Sequential Ag+/biothiol and synchronous Ag+/Hg2+ biosensing with zwitterionic Cu2+-based metal–organic frameworks

Abstract

Zwitterionic metal–organic frameworks (MOFs) of {[Cu(Cbdcp)(Dps)(H₂O)₃]·6H₂O}_n (MOF 1) and [Cu₄(Dcbb)₄(Dps)₂(H₂O)₂]_n (MOF 2) (H₃CbdcpBr = N-(4-carboxybenzyl)-(3,5-dicarboxyl)pyridinium bromide; H₂DcbbBr = 1-(3,5-dicarboxybenzyl)-4,4′-bipyridinium bromide; Dps = 4,4′-dipyridyl sulfide) quench the fluorescence of cytosine-rich DNA tagged with 5-carboxytetramethylrhodamine (TAMRA, emission at 582 nm, denoted as C-rich P-DNA-1) and yield the corresponding P-DNA-1@MOF hybrids. Exposure of these hybrids to Ag⁺ results in the release of the P-DNA-1 strands from the MOF surfaces as double-stranded, hairpin-like C–Ag^I–C (ds-DNA-1@Ag⁺) with the restoration of TAMRA fluorescence. The ds-DNA-1@Ag⁺ formed on the surface of 1 can subsequently sense biothiols cysteine (Cys), glutathione (GSH), and homocysteine (Hcy) due to the stronger affinity of mercapto groups for Ag⁺ that serves to unfold the ds-DNA-1@Ag⁺ duplex, reforming P-DNA-1, which is re-adsorbed by MOF 1 accompanied by quenching of TAMRA emission. Meanwhile, MOF 2 is also capable of co-loading a thymine-rich probe DNA tagged with 5-carboxyfluorescein (FAM, emission at 518 nm, denoted as T-rich P-DNA-2) to achieve synchronous sensing of Ag⁺ and Hg²⁺, resulting from the simultaneous yet specific ds-DNA-1@Ag⁺ and T–Hg^II–T duplex (ds-DNA-2@Hg²⁺) formation, as well as the distinctive emission wavelengths of TAMRA and FAM. Detection limits are as low as 5.3 nM (Ag⁺), 14.2 nM (Cys), 13.5 nM (GSH), and 9.1 nM (Hcy) for MOF 1, and 7.5 nM (Ag⁺) and 2.6 nM (Hg²⁺) for MOF 2, respectively. The sequential sensing of Ag⁺ and biothiols by MOF 1, and the synchronous sensing of Ag⁺ and Hg²⁺ by MOF 2 are rapid and specific, even in the presence of other mono- and divalent metal cations or other biothiols at much higher concentrations. Molecular simulation studies provide insights regarding the molecular interactions that underpin these sensing processes.