Analysis of Molecular Interaction of Drugs within β-Cyclodextrin Cavity by Solution-State NMR Relaxation

Abstract

The prime focus of the present study is to employ NMR relaxation measurement to address the intermolecular interactions, as well as motional dynamics, of drugs, viz., paracetamol and aspirin, encapsulated within the β-cyclodextrin (β-CD) cavity. In this report, we have attempted to demonstrate the applicability of nonselective (R), selective (R), and bi-selective (R) spin-lattice relaxation rates to infer dynamical parameters, for example, the molecular rotational correlation times (τ) and cross-relaxation rates (σ) of the encapsulated drugs. Molecular rotational correlation times of the free drugs were calculated using the selective relaxation rate in the fast molecular motion time regime (ωτ ≪ 1 and R/R ≈ 1.500), whereas that of the 1:1 complexed drugs were found from the ratio of R/R in the intermediate motion time regime (ωτ ∼ 1 and R/R ≈ 1.054), and these values were compared with each other to confirm the formation of inclusion complexes. Furthermore, the cross-relaxation rates were used to evaluate the intermolecular proton distances. Also, density functional theory calculations were performed to determine the minimum energy geometry of the inclusion complexes and the results compared with those from experiments. The report, thus, presents the possibility of utilizing NMR relaxation data, a more cost-effective experiment, to calculate internuclear distances in the case of drug-supramolecule complexes that are generally obtained by extremely time consuming two-dimensional nuclear Overhauser enhancement-based methods. A plausible mode of insertion of the drug molecules into the β-CD cavity has also been described based on experimental NMR relaxation data analysis.

Do Cyclodextrins Encapsulate Volatiles in Deep Eutectic Systems?

“…36,38,46 Both the R 1 NS /R 1 SE ratio and are related to the motional regime of the guest, which in turns reflects its equilibrium between the free and bound states. 28,35,45 Here we applied this method to get information about the dynamics of the selected VOCs in reline and on how it changes in the presence and absence of β-cyclodextrin. As overlapping peaks are not suitable for selective inversion, after investigation of 1 H NMR spectrum, the most isolated peaks were chosen for observation, namely protons H 3 ,H 5 for aniline and methyl protons for toluene (see Figs.…”

“…This value is expected when the molecule is in the extreme narrowing region ( 0 ≪ 1). 38,45 For toluene in ChU/βCD/H 2 O, the value of the R To confirm that the reduced diffusion of the guest in the presence of βCD is not due to viscosity changes caused by the addition of the macrocyclic oligosaccharide, the self-diffusion coefficient of H 2 O was used as an internal reference. 61 A look at Fig.…”

“…39,43,44 In the case of inclusion complexes with cyclodextrins, the application of 1 H nonselective, selective, and bi-selective spin−lattice relaxation rates can be used to address intermolecular interactions and motional dynamics of drugs encapsulated within the βCD cavity. 45 A theoretical description is provided for the interested reader in the SI. Basically, measuring R 1 NS and R 1…”

Inclusion complexes of tricyclic drugs and β-cyclodextrin: Inherent chirality and dynamic behaviour

“…The application of 1 H relaxation experiments to study aggregation, interactions and/or binding processes with macromolecules, including cyclodextrins, is well known (De Sousa et al, 2008;Fielding, 2007;Li et al, 2007;Reddy et al, 2015;Rossi et al, 2001;Schneider et al, 1998;Tinoco and Figueroa-Villar, 1999;Tošner et al, 2006). Recently, the use of non-selective ( ), selective ( ) and bi-selective ( ) spin-lattice relaxation rates was revised as a tool to derive informative dynamical parameters characterizing the inclusion complexes formed by two drugs, paracetamol and aspirin, with βCD (Kumar et al, 2017). We also demonstrated that non-selective and selective relaxation T 1 experiments can successfully be applied to get information on the rotational motion of encapsulated drugs in complex media such as deep eutectic systems (Di Pietro et al, 2020).…”

“…Following the methodology by Kumar et al (2017), in the present work we measured and analysed , and for the complexes of AMT and CBZ with βCD to access valuable dynamical parameters, namely the molecular rotational correlation times ( ) and the cross-relaxation rates ( ) of drugs encapsulated in βCD cavities. A detailed theoretical treatment is given in the SI.…”