Revisiting the internal conformational dynamics and solvation properties of cyclodextrins

Abstract

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...

The Hydrophobic Effect Revisited—Studies with Supramolecular Complexes Imply High‐Energy Water as a Noncovalent Driving Force

“…Neutron diffraction of crystalline β‐CD dodecahydrate showed on average 6.1 disordered water molecules inside the cavity27, 28 (Figure 3 c), in agreement with MD and Monte Carlo (MC) simulations 28. 29 The MD results further suggested that the number of water molecules inside the cavity roughly doubles per glucose unit, and that the residence time of an encapsulated water molecule is inversely proportional to the cavity size 30. Earlier simulations showed for α‐CD only 2–3 water molecules, and for γ‐CD more than for β‐CD, namely, 8.8 water molecules 29.…”

Molecular View into the Cyclodextrin Cavity: Structure and Hydration

“…Numerous MD simulation studies have investigated the conformational dynamics and hydration of native and substituted CDs using various force fields like CVFF, 35 CSFF/CHARMM, 36 − 40 GROMOS, 41 − 44 GLYCAM98, 45 q4mdCD, 46 and OPLS. 47 , 48 The accuracy of the MD results, indeed, depends on the reliability of the underlying molecular model.…”

“…Numerous MD simulation studies have investigated the conformational dynamics and hydration of native and substituted CDs using various force fields like CVFF, CSFF/CHARMM, − GROMOS, − GLYCAM98, q4mdCD, and OPLS. , The accuracy of the MD results, indeed, depends on the reliability of the underlying molecular model. Development of force field for carbohydrates had been a challenge to the computational chemists, compared to protein, lipids, or other biomolecules, owing to the conformational heterogeneity of carbohydrates. , A comparative study on the newer carbohydrate force fields reports equivalent performance of 53A6 GLYC , 56A6 Carbo_R , 2016H66, CHARMM36, and amber-based q4mdCD force fields in reproducing the structural details of CD, closely agreeing with the crystallographic data.…”

Neues zum hydrophoben Effekt – Studien mit supramolekularen Komplexen zeigen hochenergetisches Wasser als nichtkovalente Bindungstriebkraft

“…Neutronenstreuungsexperimente mit kristallinem β‐CD‐Dodecahydrat zeigten durchschnittlich 6.1 ungeordnete Kavitätswassermoleküle27, 28 (Abbildung 3 c), was mit den Resultaten von MD‐ und Monte‐Carlo(MC)‐Simulationen übereinstimmte 28. 29 Gestützt auf die MD‐Methode wurde die Vermutung angestellt, dass sich die Zahl der Kavitätswassermoleküle in etwa pro weitere Glucoseeinheit verdoppelt und dass die Verweilzeit der eingeschlossenen Wassermoleküle invers proportional zur Kavitätsgröße ist 30. Frühere Simulationen ergaben für α‐CD nur 2–3 Kavitätswassermoleküle und für γ‐CD mehr als für β‐CD, nämlich 8.8 29.…”