2.4 CuAAC in Carbohydrate Conjugation

Copper(I)-catalyzed azide–alkyne cycloaddition reactions (CuAAC), as a versatile, reliable, and modular strategy, have been widely investigated in the area of glycoscience during the last 20 years. Herein, we presented a brief overview of CuAAC click approaches for easy access to diverse simple and complex triazole-appended carbohydrate-containing molecular architectures. Both intermolecular and intramolecular CuAAC conjugation of glycosylated azides and terminal alkynes have been widely employed for the regioselective triazole-forming reaction under standard click conditions.

Multiple epistatic DNA variants in a single gene affect gene expression in trans

DNA variants that alter gene expression in trans are important sources of phenotypic variation. Nevertheless, the identity of trans-acting variants remains poorly understood. Single causal variants in several genes have been reported to affect the expression of numerous distant genes in trans. Whether these simple molecular architectures are representative of trans-acting variation is unknown. Here, we studied the large RAS signaling regulator gene IRA2, which contains variants with extensive trans-acting effects on gene expression in the yeast Saccharomyces cerevisiae. We used systematic CRISPR-based genome engineering and a sensitive phenotyping strategy to dissect causal variants to the nucleotide level. In contrast to the simple molecular architectures known so far, IRA2 contained at least seven causal nonsynonymous variants. The effects of these variants were modulated by non-additive, epistatic interactions. Two variants at the 5′-end affected gene expression and growth only when combined with a third variant that also had no effect in isolation. Our findings indicate that the molecular basis of trans-acting genetic variation may be considerably more complex than previously appreciated.

Assembling Complex Structures through Cascade and Cycloaddition Processes via Non-Acceptor Gold or Rhodium Carbenes

The ability of highly energetic metal-carbene intermediates to engage in complex cascade or formal-cycloaddition processes is one of the most powerful tools for building intricate molecular architectures in a straightforward manner. Among this type of organometallic intermediates, non-acceptor metal carbenes are particularly challenging to access and, therefore, have experienced a slower development. In this regard, our group has exploited the use of electrophilic gold(I) complexes to selectively activate certain classes of substrates and generate this type of intermediates. Thus, very different type of molecules, such as enynes or 7-substituted cyclohepatrienes, lead to the formation of carbenes under gold(I) catalysis. Related rhodium(II) carbenes can also be generated from cyclohepatrienes. In this account, we aim to summarize our efforts towards the in-situ generation of these highly versatile organometallic species, and the study of their reactivity through formal cycloadditions or complex cascade reactions.

Manifold Dynamic Non-Covalent Interactions for Steering Molecular Assembly and Cyclization

Deciphering rich non-covalent interactions that govern many chemical and biological processes is crucial for the design of drugs and controlling molecular assemblies and their chemical transformations. However, real-space characterization of these weak interactions in complex molecular architectures at single bond level has been a longstanding challenge. Here, we employed bond-resolved scanning probe microscopy combined with an exhaustive structural search algorithm and quantum chemistry calculations to elucidate multiple non-covalent interactions that control the cohesive molecular clustering of a well-design precursor and their chemical reactions. The presence of two flexible bromo-triphenyl moieties in precursor leads to the assembly of distinct non-planar dimer and trimer clusters by manifold non-covalent interactions, including hydrogen bonding, halogen bonding, C − H···π and lone pair···π interactions. The dynamic nature of weak interactions allows for transforming dimers into energetically more favourable trimers as molecular density increases. The formation of trimers also facilitates thermally-triggered intermolecular Ullman coupling reactions, while the disassembly of dimers favours intramolecular cyclization, as evidenced by bond-resolved imaging of metalorganic intermediates and final products. The richness of manifold non-covalent interactions offers unprecedented opportunities for controlling the assembly of complex molecular architectures and steering on-surface synthesis of quantum nanostructures.