Experimental and theoretical validations of a one-pot sequential sensing of Hg2+ and biothiols by a 3D Cu-based zwitterionic metal−organic framework

Abstract

A zwitterionic three-dimensional (3D) metal−organic framework (MOF) of {[Cu(Cdcbp)(bipy)]·4H2O}n (1) has been synthesized and characterized (H3CdcbpBr = 3-carboxyl-(3,5-dicarboxybenzyl)-pyridinium bromide; bipy = 4,4′-bipyridine). MOF 1 exhibits a variety of structural traits, such as ligand conjugated, positively charged pyridinium center, and Cu(II) cations that collectively enable its efficient hybridization with the flexible, negatively charged, single-stranded, and thymine-rich (T-rich) DNA. The T-rich DNA is labeled with carboxyfluorescein (FAM) fluorescent probe (characterized as P-DNA), but the resultant MOF 1 – P-DNA hybrid (characterized as P-DNA@1) is non-emissive (off-state) because of the fluorescent quenching by MOF 1. The P-DNA@1 hybrid functions as an effective and selective sensor for Hg2+ due to the formation of rigid hairpin-like T-Hg2+-T double-stranded DNA (ds-DNA@Hg2+) which is subsequently ejected by MOF 1, triggering a recovery of the P-DNA fluorescence (on-state). Subsequent addition of biothiols further sequestrates Hg2+ from the ds-DNA@Hg2+ duplex driven by the stronger Hg–S coordination, thus release the P-DNA and, in turn, resorbed by MOF 1 to regain the initial hybrid (off-state). P-DNA@1 hybrid thus detects Hg2+ and biothiols sequentially via a fluorescence “off-on-off” mechanism. The limits of detection (LOD) for Hg2+, biothiols, including cysteine (Cys), glutathione (GSH) and homocysteine (Hcy) are 3.0, 14.2, 15.1 and 8.0 nM, respectively, with the detection time of 60 min for Hg2+, and instantaneous detection for all the three biothiols. The detection mechanism is further confirmed by circular dichroism (CD), fluorescence anisotropy (FA), binding constant and molecular simulation. This sequential detection of Hg2+ and biothiols counter-proofs the presence of each other and may shed light to the occurrence of related diseases, such as neurodegenerative disorders of Parkinson's disease (PD), and Alzheimer's disease (AD).