Determination of the Inclusion Geometry for the β-Cyclodextrin/Benzoic Acid Complex by NMR and Molecular Modeling

Salvatierra, D.; Jaime, Carlos; Virgili, A.; Sánchez‐Ferrando, Francisco

doi:10.1021/jo9612032

Cited by 118 publications

(57 citation statements)

References 39 publications

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“…The βCD anomeric proton H(1) was used as internal reference (0 ppm) for the magnetic shift units, as described in the literature [21], since its location insures the smallest shift and the residual protons in deuterated water are too large and may undergo exchange with small amounts of nondeuterated water [21]. The measurements were performed at 40ºC.…”

Section: Fourier Transform Infrared Spectroscopy (Ft-ir)mentioning

confidence: 99%

“…3.5. -Nuclear magnetic resonance NMR proton spectroscopy has been a frequently used spectroscopic analytical tool to study the inclusion of guest molecules into a host [5,10,21,34]. Here we have addressed the possible inclusion/complexation of the two drugs considered (IB and IN) in a host macrocycle (βCD) with simple 1D proton spectroscopy, combined with other complementary characterisation techniques.…”

Section: -Indomethacinmentioning

confidence: 99%

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The influence of the preparation methods on the inclusion of model drugs in a β-cyclodextrin cavity

Salústio

Feio

Figueirinhas³

et al. 2009

European Journal of Pharmaceutics and Biopharmaceutics

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The work aims to prove the complexation of two models drugs (ibuprofen, IB and indomethacin, IN) by beta-cyclodextrin (βCD), the effect of the water in such process, and the comparison of their complexation yields. Two methods were considered: kneading of a binary mixture of the drug:βCD and inclusion of either IB or IN in aqueous solutions of βCD. In the latter method the water was removed by air stream, spray-drying and freeze-drying. To prove the formation of complexes in final products optical microscopy, UV spectroscopy, IR spectroscopy, DSC, X-Ray and NMR were considered. Each powder was added to an acidic solution (pH = 2) to quantify the concentration of the drug inside βCD cavity. Others media (pH = 5 and 7) were used to prove the existence of drug not complexed in each powder as the drugs solubility increases with the pH. It was observed that complexation occurred in all powders, and that the fraction of drug inside the βCD did not depend neither on the method of complexation nor on the processes of drying considered.

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Section: Fourier Transform Infrared Spectroscopy (Ft-ir)mentioning

confidence: 99%

Section: -Indomethacinmentioning

confidence: 99%

The influence of the preparation methods on the inclusion of model drugs in a β-cyclodextrin cavity

Salústio

Feio

Figueirinhas³

et al. 2009

European Journal of Pharmaceutics and Biopharmaceutics

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“…[23][24][25][26][27][28] However, conformational analyses of energetically stable conformations of the CDs 12-14 and their complexes [15][16][17][18][19][20][21][22] have been the main targeted subjects. Molecular dynamics (MD) simulations are more timeconsuming but provide a better connection between atomistic constitution and macroscopic properties when compared to pure geometry optimizations methods.…”

mentioning

confidence: 99%

Revisiting the internal conformational dynamics and solvation properties of cyclodextrins

