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Flavonoids are a large family of compounds associated with a broad range of biologically useful properties. In recent years, synthetic compounds that contain two flavonoid units linked together have attracted attention in drug discovery and development projects. Numerous flavonoid dimer systems, incorporating a range of monomers attached via different linkers, have been reported to exhibit interesting bioactivities. From a medicinal chemistry perspective, the 1,2,3-triazole ring system has been identified as a particularly attractive linker moiety in dimeric derivatives (owing to several favourable attributes including proven biological relevance and metabolic stability) and triazole-bridged flavonoid dimers possessing anticancer and antimalarial activities have recently been reported. However, there are relatively few examples of libraries of triazole-bridged flavonoid dimers and the diversity of flavonoid subunits present within these is typically limited. Thus, this compound type arguably remains underexplored within drug discovery. Herein, we report a modular strategy for the synthesis of novel and biologically interesting triazole-bridged flavonoid heterodimers and also very rare heterotrimers from readily available starting materials. Application of this strategy has enabled step-efficient and systematic access to a library of structurally diverse compounds of this sort, with a variety of monomer units belonging to six different structural subclasses of flavonoid successfully incorporated.

Modern quantum chemical electronic structure methods typically applied to localized chemical bonding are developed to predict atomic structures and free energies for meso-tetraalkylporphyrin self-assembled monolayer (SAM) polymorph formation from organic solution on highly ordered pyrolytic graphite surfaces. Large polymorph-dependent dispersion-induced substrate-molecule interactions (e.g., -100 kcal mol-1 to -150 kcal mol-1 for tetratrisdecylporphyrin) are found to drive SAM formation, opposed nearly completely by large polymorph-dependent dispersion-induced solvent interactions (70-110 kcal mol-1) and entropy effects (25-40 kcal mol-1 at 298 K) favoring dissolution. Dielectric continuum models of the solvent are used, facilitating consideration of many possible SAM polymorphs, along with quantum mechanical/molecular mechanical and dispersion-corrected density functional theory calculations. These predict and interpret newly measured and existing high-resolution scanning tunnelling microscopy images of SAM structure, rationalizing polymorph formation conditions. A wide range of molecular condensed matter properties at room temperature now appear suitable for prediction and analysis using electronic structure calculations. [ABSTRACT FROM AUTHOR]

The concise and step-economical total syntheses of three hydroxyaurones and one polymethoxyflavone from readily available starting materials is described. A divergent synthetic strategy is employed, which centres on a common chalcone scaffold from which both the aurone and flavone frameworks can be accessed through the use of different oxidative cyclisation methods. These are the first reported total syntheses of these biologically interesting compounds. [ABSTRACT FROM AUTHOR]