Mechanistic study of opposite migration order of dimethindene enantiomers in capillary electrophoresis in the presence of native beta-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin

The possible mechanisms of the opposite affinity pattern of the enantiomers of dimethindene [(R,S)-N,N-dimethyl-3[1(2-pyridyl)ethyl]indene-2-ethylamine] (DIM) towards native beta-cyclodextrin (beta-CD) and heptakis(2,3,6-tri-O-methyl-)-beta-CD (TM-beta-CD) were studied using capillary electrophoresis (CE), NMR spectrometry, electrospray ionization mass spectrometry (ESI-MS) and X-ray crystallography. NMR spectrometry allowed to estimate the stoichiometry of the complex and to determine the binding constants. As found using ESI-MS, together with more abundant 1:1 complex, a complex with 1:2 stoichiometry may also be present in a rather small amount in a solution of DIM and beta-CD. One-dimensional ROESY experiments indicated that the geometry of the complexes of DIM with native beta-CD depends on the ratio of the components in the solution. In the 1:1 solution of DIM and beta-CD the complex may be formed by inclusion of the indene moiety of DIM into the cavity of beta-CD on the primary side and into the cavity of TM-beta-CD into the secondary side. The most likely structural reason for lower affinity of the enantiomers of DIM towards the cavity of TM-beta-CD compared to native beta-CD could be elucidated. The indene moiety does not enter the cavity of TM-beta-CD as deeply as the cavity of beta-CD. This may be the most likely explanation of significantly higher affinity constants of DIM enantiomers towards the latter CD compared to the former one. The marked difference between the structure of the complexes may also be responsible for the opposite affinity pattern of the DIM enantiomers towards beta-CD and TM-beta-CD.     

Studying aminoglycoside antibiotic binding to HIV-1 TAR RNA by electrospray ionization mass spectrometry

The recognition of the aminoglycosides neomycin and streptomycin by HIV-1 TAR RNA was studied by electrospray ionization mass spectrometry (ESI-MS). Members of the aminoglycoside family of antibiotics are known to target a wide variety of RNA molecules. Neomycin and streptomycin inhibit the formation of the Tat protein–TAR RNA complex, an assembly that is believed to be necessary for HIV replication. The noncovalent complexes formed by the binding of aminoglycosides to TAR RNA and the Tat–TAR complex were detected by ESI-MS. Neomycin has a maximum binding stoichiometry of three and two to TAR RNA and to the Tat–TAR complex, respectively. Data from the ESI-MS experiments suggest that a high affinity binding site of neomycin is located near the three-nucleotide bulge region of TAR RNA. This is consistent with previous solution phase footprinting measurements [H.-Y. Mei et al., Biochemistry 37 (1998) 14204]. Neomycin has a higher affinity toward TAR RNA than streptomycin, as measured by ESI-MS competition binding experiments. A noncovalent complex formed between a small molecule inhibitor of TAR RNA, which has a similar solution binding affinity as the aminoglycosides, and TAR RNA is much less stable than the RNA–aminoglycoside complexes to collisional dissociation in the gas phase. It is believed that the small molecule inhibitor interacts with TAR RNA via hydrophobic interactions, whereas the aminoglycosides bind to RNAs through electrostatic forces. This difference in gas phase stabilities may prove useful for discerning the types of noncovalent forces holding complexes together.     

