Oxo-triaryl methyl (oxTAM) as targeted drug delivery vehicle for fludarabine and cytarabine anticancer drugs: A first-principles insight.

The design and development of efficient and responsive drug carriers always remain a challenge in targeted cancer treatment, where the traditional nanocarriers suffer the drawbacks of limited stability, a lack of selectivity, and slow release of the drug. In this perspective, the oxygenated triaryl methyl (oxTAM) nanocarrier is known for its tunability, and redox activity offers a promising alternative. In the present work, we hypothesize that the oxTAM carrier can function as an efficient and effective drug carrier for selected anticancer drugs like Fludarabine (Flu) and Cytarabine (Cyt) due to its ability to make stable noncovalent interactions and release of drugs in acidic conditions. The potential application of oxTAM as drug carrier is explored by using ωB97XD/6-31+G(d,p) functional. The interaction in energy analysis (Eint) and interacting distances (Edis) reveal that oxTAM shows excellent interaction for Flu (-1.77 eV, 1.92 Å) drug. Non-covalent interaction index (NCI) indicates the existence of van der Waals interaction and hydrogen bonding (O-H bond) between the interacting moieties. The results of dipole moment and quantum chemical descriptors show the high reactivities of oxTAM for Flu and Cyt drugs. Electronic analysis including natural bond orbital (NBO) charge transfer demonstrates the higher response of Flu drug towards oxTAM. In addition, the reduced adsorption stability upon protonation in an acidic environment can quickly release drug molecules from the carrier. Short recovery time indicates easy drug delivery at the targeted site. From all these results, we concluded that oxTAM can be a potential candidate for further experimental exploration in drug delivery systems.