Photophysical and Duplex‐DNA‐Binding Properties of Distamycin Dimers Based on 4,4′‐ and 2,2′‐Dialkoxyazobenzenes as the Core

Distamycin‐based tetrapeptide ( 1 ) was covalently tethered to both ends of the central dihydroxyazobenzene moiety at either the 2,2′ or 4,4′ positions. This afforded two isomeric, distamycin–azobenzene–distamycin systems, 2 (para) and 3 (ortho), both of them being photoisomerizable. Illumination of these conjugates in solution at approximately 360 nm induced photoisomerization and the time course of the process was followed by UV/Vis and ¹H NMR spectroscopy. The kinetics of the thermal reversion at various temperatures of cis to trans isomers of the conjugates obtained after photoillumination were also examined. This afforded the respective thermal‐activation parameters. Both the molecular architecture and the location of the substituent around the core azobenzene determined the rate and activation‐energy barrier for the cis‐to‐trans back‐isomerization of these conjugates in solution. Duplex–DNA binding of the conjugates and the changes in DNA‐binding efficiency upon photoisomerization was also examined by CD spectroscopy, thermal denaturation studies, and a Hoechst displacement assay. The conjugate 2 showed higher DNA‐binding affinity and a greater change in the DNA‐binding efficiency upon photoisomerization compared with its 2,2′‐disubstituted counterpart. The experimental findings were substantiated by using molecular‐docking studies involving each conjugate with a model duplex d[(GC(AT)₁₀CG)]₂ DNA molecule.     

Cover Picture: Inclusion Behavior of β‐Cyclodextrin with Bipyridine Molecules: Factors Governing Host‐Guest Inclusion Geometries (Chem. Asian J. 3/2009)

A sytematic investigation of the molecular inclusion behavior by β‐cyclodextrin (gold) towards constitutionally different yet structurally similar bipyridine guests, demonstrates that differences of the nitrogen atom positions and the bridge bond linking the two pyridine rings of the bipyridine guests can significantly affect the binding abilities, inclusion geometries, and self‐assembly behavior of β‐cyclodextrin in both the solution and solid states. J. F. Stoddart and co‐workers suggest that these new superstructural and quantitative observations, with judicious constitutional design, allow highly ordered supramolecular arrays to be achieved conveniently in a controllable way. For more information, see their Full Paper on page 446 ff.