Le Steenberg (hatemask4)

Site-directed mutagenesis was utilized to assess the role individual active-site residues play in guiding selective DKP dimerization. Finally, computational approaches were employed to evaluate plausible mechanisms regarding NzeB function and its ability to catalyze both C-C and C-N bond formation. These results provide a structural and computational rationale for the catalytic versatility of NzeB, as well as new insights into variables that control selectivity of CYP450 diketopiperazine dimerases.Here, we show that charge-transfer interactions determine whether donor and acceptor ditopic ligands will associate in a complementary or self-complementary fashion upon metal-ion clipping. Anthracene-based ( 9,10 L D and 1,5 L D ) and anthraquinone-based ( 1,5 L A ) ditopic ligands containing two imidazole side arms as zinc coordination sites were designed. The 9,10 L D and 1,5 L A systems associated in a complementary fashion (L A /L D /L A ) upon clipping by two zinc ions (Zn2+) to form an alternating donor-acceptor assembly [( 9,10 L D )( 1,5 L A )2-(Zn2+)2]. However, once the charge-transfer interactions were perturbed by subtle modifications of the imidazole side arms ( 9,10 L D ' ( S ) and 1,5 L A ' ( S ) ), self-complementary association (L D '/L D '/L D '/L D ' and L A '/L A '/L A '/L A ') between the donor ( 9,10 L D ' ( S ) ) and acceptor ( 1,5 L A ' ( S ) ) ligands predominantly occurred to form homoassemblies [( 9,10 L D ' ( S ) )4-(Zn2+)2 and ( 1,5 L A ' ( S ) )4-(Zn2+)2]. As in the case of a homochiral pair ( 9,10 L D ' ( S ) and 1,5 L A ' ( S ) ), self-complementary association (narcissistic self-sorting) occurred in the Zn2+ assembly with heterochiral combinations of the donor and acceptor ligands ( 9,10 L D ' ( S ) / 1,5 L A ' ( R ) and 9,10 L D ' ( S ) / 1,5 L A ' ( R ) / 1,5 L A ' ( R ) ). Narcissistic self-sorting also took place between the positional isomer of the donor ligands ( 9,10 L D and 1,5 L D ) to form individual homoligand assemblies [( 9,10 L D )4-(Zn2+)2 and ( 1,5 L D )4-(Zn2+)2]. learn more Conversely, statistical association took place in the Zn2L4 assembly process of an isomorphous pair of the donor and acceptor ligands ( 1,5 L D and 1,5 L A ).Cyclopropanes are important structural motifs found in numerous bioactive molecules, and a number of methods are available for their synthesis. However, one of the simplest cyclopropanation reactions involving the intramolecular coupling of two C-H bonds on gem-dialkyl groups has remained an elusive transformation. We demonstrate herein that this reaction is accessible using aryl bromide or triflate precursors and the 1,4-Pd shift mechanism. The use of pivalate as the base was found to be crucial to divert the mechanistic pathway toward the cyclopropane instead of the previously obtained benzocyclobutene product. Stoichiometric mechanistic studies allowed the identification of aryl- and alkylpalladium pivalates, which are in equilibrium via a five-membered palladacycle. With pivalate, a second C(sp3)-H activation leading to the four-membered palladacycle intermediate and the cyclopropane product is favored. A catalytic reaction was developed and showed a broad scope for the generation of diverse arylcyclopropanes, including valuable bicyclo[3.1.0] systems. This method was applied to a concise synthesis of lemborexant, a recently approved anti-insomnia drug.We report herein a strategy to construct enantiopure inherently chiral macrocycles, ABCD-type heteracalix[4]aromatics, through a catalytic enantioselective intramolecular C-N bond forming reaction. A chiral ligand-palladium complex was found to efficiently induce the inherent chirality of molecules during the macrocyclization process with ee values up to >99%. The resulting ABCD-type heteracalix[4]aromatics displayed excellent and pH-triggered switchable electronic circular dichroism and circularly polarized luminescence properties.Profiling the heterogeneous phenotypes of live cancer cells is a key