‐CD. The enantioselectivity of TIPS‐β‐CD‐MNPs towards 1‐(1‐naphthyl)ethylamine was six times higher than that of the parent β‐CD modified Fe₃O₄ particles.     

Synthesis and Silica‐Based Immobilization of Monofunctionalized Heptakis(2,6‐di‐O‐methyl‐3‐O‐pentyl)‐β‐cyclodextrin for Enantioselective Capillary‐HPLC

Heptakis(2,6‐di‐O‐methyl‐3‐O‐pentyl)‐β‐cyclodextrin was monofunctionalized by the regioselective introduction of exactly one ω‐epoxyoctyl group at the primary site of the cyclodextrin. The site‐specifically substituted cyclodextrin was immobilized to commercially available aminopropyl silica by nucleophilic opening of the epoxy function of the spacer substituent resulting in a lipophilic chiral stationary phase with broad applicability for enantiomer separations in capillary‐HPLC under reversed‐phase conditions.     

Capillary electrophoretic enantioseparation of basic drugs using a new single‐isomer cyclodextrin derivative and theoretical study of the chiral recognition mechanism

A novel single‐isomer cyclodextrin derivative, heptakis {2,6‐di‐O‐[3‐(1,3‐dicarboxyl propylamino)‐2‐hydroxypropyl]}‐β‐cyclodextrin (glutamic acid‐β‐cyclodextrin) was synthesized and used as a chiral selector in capillary electrophoresis for the enantioseparation of 12 basic drugs, including terbutaline, clorprenaline, tulobuterol, clenbuterol, procaterol, carvedilol, econazole, miconazole, homatropine methyl bromide, brompheniramine, chlorpheniramine and pheniramine. The primary factors affecting separation efficiency, which include the background electrolyte pH, the concentration of glutamic acid‐β‐cyclodextrin and phosphate buffer concentration, were investigated. Satisfactory enantioseparations were obtained using an uncoated fused‐silica capillary of 50 cm (effective length 40 cm) × 50 μm id with 120 mM phosphate buffer (pH 2.5–4.0) containing 0.5–4.5 mM glutamic acid‐β‐cyclodextrin as background electrolyte. A voltage of 20 kV was applied and the capillary temperature was kept at 20°C. The results proved that glutamic acid‐β‐cyclodextrin was an effective chiral selector for studied 12 basic drugs. Moreover, the possible chiral recognition mechanism of brompheniramine, chlorpheniramine and pheniramine on glutamic acid‐β‐cyclodextrin was investigated using the semi‐empirical Parametric Method 3.     

Photoirradiation surface molecularly imprinted polymers for the separation of 6‐O‐α‐d‐maltosyl‐β‐cyclodextrin

Photoirradiation surface molecularly imprinted polymers for the separation of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin were synthesized using functionalized silica as a matrix, 4‐(phenyldiazenyl)phenol as a light‐sensitive monomer, and 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin as a template. Fourier transform infrared spectroscopy results indicated that 4‐(phenyldiazenyl)phenol was grafted onto the surface of functionalized silica. The obtained imprinted polymers exhibited specific recognition toward 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin. Equilibrium binding experiments showed that the photoirradiation surface molecularly imprinted polymers obtained the maximum adsorption amount of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin at 20.5 mg/g. In binding kinetic experiments, the adsorption reached saturation within 2 h with binding capacity of 72.8%. The experimental results showed that the adsorption capacity and selectivity of imprinted polymers were effective for the separation of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin, indicating that imprinted polymers could be used to isolate 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin from a conversion mixture containing β‐cyclodextrin and maltose. The results showed that the imprinted polymers prepared by this method were very promising for the selective separation of 6‐O‐α‐d ‐maltosyl‐β‐cyclodextrin.     

Cyclodextrin encapsulation of the functional group diminishes an antioxidant's free radical scavenging rates

Scavenging rates of cyclodextrin‐solubilized lipophilic antioxidants, namely catechin, epicatechin, epigallocatechin gallate, and resveratrol, against alkoxyl (RO^?) radical were measured with the use of electron paramagnetic resonance (EPR) spin‐trapping method. Results indicated that the scavenging rates of catechin and resveratrol were notably dependent on the solubilizer used, i.e., native β‐cyclodextrin (β‐CD) or heptakis(2,6‐di‐O‐methyl)‐β‐cyclodextrin (DM‐β‐CD). But, epicatechin and epigallocatechin gallate showed almost no dependence on the cyclodextrin used. Catechin's scavenging rate in β‐CD was 66% lower than in DM‐β‐CD; in contrast, resveratrol in β‐CD showed 45% higher rate than in DM‐β‐CD. Based on the reported solution‐NMR structure of the inclusion complex of these antioxidants, it was concluded that the scavenging rate is decreased when the cyclodextrin cavity preferentially encapsulates the antioxidant‐function bearing group, i.e., O‐ and p‐quinolinol group in catechin and resveratrol, respectively. The depth of inclusion of the functional group determines the extent of the scavenging rate difference, suggesting that the cavity wall of the cyclodextrin acts like a barrier that hinders the approach of attacking free radicals. © 2012 Wiley Periodicals, Inc. Int J Chem Kinet 44: 598–603, 2012     

