Spectrophotometric and calorimetric titration studies on molecular recognition of camphor and borneol by nucleobase-modified beta-cyclodextrins

A series of modified beta-cyclodextrins with nucleobase substituents, that is, mono(6-ade-6-deoxy)-beta-cyclodextrin (2) and mono(6-ura-6-deoxy)-beta-cyclodextrin (3) as well as mono(6-thy-6-deoxy)-beta-cyclodextrin (4), were selected as molecular receptors to investigate their conformation and inclusion complexation behaviors with some chiral molecules, that is, (+)-camphor, (-)-camphor, (+)-borneol, and (-)-borneol, by spectrophotometric and microcalorimetric titrations in aqueous phosphate buffer solution (pH 7.2) at 298.15 K. Circular dichroism and NMR studies demonstrated that these nucleobase-modified beta-cyclodextrins adopted a co-inclusion mode upon complexation with guest molecules; that is, the originally self-included nucleobase substituents of the host did not move out from the beta-cyclodextrin cavity, but coexisted with guest molecule in the beta-cyclodextrin cavity upon inclusion complexation. Significantly, these nucleobase-modified beta-cyclodextrins efficiently enhanced the molecular binding ability and the chiral recognition ability of native beta-cyclodextrin, displaying enantioselectivity up to 3.7 for (+)-camphor/(-)-camphor pair by 2 and 3.5 for (-)-borneol/(+)-borneol pair by 3. The enhanced molecular/chiral recognition abilities of 2-4 toward (+/-)-camphor were mainly attributed to the increased entropic gains due to the extensive desolvation effects, while the favorable enthalpic gains originating from the good size-fit relationship as well as the hydrogen bond interactions between host and guest result in the enhanced molecular/chiral recognition abilities of 2-4 toward (+/-)-borneol.     

竞争包结法研究β-环糊精及其两种衍生物对一些手性脂肪族客体分子的识别作用

以酚酞作为光谱探针 ,采用紫外 可见光谱滴定法测定了 β 环糊精 (β CD)、单 (6 氧 α 麦芽糖 ) β 环糊精 (6 G2 β CD )和单 [2 氧 (2 羟丙基 ) ] β 环糊精 (2 HP β CD )在 2 5℃时 ,pH =10 5缓冲液中(0 0 2 5mol/L)与几种脂肪族手性客体分子所形成超分子配合物的稳定常数 .结果表明 ,多种弱相互作用力协同作用于环糊精的配位过程 ,主 客体间的尺寸匹配决定所形成配合物的稳定性 .环糊精衍生物的取代基影响主体的配位能力 ,对于尺寸较小的客体分子配位能力的大小一般为 2 HP β CD >β CD >6 G2 β CD .另一方面 ,3种环糊精主体化合物对一些脂肪族客体分子也表现出一定的手性识别能力 ,对 (+ ) 异构体给出相对较强的键合能力 ,其中 ,2 HP β CD对 (+ ) /(- ) 樟脑的配位选择性为 1 2 5 .     

Supramolecular self-assemblies of beta-cyclodextrins with aromatic tethers: factors governing the helical columnar versus linear channel superstructures

A series of 6-O-(p-substituted phenyl)-modified beta-cyclodextrin derivatives, i.e., 6-O-(4-bromophenyl)-beta-CD (1), 6-O-(4-nitrophenyl)-beta-CD (2), 6-O-(4-formylphenyl)-beta-CD (3), 6-phenylselenyl-6-deoxy-beta-CD (4), and 6-O-(4-hydroxybenzoyl)-beta-CD (5), were synthesized, and their inclusion complexation behavior in aqueous solution and self-assembling behavior in the solid state were comparatively studied by NMR spectroscopy, microcalorimetry, crystallography, and scanning tunneling microscopy. Interestingly, (seleno)ethers 1-4 and ester 5 displayed distinctly different self-assembling behavior in the solid state, affording a successively threading head-to-tail polymeric helical structure for the (seleno)ethers or a mutually penetrating tail-to-tail dimeric columnar channel structure for the ester. Combining the present and previous structures reported for the relevant beta-CD derivatives, we further deduce that the pivot heteroatom, through which the aromatic substituent is tethered to beta-CD, plays a critical role in determining the helix structure, endowing the 2-fold and 4-fold axes to the N/O- and S/Se-pivoted beta-CD aggregates, respectively. This means that one can control the self-assembling orientation, alignment, and helicity in the solid state by finely tuning the pivot atom and the tether length. Further NMR and calorimetric studies on the self-assembling behavior in aqueous solution revealed that the dimerization step is the key to the formation of linear polymeric supramolecular architecture, which is driven by favorable entropic contributions.     

