Chiral Induction in a Self-Assembled Pd4 Coordination Cage with Chiral Guests.

The dynamic interplay of coordination bonds within metal-organic cages offers a unique avenue for structural evolution in response to external stimuli, presenting a promising strategy for the construction of chiral assemblies. This adaptability is crucial for the selective synthesis of homochiral assemblies and advancement of asymmetric catalysis. In this study, we report the self-assembly of an achiral square-planar Pd(II) acceptor with a C2-symmetric tetrapyridyl donor resulted in the formation of a racemic mixture of the chiral octahedral cage Pd4L2. The existence of this racemic mixture was confirmed using circular dichroism spectroscopy as well as single crystal X-ray diffraction analysis. We encoded chiral information into the asymmetric cavity of the cage by encapsulating chiral aromatic guests through efficient π-π stacking and hydrophobic interactions in aqueous media. The inclusion of a chiral guest induces a preference for one enantiomeric conformation of the cage over the other, effectively shifting the equilibrium towards a single, enantiopure host-guest complex. While the concept of chiral guest recognition by a chiral host is well-established, this work constitutes a remarkable example of guest-mediated chirality transfer leading to the formation of a single enantiopure coordination complex from achiral building blocks.

Coumarins hinged directly on benzimidazoles and their ribofuranosides to inhibit hepatitis C virus.

A new compound library that contained 20 hinged benzimidazole-coumarin hybrids and their ß-d-ribofuranosides was established. The anti-hepatitis C virus (HCV) activity of all novel coumarin derivatives, which were obtained by use of organic synthetic methods, was tested. Two of these hybrids exhibited appealing EC50 values of as low as 3.0 and 5.5 µM. The best selectivity index was 14. The incorporation of a d-ribofuranose into the hinged hybrids provided the corresponding nucleosides with the ß configuration, one of which inhibited HCV replication with an EC50 value of 20 µM. Additionally, the structure-activity relationship is elucidated on the basis of the functional groups that were attached to the nuclei of benzimidazole, coumarin, and ribofuranose of the hybrids.

Structure-activity relationship of new anti-hepatitis C virus agents: heterobicycle-coumarin conjugates.

For establishment of the structure-activity relationship, 19 heterobicycle-coumarin conjugated compounds with the -SCH(2)- linker were synthesized and found to possess significant antiviral activities. Prominent examples included imidazopyridine-coumarin 12c, purine-coumarin 12d, and benzoxazole-coumarin 14c, which inhibited HCV replication at an EC(50) of 6.8, 2.0, and 12 microM, respectively. The heteroatoms in bicycles and the substituent effect on coumarin played essential roles.

Synthesis of new benzimidazole-coumarin conjugates as anti-hepatitis C virus agents.

Nineteen new conjugated compounds were successfully synthesized by a one-flask method from benzimidazole and coumarin derivatives. A methylenethio linker was used to connect these two kinds of derivatives. In addition, substituted benzimidazol-2-thiones were also coupled with beta-D-glucose peracetate; the resultant glucosides were further converted to the corresponding 2-(methylthio)coumarin derivatives. Their activity against the hepatitis C virus was tested; two of the most potent compounds 2-[(6'-bromocoumarin-3'-yl)methylenethio]-5-fluorobenzimidazole (4i) and its derivative 1-[(2'',3'',4'',6''-tetra-O-acetyl)glucopyranos-1''-yl]-2-[(6'-bromocoumarin-3'-yl)methylenethio]benzimidazole (7c) showed EC(50) values of 3.4 microM and 4.1 microM, respectively. At a concentration of 5.0 microM, compound 7c inhibited HCV RNA replication by 90% and had no effect on cell proliferation. Given these data, a structure-activity relationship was established.