A family of single‐isomer,dicationic cyclodextrin chiral selectors for capillary electrophoresis: Mono‐6A‐ammonium‐6C‐butylimidazolium‐β‐cyclodextrin chlorides

The first member of the single‐isomer, dicationic cyclodextrin (CD) family, 6^A‐ammonium‐6^C‐butylimidazolium‐β‐cyclodextrin chlorides (AMBIMCD), has been synthesized, analytically characterized, and used to separate a variety of acidic enantiomers and amino acids by CE. Starting from mono‐6^A‐azido‐β‐cyclodextrin, the cationic imidazolium and ammonium moieties were subsequently introduced onto primary ring of β‐cyclodextrin via nucleophilic addition and Staudinger reaction. The analytically pure AC regio‐isomer CD was further obtained via column chromatography. This dicationic CD exhibited excellent enantioselectivities for selected analytes at concentration as low as 0.5 mM, which were even better than those of its mono‐imidazolium or ammonium‐substitued counterpart CDs at 10 equivalent concentrations. The effective mobilities of all studied analytes were found to decrease with the concentration of AMBIMCD. Inclusion complexation in combination with eletrostatic interactions seemed to account for the enhanced chiral discrimination process.     

Separation of brombuterol enantiomers in capillary electrophoresis with cyclodextrin‐type chiral selectors and investigation of structure of selector‐selectand complexes using nuclear magnetic resonance spectroscopy

The major goal of this study was to determine the affinity pattern of brombuterol (BB) enantiomers toward various cyclodextrins (CD) and to evaluate the potential of NMR spectroscopy for understanding fine mechanisms of interactions between CDs and BB enantiomers. Separation of BB enantiomers was performed in a fused‐silica capillary using a phosphate buffer, pH 2.5, at the room temperature in the normal polarity mode. It was shown once again that CE in combination with NMR spectroscopy represents a very sensitive tool for studies of affinity patterns and structure of CD complexes with chiral guests. Although opposite affinity patterns of BB enantiomers were observed toward native β‐ and γ‐CDs, no significant differences between the structures of the complexes of these two CDs with BB were detected by NMR spectroscopy. In contrary to this, the opposite affinity pattern of BB enantiomers toward β‐CD and its two sulfated derivatives, heptakis (2,3‐O‐diacetyl‐6‐sulfo)‐β‐CD (HDAS‐β‐CD) and heptakis (2‐O‐methyl‐3,6‐di‐O‐sulfo)‐β‐CD (HMDS‐β‐CD) was associated with major differences in the structure of the complexes. In addition, it was shown again that HMDS‐β‐CD provides separation of enantiomers without formation of inclusion‐type complex with the chiral analyte.     

Effect of urea on analyte complexation by 2,6‐dimethyl‐β‐CD in peptide enantioseparations by CE

The aim of the present study was the investigation of the effect of urea on analyte complexation in CD‐mediated separations of peptide enantiomers by CE in the pH range of about 2–5. pH‐independent complexation and mobility parameters in the absence and presence of 2 M urea were obtained by three‐dimensional, non‐linear curve fitting of the effective analyte mobility as a function of pH and heptakis‐(2,6‐di‐O‐methyl)‐β‐CD concentration. Urea led to decreased binding strength of the CD towards the protonated and neutral analyte enantiomers as well as to decreased mobilities of the free analytes. In contrast, mobilities of the fully protonated enantiomer–CD complexes as well as the pK_a values of the free and complexed analytes increased. The effect of urea on separation efficiency varied with pH and CD concentration. In the case of Ala‐Tyr and Ala‐Phe, separations improved in the presence of urea at pH 2.2. In contrast, separations were impaired by urea at pH 3.8 and low concentrations of the CD. Decreased separation efficiency was noted for Asp‐PheOMe and Glu‐PheNH₂ at low CD concentrations when urea was added but separations improved at higher CD concentrations over the entire pH range studied. The effect of urea on analyte complexation appeared to be primarily non‐stereoselective. Furthermore, the pH‐dependent reversal of the enantiomer migration order observed for Ala‐Tyr and Ala‐Phe can be rationalized by the complexation and mobility parameters.     

