Trans-cis Photoisomerization of 1-Methyl-4-(4′-hydroxystyryl)pyridinium in inclusion complexes ofβ-cyclodextrin and its derivatives

The effects of -cyclodextrin (-CyD), heptakis(2,6-di-O-methyl)--cyclodextrin (DMCyD) and heptakis(2,3,6-tri-O-methyl)--cyclodextrin (TMCyD) ontrans-cis photoisomerization of 1-ethyl-4-(4-hydroxystyryl)pyridinium (POH) have been studied in aqueous solutions. The ratio of [cis]/[trans] for POH in the photostationary state at pH 8.54 was remarkably reduced by the presence of CyD or DMCyD. The reduction of the [cis]/[trans] ratio in the photostationary state was explained in terms of the shift of the equilibrium of POH ₊ ^trans PO _trans + H^– toward PO _trans formation. The binding constants of CyD and DMCyD for PO _trans were 2.00- and 1.36-fold larger than those for POH ₊ ^trans , respectively. The binding constants of TMCyD for both species are much smaller than those of CyD and DMCyD. This result indicates that PO _trans , which has a betain structure, forms stable complexes with CyD and DMCyD with its hydrophobic parts inside and the charged parts outside the CyD cavities.     

Hexafluoroacetone as Protecting and Activating Reagent. Glycosylated Malic, Citramalic, and Thiomalic Acid Derivatives, New Glycosylated Building Blocks for Drug Design [1]

Summary. Glycosylated -hydroxy and -mercapto acids have been synthesized starting from malic/citramalic/thiomalic acid and Ac₄--D-Glc-NH₂/Bzl₄--D-Glc-NH₂ using hexafluoroacetone as protecting and activating reagent.Dedicated to Prof. Dr. Horst Wilde on the occasion of his 65^th birthday     

Binding of vitamin A byβ-cyclodextrin and heptakis(2,6-O-dimethyl)-β-cyclodextrin

Inclusion complexation of all-trans-retinol, retinal and retinoic acid with -cyclodextrin (-CD) and heptakis(2,6-O-dimethyl)--cyclodextrin (DM--CD) were investigated by means of UV-vis spectroscopy. The association constants (K _a) obtained for vitamin A with DM--CD is greater than with -CD. On the other hand, for the same host compoundK _a values of retinol, retinal and retinoic acid are very close to each other.     

Reatarding effect of nitrogen ylide for the polymerization of N-vinyl pyrrolidone

-Picolinium-p-chlorophenacylide (-PCFY) acts as a retarder for polymerization of N-vinyl pyrrolidone. The polymerization runs were carried out at 60°C using benzene as an inert solvent. The kinetic equation for the present system may be written asR _p [-PCPY]^–1.0 [AIBN]^0.66[N-VP]^1.0. The value of overall energy of activation for polymerization in presence and absence of-PCPY was computed as 44.0 and 42.3 kJ mol^–1, respectively. The inverse relationship ofR _p and¯M _v with-PCPY suggests that-PCPY acts as a polymerization retarder. The retarding effect is also evidenced by higher initiator exponent value and higher value of energy of activation in presence of ylide. A mechanism is also proposed in which polymer propagating chain combines with one ylide component to give resonance stabilized radical.     

Preparation and Characterization of Branched β-Cyclodextrins Having Manno-Oligosaccharide Side Chains Derived from Yeast Mannan and Study of Their Functions

Branched -cyclodextrins (-CDs) having manno-oligosaccharide side chains were investigated. Three kinds of monobranched -CDs and five kinds of dibranched -CDs were chemically synthesized using the trichloroacetimidate method. Their structures were analyzed by HPLC, MS, and NMR spectroscopies. The specific interaction between those compounds and mannose-binding lectins (Concanavalin A and Pisum sativum agglutinin) was investigated by inhibition tests of hemagglutinating activity and by using an optical biosensor of the IAsys apparatus with a resonant mirror detector. The results showed that all branched -CDs interactedwith lectins. The binding affinity was 6¹,6⁴-(Man₃)₂- 6¹,6⁴-(Man₂)₂- > 6¹,6⁴-(Man₄)₂--CD when the derivatives were compared on the basis of side chain length and 6¹,6³- 6¹,6⁴- > 6¹,6²-(Man₂)₂--CD when compared on the basis of side chain position.     

