Synthetic Catalysts for Selective Glycan Cleavage from Glycoproteins and Cells.

In situ modification of glycans requires extraordinary molecular recognition of highly complex and subtly different carbohydrates, followed by reactions at precise locations on the substrate. We here report synthetic catalysts that under physiological conditions cleave a predetermined oligosaccharide block such as a branched trimannose or the entire N-glycan of a glycoprotein, while nontargeted glycoproteins stay intact. The method also allows α2-6-sialylated galactosides to be removed preferentially over the α2-3-linked ones from cell surfaces, highlighting the potential of these synthetic glycosidases for glycan editing.

Tuning Active Site Electron Density for Enhanced Molecular Recognition and Catalysis.

Enzymes have an extraordinary ability to utilize aromatic interactions for molecular recognition and catalysis. We here report molecularly imprinted nanoparticle receptors. The aromatic "wall" material in the imprinted binding site is used to enhance the molecular recognition of aromatic guests that have similar charges, shapes, and sizes but differ in π-electron density. Additionally, aromatic interactions are employed to activate an electron-rich aryl leaving group on a glycoside, mimicking the nucleoside hydrolase of the parasite Trypanosoma vivax.

Rational Design and Synthesis of an Artificial Enzyme for SN2 Reactions through Micellar Imprinting.

The rational design of catalysts with enzyme-like properties is an elusive goal of chemists despite tremendous interest. Molecular imprinting inside surfactant micelles, followed by postmodification, creates a tailored active site in a water-soluble polymeric "artificial enzyme" for the benzylation of 4-nitrophenol. The reaction happens under neutral conditions with excellent substrate selectivity. Similar to many enzymes, electrostatics play vital roles in catalysis and can be tuned through different bases introduced into the active site.

Carbonic anhydrase mimics with rationally designed active sites for fine-tuned catalytic activity and selectivity in ester hydrolysis.

Numerous hydrolytic enzymes utilize zinc as a cofactor for catalysis. We here report water-soluble polymeric nanoparticles with zinc ions in active sites and a nearby base as a mimic of carbonic anhydrase (CA). Their pKa of 6.3-6.4 for zinc-bound water is lower than the 6.8-7.3 value for natural enzymes, which allows the catalyst to hydrolyze nonactivated alkyl esters under neutral conditions-a long sought-after goal for artificial esterases. The size and shape of the active site can be rationally tuned through a template used in molecular imprinting. Subtle structural changes in the template, including shifting an ethyl group by one C-N bond and removal of a methylene group, correlate directly with catalytic activity. A catalyst can be made to be highly specific or have broad substrate specificity through modular synthesis of templates.

Artificial Esterase for Cooperative Catalysis of Ester Hydrolysis at pH 7.

Ester is one of the most prevalent functional groups in natural and man-made products. Natural esterases hydrolyze nonactivated alkyl esters readily but artificial esterases generally use highly activated p-nitrophenyl esters as substrates. We report synthetic esterases constructed through molecular imprinting in cross-linked micelles. The water-soluble nanoparticle catalysts contain a thiouronium cation to mimic the oxyanion hole and a nearby base to assist the hydrolysis. Whereas this catalytic motif readily affords large rate acceleration for the hydrolysis of p-nitrophenyl hexanoate, nonactivated cyclopentyl hexanoate demands catalytic groups that can generate a strong nucleophile (hydroxide) in the active site. The hydroxide is stabilized by the protonated base when the external solution is at pH 7, enabling the hydrolysis of activated and nonactivated esters under neutral conditions.

Imprinted Polymeric Nanoparticles as Artificial Enzymes for Ester Hydrolysis at Room Temperature and pH 7.

Natural esterases hydrolyze esters under physiological pHs but chemists often have to use strongly acidic or basic conditions for the same hydrolysis. We report synthetic nanoparticle catalysts that hydrolyze nonactivated alkyl esters at room temperature and neutral pH, with enzyme-like catalytic mechanisms and exquisite substrate selectivity. Unlike natural enzymes that denature easily at elevated temperatures, the synthetic catalysts become more active at higher temperatures.

Metal-Organic Framework MIL-101(Cr) as an Efficient Heterogeneous Catalyst for Clean Synthesis of Benzoazoles.

A metal-organic framework [MIL-101(Cr)] was used as an efficient heterogeneous catalyst in the synthesis of benzoazoles (benzimidazole, benzothiazole, and benzoxazole), and quantitative conversion of products were obtained under optimized reaction conditions. The catalyst could be simply extracted from the reaction mixture, providing an efficient and clean synthetic methodology for the synthesis of benzoazoles. The MIL-101(Cr) catalyst could be reused without a remarkable decrease in its catalytic efficiency.