Chiral separation of 12 pairs of enantiomers by capillary electrophoresis using heptakis‐(2,3‐diacetyl‐6‐sulfato)‐β‐cyclodextrin as the chiral selector and the elucidation of the chiral recognition mechanism by computational methods

Chiral separation of 12 pairs of basic analyte enantiomers including oxybutynin, bambuterol, tradinterol, clenbuterol, clorprenaline, terbutaline, tulobuterol, citalopram, phencynonate, fexofenadine, salbutamol, and penehyclidine was conducted by capillary electrophoresis using a single‐isomer anionic β‐cyclodextrin derivative, heptakis‐(2,3‐diacetyl‐6‐sulfato)‐β‐cyclodextrin as the chiral selector. Parameters influencing separation were studied, including background electrolyte pH, heptakis‐(2,3‐diacetyl‐6‐sulfato)‐β‐cyclodextrin concentration, buffer concentration, and separation voltage. A background electrolyte consisting of 50 mM Tris‐H₃PO₄ and 6 mM heptakis‐(2,3‐diacetyl‐6‐sulfato)‐β‐cyclodextrin at pH 2.5 was found to be highly efficient for the separation of most enantiomers, with other conditions of normal polarity mode at 10 kV, detection wavelength of 210 nm using hydrodynamic injection for 3 s. Under the optimal conditions, baseline resolution (>1.50) for 11 pairs of enantiomers and somewhat lower resolution for penehyclidine enantiomers (1.17) were generated. Moreover, the possible mechanism of separation of clenbuterol, oxybutynin, salbutamol, and penehyclidine was investigated using a computational modeling method.     

Capillary electrophoretic enantioseparation of m‐nisoldipine using two different β‐cyclodextrins

The methods for the enantioseparation of m‐nisoldipine, a new 1,4‐dihydropyridine calcium ion antagonist, were developed. The elaborated methods of m‐nisoldipine enantiomers separation were successfully performed using an anionic CD–sulfobutyl ether‐β‐CD (SBE‐β‐CD) or carboxymethyl‐β‐CD as chiral selector. However, the results indicated that SBE‐β‐CD was a better chiral selector for enantioseparation of the neutral m‐nisoldipine. Furthermore, comparing the two SBE‐β‐CDs, the derivative with a higher degree of substitution (DS) of 7.0 induced better enantioresolution than the one with low DS (4.0). In addition, possible chiral recognition mechanisms of dihydropyridines were discussed.     

Capillary electrophoretic and nuclear magnetic resonance studies on the opposite affinity pattern of propranolol enantiomers towards various cyclodextrins

In the present study the migration order of the propranolol enantiomers with various native CDs and neutral and charged CD derivatives was examined in capillary electrophoresis (CE). The reversal of the enantiomer migration order was observed due to sulfation of β‐CD on its primary hydroxy groups. The structures of intermolecular selector‐select and temporary diastereomeric associates in solution were elucidated based on 1D rotating frame nuclear Overhauser effect spectroscopy (1D ROESY) experiments. Major structural differences were observed between the propranolol complexes with native β‐CD and heptakis(6‐O‐sulfo)‐β‐CD.     

Synthesis of well‐defined cyclodextrin‐core star polymers

The synthesis of 21‐arm methyl methacrylate (MMA) and styrene star polymers is reported. The copper (I)‐mediated living radical polymerization of MMA was carried out with a cyclodextrin‐core‐based initiator with 21 independent discrete initiation sites: heptakis[2,3,6‐tri‐O‐(2‐bromo‐2‐methylpropionyl]‐β‐cyclodextrin. Living polymerization occurred, providing well‐defined 21‐arm star polymers with predicted molecular weights calculated from the initiator concentration and the consumed monomer as well as low polydispersities [e.g., poly(methyl methacrylate) (PMMA), number‐average molecular weight (M_n) = 55,700, polydispersity index (PDI) = 1.07; M_n = 118,000, PDI = 1.06; polystyrene, M_n = 37,100, PDI = 1.15]. Functional methacrylate monomers containing poly(ethylene glycol), a glucose residue, and a tert‐amine group in the side chain were also polymerized in a similar fashion, leading to hydrophilic star polymers, again with good control over the molecular weight and polydispersity (M_n = 15,000, PDI = 1.03; M_n = 36,500, PDI = 1.14; and M_n = 139,000, PDI = 1.09, respectively). When styrene was used as the monomer, it was difficult to obtain well‐defined polystyrene stars at high molecular weights. This was due to the increased occurrence of side reactions such as star–star coupling and thermal (spontaneous) polymerization; however, low‐polydispersity polymers were achieved at relatively low conversions. Furthermore, a star block copolymer consisting of PMMA and poly(butyl methacrylate) was successfully synthesized with a star PMMA as a macroinitiator (M_n = 104,000, PDI = 1.05). © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2206–2214, 2001