Identification of face-to-face inclusion complex formation of cyclodextrin bearing an azobenzene group by electrospray ionization mass spectrometry

The solution-based self-assembly of native and permethylated cyclodextrins (CD) bearing an azobenzene substituent has been studied by electrospray ionization mass spectrometry (ESI-MS). The results revealed that the CD molecules form either a contact or a face-to-face inclusion complex depending on the interaction of their substituents. The mass spectrometric study further demonstrated that the inclusion complex is formed through the interaction between the host CD cavity and the guest-substituent and that a contact complex is formed by hydrogen-bonding of the hydroxyl functions at the rims of the CD molecule. We also found that in order to detect the face-to-face inclusion complex by ESI-MS, the following conditions have to be met: (1) The CD moieties must be permethylated to avoid formation of the contact complex, (2) they must possess a guest-substituent of suitable length, such as an azobenzene moiety, and (3) they must possess an NH(2) or OH group at the substituent terminals for protonation and for detection as cations by ESI-MS. Formation of the inclusion complexes was further confirmed by the synthesis of a capped inclusion dimer and a capped monomer. Collision-induced dissociation (CID) experiments have been carried out for the contact, the host-guest inclusion, and the capped inclusion dimers, and the contact complexes are found to be the most stable among them.     

Efficient determination and evaluation of model cyclodextrin complex binding constants by electrospray mass spectrometry

Electrospray ionization mass spectrometry (ESI-MS) is now routinely used for the detection of cyclodextrin noncovalent complexes, complementing previously established methods. Host-guest complexes formed in solution are also stable for characterization by ESI in the gas phase. This paper reports the first investigations to characterize the stability of three inclusion complexes between beta-cyclodextrin (beta-CD) and three model "guest" molecules, by determining the cyclodextrin compound complex stability constant (K(st)) with the use of mass spectrometric studies. The relative signal intensity of the complexes were monitored in the positive ion mode by mixing each "guest" molecule with an up to 50-fold molar excess of betaCD. A novel linear equation, similar to Benesi-Hildebrand, was derived allowing the determination of K(st) for 1:1 stoichiometry in all complexes. These values were compared with the K(st) obtained by spectrophotometric experiments and they were evaluated to be slightly different, indicating the validity of the described method.     

Dendritic galactosides based on a beta-cyclodextrin core for the construction of site-specific molecular delivery systems: synthesis and molecular recognition studies

In order to evaluate the ability of multivalent glycosides based on a beta-cyclodextrin core as site-specific molecular carriers, a study on both the inclusion complexation behaviour and lectin binding affinity of branched and hyperbranched beta-cyclodextrins is presented. A series of cluster galactosides constructed on beta-cyclodextrin scaffolds containing seven 1-thio-beta-lactose or beta-lactosylamine bound to the macrocyclic core through different spacer arms were synthesised. In addition, the first synthesis of three first-order dendrimers based on a beta-cyclodextrin core containing fourteen 1-thio-beta-D-galactose, 1-thio-beta-lactose and 1-thio-beta-melibiose residues was performed. Calorimetric titrations performed at 25 degrees C in buffered aqueous solution (pH 7.4) gave the affinity constants and the thermodynamic parameters for the complex formation of these beta-cyclodextrin derivatives with guests sodium 8-anilino-1-naphthalenesulfonate (ANS) and 2-naphthalenesulfonate, and lectin from peanut (Arachis hypogaea) (PNA). The persubstitution of the primary face of the beta-cyclodextrin with saccharides led to a slight increase of the binding constant values for the inclusion complexation with ANS relative to the native beta-cyclodextrin. However, the increase of the steric congestion due to the presence of the saccharide residues on the narrow rim of the beta-cyclodextrin may cause a decrease of the binding ability as shown for sodium 2-naphthalenesulfonate. The spacer arms are not passive elements and influence the host binding ability according to their chemical nature. PNA forms soluble cross-linked complexes with cluster galactosides and lactosides scaffolded on beta-cyclodextrin but not with cluster galactopyranosylamines or melibiose. Both, perbranched and hyperbranched beta-cyclodextrins, form stronger complexes with PNA than the monomeric analogues. However, the use of hyperbranched CDs does not contribute to the improvement of the complex stability relative to heptakis-glycocyclodextrin derivatives. Finally, a titration experiment with PNA and a complex formed by a heptakis lactose beta-cyclodextrin derivative with sodium 2-naphthalenesulfonate showed the formation of a soluble cross-linked complex with stronger affinity constant and higher stoichiometry than those observed for the complex formation of PNA with the same heptakis-lactose beta-cyclodextrin derivative, suggesting the formation of a three component complex.     

