Substrate-Selective Catalysis Enabled Synthesis of Azaphilone Natural Products.

Achieving substrate-selectivity is a central element of nature's approach to synthesis. By relying on the ability of a catalyst to discriminate between components in a mixture, control can be exerted over which molecules will move forward in a synthesis. This approach can be powerful when realized but can be challenging to duplicate in the laboratory.

State-of-the-Art Biocatalysis.

The use of enzyme-mediated reactions has transcended ancient food production to the laboratory synthesis of complex molecules. This evolution has been accelerated by developments in sequencing and DNA synthesis technology, bioinformatic and protein engineering tools, and the increasingly interdisciplinary nature of scientific research. Biocatalysis has become an indispensable tool applied in academic and industrial spheres, enabling synthetic strategies that leverage the exquisite selectivity of enzymes to access target molecules.

Chemoenzymatic Total Synthesis of Natural Products.

The total synthesis of structurally complex natural products has challenged and inspired generations of chemists and remains an exciting area of active research. Despite their history as privileged bioactivity-rich scaffolds, the use of natural products in drug discovery has waned. This shift is driven by their relatively low abundance hindering isolation from natural sources and the challenges presented by their synthesis.

Substrate Promiscuity of a Paralytic Shellfish Toxin Amidinotransferase.

Secondary metabolites are assembled by enzymes that often perform reactions with high selectivity and specificity. Many of these enzymes also tolerate variations in substrate structure, exhibiting promiscuity that enables various applications of a given biocatalyst. However, initial enzyme characterization studies frequently do not explore beyond the native substrates.

Stereodivergent, Chemoenzymatic Synthesis of Azaphilone Natural Products.

Selective access to a targeted isomer is often critical in the synthesis of biologically active molecules. Whereas small-molecule reagents and catalysts often act with anticipated site- and stereoselectivity, this predictability does not extend to enzymes. Further, the lack of access to catalysts that provide complementary selectivity creates a challenge in the application of biocatalysis in synthesis.

Design, structural diversity and properties of novel zwitterionic metal-organic frameworks.

Seven new zwitterionic metal-organic frameworks (ZW MOFs) of compositions {[Cd(L1)(OH)]·2HO} (1), {[Mn(L1)(OH)]·HO} (2), {[Cu(HL1)(OH)]·9HO} (3), {[Mn(L2)(OH)]·3HO} (4), [Co(L2)(OH)]·HO (5), [Ni(L2)(OH)] (6), and {[Cd(L2)(OH)]·4HO} (7), where HL1Br = 3-carboxy-1-(3,5-dicarboxybenzyl)pyridinium bromide and HL2Br = 4-carboxy-1-(3,5-dicarboxybenzyl)pyridinium bromide, have been synthesized under hydrothermal conditions. We demonstrate that the diversity of these crystal structures suggests that the tridentate and flexible nature of ZW ligands L1 and L2 make them excellent candidates for the synthesis of new ZW MOFs. A multi-charged anionic nature is a common feature of L1 and L2, and therefore, allows the rational design of ZW MOFs without the presence of additional counterions for charge compensation.

Metal-Organic Frameworks as Platforms for the Controlled Nanostructuring of Single-Molecule Magnets.

The prototypical single-molecule magnet (SMM) molecule [Mn12O12(O2CCH3)16(OH2)4] was incorporated under mild conditions into a highly porous metal-organic framework (MOF) matrix as a proof of principle for controlled nanostructuring of SMMs. Four independent experiments revealed that the SMM clusters were successfully loaded in the MOF pores, namely synchrotron-based powder diffraction, physisorption analysis, and in-depth magnetic and thermal analyses. The results provide incontrovertible evidence that the magnetic composite, SMM@MOF, combines key SMM properties with the functional properties of MOFs.