Host flexibility and space filling in supramolecular complexation of cyclodextrins: A free-energy-oriented approach

Tânia F. Cova; Bruce F. Milne; Alberto A.C.C. Pais

doi:10.1016/j.carbpol.2018.10.009

Host flexibility and space filling in supramolecular complexation of cyclodextrins: A free-energy-oriented approach

Tânia F. Cova, Bruce F. Milne, Alberto A.C.C. Pais^* (Corresponding Author)

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

Cyclodextrins (Cds) are versatile carbohydrate hosts for developing multifunctional nanostructures of pharmaceutical interest. Factors affecting the thermodynamic signatures and stability of β- and γ-Cd complexes are detailed at the atomic level. The MD/PMF-based method is combined with the description of the nature and strength of the inter-partner affinity. Naphthalene, adamantane and lycorine derivatives are used as models of drug-leading structures. Guest size affects Cd-guest contact and the inclusion degree, inducing Cd deformation, which opposes inclusion. Complexation depends on the available Cd cavity volume, as guest fitting variations and the enthalpy penalty from Cd deformation impact on the binding constants (promoting a reduction of up to 104). The often neglected Cd deformation plays, thus, an important role in the interaction behavior of larger cavity Cd-based systems, being crucial in carbohydrate-mediated recognition phenomena. It corresponds to an increase in energy of ca. 90 kJ mol−1 in the simpler analyzed model system.

Original language	English
Pages (from-to)	42-54
Number of pages	13
Journal	Carbohydrate Polymers
Volume	205
Early online date	9 Oct 2018
DOIs	https://doi.org/10.1016/j.carbpol.2018.10.009
Publication status	Published - 1 Feb 2019

Bibliographical note

Acknowledgement: The authors acknowledge the Fundação para a Ciência e a Tecnologia (FCT), Portuguese Agency for Scientific Research, through the Projects n. 016648 POCI − 01 − 0145 − FEDER − 016648 and COMPETE POCI − 01 − 0145 − FEDER − 007440. The Coimbra Chemistry Centre is also supported by FCT through the Projects PEst − OE/QUI/UI0313/2014 and POCI − 01 − 0145 − FEDER − 007630. Tânia F.G.G. Cova also acknowledges the PhD research Grant SFRH/BD/95459/2013 assigned by FCT. BFM thanks the FCT (project CENTRO − 01 − 0145 − FEDER − 000014, 2017-2020) and the Donostia International Physics Centre for financial support. The authors also wish to thank the Laboratory for Advanced Computing (LCA) of the University of Coimbra for the provision of computer time and support.

Keywords

Carbohydrates
Cyclodextrins
Host–guest complexation
Noncovalent interactions
Molecular dynamics
Free-energy

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https://www.sciencedirect.com/science/article/pii/S0144861718311858

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@article{34ca76b5652142faa51cd587cad91457,

title = "Host flexibility and space filling in supramolecular complexation of cyclodextrins: A free-energy-oriented approach",

abstract = "Cyclodextrins (Cds) are versatile carbohydrate hosts for developing multifunctional nanostructures of pharmaceutical interest. Factors affecting the thermodynamic signatures and stability of β- and γ-Cd complexes are detailed at the atomic level. The MD/PMF-based method is combined with the description of the nature and strength of the inter-partner affinity. Naphthalene, adamantane and lycorine derivatives are used as models of drug-leading structures. Guest size affects Cd-guest contact and the inclusion degree, inducing Cd deformation, which opposes inclusion. Complexation depends on the available Cd cavity volume, as guest fitting variations and the enthalpy penalty from Cd deformation impact on the binding constants (promoting a reduction of up to 104). The often neglected Cd deformation plays, thus, an important role in the interaction behavior of larger cavity Cd-based systems, being crucial in carbohydrate-mediated recognition phenomena. It corresponds to an increase in energy of ca. 90 kJ mol−1 in the simpler analyzed model system.",

keywords = "Carbohydrates, Cyclodextrins, Host–guest complexation, Noncovalent interactions, Molecular dynamics, Free-energy",

author = "Cova, {T{\^a}nia F.} and Milne, {Bruce F.} and Pais, {Alberto A.C.C.}",