NMR Spectral Assignment of Per-substituted Key-Intermediates of β-Cyclodextrin and Implications in the Structures of the Derivatives

The compounds, 6-per-O-(t-butyldimethylsilyl)--cyclodextrin(1), 2,3-per-O-benzyl-6-per-O-(t-butyldimethylsilyl)--cyclodextrin(2), 2,3-per-O-benzyl--cyclodextrin (3),2,3,6-per-O-benzyl--cyclodextrin (4),2,3,6-per-O-benzoyl--cyclodextrin (5), are used as keyintermediates in the synthesis of selectively substituted -CD derivatives. Simple and assignable ¹H and ¹³C NMR spectra (chemical shifts and coupling constants) were obtained for compounds1–4 indicating C₇ symmetry, ⁴C₁ glucose conformation and major arrangement of H6, H6' atoms at the primary side. The derivative 5, however, gave very broad peaksat room temperature. The peaks could partially be assigned at 270 K, but the broadening was still present at 220 K. This implies that there exist several conformers of similar energyand C₁ symmetry that continuously interchange, since there is not a single type of stabilizing interaction thatpredominates. We attributed this phenomenon to the presence of the carbonyl group, which probablydisfavors - stacking and induces random arrangements of the aromatic rings.     

Acid–Base Behavior in Supercritical Water: β-Naphthoic Acid–Ammonia Equilibrium

Equilibrium constants for the reaction of -naphthoic acid and ammonia, K _BHA, were measured with UV-vis spectroscopy in water from 25°C to 400°C. At high density K _BHA decreases with temperature, the normal behavior for an exothermic reaction of a stronger acid and base to a weaker acid and base. At low density, the reaction becomes endothermic as the solvation of the ionic products becomes weaker. These data were combined with literature results for the dissociation of water and ammonia to determine equilibrium constants for the dissociation of -naphthoic acid and the reaction of -naphthoic acid and OH^- Whereas the density (and dielectric constant) of water have only a modest effect on the isocoulombic reaction of -naphthoic acid and OH^-, they have a large effect on all of the other reactions which are ionogenic.     

Molecular modeling of a putative antagonist binding site on helix III of the β-adrenoceptor

Summary In recent biochemical studies it was demonstrated that residue Asp¹¹³ of the-adrenoceptor (-AR) is an indispensable amino acid for the binding of-AR antagonists. Earlier fluorescence studies showed that a tryptophan-rich region of the-AR is involved in the binding of propranolol, the prototype-AR antagonist. Bearing these two biochemical findings in mind, we explored the-AR part containing Asp¹¹³, for an energetically favorable antagonist binding site. This was done by performing molecular docking studies with the antagonist propranolol and a specific-AR peptide which included, besides Asp¹¹³, two possibly relevant tryptophan residues. In the docking calculations, the propranolol molecule was allowed to vary all its internal torsional angles. The receptor peptide was kept in an-helix conformation, while side chains relevant to ligand binding were flexible to enable optimal adaptations to the ligand's binding conformation. By means of force-field calculations the total energy was minimized, consisting of the intramolecular energies of both ligand and receptor peptide, and the intermolecular energy. We found an antagonist binding site, consisting of amino acids Asp¹¹³ and Trp¹⁰⁹, which enabled energetically favorable interactions with the receptor-binding groups of propranolol. According to these results, binding involves three main interaction points: (i) a reinforced ionic bond; (ii) a hydrogen bond; and (iii) a hydrophobic/charge transfer interaction. The deduced binding site shows a difference in affinity between the levo- and dextrorotatory isomers of propranolol caused by a difference in ability to form a hydrogen bond, which is in conformity with the experimentally observed stereoselectivity. Moreover, it also provides an explanation for the ₁-selectivity ofp-phenyl substituted phenoxypropanolamines like betaxolol. Thep-phenyl substituent of betaxolol was shown to be sterically hindered upon binding to the ₂-AR peptide, whereas this hindrance is very likely to be much less with the ₁-AR peptide. Finally, the proposed antagonist binding site is discussed in the light of some recent biochemical findings and theories.Abbreviations -AR -adrenergic receptor - cDNA complementary DNA - H-bond hydrogen bond - VdW van der Waals - QSAR quantitative structure-activity relationship - ¹²⁵I-pBABC p-(bromoacetamido)benzyl-1-[¹²⁵I]iodocarazol     