Synthesis of phosphoryl-tethered beta-cyclodextrins and their molecular and chiral recognition thermodynamics

Two novel phosphoryl-bridged bis- and tris(beta-cyclodextrin)s of different tether lengths, i.e., bis[m-(N-(6-cyclodextryl)-2-aminoethylaminosulfonyl)phenyl]-m-(chlorosulfonyl)phenylphosphine oxide (5) and tris[m-(N-(6-cyclodextryl)-8-amino-3,6-diazaoctylaminosulfonyl)phenyl]phosphine oxide (6), have been synthesized by reactions of 6-oligo(ethylenediamino)-6-deoxy-beta-cyclodextrins with tris[m-(chlorosulfonyl)phenyl]phosphine oxide. The complex stability constants (K(S)), standard molar enthalpy (Delta H degrees ), and entropy changes (Delta S degrees ) were determined at 25 degrees C for the inclusion complexation of phosphoryl-modified bis- and tris-cyclodextrins (5 and 6, respectively), mono[6-O-(ethoxyhydroxyphosphoryl)]-beta-cyclodextrin (2), mono[6-O-(diethylamino-ethoxyphosphoryl)]-beta-cyclodextrin (3), and mono[6-O-(diphenoxyphosphoryl)]-beta-cyclodextrin (4) with representative alicyclic and N-Cbz-D/L-alanine guests in 0.1 M phosphate buffer solution at pH 7.2 by means of titration microcalorimetry. The thermodynamic parameters obtained indicate that the charge-dipole interaction between the phosphoryl moiety and the negatively charged guests, as well as the conformational difference of modified beta-cyclodextrins in aqueous solution, significantly contribute to the inclusion complexation and the enhanced chiral discrimination. The interactions and binding modes between the hosts and chiral guests were further studied by two-dimensional NMR spectroscopy to elucidate the influence of the structural features of hosts on their increased chiral recognition ability and to establish the correlation between the conformation of the resulting complexes and the thermodynamic parameters obtained.     

Molecular recognition thermodynamics and structural elucidation of interactions between steroids and bridged bis(beta-cyclodextrin)s

A series of bridged bis(beta-cyclodextrin(CD))s (2-7) were synthesized, i.e., bridged bis(beta-CD)s 2 and 3 bearing binaphthyl or biquinoline tethers and bridged bis(beta-CD)s 4-7 possessing dithiobis(benzoyl) tether, and their complex stability constants (KS), enthalpy (DeltaH degrees), and entropy changes (DeltaS degrees) for the 1:2 inclusion complexation with representative steroids, deoxycholate, cholate, glycocholate, and taurocholate, have been determined in an aqueous phosphate buffer solution of pH 7.20 at 298.15 K by means of titration microcalorimetry. The original conformations of bridged bis(beta-cyclodextrin)s were investigated by circular dichroism and 1H ROESY spectroscopy. Structures of the inclusion complexes between steroids and bridged bis(beta-CD)s in solution were elucidated by 2D NMR experiments, indicating that anionic groups of two steroid molecules penetrate, respectively, into the two hydrophobic CD cavities in one 6,6'-bridged bis(beta-CD) molecule from the secondary rim to give a 1:2 binding mode upon inclusion complexation. The results obtained from titration microcalorimetry and 2D NMR experiments jointly demonstrate that bridged bis(beta-CD)s 2, 3 and 5-7 tethered by protonated amino group possessing different substituted groups can enhance not only the molecular binding ability toward steroids by electrostatic interaction but also molecular selectivity. Thermodynamically, the resulting 1:2 bis(beta-CD)-steroid complexes are formed by an enthalpy-driven process, accompanied by smaller entropy loss. The increased complex stability mainly results from enthalpy gain, accompanied by large conformational change and extensive desolvation effects for the 1:2 inclusion complexation between bis(beta-CD)s and steroids.     

