Fluorinated linkers enable the synthesis of flexible MOFs with 1D alkaline earth SBUs and a temperature-induced phase transition.

Fluorination as a functionalization of organic linkers in MOFs has shown surprising effects both on the structure of the linker itself as well as on the topology and properties of the resulting framework materials. 4,4',4''-Benzene-1,3,5-triyl-tris-(benzoate), typically abbreviated to BTB, is a well-known linker in the construction of MOFs. It is expected to be planar due to a complete sp2 hybridisation of its carbon atoms. However, some flexibility is frequently observed by twists of the outer carboxylate groups as well as by the benzoate rings. The latter is mainly influenced by substituents of the inner benzene ring. Herein, we present two novel alkaline earth metal based MOFs [EA(II)5(3F-BTB)3OAc(DMF)5] (EA(II) = Ca, Sr) utilizing a fluorinated derivative of the BTB-linker (perfluorination of the inner benzene ring) with a unique topology, crystalline sponge behaviour and a low temperature induced phase transition.

Synthesis and Biological Evaluation of Water-Soluble Esterase-Activated CO-Releasing Molecules Targeting Mitochondria.

Due to the beneficial effects of carbon monoxide as a cell-protective and anti-inflammatory agent, CO-releasing molecules (CORMs) offer some promising potential applications in medicine. In this context, we synthesized a set of acyloxy-cyclohexadiene-Fe(CO)3 complexes, all displaying a N-methyl-pyridinium triflate moiety in the ester side chain, as mitochondria-targeting esterase-triggered CORM prodrugs. Whereas the compounds in which the acyloxy substituent is attached to the 2-position of the diene-Fe(CO)3 unit (A series) spontaneously release CO upon dissolution in phosphate buffer, which remarkably is partly suppressed in the presence of porcine liver esterase (PLE), the 1-substituted isomers (B series) show the expected PLE-induced release of CO (up to 3 equiv.). The biological activity of Mito-CORMs 2/3-B and their isophorone-derived analogs 2/3-A', which also displayed PLE-induced CO release, was assessed by using human umbilical vein endothelial cells (HUVEC). Whereas Mito-CORMs 2/3-B were not cytotoxic up to 500 µM (MTT assay), Mito-CORMs 2/3-A' caused significant toxicity at concentrations above 50 µM. The anti-inflammatory potential of both Mito-CORM variants was demonstrated by concentration-dependent down-regulation of the pro-inflammatory markers VCAM-1, ICAM-1 and CXCL1 as well as induction of HO-1 in TNFα-stimulated human umbilical vein endothelial cells (HUVECs; western blotting and qPCR). Energy phenotyping by seahorse real-time cell metabolic analysis, revealed opposing shifts of metabolic potentials in cells treated either with Mito-CORMs 2/3-B (increased mitochondrial respiration and glycolytic activity) or Mito-CORMs 2/3-A' (suppressed mitochondrial respiration and increased glycolytic activity). Thus, the Mito-CORMs represent valuable tools for the safe and targeted delivery of CO to mitochondria as a subcellular compartment to induce positive anti-inflammatory effects with only minor shifts in cellular energy metabolism. Also, due to their water solubility, these compounds provide a promising starting point for further pharmacological studies.