Fast ion-chelate dissociation rates and weak ion-chelate affinities are desired kinetic and thermodynamic features for imaging probes to allow reversible binding and to prevent deviation from basal ionic levels. Nevertheless, such properties often result in poor readouts upon ion binding, frequently result in low ion specificity, and do not allow the detection of a wide range of concentrations. Herein, we show the design, synthesis, characterization, and implementation of a Zn 2+ -probe developed for MRI that possesses reversible Zn 2+ -binding properties with a rapid dissociation rate ( k off = 845 ± 35 s –1 ) for the detection of a wide range of biologically relevant concentrations. Benefiting from the implementation of chemical exchange saturation transfer (CEST), which is here applied in the 19 F-MRI framework in an approach termed ion CEST (iCEST), we demonstrate the ability to map labile Zn 2+ with spectrally resolved specificity and with no interference from competitive cations. Relying on fast k off rates for enhanced signal amplification, the use of iCEST allowed the designed fluorinated chelate to experience weak Zn 2+ -binding affinity ( K d at the mM range), but without compromising high cationic specificity, which is demonstrated here for mapping the distribution of labile Zn 2+ in the hippocampal tissue of a live mouse. This strategy for accelerating ion-chelate k off rates for the enhancement of MRI signal amplifications without affecting ion specificity could open new avenues for the design of additional probes for other metal ions beyond zinc.

Autocatalytic reaction networks are instrumental for validating scenarios for the emergence of life on Earth and for synthesizing life de novo. Here, we demonstrate that dimeric thioesters of tripeptides with the general structure (Cys‐Xxx‐Gly‐SEt)2 form strongly interconnected autocatalytic reaction networks that predominantly generate macrocyclic peptides up to 69 amino acids long. Some macrocycles of 6–12 amino acids were isolated from the product pool and were characterized by NMR spectroscopy and single‐crystal X‐ray analysis. We studied the autocatalytic formation of macrocycles in a flow reactor in the presence of acrylamide, whose conjugate addition to thiols served as a model “removal” reaction. These results indicate that even not template‐assisted autocatalytic production combined with competing removal of molecular species in an open compartment could be a feasible route for selecting functional molecules during the pre‐Darwinian stages of molecular evolution.

Autocatalytic reaction networks are instrumental for validating scenarios for the emergence of life on Earth and for synthesizing life de novo. Here, we demonstrate that dimeric thioesters of tripeptides with the general structure (Cys-Xxx-Gly-SEt) 2 form strongly interconnected autocatalytic reaction networks that predominantly generate macrocyclic peptides up to 69 amino acids long. Some macrocycles of 6-12 amino acids were isolated from the product pool and were characterized by NMR spectroscopy and single-crystal X-ray analysis. We studied the autocatalytic formation of macrocycles in a flow reactor in the presence of acrylamide, whose conjugate addition to thiols served as a model "removal" reaction. These results indicate that even not template-assisted autocatalytic production combined with competing removal of molecular species in an open compartment could be a feasible route for selecting functional molecules during the pre-Darwinian stages of molecular evolution.