Chiral beta-cyclodextrin-based polymer supports prepared via ring-opening metathesis graft-polymerization

A series of norborn-2-ene-derivatized beta-cyclodextrins (beta-CDs), 6-O-(norborn-2-ene-5-carboxyl)-beta-CD (1), tetrakis(6-O-norborn-2-ene-5-carboxyl)-beta-CD (2), (3), 6-O-(6-norborn-2-ene-5-car-6-O-(7-oxanorborn-2-ene-5-carboxyl)-beta-CD bonylaminohexoyl)-beta-CD (4), 6-O-(norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (5), tris(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (6), tetrakis(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (7) and hexakis(6-O-norborn-2-ene-5-ylmethoxymethylsilyl)-beta-CD (8), have been synthesized. Compounds 1-3 were prepared via reaction of beta-CD with norborn-2-ene-5-carboxylic chloride and 7-oxanorborn-2-ene-5-carboxylic chloride, respectively; compounds 5-8 were synthesized from norborn-2-ene-5-yl-methyldichlorosilane and beta-CD, respectively. Compound 4 was accessible by reaction of norbom-2-ene-5-carboxylaminohexoyl chloride with beta-CD. Compounds 1-8 were surface grafted onto norborn-2-ene-derivatized silica-based supports using ring-opening metathesis polymerization employing the ruthenium-based initiator bis(tricyclohexylphosphino)benzylideneruthenium dichloride [Cl2Ru(CHC6H5)(PCy3)2, Cy=cyclohexyl, 9]. Generally speaking, the resulting chiral stationary phases (CSPs) I-VIII may be prepared with high reproducibility and may be used within a pH of 2-10. Thus, relative standard deviations (sigman-1) of the mean resolution (Rs) are <7%. The CSPs were used for the enantioselective separation of beta-blockers, N-dansyl-, N-3,5-dinitrobenzoyl- and Fmoc-protected amino acids and were characterized in terms of chemical stability, selectivity (alpha') and resolution (Rs). Additionally, the role of the spacer as well as influences of capacity and the degree of substitution of the beta-CD moiety on the separation characteristics were determined.     

Complexation study of brilliant cresyl blue with beta-cyclodextrin and its derivatives by UV-vis and fluorospectrometry

The complexation reactions of brilliant cresyl blue (BCB) with beta-cyclodextrin (beta-CD), mono[2-O-(2-hydroxypropyl)]-beta-CD (2-HP-beta-CD), mono[2-O-(2-hydroxyethyl)]-beta-CD (2-HE-beta-CD), and heptakis(2,6-di-methyl) -beta-CD (DM-beta-CD) were investigated using UV-vis and fluorospectrometry. The complexation between BCB and CDs could inhibit the aggregation of BCB molecules and could cause its absorbance at 634nm gradually increasing. The fluorescence of BCB was also enhanced with the addition of CDs. The fluorescence enhancement was more notable in neutral and acidic media than in basic media. Hildebrand-Benesi equation was used to calculate the formation constants of beta-CDs with BCB based on the fluorescence differences in the CDs solution. The stoichiometry ratio was found to be 1:1. The complexing capacities of beta-CD and its three derivatives were compared and the results followed the order: 2-HP-beta-CD>2-HE-beta-CD>DM-beta-CD>beta-CD. The effect of temperature on the formation of BCB-beta-CD inclusion complexes has also been examined. The results revealed that the formation constants decreased with the increase of temperature from 1038.9 to 491.6l/mol. Enthalpy and entropy values were calculated and the values were -25.77kJ/mol and 35.04J/kmol, respectively. The thermodynamic measurements suggest that the inclusive process was enthalpic favor. The release of high-energy water molecules and Van der Waals force played an important role in the inclusive process.     

A comparative study on the binding behaviors of beta-cyclodextrin and its two derivatives to four fanlike organic guests

Four fanlike organic compounds, 1-ethoxybenzene (EOB), 1-butoxybenzene (BOB), 1-dodecyloxybenzene (DOB), and 1-(dodecyloxy)-2-methoxybenzene (DOMB), were chosen as guests, and beta-cyclodextrin (beta-CD) and its two derivatives, mono(2-O-2-methyl)-beta-CD and mono(2-O-2-hydroxy-propyl)-beta-CD, were chosen as hosts. Energy changes involved in host-guest inclusion processes were clearly obtained by applying semiempirical PM3 calculations. According to this, probable structures of the host-guest inclusion complexes were proposed. The inclusion systems in aqueous solution were investigated by UV-vis spectroscopy and nuclear magnetic resonance ((1)H NMR) titration, and the formation constants (K) of the inclusion complexes were determined using the Benesi-Hildebrand equation. Moreover, two solid inclusion complexes of beta-CD with EOB and DOB were prepared and characterized by Fourier transform infrared spectra, X-ray powder diffraction, (1)H NMR, electrospray ionization mass spectrometry, and thermogravimetric analyses. Results showed that the host-guest stoichiometries in the inclusion complexes were all 1:1 both in solid state and in aqueous solution. As for the same host, the values of K increased in the order EOB < BOB < DOB, in strong association with the fan handle in the fanlike molecules; that is to say, the K values increased with increasing carbon chain length of substituent on benzene ring. In addition, the K values of DOMB complexes were larger than those of DOB complexes for the same CD, indicating that the introduction of an extra o-methoxyl group on DOB further stabilized the CD inclusion complexes. The decomposition activation energies of EOB-beta-CD and DOB-beta-CD were very similar but significantly larger than that of free beta-CD.     

