Solid State and Solution Conformation of 6-[4-[N-tert-ButoxycarbonylN-(N′-ethyl)propanamide]imidazolyl]-6-deoxycyclomaltoheptaose: Evidence of Self-Inclusion of the Boc Group within the β-Cyclodextrin Cavity (original) (raw)
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Journal of Inclusion …, 1998
Using a simple molecular mechanics approach interaction energy profiles of simple probes (C, CH 4 , C 6 H 6 , H 2 O, NH + 4 , and HCOO − ) passing through the center of the β-CD ring cavity along the main molecular symmetry axis were first evaluated. Molecular Electrostatic Potential (MEP) values along the same path were also evaluated. The effect of the flexibility of the host β-CD molecule together with solute-solvent (H 2 O) interactions have been represented by averaging structures of MD calculations for β-CD alone and β-CD surrounded by 133 H 2 O molecules. The effect of various substitutions of β-CD has also been evaluated. Small symmetric hydrophobic probes (such as C, CH 4 , C 6 H 6 ) are predicted to form stable inclusion complexes with non-substituted and substituted β-CDs, the probe position typically being near the cavity center. The stability of the inclusion complexes will increase with increasing size and aliphatic character of the probe. Small polar and charged probes (such as H 2 O, NH + 4 , HCOO − ) are predicted to prefer the interaction with the solvent (water) in the bulk phase rather than the formation of inclusion complexes with non-substituted and substituted β-CDs. Guest-host interactions in the stable inclusion complexes with hydrophobic probes are almost entirely dominated by dispersion interactions. The MEP reaches magnitudes close to zero in the center of the non-substituted β-CD ring cavity and in most of the studied substituted β-CDs and shows maximum positive or negative values outside of the cavity, near the ring faces. Substitution of β-CD by neutral substituents leads to enhanced binding of hydrophobic probes and significant changes in the MEP profile along the β-CD symmetry axis.
Conformational and circular dichroism studies on cyclodextrin inclusion complexes
Pure and Applied Chemistry, 1997
A &mework aimed at elucidating the structure of inclusion complexes between cyclodextrins (CDx) and several chromophores of photochemical interest is presented. The scheme is composed by a set of Molecular Mechanics calculations, Monte Car10 simulations including solvent effects and reproduction of the Induced Circular Dichroism (ICD) using quantum mechanically calculated properties combined to the Kirkwood-Tinoco expressions for the induced rotational strength. Examples of molecular recognition between a,P and y-CDx and a variety of chromophores of fundamental as well as of applicative interest , such as phenols, dimethoxybenzenes and buclaninstedlerene are examined. The method proposed proves to be a suitable instrument to elucidate different geomdcal configurations and to be able to gain insight into the relationship between structural and dynamic properties of the complexes studied. &&j&&g Supramolecular self-assembly has received recently a great deal of interest in several fields of Chemistry and Biology7 as it provides the physical basis for molecular recognition , formation of enzyme-complexes with substrates and is also related to protein folding. A remarkable model for this phenomenon is represented by the inclusion of a variety of organic compounds of molecules of suitable size in cyclodextrins (CDx), cyclic oligosaccharides consisting of sii (a-CDx) , seven (p-CDx) or eight ('y-CDx) D(+) glucopyranose units linked by u-(1,4) bonds and containing a central, hydrophobic cavity with a diameter of 5-8 A (1). The stability of the inclusion is determined by the fit of the molecular shape of the guest to the surface of the cavity, with intervention of van der W a a l s forces, hydrogen bonding, decrease of strain energy and release of high energy water molecules &om the cavity.The high solubility in water of the inclusion complexes of hydrophobic molecules in CDx has been exploited for a number of applications in pharmaceutical chemistry , food technology and plant protection industries. Moreover, due to their capability in binding substrates quickly, selectively and reversibly and to behave as catalysts in many chemical reactions, CDx can be considered good model enzymes. It is , therefore, of fundamental importance to understand the physics of complexation, i.e. the driving forces which govern the
2013
Cyclodextrins (CD) are cyclic oligosaccharides composed of six to more than sixty glucose units. α-CD, β-CD and γ-CD are well known CD consisting of 6, 7 and 8 glycopyranose units, respectively, that are torus-like rings built up from glycopyranose units. The secondary hydroxyl groups are situated on one of the two edges of the ring, whereas all the primary ones are placed on the other edge. The ring is a conical cylinder, which is frequently characterized as a doughnut or wreath shaped truncated cone. The cavity is lined with hydrogen atoms and glycosidic oxygen bridges, respectively. The primary and secondary hydroxyls on the outside of the cyclodextrins make cyclodextrins water-soluble. The cavity of the cyclodextrin consists of a ring of C-H groups, a ring of glycosidic oxygen atoms and again a ring of C-H groups. This renders the interior of the cyclodextrin rings less polar. As a consequence, the hydrophilic sites which are outside of the torus enable CD to be soluble in water, whereas the apolar cavity site which provides a hydrophobic matrix, enables CD to form inclusion complex with a variety of hydrophobic guest molecules. In addition, CD contains repeating units of-OCCO-binding motif on both their primary and secondary faces. This makes CD able to form extended structures with metal cations of Group IA and IIA (MOFs). The main goal of this thesis was to design, prepare and characterize new crystal systems based on cyclodextrins properties in combination with: 1. Para aminobenzoic acid (pABA) as a drug model to study the effect of complexation phenomena on the solubility of drugs. Their structure and mode of interaction were characterized by combination a theoretical and experimental approaches. 2. Potassium hydroxide to prepare cyclodextrin Metal-Organic Frameworks (CD-MOFs) formed by coordinating the cyclodextrins to potassium cation. Consequently, taking the advantages of this interaction between cyclodextrin and alkali metal cation, formation of inclusion complexes as CD-MOFs drug carrier was favored. 3. Aegelinol, a natural product, for analytical purposes to determine the absolute configuration of this compound by formation of an inclusion complex with a host of known chirality (cyclodextrins consists of several optically active D-glucose units). This should allow direct determination of the absolute configuration of the guest (aegelinol).
