Pinto Rosana V, Antunes Fernando, Pires João, Graça Vanessa, Brandão Paula, Pinto Moisés L
CERENA, 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.
Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal.
Acta Biomater. 2017 Mar 15;51:66-74. doi: 10.1016/j.actbio.2017.01.039. Epub 2017 Jan 16.
The synthesis and structural characterization of two isostructural metal (M=Ni, Co) 3D framework structure that integrate vitamin B building blocks with NO delivery capabilities and low toxicity is presented. The compounds with a formula [M(μ-HO)(μ-vitamin B)]·2HO contain two crystallographic distinct divalent metal centres connected by a bridging water and carboxylate group from vitamin B. 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, 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. The overall results indicate that these bio based MOFs are of interest for therapeutic applications related with NO delivery. STATEMENT OF SIGNIFICANCE.
本文介绍了两种同构金属（M = Ni，Co）三维骨架结构的合成及结构表征，该结构将维生素B结构单元与一氧化氮递送能力和低毒性相结合。化学式为[M(μ-HO)(μ-维生素B)]·2HO的化合物包含两个晶体学上不同的二价金属中心，它们通过来自维生素B的桥连水和羧酸根基团相连。这些多孔化合物能够以缓慢且可逆的方式储存和释放一氧化氮（NO），在镍化合物和钴化合物上，释放量分别为2.6和2.0μmol NO/mg。在气相和液相中，NO的释放均遵循便利的缓释动力学曲线。血红蛋白测试表明，NO以生物活性形式释放到介质中，因此适合在生物系统中引发所需的反应。通过在HeLa和HEK细胞中的细胞毒性测试评估了加载和未加载NO的样品的毒性，结果表明在浓度低于180μg/cm时化合物具有低毒性。总体结果表明，这些基于生物的金属有机框架对于与NO递送相关的治疗应用具有重要意义。重要性声明。
