Stereoinvertive S1 Through Neighboring Group Participation.

Neighboring group participation, the assistance of non-conjugated electrons to a reaction center, is a fundamental phenomenon in chemistry. In the framework of nucleophilic substitution reactions, neighboring group participation is known to cause rate acceleration, first order kinetics (S1), and retention of configuration. The latter phenomenon is a result of double inversion: the first one when the neighboring group displaces the leaving group, and the second when a nucleophile substitutes the neighboring group.

Synthesis of Stereodefined Polysubstituted Bicyclo[1.1.0]butanes.

We report a highly diastereoselective synthesis of polysubstituted bicyclobutanes possessing up to three stereodefined quaternary centers and five substituents. Our strategy involves a diastereoselective carbometalation of cyclopropenes followed by a cyclization to furnish the bicyclobutane ring system. This straightforward approach allows for the incorporation of a diverse range of substituents and functional groups, notably without the need for electron-withdrawing functionalities.

Dynamic Intramolecular Cap for Preserving Metallodrug Integrity─A Case of Catalytic Fluoroquinolones.

A library of eight new fluoroquinolone-nuclease conjugates containing a guanidinoethyl or aminoethyl auxiliary pendant on the cyclen moiety was designed and synthesized to investigate their potential for overcoming the general issue of "metallodrug vulnerability" under physiological conditions. The Cu(II) and Co(III) complexes of the new designer compounds were synthesized, and their potential to operate a dynamic, intramolecular cap with DNase activity was explored. The lead Co(III)-cyclen-ciprofloxacin conjugate showed excellent hydrolytic DNase activity, which was retained in the presence of strong endogenous chelators and exhibited enhanced antibacterial activity relative to the metal-free ligand (in the absence of any adjuvants), thereby demonstrating a "proof of concept" and , respectively, for the dynamic cap hypothesis.