Unusual covalent bond-breaking reactions of beta-cyclodextrin inclusion complexes of nucleobases/nucleosides and related guest molecules

Host-guest complexes between nucleobases or nucleosides and beta-cyclodextrin can be observed by electrospray ionization mass spectrometry (ESI-MS) and their relative abundances appear to correlate with the condensed-phase binding order. Using Fourier transform ion cyclotron resonance mass spectrometry, the extent of the interactions between the host oligosaccharide and guest species have also been examined for permethylated beta-cyclodextrin : adenine/deoxyadenosine and permethylated maltoheptaose : adenine/deoxyadenosine using gas-phase exchange reactions with the gaseous amines, n-propylamine and ethylenediamine. The ease of guest exchange in the gas-phase follows the order : deoxyadenosine > adenine > deoxycytidine > cytosine, which is in contrast to their relative binding order in solution. Collision-induced dissociation (CID) has been used to probe the fragmentation behavior of oligosaccharide : nucleobase/nucleoside complexes. Under these conditions the inclusion complexes either (a) dissociate, (b) result in cleavage of the host oligosaccharide or (c) result in cleavage of the guest molecule. This study has shown that the preferred dissociation pathway of these complexes depends on the structures of both the cyclodextrin and guest molecule.     

Analysis of the metal-binding selectivity of the metallochaperone CopZ from Enterococcus hirae by electrospray ionization mass spectrometry

Metallochaperones are soluble proteins involved in metal transport and regulation in vivo. Copper metallochaperones belong to a structural family of metal binding domains displaying a ferredoxin-like fold (betaalphabetabetaalphabeta) and a consensus metal-binding motif MXCXXC. The metal-binding selectivities for this class of proteins are poorly documented so far. The present study focuses on the measurement of the selectivity of the copper metallochaperone CopZ from Enterococcus hirae for different metal ions using an experimental approach based on electrospray ionization mass spectrometry (ESI-MS). All the metal cations tested, i.e. Cu(I), Cu(II), Hg(II), Cd(II) and Co(II), form specific metal complexes with CopZ. The study of a chemically modified CopZ as well as variants of CopZ in the active site demonstrated that the complexes observed by ESI-MS, i.e. in the gas phase, corresponded to the complexes previously observed by other analytical methods in solution. Competition experiments allowed the classification of the metal ions by increasing affinities for CopZ as follows: Co < Cd < Hg < Cu. A dissociation constant in the range of 20 microM was determined for cobalt. The affinity of CopZ for the other metals tested was found to be higher, with dissociation constants smaller than micromolar.     

Bridged bis(beta-cyclodextrin)s possessing coordinated metal center(s) and their inclusion complexation behavior with model substrates: enhanced molecular binding ability by multiple recognition.

To investigate quantitatively the cooperative binding ability of several beta-cyclodextrin oligomers bearing single or multiligated metal center(s), the inclusion complexation behavior of four bis(beta-cyclodextrin)s (2-5) linked by 2,2'-bipyridine-4,4'-dicarboxy tethers and their copper(II) complexes (6-9) with representative dye guests, i.e., methyl orange (MO), acridine red (AR), rhodamine B (RhB), ammonium 8-anilino-1-naphthalenesulfonic acid (ANS), and sodium 6-(p-toludino)-2-naphthalenesulfonate (TNS), have been examined in aqueous solution at 25 degrees C by means of UV-vis, circular dichroism, fluorescence, and 2D NMR spectroscopy. The results obtained indicate that bis(beta-cyclodextrin)s 2-5 can associate with one or three copper(II) ion(s) producing 2:1 or 2:3 bis(beta-cyclodextrin)-copper(II) complexes. These metal-ligated oligo(beta-cyclodextrin)s can bind two model substrates to form intramolecular 2:2 host-guest inclusion complexes and thus significantly enhance the original binding abilities of parent beta-cyclodextrin and bis(beta-cyclodextrin) toward model substrates through the cooperative binding of two guest molecules by four tethered cyclodextrin moieties, as well as the additional binding effect supplied by ligated metal center(s). Host 6 showed the highest enhancement of the stability constant, up to 38.3 times for ANS as compared with parent beta-cyclodextrin. The molecular binding mode and stability constant of substrates by bridged bis- and oligo(beta-cyclodextrin)s 2-9 are discussed from the viewpoint of the size/shape-fit interaction and molecular multiple recognition between host and guest.     

