The π bonds between organic radicals have generated excitement as an orthogonal interaction for designing self-assembling architectures in water. A systematic investigation of the effect of the viologen cation radical structure on the strength and nature of the pimer bond is provided. A striking and unexpected feature of this π bond is that the bond strength is unchanged by substitution with electron-donating groups or withdrawing groups or with increased conjugation. Furthermore, the interaction is undiminished by sterically bulky N-alkyl groups. Theoretical modeling indicates that strong dispersion forces dominate the interaction between the radicals, rationalizing the insensitivity of the bonding interaction to substituents: The stacking of polarizable π radicals leads to attractive dispersion forces in excess of typical dispersion interactions of small molecules and helps overcome the Coulombic repulsion of bringing two cationic species into contact.

A series of substituted aryl dicyanomethyl radicals were synthesized, and the bonding thermodynamic parameters for self-dimerization were determined from van't Hoff plots obtained from variable-temperature electron paramagnetic resonance and ultraviolet−visible spectroscopy. At low temperatures, the radicals dimerize, but the colored, air-stable free radicals return upon heating. Heating and cooling cycles (5−95 °C) can be repeated without radical degradation and with striking thermochromic behavior. We find a linear free energy relationship between the Hammett para substituent parameter and the dimerization equilibrium constant, with para electron-donating substituents leading to a weaker bond and electron-withdrawing substituents leading to stronger bonds, following a captodative effect. Density functional theory investigations [B98D/6-31+G(d,p)] reveal that the dimers prefer a slip-stacked geometry and feature elongated bonds.

Development of versatile, chemically tunable photocages for photoactivated chemotherapy (PACT) represents an excellent opportunity to address the technical drawbacks of conventional photodynamic therapy (PDT) whose oxygen-dependent nature renders it inadequate in certain therapy contexts such as hypoxic tumors. As an alternative to PDT, oxygen free mechanisms to generate cytotoxic reactive oxygen species (ROS) by visible light cleavable photocages are in demand. Here, we report the detailed mechanisms by which the small molecule blebbistatin acts as a one-photon blue light-gated or twophoton near-infrared light-gated photocage to directly release a hydroxyl radical (•OH) in the absence of oxygen. By using femtosecond transient absorption spectroscopy and chemoselective ROS fluorescent probes, we analyze the dynamics and fate of blebbistatin during photolysis under blue light. Waterdependent photochemistry reveals a critical process of water-assisted protonation and excited state intramolecular proton transfer (ESIPT) that drives the formation of short-lived intermediates, which surprisingly culminates in the release of •OH but not superoxide or singlet oxygen from blebbistatin. CASPT2//CASSCF calculations confirm that hydrogen bonding between water and blebbistatin underpins this process. We further determine that blue light enables blebbistatin to induce mitochondria-dependent apoptosis, an attribute conducive to PACT development. Our work demonstrates blebbistatin as a controllable photocage for •OH generation and provides insight into the potential development of novel PACT agents.

The p bonds between organic radicals have generated excitement as an orthogonal interaction for designing self-assembling architectures in water.Asystematic investigation of the effect of the viologen cation radical structure on the strength and nature of the pimer bond is provided. As triking and unexpected feature of this p bond is that the bond strength is unchanged by substitution with electron-donating groups or withdrawing groups or with increased conjugation. Furthermore,t he interaction is undiminished by sterically bulky Nalkylg roups.T heoretical modeling indicates that strong dispersion forces dominate the interaction between the radicals, rationalizing the insensitivity of the bonding interaction to substituents:T he stacking of polarizable p radicals leads to attractive dispersion forces in excess of typical dispersion interactions of small molecules and helps overcome the Coulombic repulsion of bringing two cationic species into contact.The ability of open-shell species to form weak self-association complexes has attracted attention for av ariety of applications.I np articular,s tabilized organic p radicals can associate to form van der Waals complexes, s dimers,ormulticentered pi-bonded dimers.T he p bond in particular is afascinating one for its unusual multicenter bonding pattern that brings atoms closer than the van der Waals radii but longer than aconventional s bond (> 2.8 ), while straddling the knife edge between van der Waals interactions and conventional chemical bonds in strength and properties.Viologen cation radicals are aw ell-known class of thermally stable organic radicals that can be prepared simply by chemical or electrochemical reduction of synthetically accessible bipyridinium dications. [1] Within polar solvents that can screen the intermolecular Coulombic repulsion between like ions,t hese radicals dimerize to form such pbonded dimers,r eferred to whimsically as "pimers". p dimerization has been investigated for related p radicals, such as neutral p radicals (for example,phenalenyl radicals), [2] p anion radicals (tetracyanoethylene anion radical), [3] and cation radicals (biphenylene cation radicals), [4] but there are no detailed investigations into the effect of the radical structure on the strength and nature of the viologen cation radical p bond. Theability to switch this interaction on and off using redox control make this interaction av ersatile one for Figure 1. Library of viologen dications 1-19 synthesized as precursors to the viologen cation radicals.

A series of heterocyclic compounds containing trivalent iodine, oxygen, and boron in a five-membered ring were prepared and structurally investigated by X-ray crystallography. 1-Chloro-4-fluoro-1H-1λ(3)-benzo[d][1,2,3]iodoxoborol-3-ol was synthesized by chlorination of 2-fluoro-6-iodophenylboronic acid followed by treatment of the intermediate iododichloride with water. 1-Acetoxy-4-fluoro-1H-1λ(3)-benzo[d][1,2,3]iodoxoborol-3-ol, 1-acetoxy-1H-1λ(3)-benzo[d][1,2,3]iodoxoborol-3-ol, and similar 1-substituted trifluoroacetate derivatives of benziodoxaborole were prepared the hypochlorite oxidation of 2-fluoro-6-iodophenylboronic acid or 2-iodophenylboronic acid in acetic or trifluoroacetic acid, respectively. 1-Acetoxy substituted benziodoxaborole can be further converted to the respective trifluoroacetate by treatment with trifluoroacetic acid or to the 1-hydroxy derivative by basic hydrolysis with aqueous NaHCO(3). X-ray structural studies of 1-chloro- and 1-trifluoroacetoxy substituted benziodoxaboroles 13, 17, and 18 have shown the presence of a planar five-membered heterocyclic ring with unusually short endocyclic I-O bond distance of 2.04-2.09 Å. Slow crystallization of 4-fluoro-1-trifluoroacetoxy-1H-1λ(3)-benzo[d][1,2,3]iodoxoborol-3-ol from methanol resulted in the formation of a tetrameric macrocyclic structure 21 resulting from self-assembly of the initially formed 4-fluoro-1,3-dimethoxy-1H-1λ(3)-benzo[d][1,2,3]iodoxoborol. Structural parameters of the five-membered iodoxoborol ring, such as the planar geometry and the short B-O and O-I bonds lengths in 13, 17, and 18 compared to those in 21 and known benziodoxoles are indicative of partially aromatic character of this ring. Density functional theory (DFT) predicted NIST (0) and NIST (1) indexes for 1-chloro- and 1-trifluoroacetoxy substituted benziodoxaboroles, however, are indicative of significantly lower aromaticity compared to the classic aromatic systems.