note = "Acknowledgement: The authors acknowledge the Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia (FCT), Portuguese Agency for Scientific Research, through the Projects n. 016648 POCI − 01 − 0145 − FEDER − 016648 and COMPETE POCI − 01 − 0145 − FEDER − 007440. The Coimbra Chemistry Centre is also supported by FCT through the Projects PEst − OE/QUI/UI0313/2014 and POCI − 01 − 0145 − FEDER − 007630. T{\^a}nia F.G.G. Cova also acknowledges the PhD research Grant SFRH/BD/95459/2013 assigned by FCT. BFM thanks the FCT (project CENTRO − 01 − 0145 − FEDER − 000014, 2017-2020) and the Donostia International Physics Centre for financial support. The authors also wish to thank the Laboratory for Advanced Computing (LCA) of the University of Coimbra for the provision of computer time and support.",

year = "2019",

month = feb,

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doi = "10.1016/j.carbpol.2018.10.009",

language = "English",

volume = "205",

pages = "42--54",

journal = "Carbohydrate Polymers",

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T2 - A free-energy-oriented approach

AU - Cova, Tânia F.

AU - Milne, Bruce F.

AU - Pais, Alberto A.C.C.

N1 - Acknowledgement: The authors acknowledge the Fundação para a Ciência e a Tecnologia (FCT), Portuguese Agency for Scientific Research, through the Projects n. 016648 POCI − 01 − 0145 − FEDER − 016648 and COMPETE POCI − 01 − 0145 − FEDER − 007440. The Coimbra Chemistry Centre is also supported by FCT through the Projects PEst − OE/QUI/UI0313/2014 and POCI − 01 − 0145 − FEDER − 007630. Tânia F.G.G. Cova also acknowledges the PhD research Grant SFRH/BD/95459/2013 assigned by FCT. BFM thanks the FCT (project CENTRO − 01 − 0145 − FEDER − 000014, 2017-2020) and the Donostia International Physics Centre for financial support. The authors also wish to thank the Laboratory for Advanced Computing (LCA) of the University of Coimbra for the provision of computer time and support.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Cyclodextrins (Cds) are versatile carbohydrate hosts for developing multifunctional nanostructures of pharmaceutical interest. Factors affecting the thermodynamic signatures and stability of β- and γ-Cd complexes are detailed at the atomic level. The MD/PMF-based method is combined with the description of the nature and strength of the inter-partner affinity. Naphthalene, adamantane and lycorine derivatives are used as models of drug-leading structures. Guest size affects Cd-guest contact and the inclusion degree, inducing Cd deformation, which opposes inclusion. Complexation depends on the available Cd cavity volume, as guest fitting variations and the enthalpy penalty from Cd deformation impact on the binding constants (promoting a reduction of up to 104). The often neglected Cd deformation plays, thus, an important role in the interaction behavior of larger cavity Cd-based systems, being crucial in carbohydrate-mediated recognition phenomena. It corresponds to an increase in energy of ca. 90 kJ mol−1 in the simpler analyzed model system.

AB - Cyclodextrins (Cds) are versatile carbohydrate hosts for developing multifunctional nanostructures of pharmaceutical interest. Factors affecting the thermodynamic signatures and stability of β- and γ-Cd complexes are detailed at the atomic level. The MD/PMF-based method is combined with the description of the nature and strength of the inter-partner affinity. Naphthalene, adamantane and lycorine derivatives are used as models of drug-leading structures. Guest size affects Cd-guest contact and the inclusion degree, inducing Cd deformation, which opposes inclusion. Complexation depends on the available Cd cavity volume, as guest fitting variations and the enthalpy penalty from Cd deformation impact on the binding constants (promoting a reduction of up to 104). The often neglected Cd deformation plays, thus, an important role in the interaction behavior of larger cavity Cd-based systems, being crucial in carbohydrate-mediated recognition phenomena. It corresponds to an increase in energy of ca. 90 kJ mol−1 in the simpler analyzed model system.

KW - Carbohydrates

KW - Cyclodextrins

KW - Host–guest complexation

KW - Noncovalent interactions

KW - Molecular dynamics

KW - Free-energy

U2 - 10.1016/j.carbpol.2018.10.009

DO - 10.1016/j.carbpol.2018.10.009

M3 - Article

SN - 0144-8617

VL - 205

SP - 42

EP - 54

JO - Carbohydrate Polymers

JF - Carbohydrate Polymers

ER -

Host flexibility and space filling in supramolecular complexation of cyclodextrins: A free-energy-oriented approach

Abstract

Bibliographical note

Keywords

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