Unusual complex between 18-Crown-6 and tetramethylammonium cation—detection by electrospray ionization mass spectrometry

Complexes between crown ethers and quaternary ammonium cations have been studied by electrospray ionisation mass spectrometry (ESI-MS). The ESI-MS method has been shown to allow observation of not only stable inclusion complexes between large crown ethers and tetramethylammonium cation (e.g. [DB30C10 + (CH₃)₄N]⁺ ion) but also of unstable inclusion complexes between smaller crown ethers and quaternary ammonium cations which are difficult to observe by other methods, namely [18C6 + (CH₃)₄N]⁺ ion. Stability of the complexes between crown ethers containing aromatic ring and tetramethylammonium cation is enhanced by cation-Π interactions. The molecule of 18C6 does not contain aromatic rings, thus [18C6 + (CH₃)₄N]⁺ ion exists due to the formation of C–H···O hydrogen bonds. Such a complex is quite unusual, since C–H···O hydrogen bonds are very weak and usually coexist with other strong interactions.     

Capillary electrophoretic study of interactions of metal ions with crown ethers,a sulfated beta-cyclodextrin,and zwitterionic buffers present as additives in the background electrolyte

Stability constants of K, Na, Ca, and Ba with 18-crown-6, K, Na, Li with sulfated beta-cyclodextrin and K, Li, Ca, Mg, Sr, and Ba ions with ([2-hydroxy-1,1-bis(hydroxymethyl) ethyl]-amino)-1-propanesulfonic acid (TAPS) were determined by capillary electrophoresis and computed using a general least squares minimizing program CELET. The results for 18-crown-6 agreed well with those evaluated by graphical methods or reported in the literature. Previously unknown stability constants of sulfated beta-cyclodextrins and TAPS determined for alkali and alkaline earth metals show that sulfated beta-cyclodextrin interacts with monovalent metals allowing to manipulate their effective mobility. It interacts stronger with divalent metal cations. TAPS, as zwitterionic buffer widely used in various analytical, biochemical and other applications, forms complexes with alkali and alkaline earth cations, and although the stability constants are rather low, the equilibria should be taken into account when TAPS is used and metal cations are present in solution at the same time.     

Studies on the non-covalent complexes between oleanolic acid and cyclodextrins using electrospray ionization tandem mass spectrometry

Non-covalent inclusion complexes formed between an anti-inflammatory drug, oleanolic acid (OA), and alpha-, beta- and gamma-cyclodextrins (CDs) were investigated by means of solubility studies and electrospray ionization tandem mass spectrometry (ESI-MS(n)). The order of calculated association constants (K(1 : 1)) of complexes between OA and different CDs in solution is in good agreement with the order of their relative peak intensities and the relative CID energies of the complexes under the same ESI-MS(n) conditions. These results indicate a direct correlation between the behaviors of solution- and gas-phase complexes. ESI-MS can thus be used to evaluate solution-phase non-covalent complexes successfully. The experimental results show that the most stable 1 : 1 inclusion complexes between three CDs and OA can be formed, but 2 : 1 CD-OA complexes can be formed with beta- and gamma-CDs. Multi-component complexes of alpha-CD-OA-beta-CD (1 : 1 : 1), alpha-CD-OA-gamma-CD (1 : 1 : 1) and beta-CD-OA-gamma-CD (1 : 1 : 1) were found in equimolar CD mixtures with excess OA. The formation of 2 : 1 and multi-component 1 : 1 : 1 non-covalent CD-OA complexes indicates that beta- and gamma-CD are able to form sandwich-type inclusion non-covalent complexes with OA. The above results can be partly supported by the relative sizes of OA and CD cavities by molecular modeling calculations. All the complexes allow the detection of gaseous deprotonated CD-OA complexes in the negative ion mode at high abundances. The relative stabilities of the CDs-OA inclusion complexes in the gas phase can be evaluated from the relative CID energies in the ion trap (alpha-CD-OA < beta-CD-OA < gamma-CD-OA) in the negative ion mode.     