Molecular recognition thermodynamics of bile salts by beta-cyclodextrin dimers: Factors governing the cooperative binding of cyclodextrin dimers

The complex stability constants (K(S)), standard molar enthalpy (DeltaH degrees), and entropy changes (DeltaS degrees) for the inclusion complexation of two families of beta-cyclodextrin (beta-CD) dimers, i.e. beta-CD dimers Se1-Se4 bearing 2,2'-diselenobis(benzoyl) tether (Se-dimers) and beta-CD dimers Py1-Py4 bearing 2,2'-bipyridine-4,4'-dicarboxy tether (Py-dimers), with four bile salt guests, i.e. sodium cholate (CA), sodium deoxycholate (DCA), sodium glycocholate (GCA), and sodium taurocholate (TCA), were determined at 25 degrees C in Tris buffer solution (pH 7.4) at 298.15 K by means of isothermal titration microcalorimetry. The thermodynamic parameters obtained, together with the ROESY spectra of interactions between beta-CD dimers and bile salts, consistently suggest that the length, flexibility, and structure of spacers linking the two beta-CD cavities not only determine the binding modes but also significantly alter the molecular selectivity of beta-CD dimers.     

Organic anion recognition of naphthalenesulfonates by steroid-modified beta-cyclodextrins: enhanced molecular binding ability and molecular selectivity

Two beta-cyclodextrin (beta-CD) derivatives bearing steroid groups (1 and 2) were synthesized by the condensation of mono(6-aminoethylamino-6-deoxy)-beta-CD with cholic acid and deoxycholic acid, respectively, and their original conformations and binding behavior to the organic anion of naphthalenesulfonate derivatives were investigated by using 1H NMR spectroscopy and spectrofluorometric titration in combination with computational methods. The 2D NMR experiments reveal that the steroid groups attached to the beta-CD rim could be deeply embedded in the beta-CD cavity to form the intramolecular (for 1) or intermolecular (for 2) inclusion complexes in aqueous solution. Upon complexation with naphthalenesulfonate derivatives, modified beta-CDs display two obviously different binding modes, that is, the competitive inclusion mode and the induced-fit inclusion mode, which is consistent with the results of molecular modeling study. The two modes and the strict size/shape fitting relationship between the hosts and guests reasonably explain the different binding behaviors and molecular selectivity of host beta-CDs 1 and 2 toward the naphthalenesulfonate guests. Therefore, the cholic acid- or deoxycholic acid-modified beta-CDs could effectively recognize the size/shape of guest molecules as compared with the parent beta-CD, giving good molecular selectivity up to 24.9 for the disodium 2,6-naphthalenedisulfonate/disodium 1,5-naphthalenedisulfonate pair by the host 1.     

Synthesis of bridged and metallobridged bis(beta-cyclodextrin)s containing fluorescent oxamidobisbenzoyl linkers and their selective binding towards bile salts

A series of beta-cyclodextrin (beta-CD) dimers containing fluorescent 2,2'-oxamidobisbenzoyl and 4,4'-oxamidobisbenzoyl linkers--that is, 6,6'-[2,2'-oxamidobis(benzoylamino)]ethyleneamino-6,6'-deoxy-bis(beta-CD) (2), 6,6'-[2,2'-oxamidobis(benzoylamino)]diethylenediamino-6,6'-deoxy-bis(beta-CD) (3), 6,6'-[4,4'-oxamidobis(benzoylamino)]ethyleneamino-6,6'-deoxy-bis(beta-CD) (4), and 6,6'-[4,4'-oxamidobis(benzoylamino)]diethylenediamino-6,6'-deoxy- bis(beta-CD) (5)--were synthesized from the corresponding oxamidobis(benzoic acid)s through treatment with mono[6-aminoethyleneamino-6-deoxy]-beta-CD or mono[6-diethylenetriamino-6-deoxy]-beta-CD. Further treatment of 2-5 with copper perchlorate gave their Cu(II) complexes 6-9 in satisfactory yields. The conformation and binding behavior of 2-9 towards two bile salt guests--sodium cholate (CA) and sodium deoxycholate (DCA)--was comprehensively investigated by circular dichroism, 2D NMR spectroscopy, and fluorescence spectroscopy in Tris-HCl buffer solution (pH 7.2) at 25 degrees C. Thanks to the cooperative host-linker-guest binding mode, the stoichiometric 1:1 complexes formed by bis(beta-CD)s 2-5 with bile salts gave high stability constants (KS values) of up to 10(3)-10(4) M(-1). Significantly, benefiting from the intramolecular 1:2 or 2:4 binding stoichiometry, the resulting complexes of metallobis(beta-CD)s 6-9 with bile salts gave much higher KS values of up to 10(6)-10(7) M(-2). The enhanced binding abilities of bis(beta-CD)s and metallobridged bis(beta-CD)s are discussed from the viewpoints of induced-fit interactions and multiple recognition between host and guest.     

