Intermolecular Interactions between Doxorubicin and β-Cyclodextrin 4-Methoxyphenol Conjugates

Abstract

Newly synthesized derivatives of β-cyclodextrin, mono(6-deoxy-6-(1-1,2,3-triazo-4-yl)-1-propane-3-O-(4-methoxyphenyl))β-cyclodextrin (1) and mono(6-deoxy-6thio(1-propane-3-O-(4-methoxyphenyl))) β-cyclodextrin (2) were designed to be receptors of the anticancer drug doxorubicin, which could potentially decrease the adverse effects of the drug during treatment. In both aqueous and aqueous dimethyl sulfoxide (DMSO) solutions, doxorubicin forms an inclusion complex with the new cyclodextrin derivatives with formation constants of K(s) = 2.3 × 10(4) and K(s) = 3.2 × 10(5) M(-1) for cyclodextrins 1 and 2, respectively. The stabilities of the complexes are 2-3 orders of magnitude greater than those with native β-cyclodextrin, and the flexibility of the linker of the side group of the cyclodextrins contributes to this stability. In a hydrogen-bond-accepting solvent, such as pure DMSO, an association that includes hydrogen bonding and chloride ions is favored over the binding of doxorubicin in the cavity of the cyclodextrin derivative. This contrasts with an aqueous medium in which a strong inclusion complex is formed. Cyclic voltammetry, UV-vis, (1)H NMR, and molecular modeling studies of solutions in DMSO and of solutions in water/DMSO demonstrated that the two different modes of intermolecular interaction between doxorubicin and the cyclodextrin derivative depended on the solvent system being utilized.

Study of near‐symmetric cyclodextrins by compressed sensing 2D NMR

“…Mono(6‐deoxy‐6‐(1‐1,2,3‐triazo‐4‐yl)‐1‐propane‐3‐ O ‐(phenyl)) β ‐CD was synthesized according to the procedure described elsewhere …”

“…The aim of this work is to present that compressed sensing 2D NMR spectra allow for the full spectral assignment of near‐symmetric mono(6‐deoxy‐6‐(1‐1,2,3‐triazo‐4‐yl)‐1‐propane‐3‐ O ‐(phenyl)) β ‐CD. In this functionalized CD, designed to be a receptor of the anticancer drug doxorubicin, one sugar unit was modified at the C6 position.…”

“…In this functionalized CD, designed to be a receptor of the anticancer drug doxorubicin, [47] one sugar unit was modified at the C6 position.…”

Synthesis and Inclusion Study of a Novel γ-Cyclodextrin Derivative as a Potential Thermo-Sensitive Carrier for Doxorubicin

“…Calculation of Binding Constant K of 3b to DOX: It has been well reported in the literature that, addition of native γ-CD added to DOX at a ratio of up to 5000 : 1 could significantly stabilize DOX in aqueous solution via complex formation. 32) Other reports, 33) in which DOX encapsulation within CDs could significantly lower the fluorescence and absorbance signals of the guest molecule, demonstrated that CDs can be considered as a fluorophore quencher for DOX. Therefore, the binding constant can be calculated according to modified Stern-Volmer 24) Eq.…”

Soluble cyanine dye/β-cyclodextrin derivatives: Potential carriers for drug delivery and optical imaging

“…[34] CyD chemical modification, by covalently attaching the appropriate moieties, can substantially increase the stability of the CyD-drug complex and such measures have been taken as a means for making complex-controlled target drug carriers. [34][35][36][37][38] Additionally, the appended group contains cyanine dyes, with long wavelength colorimetric and fluorometric photoactivities, as cyanine-CyD carriers can also be useful for optical and near-infrared fluorescence imaging in living cells or biological tissues.…”