Pereira¹,

Moura²,

Freitas³

et al. 2007

J. Braz. Chem. Soc.

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Simulações de dinâmica molecular são utilizadas para investigar a dinâmica conformacional interna e propriedades de solvatação das três ciclodextrinas naturais, α-, β-e γ-ciclodextrina em água e temperatura ambiente. Estes oligossacarídeos derivados da glicose apresentam uma estrutura molecular peculiar que lhes confere a habilidade de formar complexos de inclusão e modificar as propriedades físico-químicas das moléculas complexadas. As características estruturais das ciclodextrinas em solução são determinantes para a complexação. As análises das trajetórias obtidas mostram que ligações de hidrogênio secundárias entre resíduos de glicose adjacentes estão presentes em solução e apresentam um caráter altamente dinâmico, onde ligações de hidrogênio alternativas podem ser formadas com moléculas de água. Apesar do baixo caráter hidrofílico, as cavidades apresentam-se solvatadas e o número de moléculas de água dentro da cavidade é aproximadamente duplicada por unidade de glicose adicionada ao macrociclo. Os tempos de residência para as moléculas de água dentro das cavidades são inversamente proporcionais ao seu respectivo tamanho.Molecular dynamics simulations were used to investigate the internal conformational dynamics and solvation properties of the three natural cyclodextrins, α-, β-and γ-cyclodextrin in aqueous solution at room temperature. These glucose-derived oligosacharides present a molecular structure that confers them the ability to complex guest molecules and change their physicochemical properties. The structural behavior of cyclodextrins in solution is crucial for their complexation abilities. Analyses of the obtained trajectories show that inter-glucose hydrogen bonds between the secondary hydroxyl groups are present in solution, but show a very dynamical character where alternative hydrogen bonds to water molecules can be formed. Despite the lower hydrophilicity of the cyclodextrins inner-cavities, they were found to be solvated and the number of water molecules inside the cavity roughly doubles per glucose unit added to the ring. The residence times for water molecules inside the cavities are inversely proportional to the cavity size. Keywords: cyclodextrins, molecular dynamics, solvation, flexibility IntroductionCyclodextrins (CDs) have been extensively studied since their discovery in the late nineteenth century.1 Their peculiar properties and behavior have interested scientists in many different fields.2 These cyclic oligosaccharides, obtained from starch by glucanotransferase degradation, are formed by a certain number of α-D-glucopyranose units linked by α(1→4) glycosidic bonds. This arrangement produces a truncated cone shape with a central cavity relatively hydrophobic and an external surface relatively hydrophilic.1-3 Naturally occurring CDs, known as α-, β-and γ-CD, present six, seven and eight glucose units, respectively.1-3 The structural features of these saccharides allow them to form inclusion complexes with a great variety of compounds.3 Due to their ability to form host-guest complexe...

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“…These bimodal structures have been reported for other β-CD-substrate complexes. 22,23 The insertion of NA from primary rim induced the 1 H chemical shift of the H-6 protons and the ROESY cross-peaks. In the case of the complexes with CM-β-CD, the observed ROESY spectrum is more complicated due to heterogeneity of the anionic CD.…”

Section: Methodsmentioning

confidence: 99%

NMR Spectroscopic Analysis on the Chiral Recognition of Noradrenaline by β-Cyclodextrin ( β-CD) and Carboxymethyl- β-cyclodextrin (CM- β-CD)

Lee¹,

Yi²,

Jung³

2004

Bulletin of the Korean Chemical Society

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β-CD and CM-β-CD as chiral NMR shift agents were used to resolve the enantiomers of noradrenaline (NA).The stoichiometry of each complex formed between the CDs and the enantiomers of NA was found to be 1 : 1 through the continuous variation plots. The binding constants (K) of the complexes were determined from indicating that CM-β-CD was the better chiral NMR solvating agents for the recognition of the enantiomers of NA. Two dimensional rotating frame nuclear Overhauser enhancement spectroscopy (ROESY) experiments were also performed to explain the binding properties in terms of spatial fitting of the NA molecule into the macrocyclic cavities.

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Determination of the Inclusion Geometry for the β-Cyclodextrin/Benzoic Acid Complex by NMR and Molecular Modeling

Cited by 118 publications

References 39 publications

The influence of the preparation methods on the inclusion of model drugs in a β-cyclodextrin cavity

The influence of the preparation methods on the inclusion of model drugs in a β-cyclodextrin cavity

Revisiting the internal conformational dynamics and solvation properties of cyclodextrins

NMR Spectroscopic Analysis on the Chiral Recognition of Noradrenaline by β-Cyclodextrin ( β-CD) and Carboxymethyl- β-cyclodextrin (CM- β-CD)

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