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Vitamin B3 metal-organic frameworks as potential delivery vehicles for therapeutic nitric oxide
Rosana V Pinto1, Fernando Antunes2, João Pires2
1CERENA, Departamento de Engenharia Química, Instituto Superior Técnico, Universidade de Lisboa, 1049-001 Lisboa, Portugal; Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal.
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 NOmgsolid-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.
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