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 B-3 building blocks with NO delivery capabilities and low toxicity is presented. The compounds with a formula [M2( mu-H2O)(mu-vitamin B-3)4]"2H(2)O 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 2.0 mu mol NO mg(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 180 mu g cm(-3). The overall results indicate that these bio based MOFs are of interest for therapeutic applications related with NO delivery. Statement of Significance The synthesis and characterization of new vitamin B3 porous metal-organic frameworks (MOFs) is presented in this work for the first time. Few other examples of porous MOFs build up of vitamin exist in the literature with adsorbing capacity like our materials. The ligand (vitamin B3) in these MOFs is much more biocompatible than the usual ligands like, for example, benzene carboxylic acids (terephthalic acid or trimesic acid) and imidazole based ligands. No other vitamin based MOFs have been studied for NO storage. The effects on cell cultures of the materials loaded with NO are studied for the first time and the cell line used is a human primary cell line representative of the human skin. This is relevant for future applications related to wound healing. (c) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

keywords

SLOW-RELEASE; DRUG-DELIVERY; GAS-STORAGE; IN-VITRO; NANOPARTICLES; COORDINATION; NO; ADSORPTION; ZEOLITES; BEHAVIOR

subject category

Engineering; Materials Science

authors

Pinto, RV; Antunes, F; Pires, J; Graca, V; Brandao, P; Pinto, ML

our authors

acknowledgements

The work was financed by Fundacao para a Ciencia e a Tecnologia (FCT) through project IF/00993/2012/CP0172/CT0013. This work was developed in the scope of the Projects POCI-01-0145-FEDER-0076791UID/CTM/50011/2013 (CICECO), UID/MULTI/00612/2013 (CQB), UID/ECI/04028/2013 (CERENA), financed by national funds through the FCT/MEC and cofinanced by FEDER under the PT2020 Partnership Agreement. M.L.P. is also grateful to Investigador FCT program. The authors are grateful to Jose R.B. Gomes for the helpful discussion regarding the DFT methods used.

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