Studies on the chiral recognition of peptide enantiomers by neutral and sulfated beta-cyclodextrin and heptakis-(2,3-di-O-acetyl)-beta-cyclodextrin using capillary electrophoresis and nuclear magnetic resonance

The separation of dipeptide and tripeptide enantiomers using a neutral single isomer cyclodextrin (CD) derivative, heptakis-(2,3-di-O-acetyl)-beta-CD (DIAC-beta-CD), was investigated with respect to the amino acid sequence applying standard separation conditions. With only one exception the DD-enantiomers migrated faster than the LL-stereoisomers. Separations obtained for the same set of peptides using beta-CD and the sulfated single isomer derivatives heptakis-(2,3-di-O-acetyl-6-sulfo)-beta-CD (HDAS-beta-CD) and heptakis-6-sulfo-beta-CD (HS-beta-CD) revealed identical enantiomer migration order in the presence of the 2,3-disubstituted derivatives DIAC-beta-CD and HDAS-beta-CD. In contrast, reversed migration sequence was found for beta-CD and HS-beta-CD compared to DIAC-beta CD and HDAS-beta-CD indicating the importance of the substitution pattern on the wider rim of the CD cavity on the chiral recognition of the peptide enantiomers by the CDs. Nuclear magnetic resonance (NMR) experiments indicated different complexation modes between the enantiomers and the CDs depending on the presence of acetyl substituents on the wider rim of the CD torus. Thus, the CD-induced chemical shifts observed in samples containing Ala-Phe or Ala-Tyr and beta-CD or HS-beta-CD were consistent with an inclusion of the aromatic moiety into the CD cavity. Although the CD-induced chemical shifts in the presence of DIAC-beta-CD and HDAS-beta-CD did not allow direct conclusions on the complexation mode they substantially differed from those observed in the presence of 2,3-unsubstituted CDs indicating different structures of the peptide-CD complexes.     

Self-inclusion behavior and circular dichroism of aliphatic chain-linked beta-cyclodextrin-viologen compounds and their reduced forms depending on the side of modification

[Reaction: see text]. The self-inclusion behavior and induced circular dichroism (ICD) characteristics of two beta-cyclodextrin (beta-CD) derivatives, in which a 1-methyl-4,4'-bipyridinium (viologen) group is connected by an octamethylene chain to either the primary (2(2+)) or secondary (3(2+)) side of beta-CD, and of their reduced forms, are investigated. 1H NMR studies showed that 2(2+) forms an intramolecular self-inclusion complex with K(in) = 3.1 +/- 0.4, whereas 3(2+) forms a head-to-head type of dimer with K(D) = 65 +/- 10 M(-1) at 25 degrees C. 2(2+) and 3(2+) form [2]pseudorotaxanes with alpha-CD, with the secondary side of the alpha-CD facing the viologen moiety. The ICD characteristics of mono-6-[4-(1-methyl-4-pyridinio)-1-pyridinio]-beta-CD (1(2+)), 2(2+), 3(2+), and methyloctyl viologen-beta-CD complexes were obtained for the oxidized and reduced states of the viologen units. The results indicated dimer formation for 1 degrees , and intramolecular complexation for 2*+ and 2 degrees in which the reduced viologen units are outside the beta-CD cavity. The results also indicated intramolecular complexation for 3*+ and 3 degrees, but with reduced viologen units inside the cavity. This work provides unequivocal evidence of the preference of the secondary side of cyclodextrins for viologen groups, regardless of their oxidation states, and the dependence of ICD of the viologen chromophores on their location with respect to the CD cavity.     