Binding forces in complexation ofp-alkylphenols withβ-cyclodextrin and methylatedβ-cyclodextrins

Fluorescence spectroscopy has been used to determine the binding constants (K) for inclusion complexes of six kinds ofp-Akyphenols with-cyclodextrin (-CDx), heptakis(2,6-di-O-methyl)--CDx (DMe--CDxg), and heptakis(2,3,6-tri-O-methyl)--CDx (TMe--CDx). The stability of the inclusion complex of each cyclodextrin increases with increasing alkyl chain length of thep-alkylphenol. TheK values decrease in the order of DMe--CDx,-CDx, and TMe--CDx for each guest. In complexation of 3-(p-hydroxyphenyl)-1-propanol (3) with-CDx as well as with DMe--CDx, negative enthalpy (H) and positive entropy changes (S) have been obtained, suggesting both van der Waals and hydrophobic interactions as binding forces. The inclusion of 3 by TMe--CDx, however, is an enthalpically favorable but entropically unfavorable process. The van der Waals interactions may be the main binding forces for complexing3 with TMe--CDx.     

Ab initio MP2 calculations of the products of acetylene addition to HgCl2

Gas-phase reaction of acetylene with HgCl₂ resulting in -chlorovinylmercury derivatives and their interaction with Cl^– and I^– anions and KI molecule was studied by the ab initio MP2 method with the Dunning—Hay double zeta basis set and LanL pseudopotential for Hg, K, and I atoms. The reaction was shown to proceed via a -complex of acetylene and HgCl₂ (the calculated enthalpy of formation is –6.5 kcal mol^–1). According to calculations, the activation energy of formation of cis--chlorovinylmercury chloride from acetylene and HgCl₂ is 31 kcal mol^–1. Chloride and iodide anions and KI molecule are readily added to both cis- and trans-isomer of -chlorovinylmercury chloride to give stable species.     

FT-IR and raman spectra of a series of metallo-β-cyclodextrin complexes

A series of metallo--CD complexes were prepared and formulated as [M₂(OH)₂ -CD·2 H₂O] ^n– . Changes in the FT-IR and Raman Spectra of-CD on coordination may be taken as evidence for complexation and support for a hydroxy bridged binuclear structure. Further support was obtained from uv/visible and magnetic moment measurements.     

Complex formation of some nonionic surfactants with hydroxypropyl-β-cyclodextrin and with heptakis (2,6-di-O-methyl)-β-cyclodextrin

The interaction of six nonionic surfactants -[4-(1,1,3,3-tetra-methylbutyl)phenyl]--hydroxypoly(oxy-1,2-ethanediyl) with hydroxypropyl--cyclodextrin (HPCD) and dimethyl--cyclodextrin (DIMEB) was studied by reversed-phase thin-layer chromatography in the presence and absence of sodium chloride. Each surfactant formed complexes with both cyclodextrin derivatives; however, the strength of interaction varied considerably. DIMEB formed more stable inclusion complexes with the surfactants than did HPCD. A longer ethyleneoxide chain decreased the strength of interaction, whereas sodium chloride exerted a negligible impact. Principal component analysis indicated that both the hydrophobicity and the specific hydrophobic surface are of the surfactant influenced the complex formation indicating the hydrophobic character of the interaction.Dedicated to Professor József Szejtli.     

