The spontaneous assembly of aromatic cation radicals (D(+•)) with their neutral counterpart (D) affords dimer cation radicals (D(2)(+•)). The intermolecular dimeric cation radicals are readily characterized by the appearance of an intervalence charge-resonance transition in the NIR region of their electronic spectra and by ESR spectroscopy. The X-ray crystal structure analysis and DFT calculations of a representative dimer cation radical (i.e., the octamethylbiphenylene dimer cation radical) have established that a hole (or single positive charge) is completely delocalized over both aromatic moieties. The energetics and the geometrical considerations for the formation of dimer cation radicals is deliberated with the aid of a series of cyclophane-like bichromophoric donors with drastically varied interplanar angles between the cofacially arranged aryl moieties. X-ray crystallography of a number of mixed-valence cation radicals derived from monochromophoric benzenoid donors established that they generally assemble in 1D stacks in the solid state. However, the use of polychromophoric intervalence cation radicals, where a single charge is effectively delocalized among all of the chromophores, can lead to higher-order assemblies with potential applications in long-range charge transport. As a proof of concept, we show that a single charge in the cation radical of a triptycene derivative is evenly distributed on all three benzenoid rings and this triptycene cation radical forms a 2D electronically coupled assembly, as established by X-ray crystallography.

Spray-dried dispersions (SDDs) are fascinating polymer−drug mixtures that exploit the amorphous state of a drug to dramatically elevate its apparent aqueous solubility above equilibrium. For practical usage in oral delivery, understanding how polymers mechanistically provide physical stability during storage and prevent supersaturated drugs from succumbing to precipitation during dissolution remains a formidable challenge. To this end, we developed a versatile polymeric platform with functional groups analogous to hydroxypropyl methyl cellulose acetate succinate (HPMCAS, a heterogeneous leading excipient candidate for SDDs) and studied its interactions with Biopharmaceutical Classification System Class II drug models probucol, danazol, and phenytoin at various dosages. By conducting reversible addition−fragmentation chain transfer polymerizations with monomeric components chemically analogous to HPMCAS, we synthetically dismantled the highly polydisperse architecture of HPMCAS into well-defined polymer systems (i.e., targetable M n , Đ < 1.3, tunable T g ). In the powdered SDD form, by wide-angle X-ray diffraction all HPMCAS analogs yielded amorphous danazol and phenytoin up to 50 wt % loading, whereas for probucol, hydrophobic methoxy functionality and high polymeric T g were key to inhibit immediate partitioning into crystalline domains. Nonsink in vitro dissolution tests revealed distinct release profiles. The polymer containing only acetyl and succinoyl substituents spray-dried with probucol increased the area under the dissolution curve by a factor of 180, 112, and 26 over pure drug at 10, 25, and 50 wt % loading, respectively. For crystallization-prone danazol and phenytoin, we observed that the water-soluble polymer with hydroxyl groups inhibited crystal growth and enabled high burst release and supersaturation maintenance. Our findings provide fundamental insight into how excipient microstructures can complex with drugs for excipient formulation applications.

A comprehensive approach to target exact molecular weights and chemical compositions for multimonomeric statistical copolymers using a new controlled statistics method with reversible addition−fragmentation chain transfer free-radical (RAFT) polymerization is presented. The system chosen to illustrate this procedure is an acrylic quarterpolymer consisting of methyl acrylate, 2-carboxyethyl acrylate, 2-hydroxypropyl acrylate, and 2-propylacetyl acrylate, modeling a well-known macromolecule utilized to deliver poorly water-soluble drugs (hydroxypropyl methylcellulose acetate succinate, HPMCAS). The relative reactivities at 70 °C between monomer pairs were measured and employed to predict the feed ratio necessary for synthesizing well-defined compositions based on the Walling-Briggs model. Application of Skeist's equations addressed compositional drift and anticipated the general monomer incorporation distribution as a function of conversion, which was verified experimentally. This new and simple paradigm combining both predictive models provides complementary synthetic and predictive tools for designing macromolecular chemical architectures with hierarchical control over spatially dependent structure−property relationships for complex applications such as oral drug delivery.

Tetraarylethylenes can be sequentially transformed into 9,10-diarylphenanthrenes and dibenzo[g,p]chrysenes using 1 and 2 equiv of DDQ, respectively, in CH(2)Cl(2) containing methanesulfonic acid, in excellent yields. Efficient access to substituted dibenzochrysenes from tetraarylethylenes establishes the versatility of this procedure over the existing multistep syntheses of dibenzochrysenes. Moreover, the ready regeneration of DDQ from easily recovered reduced DDQ-H(2) continues to advance the use of DDQ/H(+) for the oxidative C-C bond forming reactions.

Triptycenes spontaneously assemble into two-dimensional networks in which long-range charge transport is facilitated by the extensive electronic coupling through the triptycene framework (intramolecularly) and by cofacial π-stacking (intermolecularly). While designing and synthesizing next-generation triptycenes containing polyaromatic chromophores, the electronic coupling amongst the chromophores was observed to be highly dependent on the nature and position of the substituents. Herein, we demonstrate using hexaalkoxytriptycenes that the electronic coupling amongst the chromophores is switched on and off by a simple repositioning of the substituents, which alters the nodal arrangement of the HOMOs of the individual chromophores. A visual inspection of the HOMOs can thus provide a ready evaluation of the electronic coupling in polychromophoric molecules/assemblies, and will serve as an important tool for the rational design of modern charge-transport materials.