Mechanistic study on the opposite migration order of clenbuterol enantiomers in capillary electrophoresis with beta-cyclodextrin and single-isomer heptakis(2,3-diacetyl-6-sulfo)-beta-cyclodextrin

Opposite migration order was observed for the enantiomers of the chiral beta2-adrenergic drug clenbuterol (CL) in capillary electrophoresis (CE) when resolved with native beta-cyclodextrin (beta-CD) and heptakis (2,3-diacetyl-6-sulfo)-beta-CD (HDAS-beta-CD). The possible mechanisms of the affinity reversal of the CL enantiomers depending on the structure of the CD were studied using 1H-nuclear magnetic resonance (1H-NMR) spectrometry and one-dimensional rotating frame nuclear Overhauser and exchange spectrometry (1-D ROESY). Significant differences were observed between the structure of the (+/-)-CL complexes with beta-CD and HDAS-beta-CD.     

Complexation of polyvalent cyclodextrin ions with oppositely charged guests: entropically favorable complexation due to dehydration

Thermodynamic parameters for complexation of polyvalent cyclodextrin (CD) cation and anion with oppositely charged guests have been determined in D2O containing 0.02 M NaCl by means of 1H-NMR spectroscopy. Protonated heptakis(6-amino-6-deoxy)-beta-CD (per-NH3+-beta-CD) forms stable inclusion complexes with monovalent guest anions. The enthalpy (deltaH) and entropy changes (deltaS) for complexation of per-NH3+-beta-CD with p-methylbenzoate anion (p-CH3-Ph-CO2-) are 3.8 +/- 0.7 kJ mol(-1) and 88.6 +/- 2.2 J mol(-1) K(-1), respectively. The deltaH and deltaS values for the native beta-CD-p-CH3-Ph-CO2- system are -8.6 +/- 0.1 kJ mol(-1) and 15.3 +/- 0.7 J mol(-1) K(-1), respectively. The thermodynamic parameters clearly indicate that dehydration from both the host and guest ions accounts for the entropic gain in inclusion process of p-CH3-Ph-CO2- into the per-NH3+-beta-CD cavity. The fact that the neutral guests such as 2,6-dihydroxynaphthalene and p-methylbenzyl alcohol hardly form the complexes with per-NH3+-beta-CD exhibits that van der Waals and/or hydrophobic interactions do not cause the complexation of the polyvalent CD cation with the monovalent anion. The acetate anion is not included into the per-NH3+-beta-CD cavity, while the butanoate and hexanoate anions form the inclusion complexes. The complexation of the alkanoate anions is entropically dominated. Judging from these results, it may be concluded that Coulomb interactions cooperated with inclusion are required for realizing the large entropic gain due to extended dehydration. Entropically favorable complexation was also observed for the anionic CD-cationic guest system. The present study might present a general mechanism for ion pairing in water.     

Spectrophotometric study on the controlling factor of molecular selective binding of dyes by bridged bis(beta-cyclodextrin)s with diselenobis(benzoyl) linkers

A series of beta-cyclodextrin (beta-CD) dimers with 4,4'-diselenobis(benzoyl) linkers, that is, 6,6'-[4,4'-diselenobis(benzoyloxyl)]-bridged bis(beta-CD) (1a), 6,6'-[4,4'-diselenobis[2-(benzoylamino)ethyleneamino]]-bridged bis(beta-CD) (2a), and 6,6'-[4,4'-diselenobis[2-(benzoylamino)-3,6-diazaoctylamino]]-bridged bis(beta-CD) (3a), were synthesized in moderate yields by the reaction of 4,4'-diselenobis(benzoic acid) with beta-CD or oligo(ethylenediamino)-6-deoxy-beta-CD. Their binding behaviors with some structure-related substrates, such as acridine red (AR), neutral red (NR), rhodamine B (RhB), ammonium 8-anilino-1-naphthalenesulfonate (ANS), and 6-p-toluidino-2-naphthalenesulfonic acid (TNS), were investigated in aqueous phosphate buffer solution (pH 7.20) at 298.15 K by means of fluorescence, NMR, as well as circular dichroism spectroscopy and compared with those of their 2,2'-diselenobis(benzoyl)-linked analogues, that is, 6,6'-[2,2'-diselenobis(benzoyloxyl)]-bridged bis(beta-CD) (1b), 6,6'-[2,3'-diselenobis[2-(benzoylamino)ethyleneamino]]-bridged bis(beta-CD) (2b), and 6,6'-[2,2'-diselenobis[2-(benzoylamino)-3,6-diazaoctylamino]]-bridged bis(beta-CD) (3b). The results showed that bis(beta-CD)s 1a-3a, whose Se-Se bonds were located at the para position of the carboxyl group, gave stronger binding abilities toward nonlinear guests (RhB and ANS) than their analogues 1b-3b, whose Se-Se bonds were located at the ortho position relative to the carboxyl group. The molecular binding ability and selectivity of model substrates by these ditopic hosts were sufficiently discussed to reveal not only the cooperative contributions of the linker group and CD cavities upon inclusion complexation with dye guest molecules but also the controlling factors for the molecular selective binding.     

