Structural diversity in the host–guest complexes of the antifolate pemetrexed with native cyclodextrins: gas phase, solution and solid state studies

Abstract

The complexation of the antifolate pemetrexed (PTX) with native cyclodextrins was studied. This process, along with the findings gathered for the structurally related folic acid was treated as a model for exploiting host–guest interactions of this class of guest molecules in the gas phase, in solution and in the solid state. Mass spectrometry was employed for the investigation of the architecture and relative gas-phase stabilities of these supramolecular complexes. The mode of complexation was further tracked by 1D and 2D NMR proving the formation of the exclusion-type complex with α-CD and pseudorotaxane inclusion-type complexes with β-, and γ-CDs. UV–vis titrations at pH 7.4 gave association constants for the obtained complexes. The stability of the complexes increases in the series: α-CD/PTX < γ-CD/PTX << β-CD/PTX. The association of PTX with a monomer cyclodextrin equivalent – methyl α-D-glucopyranoside – was investigated for a deeper understanding of the type of host–guest interactions. Solid state studies of PTX/CDs were performed using FTIR–ATR and Raman spectroscopy techniques.

Adsorption of Paraquat by Poly(Vinyl Alcohol)-Cyclodextrin Nanosponges

“…The pristine β-CD spectra exhibited the characteristic bands at 1463 cm −1 for CH deformation, 1414 cm −1 for C–O–C symmetric and antisymmetric stretching, 1389 cm −1 for CH stretching and wagging, 1338 cm −1 for CH 2 deformation, 1252 cm −1 for OH in plane bending and CH 2 stretching, 1125 cm −1 for C–O–C symmetric stretching, 1081 cm −1 for C–O–C symmetric and antisymmetric stretching of glycosidic bonds, 1041 cm −1 for C–O stretching, 947 cm −1 for skeletal mode of α-(1–4) linkage (delocalized mode), 931 cm −1 for glucopyranose (C–O–C) skeletal mode of α-anomers, 855 cm −1 for OCH side group deformational of d -glucopyranose units, 757 cm −1 for d -glucopyranose ring breathing mode, 709 cm −1 for CH out of plane bending, 575 cm −1 for OH wagging, 479 cm −1 for skeletal vibrations of amylose, 439 cm −1 for CH stretching, 356 cm −1 for OH stretching, 318 cm −1 for external C–OH out of plane bending of glucopyranose units, and 155 cm −1 for the breathing motions of oxygen atoms in the macrocyclic ring. These results were in agreement with the literature [ 89 , 90 , 91 , 92 ].…”

Adsorption of Cationic Contaminants by Cyclodextrin Nanosponges Cross-Linked with 1,2,3,4-Butanetetracarboxylic Acid and Poly(vinyl alcohol)

“…The β-CD spectra exhibited the specific bands at 1463 cm −1 for CH deformation, 1338 cm −1 for CH2 deformation, 1252 cm −1 for OH in-plane bending and CH2 stretching, 1125 cm −1 for C-O-C symmetric stretching, 1081 cm −1 for C-O-C symmetric and antisymmetric stretching of glycosidic bonds, and 479 cm −1 for skeletal vibrations of amylose. These results were in agreement with the literature [133] [134] [135] [136]. For BP5 nanosponges, the particular peaks were found at 1229 cm −1 for CH2 stretching, 1144 cm −1 for CC and CO stretching, 1043 cm −1 for C-O stretching, and 810 cm −1 for C-O-C stretching.…”

Noncovalent Complexes of Cyclodextrin with Small Organic Molecules: Applications and Insights into Host–Guest Interactions in the Gas Phase and Condensed Phase

“…Other references suggest that the complementarity of the cavity size is also an important factor for the complexation. Mechanism studies for CD complexes in the gas phase have been performed using a combination of the mass spectrometric methods, namely, gas chromatography–mass spectrometry (GC–MS), ion mobility mass spectrometry (IMS–MS), infrared multiphoton dissociation (IRMPD) spectroscopy, and theoretical calculations involving various combinations of molecular dynamics (MD), semi-empirical, and density functional theory (DFT) methods [ 2 , 26 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. Recently, structural analysis was conducted using action–FRET (Fluorescence Resonance Energy Transfer), a gas phase version of FRET in which chromophore-tagged β-cyclodextrin and amyloid-β fragment peptides were utilized [ 61 ].…”