Cyclization of O-benzoyl-β-piperidinopropionamidoximes to form 5-phenyl-3-(β-piperidino)ethyl-1,2,4-oxadiazoles

The reactions of -piperidinopropionamidoxime with substituted benzoyl chlorides afforded O-benzoylation products, which underwent cyclization to form 5-phenyl-3-(-piperidino)ethyl-1,2,4-oxadiazoles upon heating in dimethylformamide in the presence of molecular sieves at 60 °C for 1—2.5 h. Heating of O-benzoyl--piperidinopropionamidoxime in dimethylformamide in the presence of K₂CO₃ at 85 °C for 4 h afforded a mixture of 5-phenyl-3-(-piperidino)ethyl-1,2,4-oxadiazole, benzoic acid, and N-(-piperidino)ethylurea.     

Inclusion of Ring A of Cholesterol Inside the β-Cyclodextrin Cavity: Evidence from Oxidation Reactions and Structural Studies

The disposition of cholesterol inside the -cyclodextrin cavity(-CD) was deduced from oxidation of cholesterol secondary alcoholgroups by Ca(OCl)₂ and H₂O₂ in thepyridine–acetic acid system. The amount of cholest-4-ene-3-one formedwas found to be proportional to the concentration of -cyclodextrin,resulting in 56.1% of ketone. The oxidation rate was enhanced by-cyclodextrin and its methyl, polymer and 1 : 1copper(II)–-cyclodextrin derivatives. Detailed investigationsinvolving UV-visible, ¹³C- and ¹H-NMR(T₁, 1D NOE and ROESY) spectroscopic studies were carried out.A binding constant value of 15,385 ± 1500 M^-2 wasobtained for the 2 : 1heptakis-2,6-di-O-methyl--cyclodextrin(DM-CD) : cholesterolcomplex in chloroform from UV studies. Proton and solid state¹³C-CP MAS spectra of the -CD–cholesterol mixtureshowed large magnitude shifts for the protons from the wider end of the-CD cavity as well as those of ring A and ring B of cholesterol. Both1D NOE and ROESY measurements indicated the proximity between ring A andring B protons of cholesterol and the wider end protons of -CD andDM-CD. Besides, analysis of _c,_i and tau;_m from T₁measurements showed not only a lowering of rotational motions but a value of 0.016–0.048 for some of the cholesterol protons, typical of aweak complex. Based on these studies, a probable structure for the 2 : 1complex involving two molecules of -CD/DM-CD was proposed withportions of ring A and ring B being present inside the wider end of the-CD/DM-CD cavity and ring D and the side chain attached atposition 17, projecting into the wider end of the secondCD/DM-CD molecule.     

The Comparison of the Orientation of Sodium 3-Hydroxy-2-Naphthalenecarboxylate in the Cavity of β-Cyclodextrin and Heptakis-(2,3,6-Tri-O-Methyl)-β-Cyclodextrin

Conformational analysis of inclusion complexes of sodium 3-hydroxy-2-naphthalenecarboxylate with -cyclodextrin and heptakis-(2,3,6-tri-o-methyl)--cyclodextrin in D₂O was investigated by 1D and 2D ¹HNMR measurements. The results show that part of the naphthyl group of sodium 3-hydroxy-2-naphthalenecarboxylate is situated in the 2,3-OH side of the -cyclodextrin cavity asymmetrically while the whole naphthyl group is included in the heptakis-(2,3,6-tri-o-methyl)--cyclodextrin cavity with the caboxylate and hydroxy group close to the 6-OCH₃ group.     

ESR spectra of γ-irradiated samples of iron(iii) binuclear complexes

-Irradiation of -oxo-bridged binuclear iron complexes Fe^III ₂OL _n in a glycerol or dimethylformamide matrix at 77 K affords unstable mixed-valence Fe^IIF^III forms resulting from the transfer of a mobile electron generated by the ionizing radiation. These nonequilibrium forms retain the ligand environment of the original complexes, and their ESR spectra at 77–200 K are characterized by an asymmetric signal with an axially anisotropicg-factor, which is in agreement with the spectra of the Fe^IIFe syu forms obtained by chemical reduction.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 869–871, April, 1996.     

