pH-Responsive Metal-Organic Framework Thin Film for Drug Delivery.

In this work, surface-supportive MIL-88B(Fe) was explored as a pH-stimuli thin film to release ibuprofen as a model drug. We used surface plasmon resonance microscopy to study the pH-responsive behaviors of MIL-88B(Fe) film in real time. A dissociation constant of (6.10 ± 0.86) × 10-3 s-1 was measured for the MIL-88B(Fe) film in an acidic condition (pH 6.3), which is about 10 times higher than the dissociation of the same film in a neutral pH condition. MIL-88B(Fe) films are also capable of loading around 6.0 µg/cm2 of ibuprofen, which was measured using a quartz crystal microbalance (QCM). Drug release profiles were compared in both acidic and neutral pH conditions (pH 6.3 and 7.4) using a QCM cell to model the drug release in healthy body systems and those containing inflammatory tissues or cancerous tumors. It was found that the amount of drug released in acidic environments had been significantly higher compared to that in a neutral system within 55 h of testing time. The pH-sensitive chemical bond breaking between Fe3+ and the carboxylate ligands is the leading cause of drug release in acidic conditions. This work exhibits the potential of using MOF thin films as pH-triggered drug delivery systems.

Iron-containing metal-organic framework thin film as a drug delivery system.

Selective bulk metal-organic frameworks (MOFs) have exhibited great potential in biomedical applications. However, topical treatments and drug elution coatings will require uniform films as drug delivery systems. This work studies the use of surface supportive MOF thin films for drug loading and releasing. More specifically, we focus on an iron-containing MOF, MIL-88B(Fe), on a COOH-terminated self-assembled monolayer (SAM) modified Au surface for encapsulating ibuprofen as a model drug. A combined experimental and computational approach was employed to study the fabrication of MIL-88B(Fe) film on functionalized Au surfaces. We used several surface characterization techniques, including infrared spectroscopy and scanning electron microscopy, to confirm the chemical composition and morphological changes of the surface after each modification step. The resulting MIL-88B(Fe) thin film was found capable of loading 8.7 wt% of ibuprofen using quartz crystal microbalance analysis. Moreover, we applied cluster simulations to study the binding mechanisms of MIL-88B(Fe) and its interactions with ibuprofen based on the density functional theory (DFT). The unsaturated Fe site was confirmed kinetically more favorable to bind to the COOH-end group on the SAM. Hydrogen bonding and π-CH interactions between ibuprofen and MIL-88B(Fe) promote ibuprofen being retained inside of the cages of MIL-88B(Fe).

Chiroptical characterization tools for asymmetric small molecules - experimental and computational approaches for electronic circular dichroism (ECD) and anisotropy spectroscopy.

Synchrotron radiation electronic circular dichroism (SRECD) and anisotropy spectroscopy for both enantiomers of a group of small non-planar chiral molecules are reported here. The experimental SRECD spectra are compared to computational ECD spectra generated using time-dependent density functional theory and a thermal averaging over relevant molecular configurations. The combination of these experimental and computational characterization methodologies for such molecules enables the prediction and understanding of the spectral behavior of other small molecules, in addition to chiroptically characterizing members of the mandelic acid family substructure. Enantiomeric purity of samples can be evaluated in comparison with these spectra and the extent of photolytic enantioinduction can also be predicted using these experimental/calculated SRECD and anisotropy spectra.