Dynamic Surface Modification of Metal–Organic Framework Nanoparticles via Alkoxyamine Functional Groups

Abstract

External surface engineering of metal–organic framework nanoparticles (MOF NPs) is emerging as an important design strategy, leading to optimized chemical and colloidal stability. To date, most of the MOF surface modifications have been performed either by physical adsorption or chemical association of small molecules or (preformed) polymers. However, most of the currently employed approaches cannot precisely control the polymer density, and dynamic modifications at the surfaces on demand have been a challenging task. Here, we introduce a general approach based on covalent modification employing alkoxyamines as a versatile tool to modify the outer surface of MOF nanoparticles (NPs). The alkoxyamines serve as initiators to grow polymers from the MOF surface via nitroxide-mediated polymerization (NMP) and allow dynamic attachment of small molecules via a nitroxide exchange reaction (NER). The successful surface modification and successive surface polymerization are confirmed via time-of-flight secondary ion mass spectrometry (ToF-SIMS), size exclusion chromatography (SEC), and nuclear magnetic resonance (NMR) spectroscopy. The functionalized MOF NPs exhibit high suspension stability and good dispersibility while retaining their chemical integrity and crystalline structure. In addition, electron paramagnetic resonance spectroscopy (EPR) studies prove the dynamic exchange of two different nitroxide species via NER and further allow us to quantify the surface modification with high sensitivity. Our results demonstrate that alkoxyamines serve as a versatile tool to dynamically modify the surface of MOF NPs with high precision, allowing us to tailor their properties for a wide range of potential applications, such as drug delivery or mixed matrix membranes.

Organic Synthesis Using Nitroxides

“…It is possible to exchange the nitroxide entity in an alkoxyamine upon heating in the presence of a second nitroxide, which is generally used in large excess to ensure complete exchange. This strategy was successfully applied to nitroxide-exchange reactions on surfaces, zeolites, or metal organic frameworks (MOFs) . Remarkably, this technique was also applied to covalently link zeolites. , Furthermore, it is also possible to simply liberate a nitroxide from the corresponding alkoxyamine under oxygen atmosphere at elevated temperature.…”

“…This strategy was successfully applied to nitroxide-exchange reactions on surfaces, 1389 zeolites, 1390 or metal organic frameworks (MOFs). 1391 Remarkably, this technique was also applied to covalently link zeolites. 1392,1393 Furthermore, it is also possible to simply liberate a nitroxide from the corresponding alkoxyamine under oxygen atmosphere at elevated temperature.…”

Biofunctionalization of Metal–Organic Framework Nanoparticles via Combined Nitroxide‐Mediated Polymerization and Nitroxide Exchange Reaction

“…We have shown nitroxide exchange reaction of TEMPO with the nitroxide (2-lambda1-oxidanyl-1,1,3,3-tetramethylisoindole, known as TMIIO). [20,30] We evaluated this possibility by attaching a tumor targeting RGD-sequence (Figure 4A) to the polymer via a nitroxide-exchange reaction. RGD is an amino acid sequence consisting of a Arg-Gly-Asp peptide first described in 1970.…”

Quantifying Ligand Binding to the Surface of Metal–Organic Frameworks

“…Metal–organic frameworks (MOFs) are extended coordination solids that typically form as crystalline or microcrystalline particles with a variety of rich pore structures . The modification of the external surfaces of MOF via coordination chemistry is critical to many features of these materials, particularly the modulation of their nucleation/growth as well as the immobilization of small molecules or polymers for a variety of applications. − Despite many studies that rely on the surface chemistry of MOFs, few studies have quantified these interactions. , This is probably due, in part, to the porous nature of the MOF surface, which creates some ambiguity about where (interior vs exterior) and how molecules interact with the framework.…”

“…2−8 Despite many studies that rely on the surface chemistry of MOFs, few studies have quantified these interactions. 9,10 This is probably due, in part, to the porous nature of the MOF surface, which creates some ambiguity about where (interior vs exterior) and how molecules interact with the framework.…”