The synthesis of a new family of naphthalenoid C 2symmetric clefts has been realized through a four-step synthetic sequence giving three C 2 -symmetric clefts and a rare nonsymmetric example. Subsequently, stereoselective reduction of the carbonyl groups at C-8 and C-16 then provides cleft molecules with hydrogen bonding potential. Using single-crystal X-ray and computational analysis, the cleft angle of the dione has been determined.

The discovery of new scaffolds that selectively interact with biomolecules (e.g. DNA) supports the development of new medicinal and chemical biology tools, such as novel therapeutics and sensors. Whilst their binding and specificity is dependent on several well established factors, there has been an increasing emphasis on identifying scaffolds that possess intrinisic 3-dimensionality. Herein, we report the synthesis, photophysical and preliminary ds-DNA binding properties of a novel series C2-symmetric carbocyclic cleft scaffolds. The synthesis of two cleft ligands has been realised through a 4-step procedure with the structures of each molecule established through single crystal X-ray crystallography. The unique 3-dimension shape of these cleft molecules has allowed for accurate positioning of extended aromatic groups, which assist in their interaction with ds-DNA. This interaction was probed through UV-Vis titration studies of the racemic ligands with ct-DNA and the preliminary studies establish that the mode-of-binding with ct-DNA is via intercalation, which is further supported using computational DNA-docking studies.

The discovery of new scaffolds that selectively interact with biomolecules is vital in the development of new medicinal and chemical biology tools, therapeutics and sensors. Their binding and specificity is reliant on several well established factors, but there has been an increasing emphasis on identifying scaffolds that possess intrinisic 3-dimensionality. Herein, we report the synthesis, photophysical and preliminary ds-DNA binding properties of a new series of 3-D C2-symmetric carbocyclic cleft scaffolds. Their synthesis is realised through a 4-step procedure with the structures of each molecule established through single crystal X-ray crystallography. Their interaction with ds-DNA is probed using UV-Vis titration of the racemic ligands with ct-DNA with the preliminary studies establishing that the mode-of-binding as intercalative, with Kb values between 1.28 x 106 to 2.32 x 105 M-1. This is further supported using computational DNA-docking studies that demonstrate that complementarity 3D shapes of these ligands is essential for B-DNA binding.