Encapsulation of isohexenylnaphthazarins in cyclodextrins

Naturally occurring isohexenylnaphthazarins (IHN), such as Alkannin, Shikonin (A/S) and their derivatives, are potent pharmaceutical substances with a wide spectrum of biological activity. In the present study, inclusion complexes of alkannin and shikonin commercial samples and IHN derivatives in the form of an oily extract of Alkanna tinctoria roots were formed with beta-cyclodextrin (CD) and beta-HPCD. These complexes were investigated to evaluate the effect of complexation on their aqueous solubility, decoloration, and also the percentage of polymeric A/S and IHN derivatives enclosed in the CDs cavity, since these decrease the active monomeric IHN. Both beta-CD and beta-HPCD increased the aqueous solubility of A/S and IHN derivatives and thus inclusion complexes can be used as drug delivery systems for A/S in both internal (capsules, tablets) and external hydrophilic pharmaceutical and cosmetic preparations (creams, gels, sprays) with enhanced bioavailability. The inclusion complexes formed had a pale purple colour, contributing to the partial decoloration of the A/S and thus of the fi nal pharmaceutical preparations. Finally, CDs selectively included more monomeric and less polymeric IHN, compared with the initial each time sample that is encapsulated; thus inclusion complexes may present enhanced biological activity.     

(trans-1,4-bis[(4-pyridyl)ethenyl]benzene)(2,2'-bipyridine)ruthenium(II) complexes and their supramolecular assemblies with beta-cyclodextrin

Two novel ruthenium polypyridine complexes, [Ru(bpy)(2)Cl(BPEB)](PF(6)) and ([Ru(bpy)(2)Cl](2)(BPEB))(PF(6))(2) (BPEB = trans-1,4-bis[2-(4-pyridyl)ethenyl]benzene), were synthesized and their characterization carried out by means of elemental analysis, UV-visible spectroscopy, positive ion electrospray (ESI-MS), and tandem mass (ESI-MS/MS) spectrometry, as well as by NMR spectroscopy and cyclic voltammetry. Cyclic and differential pulse voltammetry for the mononuclear complex showed three set of waves around 1.2 V (Ru(2+/3+)), -1.0 V (BPEB(0/)(-)), and -1.15 (BPEB(-/2-)). This complex exhibited aggregation phenomena in aqueous solution, involving pi-pi stacking of the planar, hydrophobic BPEB ligands. According to NMR measurements and variable-temperature experiments, the addition of beta-cyclodextrin (betaCD) to [Ru(bpy)(2)Cl(BPEB)](+) leads to an inclusion complex, breaking down the aggregated array.     

