Vitamin B3 metal-organic frameworks as potential delivery vehicles for therapeutic nitric oxide

Abstract

The synthesis and structural characterization of two isostructural metal (M=Ni, Co) 3D framework structure that integrate vitamin B₃ building blocks with NO delivery capabilities and low toxicity is presented. The compounds with a formula [M₂(μ₂-H₂O)(μ-vitamin B₃)₄]·2H₂O contain two crystallographic distinct divalent metal centres connected by a bridging water and carboxylate group from vitamin B₃. The porous compounds have the capability of storing and releasing nitric oxide (NO) in a slow and reversible manner, with released amounts of 2.6 and 2.0μmol NOmg_solid^-1, on the Ni and Co compound, respectively. The NO release followed a convenient slow release kinetic profile in both gas and liquid phases. Haemoglobin tests demonstrated that NO is released to the medium in a biologically active form, thus suitable to trigger the desired response in biological systems. The toxicity of the samples with and without loaded NO was evaluated from cytotoxicity tests in HeLa and HEKn cells, showing low toxicity of the compounds at concentrations below 180μgcm^-3. The overall results indicate that these bio based MOFs are of interest for therapeutic applications related with NO delivery. STATEMENT OF SIGNIFICANCE.

Keywords: Adsorption; Controlled delivery systems; Metal-organic frameworks; Nitric oxide; Vitamin B(3).