Ultra-Microporous Fe-MOF with Exceptional NO Delivery Kinetics in Biological Media for Therapeutic Application

Nitric oxide (NO), as a key element in the regulation of essential biological mechanisms, presents huge potential as a therapeutic agent in the treatment and prevention of chronic diseases. Metal-organic frameworks (MOFs) with open metal sites are promising carriers for NO therapies but delivering it over an extended period in biological media remains a great challenge due to (i) a fast degradation of the material in body fluids and/or (ii) a rapid replacement of NO by water molecules onto the Lewis acid sites. Here, we propose an unprecedented NO adsorption mechanism based on a new ultra-narrow pores Fe bisphosphonate MOF, denoted MIP-210(Fe) or Fe(H2O)(Hmbpa) (Hmbpa = p-xylenediphosphonic acid). In MIP-210(Fe), the coordination of NO through the Fe(III) sites is unusually preferred, replacing the water, and creating a stable interaction with the free H2O and P-OH groups delimiting the very narrow pores. This, associated with the high chemical stability of the MOF enables a very slow replacement of NO by water molecules in biological media, achieving an extraordinarily extended NO delivery over at least 72 hours, exceeding by far the NO kinetics release reported by others porous materials, paving the way for the development of safe and successful gas therapies.