Coordination polymers derived from non-steroidal anti-inflammatory drugs for cell imaging and drug delivery

Abstract

A new series of MnII coordination polymers, namely, [{Mn(L)(H₂O)₂}⋅2 Nap]_∞(CP1), [{Mn(L)(Ibu)₂(H₂O)₂}]_∞ (CP2), [{Mn(L)(Flr)₂(H₂O)₂}]_∞ (CP3), [{Mn(L)(Ind)₂(H₂O)₂}⋅H₂O]_∞ (CP4), [{Mn₂(L)₂(μ-Flu)₄(H₂O)}⋅L]_∞ (CP5), [{Mn₂(L)₂(μ-Tol)₄(H₂O)₂}]_∞ (CP6) and [{Mn₂(L)₂(μ-Mef)₄(H₂O)₂}]_∞ (CP7) (Nap=naproxen, Ibu=ibuprofen, Flr=flurbiprofen, Ind=indometacin, Flu=flufenamic acid, Tol=tolfenamic acid and Mef=mefenamic acid) derived from various non-steroidal anti-inflammatory drugs (NSAIDs) and the organic linker 1,2-bis(4-pyridyl)ethylene (L) have been synthesized with the aim of being used for cell imaging and drug delivery. Single-crystal X-ray diffraction (SXRD) studies revealed that the NSAID molecules were part of the coordination polymeric network either through coordination to the metal center (in the majority of the cases) or through hydrogen bonding. Remarkably, all the MnII coordination polymers were found to be soluble in DMSO, thereby making them particularly suitable for the desired biological applications. Two of the coordination polymers (namely, CP1 and CP3) reported herein, were found to be photoluminescent both in the solid as well as in the solution state. Subsequent experiments (namely, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), and PGE₂ (prostaglandin E₂) assays) established their biocompatibility and anti-inflammatory response. In vitro studies by using a macrophage cell line (i.e., RAW 264.7) revealed that both CP1 and CP3 were excellent cell imaging agents. Finally, biodegradability studies under simulated physiological conditions in phosphate-buffered saline (PBS) at pH 7.6 showed that slow and sustained release of the corresponding NSAID was indeed possible from both CP1 and CP3.