Structural distortion of β-cyclodextrin plays a key role for the pH-dependent host-guest chemistry with doxorubicin, evident by electrochemical and molecular dynamics approach

β-cyclodextrin (β-CD) is the potential drug carrier to deliver antitumor drugs like doxorubicin<br> (DOX). However, the mechanism for the inclusion complex formation is still unclear and<br> needs to be explored. This study investigated the effect of pH on the inclusion of DOX into<br> thiolated β-CD (β-CD-SH) by electrochemical and molecular dynamics (MD) simulation.<br> The electrochemical study shows a clear difference at different pH. The redox peak due to the<br> DOX is strongly influenced by pH. At neutral pH, the peak intensity decreases with time,<br> while slight variation is observed at acidic and basic pH. Depicting the association of DOX to<br> the β-CD-SH cavity at neutral pH. Also, due to the association, the charge transfer resistance<br> variation increased with time at neutral pH, decreased at basic and acidic pH. The<br> electrochemical study was further supported by MD simulation, suggesting that the<br> cyclodextrins ring gets slightly elongated due to the flipping of glucose units,<br> specifically at neutral pH leads to a strong association. Also, another significant result<br> observed that the DOX forms an inclusion complex with β-CD-SH in quinol conformation,<br> not in quinone. Briefly, the study provides the necessary molecular binding information for<br> designing an effective β-CD based targeted drug delivery system.