Exploration of the Conformational Scenario for α-, β-, and γ-Cyclodextrins in Dry and Wet Conditions, from Monomers to Crystal Structures: A Quantum-Mechanical Study

Int J Mol Sci. 2023 Nov 27;24(23):16826. doi: 10.3390/ijms242316826.

Abstract

Cyclodextrins (CDs) constitute a class of cyclic oligosaccharides that are well recognized and largely applied in the drug delivery field, thanks to their biocompatibility, low cost, and the possibility to be derivatized in order to tune and optimize the complexation/release of the specific drug. The conformational flexibility of these systems is one of their key properties and requires a cost-effective methodology to be studied by combining the accuracy of results with the possibility of exploring a large set of conformations. In the present paper, we have explored the conformational potential energy surface of the monomers and dimers of α-, β-, and γ-cyclodextrins (i.e., 6, 7, and 8 monomeric units, respectively) by means of fast but accurate semiempirical methods, which are then refined by state-of-the-art DFT functionals. Moreover, the crystal structure is considered for a more suitable comparison with the IR spectrum experimentally recorded. Calculations are carried out in the gas phase and in water environments, applying both implicit and explicit treatments. We show that the conformation of the studied molecules changes from the gas phase to the water, even if treated implicitly, thus modifying their complexation capability.

Keywords: IR spectra; conformational exploration; cyclodextrin; density functional theory.

MeSH terms

  • Cyclodextrins* / chemistry
  • Models, Molecular
  • Molecular Conformation
  • Water / chemistry
  • gamma-Cyclodextrins*

Substances

  • gamma-Cyclodextrins
  • Cyclodextrins
  • Water

Grants and funding

This work has been partially supported by the Spoke 7 “Materials and Molecular Sciences” of ICSC–Centro Nazionale di Ricerca in High-Performance Computing, Big Data and Quantum Computing, funded by the European Union–NextGenerationEU (PNRR, CN1-SPOKE 7 Materials and Molecular Sciences CUP D13C22001340001-CN00000013). R.F. is indebted to MUR for his PhD grant PON DM1061.