A quantitative structure activity relationship approach to probe the influence of the functionalization on the drug encapsulation of porous metal-organic frameworks

Abstract

A series of 10 MIL-88B(Fe) iron(III) dicarboxylate MOFs wherein the organic linker is functionalized by a large variety of polar and apolar functional groups (–H, –Br, –F, –CF3, –CH3, –NH2, –NO2, –OH) was investigated as a potential carrier for encapsulating drugs, using the cosmetic amphiphilic caffeine as a model molecule. Encapsulation using impregnation followed by thermogravimetric analysis (TGA) and high performance liquid chromatography (HPLC) measurements to quantitatively estimate the caffeine uptake, have been first performed on the functionalized MIL-88B(Fe) samples. This set of experimental data was further used as an ideal platform to conduct a quantitative structure activity relationship approach based on multiple linear regression (MLR) method with the aim to find out the most relevant chemical and structural features of the MIL-88B(Fe) that significantly affect the therapeutic molecule uptake. Individual QSAR models showed that tuning the polarity and the H-donor capacity of the organic linker can enhance the caffeine encapsulation, suggesting that the functional groups serve as anchoring points for the drug molecule, consistent with previous conclusions drawn from molecular simulations performed on similar functionalized MOFs. Consensus modeling approach based on the selection of the most diverse individual models was also employed to build more representative QSAR models over the chemical space that could be further used to predict the drug encapsulation performance of the MOFs grafted by other functional groups.