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A general method to synthesize conjugated molecules with a benzofulvene core is reported. Up to four conjugated substituents have been introduced via a three-step sequence including (1) synthesis of 1,2-bis(arylethynyl)benzenes; (2) exo-dig electrophilic cyclization promoted by iodine; and (3) cross-coupling reaction of the resulting bis-iodobenzofulvenes with organoboron, organotin, or ethynyl derivatives under Pd catalysis. Structural aspects of the new compounds are discussed.

Weak and ultraweak protein-protein association play a role in molecular recognition and can drive spontaneous self-assembly and aggregation. Such interactions are difficult to detect experimentally, and are a challenge to the force field and sampling technique. A method is proposed to identify low-population protein-protein binding modes in aqueous solution. The method is designed to identify preferential first-encounter complexes from which the final complex(es) at equilibrium evolve. A continuum model is used to represent the effects of the solvent, which accounts for short- and long-range effects of water exclusion and for liquid-structure forces at protein/liquid interfaces. These effects control the behavior of proteins in close proximity and are optimized on the basis of binding enthalpy data and simulations. An algorithm is described to construct a biasing function for self-adaptive configurational-bias Monte Carlo of a set of interacting proteins. The function allows mixing large and local changes in the spatial distribution of proteins, thereby enhancing sampling of relevant microstates. The method is applied to three binary systems. Generalization to multiprotein complexes is discussed.