Sequential Ag/biothiol and synchronous Ag/Hg biosensing with zwitterionic Cu-based metal-organic frameworks.

Zwitterionic metal-organic frameworks (MOFs) of {[Cu(Cbdcp)(Dps)(HO)]·6HO} (MOF 1) and [Cu(Dcbb)(Dps)(HO)] (MOF 2) (HCbdcpBr = N-(4-carboxybenzyl)-(3,5-dicarboxyl)pyridinium bromide; HDcbbBr = 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-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 Hg, resulting from the simultaneous yet specific ds-DNA-1@Ag and T-Hg-T duplex (ds-DNA-2@Hg) 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 (Hg) for MOF 2, respectively. The sequential sensing of Ag and biothiols by MOF 1, and the synchronous sensing of Ag and Hg 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.