Novel behavior of O-methylated beta-cyclodextrins in inclusion of meso-tetraarylporphyrins

[structure: see text] The mechanism for formation of extremely stable 1:2 inclusion complexes of water-soluble meso-tetraarylporphyrins with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin (TMe-beta-CD) in aqueous solutions has been studied by means of NMR spectroscopy and isothermal titration calorimetry. To simplify the system, 5,10,15-tris(3,5-dicarboxylatophenyl)-20-phenylporphyrin (1) was used as a guest porphyrin, because 1 forms only a 1:1 inclusion complex with cyclodextrin (CD). As host compounds, native beta-CD and the O-methylated-beta-CDs such as heptakis(2,3-di-O-methyl)- (2,3-DMe-beta-CD), heptakis(2,6-di-O-methyl)- (2,6-DMe-beta-CD), and TMe-beta-CDs were used. The thermodynamic parameters for complexation such as binding constants (K) and enthalpy (DeltaH degrees ) and entoropy changes (DeltaS degrees ) were determined by means of isothermal titration calorimetry. The K value for complexation of 1 with CD increases in the order beta-CD (K = (1.2 +/- 0.1) x 10(3) M(-)(1)) < 2,6-DMe-beta-CD ((1.2 +/- 0.1) x 10(4) M(-)(1)) < TMe-beta-CD ((6.9 +/- 0.4) x 10(6) M(-)(1)) < 2,3-DMe-beta-CD ((8.5 +/- 0.5) x 10(6) M(-)(1)), indicating participation of the secondary OCH(3) groups in extremely strong complexation of 1 with CD. Complex formation of 1 with beta-CD and 2,6-DMe-beta-CD is an enthalpically and entropically favorable process, while that with TMe-beta-CD and 2,3-DMe-beta-CD is an enthalpically much more favorable but an entropically less favorable process. The thermodynamic parameters suggest that inclusion of 1 into the cavities of TMe-beta-CD and 2,3-DMe-beta-CD is promoted by van der Waals interactions, which are stronger than those in the cases of beta-CD and 2,6-DMe-beta-CD. (13)C NMR spectra show that the conformations of both TMe-beta-CD and 2,3-DMe-beta-CD are altered upon inclusion of 1, while those of beta-CD and 2,6-DMe-beta-CD are mostly retained. On the basis of these results, it can be concluded that induced-fit type complexation of 1 with TMe-beta-CD and 2,3-DMe-beta-CD causes extremely strong binding of the host to the guest.     

2-O-(2-hydroxybutyl)-beta-cyclodextrin as a chiral selector for the capillary electrophoretic separation of chiral drugs.

A new beta-cyclodextrin (beta-CD) derivative, 2-O-(2-hydroxybutyl)-beta-CD (HB-beta-CD), was successfully synthesized and used as chiral selector in capillary zone electrophoresis. Six chiral drugs, such as anisodamine, ketoconazole, propranolol, promethazine, adrenaline and chlorphenamine enantiomers, belonging to different classes of compounds of pharmaceutical interest were resolved. The chiral resolution (R(S)) was strongly influenced by the concentrations of the cyclodextrin derivative, the background electrolyte, and the pH of the background electrolyte. Under the conditions of 50 mmol/L tris-phosphate buffer at pH 2.5 containing 5 mmol/L 2-O-(2-hydroxybutyl)-beta-CD, the baseline separation of enantiomers, such as anisodamine (R(S) = 3.10), ketoconazole (R(S) = 3.01), propranolol (R(S) = 3.87), promethazine (R(S) = 3.63), adrenaline (R(S) = 3.42) and chlorphenamine (R(S) = 2.96), could be achieved.     

