Exploring Dacarbazine Complexation with a Cellobiose-Based Carrier: A Multimethod Theoretical, NMR, and...

Area of Science:

• Supramolecular Chemistry
• Medicinal Chemistry
• Computational Chemistry

Background:

• Dacarbazine (DTIC) is a vital anticancer drug.
• DTIC's photosensitivity complicates its stability and host interactions.
• Supramolecular host-guest chemistry offers potential solutions for drug stabilization.

Purpose of the Study:

• To investigate the complexation of DTIC with a novel hybrid urea-carbohydrate-diazacrown host, TN.
• To characterize the interaction patterns and thermodynamic parameters of the TN:DTIC complex.
• To evaluate TN's potential for DTIC stabilization and drug delivery.

Main Methods:

• Density Functional Theory (DFT) calculations for computational analysis.
• Experimental 1H Nuclear Magnetic Resonance (NMR) spectroscopy in D2O.
• Conductometric measurements at varying temperatures (293–313 K).

Main Results:

• DFT calculations predicted non-inclusion complex formation via hydrogen bonding between DTIC and TN's sugar, urea, and diazacrown moieties.
• 1H NMR studies confirmed these interactions, showing significant chemical shifts in sugar protons.
• Thermodynamic analysis revealed spontaneous, exothermic, and enthalpy-driven complexation with decreased entropy.

Conclusions:

• TN forms strong complexes with DTIC, surpassing interactions seen with cyclodextrins.
• Extensive hydrogen-bonding networks are key to the stability of the TN:DTIC complex.
• TN shows promise as a multifunctional platform for stabilizing DTIC and potentially other photosensitive drugs.