Single Fluorinated Agent for Multiplexed 19 F-MRI with Micromolar Detectability Based on Dynamic Exchange.

The weak thermal polarization of nuclear spins limits the sensitivity of MRI, even for MR-sensitive nuclei as fluorine-19. Therefore, despite being the source of inspiration for the development of background-free MRI for various applications, including for multiplexed imaging, the inability to map very low concentrations of targets using 19 F-MRI raises the need to further enhance this platform's capabilities. Here, we employ the principles of CEST-MRI in 19 F-MRI to obtain a 900-fold signal amplification of a biocompatible fluorinated agent, which can be presented in a "multicolor" fashion. Capitalizing on the dynamic interactions in host-guest supramolecular assemblies in an approach termed GEST, we demonstrate that an inhalable fluorinated anesthetic can be used as a single 19 F-probe for the concurrent detection of micromolar levels of two targets, with potential in vivo translatability. Further extending GEST with new designs could expand the applicability of 19 F-MRI to the mapping of targets that have so-far remained non-detectable.

Elucidating dissociation activation energies in host-guest assemblies featuring fast exchange dynamics.

The ability to mediate the kinetic properties and dissociation activation energies (E a) of bound guests by controlling the characteristics of "supramolecular lids" in host-guest molecular systems is essential for both their design and performance. While the synthesis of such systems is well advanced, the experimental quantification of their kinetic parameters, particularly in systems experiencing fast association and dissociation dynamics, has been very difficult or impossible with the established methods at hand. Here, we demonstrate the utility of the NMR-based guest exchange saturation transfer (GEST) approach for quantifying the dissociation exchange rates (k out) and activation energy (E a,out) in host-guest systems featuring fast dissociation dynamics. Our assessment of the effect of different monovalent cations on the extracted E a,out in cucurbit[7]uril:guest systems with very fast k out highlights their role as "supramolecular lids" in mediating a guest's dissociation E a. We envision that GEST could be further extended to study kinetic parameters in other supramolecular systems characterized by fast kinetic properties and to design novel switchable host-guest assemblies.

Dynamic Interactions in Synthetic Receptors: A Guest Exchange Saturation Transfer Study.

The accumulated knowledge regarding molecular architectures is based on established, reliable, and accessible analytical tools that provide robust structural and functional information on assemblies. However, both the dynamicity and low population of noncovalently interacting moieties within studied molecular systems limit the efficiency and accuracy of traditional methods. Herein, the use of a saturation transfer-based NMR approach to study the dynamic binding characteristics of an anion to a series of synthetic receptors derived from bambusuril macrocycles is demonstrated. The exchange rates of BF4 - are mediated by the side chains on the receptor (100 s-1

New and conventional pore size tests in virus-removing membranes.

Microorganisms are retained by ultrafiltration (UF) membranes mainly due to size exclusion. The sizes of viruses and membrane pores are close to each other and retention of viruses can be guaranteed only if the precise pore diameter is known. Unfortunately and rather surprisingly, there is no direct method to determine the membrane pore size. As a result, the UF membranes are not trusted to remove the viruses, and the treatment plants are required to enhance viral disinfection. Here we propose a new, simple and effective method for UF pore size determination using aquasols of gold and silver nanoparticles. We synthesized highly monodispersed suspensions ranging in diameter from 3 to 50 nm, which were later transferred through polymer and ceramic UF membranes. The retention percentage was plotted against the particle diameter to determine the pore size for which a membrane has a retention capability of 50, 90 and 100%. The d(50), d(90) and d(100) values were compared with data obtained from conventional transmembrane flux, polyethylene glycol, and dextran tests, and with the retention of phi X 174 and MS2 bacteriophages. The absolute pore size, d(100), for the majority of tested UF membranes is within 40-50 nm, and can only be detected with the new tests. The average 1.2 log retention of hydrophilic phi X 174 was predicted accurately by models based on the virus hydrodynamic radii and d(100) pore size. The 2.5 log MS2 retention suggests hydrophobic interactions in addition to simple ball-through-cylinder geometry.