Separation of steroids using temperature-dependent inclusion chromatography

The influence of temperature on retention and separation of estrogens, progesterone derivatives and beta-cyclodextrin in reversed-phase high-performance liquid chromatography has been studied. Steroids were detected using direct UV detection at 240 and 280 nm. Detection of beta-cyclodextrin was achieved using a post-column indirect photometric method. Chromatographic experiments were performed using an acetonitrile-water mobile phase (30%, v/v) and a wide range of column temperatures from 0 to 80 degrees C with 20 degrees C steps. Linear Van't Hoff plots were observed for steroids and beta-cyclodextrin when an unmodified binary mobile phase was applied. The retention of steroids was strongly influenced by temperature when the mobile phase was modified with beta-cyclodextrin at a concentration of 12 mM. Particularly, for 17beta-estradiol and 20alpha-hydroxyprogesterone a strong deviation from the linear Van't Hoff plots and a remarkable affinity for beta-cyclodextrin was observed. Polynomial regression calculations were performed to fit the set of experimental data points. Using third-order polynomial equations, minimum separation factor values (alphamin) were calculated for temperatures from -10 to + 100 degrees C with 1 degrees C steps. The best chromatographic conditions for separation of multicomponent samples were chosen. A possible retention mechanism for solutes in the presence of macrocyclic additives is discussed. The results presented describe the role of temperature in high-performance liquid chromatography systems in which the mobile phase is modified with an inclusion agent.     

Encapsulation of sodium nimesulide and precursors in beta-cyclodextrin

Crystalline 1:1 inclusion complexes with beta-cyclodextrin (beta-CD) and the sodium salt of nimesulide (4-nitro-2-phenoxymethanesulfonanilide), and the sodium salt of the derivative 2-phenoxymethanesulfonanilide, have been prepared by co-precipitation from aqueous solution. The presence of true inclusion complexes was supported by elemental analysis, thermogravimetry and powder X-ray diffraction. FTIR and 13C CP MAS NMR spectroscopy confirmed that no chemical modification of the guests occurred upon formation of inclusion complexes. The reaction of the precursors 2-phenoxynitrobenzene and 2-phenoxyaniline with beta-CD was also studied and crystalline inclusion complexes with a 2:1 (host-to-guest) stoichiometry were isolated. The interaction of the different guest species with beta-CD host molecules was studied theoretically by carrying out ab initio calculations. Favourable inclusion geometries were obtained for the four guests mentioned above. On the other hand, it was found that the inclusion of the neutral guests nimesulide and 2-phenoxymethanesulfonanilide was considerably less favourable. This is in agreement with the experimentally observed difficulty in isolating true inclusion complexes containing these guests and beta-CD. The calculated lower stability is attributed to the different steric hindrance arising from the different conformational preferences of neutral and anionic forms.     

Study on the interaction of methylene blue with cyclodextrin derivatives by absorption and fluorescence spectroscopy

The ability of beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and carboxymethyl-beta-cyclodextrin (CM-beta-CD) to break the aggregate of the methylene blue (MB) and to form 1:1 inclusion complexes has been studied by absorption and fluorescence spectroscopy. Experimental conditions including concentrations of various cyclodextrins (beta-CD, HP-beta-CD and CM-beta-CD) and media acidity were investigated for the inclusion formation in detail. The formation constants are calculated by using steady-state fluorimetry, from which the inclusion capacity of different cyclodextrins (CDs) is compared. The results suggest that the charged beta-cyclodextrin (CM-beta-CD) is more suitable for inclusion of the cationic dye MB than the neutral beta-cyclodextrins (beta-CD, HP-beta-CD) at pH>5. A mechanism is proposed which is consistent with the stronger binding of MB with CM-beta-CD compared with the other CDs at pH>5.     

NMR studies of chiral recognition mechanisms: interaction of enantiomers of N-imidazole derivatives with cyclodextrin hosts. Correlation with the CD-EKC studies

The inclusion complexes formed between two chiral N-imidazole derivatives and four cyclodextrins (α-, β-, γ-, and highly sulfated-β-CDs) were investigated by one- and two-dimensional ¹H NMR. With the additional results of an ESI-MS study, a 1:1 stoichiometry was proven for all the complexes studied. The complexes were also characterized in terms of binding constants and the results were compared to those obtained by CD-EKC. An identical affinity order for the various CDs was obtained with both techniques. Furthermore, the affinity order for both enantiomers determined by their binding constants values is confirmed by the enantiomer migration orders previously determined by CD-EKC. The structural data obtained by the 2D-ROESY experiments allowed us to understand the interaction mechanisms and to propose, for different analyte structures, theoretical models of inclusion orientation in the CD cavity. These models are in accordance with our previous hypothesis based on the analyte structure–enantioseparation relationships and the thermodynamic parameters determined by CD-EKC.     