Migration behavior and enantioseparation of hydrobenzoin and structurally related compounds in capillary zone electrophoresis with a dual cyclodextrin system consisting of heptakis-(2,3-dihydroxy-6-O-sulfo)-beta-cyclodextrin and beta-cyclodextrin

Migration behavior and enantioseparation of racemic hydrobenzoin and structurally related compounds, including benzoin and benzoin methyl ether, in CZE with a dual CD system consisting of heptakis-(2,3-dihydroxy-6-O-sulfo)-beta-CD (SI-S-beta-CD) and beta-CD as chiral selectors in the presence and absence of borate complexation at pH 9.0 were investigated. The results indicate that enantioseparation of hydrobenzoin is mainly governed by CD complexation of hydrobenzoin-borate complexes with SI-S-beta-CD when SI-S-beta-CD concentration is relatively high. Whereas CD complexation of hydrobenzoin-borate complexes with beta-CD plays a significant role in enantioseparation when SI-S-beta-CD concentration is comparatively low. The (S,S)-enantiomer of the hydrobenzoin-borate complex was found to interact more strongly than the corresponding (R,R)-enantiomer with both SI-S-beta-CD and beta-CD. These two types of CD show the same chiral recognition pattern, but they exhibit opposite effects on the mobility of the enantiomers of hydrobenzoin-borate complexes. Enantiomer migration reversal of hydrobenzoin occurred in the presence of borate complexation when varying the concentration of beta-CD, while keeping SI-S-beta-CD at a relatively low concentration. Binding constants of the enantiomers of benzoin-related compounds to beta-CD and those of hydrobenzoin-borate complexes to SI-beta-CD were evaluated; the mobility contributions of all complex species to the effective mobility of the enantiomers of hydrobenzoin as a function of beta-CD concentration in a borate buffer were analyzed. In addition, comparative studies on the enantioseparation of benzoin-related compounds with SI-S-beta-CD and with randomly sulfate-substituted beta-CD were made.     

Chiral recognition of helical metal complexes by modified cyclodextrins.

Chirality of metal complexes M(phen)3(n+) (M = Ru(II), Rh(III), Fe(II), Co(II), and Zn(II), and phen = 1,10-phenanthroline) is recognized by heptakis(6-carboxymethylthio-6-deoxy)-beta-cyclodextrin heptaanion (per-CO2(-)-beta-CD) and hexakis(2,3,6-tri-O-methyl)-alpha-cyclodextrin (TMe-alpha-CD) in D2O. The binding constant (K) for the Delta-Ru(phen)3(2+) complex of per-CO2(-)-beta-CD (K = 1250 M(-1)) in 0.067 M phosphate buffer at pD 7.0 is approximately 2 times larger than that for the Lambda-isomer (590 M(-1)). Definite effects of inorganic salts on stability of the complexes indicate a large contribution of Coulomb interactions to complexation. The fact that hydrophilic Ru(bpy)3(2+) (bpy = 2,2'-bipyridine) does not form a complex with per-CO2(-)-beta-CD suggests the importance of inclusion of the guest molecule into the host cavity for forming a stable ion-association complex. The positive entropy change for complexation of Ru(phen)3(2+) with per-CO2(-)-beta-CD shows that dehydration from both the host and the guest occurs upon complexation. Similar results were obtained with trivalent Rh(phen)3(3+) cation. Pfeiffer effects were observed in complexation of racemic Fe(phen)3(2+), Co(phen)3(2+), and Zn(phen)3(2+) with per-CO2(-)-beta-CD with enriched Delta-isomers. Native cyclodextrins such as alpha-, beta-, and gamma-cyclodextrins as well as heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin do not interact with Ru(bpy)3(2+). However, hexakis(2,3,6-tri-O-methyl)-alpha-cyclodextrin (TMe-alpha-CD) interacts with Ru(phen)3(2+) and Ru(bpy)3(2+) and discriminates between the enantiomers of these metal complexes. The K values for the Delta- and Lambda-Ru(phen)3(2+) ions are 54 and 108 M(-1), respectively. Complexation of the Delta- and Lambda-isomers of Ru(phen)3(2+) with TMe-alpha-CD is accompanied by negative entropy changes, suggesting that cationic Ru(phen)3(2+) is shallowly included into the cavity of the neutral host through van der Waals interactions. The Delta-enantiomer, having a right-handed helix configuration, fits the primary OH group side of per-CO2(-)-beta-CD (SCH2CO2(-) side) well, while the Lambda-enantiomer, having a left-handed helix configuration, is preferably bound to the secondary OH group side of TMe-alpha-CD. The asymmetrically twisted shape of a host cavity seems to be the origin of chiral recognition by cyclodextrin.