Medium and Substituent Effects on Dynamic Self-Assembly of Nitrosobenzenes

Nitrosobenzenes (NBs), with the nitroso (-N=O) functionality, often exist as dipolar, colorless, azodioxide dimers (AD) in the solid state. When dissolved, these ADs reversibly dissociate to blue-green colored monomers in solution, demonstrating their dynamic covalent bonding (DCB) ability at nitrogen. This DCB proceeds with no catalyst or external stimulus, which is attractive for potential molecular docking applications where an AD linkage might facilitate bringing together two payloads. This work focuses on DCB studies of o-nitrosocumene (o-NC), o- and p-methylnitrosobenzene (o-MeNB and p-MeNB), 2,6-difluoronitrosobenzene (2,6-DFNB), and p-t-butylnitrosobenzene (p-t-BuNB). Systematic variable temperature (VT) NMR spectroscopic studies in various media have been conducted for each NB system to obtain thermodynamic parameters for the reversible monomerization equilibria of (Z)- and (E)-ADs in solution. 2D NMR exchange spectroscopy (EXSY) experiments aid in identification and analysis of the exchange (interchange) of the various forms of NBs in solution. In water, a novel NMR-aggregation is documented, where NBs self-assemble into a new ensemble possessing distinct, sharp, shielded NMR signals. DOSY (diffusion ordered spectroscopy) NMR analyses reveal diffusion coefficients consistent with aggregates of nm sizes. In addition to NBs, a series of various substituted benzenes is surveyed for nanoaggregation in water to ascertain the scope of this nanoassembly process for small organic molecules. Interestingly, we observe coaggregation of isomeric nitrotoluenes, which suggests these aggregates might function as a new type of host or vessel to recruit organic molecules. This work aims to probe and characterize aqueous aggregate species and measure medium effects (temperature, solvent polarity, hydrophobic effect) on the extent of aqueous self-assembly of NBs both inside and outside of the aggregate environment. Lastly, our collaboration with the Ramamurthy group (University of Miami) utilizes supramolecular hosts (octa acid (OA), cyclodextrins (CDs), cucurbiturils (CBs), and the Fujita Pd cage) to employ small space confinement as a tool to further coerce self-assembly of NBs in water, with the aim of exerting control over AD and nanoaggregate formation for the first time. These hosts can promote NB disassembly and assembly in water, as a function of the cavity spaces and properties.