Relative affinity of 5-methoxypsoralen and 8-methoxypsoralen towards beta-cyclodextrin: a fluorescence, circular dichroism and chromatographic study

The relative affinity of 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP) towards beta-cyclodextrin, a good model for the study of lipophilic interactions in biological systems and a potential drug carrier, has been investigated using spectroscopic and chromatographic methods. The fluorescence emission of 5-MOP in aqueous solution containing beta-cyclodextrin (10(-2) M) is found to be markedly blue shifted and enhanced by a factor of 6 whereas no significant changes are observed for 8-MOP. The existence of an induced circular dichroism is evidence for the formation of a 1:1 inclusion complex (association constant K = 400 +/- 50 M-1). Moreover, chromatographic results obtained with a beta-cyclodextrin linked stationary phase are consistent with our spectroscopic results and might have interesting analytical implications. These results clearly demonstrate that, in contrast to 8-MOP, 5-MOP exhibits a strong affinity for hydrophobic medium. Interesting pharmacological and analytical applications may result from the possible inclusion of psoralen derivatives into beta-cyclodextrin.     

Comparison of cyclodextrin-barbiturate noncovalent complexes using electrospray ionization mass spectrometry and capillary electrophoresis

Various noncovalent complexes between native and derivatized cyclodextrins (CDs) and barbiturates were studied using capillary electrophoresis (CE) and electrospray ionization mass spectrometry (ESI-MS). This paper involves the study of four aspects of CD-barbiturate noncovalent inclusion complexes. The first study focused on determining the formation of CD-barbiturate inclusion complexes in ESI-MS. This determination was accomplished by the comparison of migration data from CE with ESI-MS inclusion complex peak abundances, which were found to be complementary. The second study found the possibility of predicting native beta-CD mediated CE elution orders for barbiturates using data from ESI-MS. A third study focused on the formation of barbiturate inclusion complexes with derivatized beta-CD and gamma-CD. As part of this study, the effect of the extent of side chain substitution on native CD complexation behavior was investigated. The results indicated that the number of side chains on the CD does not affect the formation of barbiturate complexes with the hydrophobic CD cavity. Finally, a comparison of the hydroxypropyl-beta-CD-barbiturate and hydroxypropyl-gamma-CD-barbiturate complexes in CE and ESI-MS was made to study the relationship between strength of drug-CD binding and enantioresolution. The results from the above studies indicated that the gas phase and the solution state complexes showed comparable behavior indicating that similar interactions played a role in stabilizing these complexes. While it was possible to use the ESI-MS data to determine drug binding to the CDs, it was not possible to predict whether a separation of the enantiomers of a chiral barbiturate would occur. However, the ESI-MS data could be used to eliminate certain CDs from consideration as chiral selectors.     

Characterization of host-guest complexes of cucurbit[n]uril (n = 6, 7) by electrospray ionization mass spectrometry

When an intramolecular cavity exists in a molecule, it can trap another chemical species to form a host-guest complex. We examine the formation of such an inclusion complex with cucurbit[n]uril (CBn, n = 6, 7) as the host to trap alkali metal or ammonium ions as the guest, by electrospray ionization mass spectrometry (ESI-MS). The results show that the inclusion complexes are formed between the three-dimensional cylinder of CBn hosts and the guest cations. Selectivity of the complex formation is dependent both on (1) ion-dipole interactions between the cylindrical portal of the CBn hosts and the guest cations and (2) the hydrophobic interactions at the inner cavity of CBn.