Molecular Interactions and Inclusion Phenomena in Substituted β-Cyclodextrins. Simple Inclusion Probes: H2O, C, CH4, C6H6, NH4 +, HCOO−

Using a simple molecular mechanics approach interaction energy profiles of simple probes (C, CH₄, C₆H₆, H₂O, NH₄ ⁺, and HCOO^-) passing through the center of the -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 -CD molecule together with solute-solvent (H₂O) interactions have been represented by averaging structures of MD calculations for -CD alone and -CD surrounded by 133 H₂O molecules. The effect of various substitutions of -CD has also been evaluated. Small symmetric hydrophobic probes (such as C, CH₄, C₆H₆) are predicted to form stable inclusion complexes with non-substituted and substituted -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 H₂O, NH₄ ⁺, 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 -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 -CD ring cavity and in most of the studied substituted -CDs and shows maximum positive or negative values outside of the cavity, near the ring faces. Substitution of -CD by neutral substituents leads to enhanced binding of hydrophobic probes and significant changes in the MEP profile along the -CD symmetry axis.     

Ab initio Study of β-lactam antibiotics

Ab initio SCF-MO-LCAO calculations have been performed with a 7s3p/3s GTO basis set for the CH₃O--lactam + OH^– reaction which is related to the mode of action of -lactam antibiotics. The comparison of the present results with the previous ones for -lactam + OH^– and 3-cephem + OH^– shows that the CH₃O substitution has a negligible effect on the amidic bond breaking of -lactam, so that this group probably influences other steps of the antibiotic reactivity of cephaloporins.     

Effect of fusion conditions ofβ-polypropylene on the new crystallization

The new crystallization of -modification of polypropylene (-PP) was studied after melring as a function of the final temperature of fusion (T _F ). The new crystallization, thermal characteristics, polymorphic composition, and structure of recrystallized samples were highly influenced by theT _F level. As a function ofT _F , three characteristic regions were outlined: Region I below the melting point of -modification, region II between the melting points of - and -modifications, and region III above the melting point of -modification. In the vicinity of the melting points of both modifications, two narrow transition regions are observed where the crystallization and structural characteristics changed abruptly withT _F . AtT _F values in region I, recrystallization of -modification proceeded without any change in the modification. IfT _F fell in region II, the sample crystallized newly into -modification. The optically negative -ring-spherulites were replaced by positive microclusters of -modification and a marked structural memory effect was observed. In region III, the above characteristic became invariant withT _F (region of blank melt). These observations may be interpreted by the role of self nuclei.     

Effects of Modified β-Cyclodextrins on the Hydrolysis Reaction of p-Nitrophenyl α-Methoxyphenylacetate

Effects of -cyclodextrin (-CD) 1and its derivatives 2–7 on the deacylationreaction of p-nitrophenyl (R or S)--methoxyphenylacetatewere studied. The-CD derivatives used were6--D-glucosyl--CD 2, sulfated-CD (7–11 sulfate groups/CD ring) 3,dimethylated -CD 4, carboxymethylated-CD (3.5 carboxymethyl groups/CD ring) 5,2-tri(2-hydroxypropyl)--CD 6, and-CD appended on poly(allylamine) 7. Therate constant (k ^CD) of thesubstrate/-CD complexes and the formationconstants (K) of the complexes were determinedfrom the dependence of the pseudo-first order rateconstants of the deacylation reaction on theconcentration of -CDs. The order ofk ^CD for the R-enantiomer at pH8.0 is 45H₂O3 6 1 2 7, whilethat for the S-enantiomer is 4 5 6H₂O 1 2 3 7: H₂O denotes the rate in theabsence of -CDs. The order of K values is3 7 6 2 1 4 5. This work indicates that, though thesecondary hydroxyl groups of -CD play criticalroles in the deacylation reactions of the esterscomplexed with -CDs, the reactivity of theester/-CD complexes depends highly on thenature of the substituents at the secondary face of-CD. It also suggests that the substratesinserted from the secondary side as well as theprimary side of -CD of poly(allylamine)-bound-CD undergo the reaction by attack of aminogroups on the polymer chain.