Journal of Inclusion Phenomena, 2002
β-Cyclodextrin (β-CD) and p-hydroxybenzaldehyde (p-HB) were studied by 1 H-NMR in deuterated aqueous solution and the stoichiometry of the resulting complex (1:1) was determined by the continuous variation method. Inclusion of p-HB in β-CD was confirmed by the observation of NMR shifts for the inside H5 protons of the β-CD cavity. In the solid state X-ray analysis was carried out and revealed the detailed structure of the inclusion complex. Two β-CDs cocrystallize with four p-HB and 9.45 water molecules [2(C 6 H 10 O 5) 7 •4C 7 H 6 O 2 •9.45H 2 O] in the triclinic space group P 1 with unit cell parameters: a = 15.262(2), b = 15.728(1), c = 16.350(1) Å, α = 92.67(1) • , β = 96.97(1) • , γ = 103.31(1) •. The anisotropic refinement of 1973 atomic parameters converged at an R-factor = 0.066 for 10157 data with F 2 o > 2σ (F 2 o). The 2:4 stoichiometry for the β-CD inclusion complex with p-HB in the crystalline state is different from that obtained in solution. β-CD forms dimers stabilized by direct O2(m)_1/O3(m)_1• • •O2(n)_2/O3(n)_2 hydrogen bonds (intradimer) and by indirect O6(m)_1• • •O6(n)_2 hydrogen bonds with one or two bridging water molecules joined in between (interdimer). These dimers are stacked like coins in a roll constructing infinite channels where the p-HB molecules are included. The p-HB molecules direct their polar CHO and OH groups into the nonpolar β-CD cavities and are hydrogen bonded to each other, yielding infinite, antiparallel chains. In addition, crystals of the complex were also investigated with thermogravimetry, vibrational spectroscopy (FTIR), and 13 C CP-MAS NMR spectroscopy. The results obtained enabled us to structurally characterize the β-CD inclusion complex with p-HB. * Supplementary data relating to this article are deposited with the British Library as Supplementary Publication No. 82299 (7 pages).
The Journal of Organic Chemistry, 2008
Concise and efficient strategies toward the synthesis of D 2h -and D 3h -symmetric cyclodextrin analogues alternating R,R′-trehalose disaccharide subunits and pseudoamide segments (cyclotrehalans, CTs) are reported. The conformational properties of these cyclooligosaccharides are governed by the rigidity of the R,R′-trehalose disaccharide repeating unit and the partial double-bond character of the N-(CdX) linkages. In contrast to the typical concave-shaped cavity of cyclodextrins (CDs), CTs feature a convexshaped hydrophobic cavity in which the -face of the monosaccharide subunits is oriented toward the inner side, as supported by NMR and modeling (molecular mechanics and dynamics) studies. In the case of cyclodimeric CTs (CT2s), the existence of intramolecular hydrogen bonds results in collapsed cavities, too small to allow the formation of inclusion complexes with organic molecules. Cyclotrimeric CTs (CT3s) display cavity sizes that are intermediate between those of RCD and CD, ideally suited for the complexation of complementary guests with ternary symmetry such as adamantane 1-carboxylate (AC). The higher flexibility of the pseudoamide bridges as compared with classical glycosidic linkages endow these glyconanocavities with some conformational adaptability properties, making them better suited than CDs for complexation of angular guests, as seen from comparative inclusion capability experiments against the fluorescent probes 6-p-toluidinonaphthalene-2-sulfonate (TNS; linear) and 8-anilinonaphthalene-1-sulfonate (ANS; angular).
Molecular organization and recognition properties of amphiphilic cyclodextrins
Pure and Applied Chemistry, 2000
The continuing challenge of using cyclodextrins (CDs) for solubilization and drug targeting has led to the preparation of a wide variety of chemically modified derivatives in order to improve the properties of these host molecules. A possible approach for pharmaceutical applications would be to combine the recognition specificity of CDs with the transport properties of organized structures such as vesicles, liposomes, or micelles.