Demonstrating accuracy of the already proposed protocol for structure elucidation of cyclodextrin inclusion complexes by validation using quantitative ROESY analysis

In this study, we attempt to ascertain the accuracy of the structures determined using our previously developed method and hence the accuracy of our method. In the present report, we have taken the guest molecule cetirizine (CTZ) and the host molecules are α-cyclodextrin (α-CD) and β-cyclodextrin (β-CD). Structures with good accuracy were elucidated using a productive fusion of experimental and computational methods. We performed molecular mechanics studies (MM) in light of experimental ROESY studies, followed by molecular dynamics studies (MD). The results from these studies were analyzed using quantitative ROESY analysis to determine the final accurate structures of the complexes. The accuracy of these structures was tested using density functional theory (DFT) that is an accurate method for structure determination. DFT studies were carried out using the functionals B3LYP and M06L with def-TZVP basis set and similarly quantitative ROESY analysis was performed for the obtained structures. The ROESY intensities of the structures obtained from MM and MD studies, were compared with ROESY intensities of the structures obtained from DFT studies. Calculated ROESY intensities of the structures obtained from B3LYP functional are comparable, with intensities of structures obtained from MM and MD studies, but M06L functional showed poor results. In addition to the accuracy of MM and MD studies, low computational cost and less time input make it good method for structural studies for CD inclusion complexes.

     

Structural determination of midazolam/beta-cyclodextrin inclusion complex by an already proposed protocol and molecular docking studies by quantitative analysis

Structural Chemistry - A lot of interest has been seen in computational methods that provide higher degree of accuracy and reliability, in structural determination and intermolecular interaction of...     

Biocompatible APTES–PEG Modified Magnetite Nanoparticles: Effective Carriers of Antineoplastic Agents to Ovarian Cancer

Magnetite nanoparticles are particularly attractive for drug delivery applications because of their size-dependent superparamagnetism, low toxicity, and biocompatibility with cells and tissues. Surface modification of iron oxide nanoparticles with biocompatible polymers is potentially beneficial to prepare biodegradable nanocomposite-based drug delivery agents for in vivo and in vitro applications. In the present study, the bare (10 nm) and polyethylene glycol (PEG)–(3-aminopropyl)triethoxysilane (APTES) (PA) modified (17 nm) superparamagnetic iron oxide nanoparticles (SPIO NPs) were synthesized by coprecipitation method. The anticancer drugs, doxorubicin (DOX) and paclitaxel (PTX), were separately encapsulated into the synthesized polymeric nanocomposites for localized targeting of human ovarian cancer in vitro. Surface morphology analysis by scanning electron microscopy showed a slight increase in particle size (27?±?0.7 and 30?±?0.45 nm) with drug loading capacities of 70 and 61.5 % and release capabilities of 90 and 93 % for the DOX- and PTX-AP-SPIO NPs, respectively (p?<?0.001). Ten milligrams/milliliter DOX- and PTX-loaded AP-SPIO NPs caused a significant amount of cytotoxicity and downregulation of antiapoptotic proteins, as compared with same amounts of free drugs (p?<?0.001). In vivo antiproliferative effect of present formulation on immunodeficient female Balb/c mice showed ovarian tumor shrinkage from 2,920 to 143 mm³ after 40 days. The present formulation of APTES–PEG-SPIO-based nanocomposite system of targeted drug delivery proved to be effective enough in order to treat deadly solid tumor of ovarian cancer in vitro and in vivo.