Research Highlights

Highlight 1

The construction of N–N axially chiral motifs is a key area of research due to their presence in natural products, pharmaceuticals, and chiral ligands. This paper reports a novel method for the direct catalytic synthesis of N–N atropisomers with both axial and central chirality via oxidative NHC (N-heterocyclic carbene) catalyzed (3 + 3) cycloaddition. The method enables the synthesis of diverse N–N axially chiral pyrroles and indoles with vicinal central chirality or a 2,3-dihydropyrimidin-4-one moiety, in moderate to good yields and excellent enantioselectivities. The reaction mechanism and enantioselectivity origin are explained through DFT calculations.

Reference: S.-J. Wang, X. Wang, S. Zhang, D. Lu, H. Yang, M.W. Wong and S. Lu, Nat. Commun. 15 (2024) 518. DOI: 10.1038/s41467-024-44743-z

Highlight 2

This study presents the first precise and highly selective on-surface ring-opening of the seven-membered ring in aromatic azulene moieties under mild conditions. Our findings offer new insights into the ring-opening of polycyclic aromatic hydrocarbons, opening possibilities for manipulating and reconstructing these structures. Bond-resolved scanning probe microscopy identified the products, while density functional theory calculations clarified the mechanism and chemical driving force. The key innovation is the manipulation of azulene’s local aromaticity through strain-induced ring rearrangement and cyclodehydrogenation.

Reference: L. Wang, X. Peng, J. Su, J. Wang, A. Gallardo, H. Yang, Q. Chen, P. Lyu, P. Jelínek, J. Liu, M. W. Wong and J. Lu, J. Am. Chem. Soc. 146 (2024) 1563-1571. DOI: 10.1021/jacs.3c11652

Highlight 3

This study presents an artificial strategy to mimic nitroreductases (NTRs) using intracellular metal-catalyzed transfer hydrogenation with native cofactors to target bacterial pathogens. We identified several Ru-arene complexes that efficiently reduce nitroarenes to amines in biological environments, including the first water-stable Ru-arene complex with this capability. The complex was applied to activate nitro-caged sulfanilamide in Gram-positive pathogens, particularly methicillin-resistant Staphylococcus aureus, and induce oxidative stress via single-electron transfer. This bioinspired approach offers a new antimicrobial chemotherapy strategy, utilizing redox-active organometallic complexes for targeted bacterial treatment.

Reference: : C. Weng, H. Yang, B. S. Loh, Y. Dong, M.W. Wong, and W. H. Ang, J. Am. Chem. Soc. 145 (2023) 6453-6461 DOI: 10.1021/jacs.3c00237

Highlight 4

This paper introduces a novel unit-cell algorithm for generating amorphous SiOC:H structures, addressing limitations of previous cubic-grid methods, such as dangling bonds and the need for pre-treatment. The new algorithm automatically handles atomic coordinates, valency, connectivity, and cell periodicity by modeling structures on the α-quartz unit cell. Amorphous characteristics are introduced by randomly distributing silicon atom types, with results validated against experimental data, showing good agreement. This approach effectively generates realistic low-k SiOC:H.

Reference: H. Yang, Y. Chen and M. W. Wong, Comp. Mat. Sci. 242 (2024) 113093. DOI: 10.1016/ j.commatsci.2024.113093

Highlight 5

The use of ionic liquids (ILs) as green and sustainable corrosion inhibitors has attracted great interest in recent years. Through first-principles DFT calculations and ab initio molecular dynamics simulations, we addressed the fundamental question on whether the adsorption of imidazolium-based IL on iron surface is physisorption or chemisorption. Our findings conclusively demonstrate that the most stable adsorption configurations involve strong chemisorption on the metal surface, facilitated by a net electron donation from the iron slab to the imidazolium ring.

Reference:Reference: M.-F. Chen, Y. Chen, Z. J. Lim and M.W. Wong. J. Mol. Liq. 367 (2022) 120489. DOI: 10.1016/j.molliq.2022.120489

Highlight 6

Protein tyrosine kinase 6 (PTK6), a non-receptor kinase in the SRC family, contains SH3, SH2, and kinase (SH1) domains, which are essential for its function in signaling pathways. While inhibitors targeting the SH1 domain have been explored, they do not fully suppress PTK6 activity, as the SH2 and SH3 domains also play critical roles. Using a computational approach that combines in silico structural-based virtual screening, drug repurposing, and consensus docking, we identified four potential ligands capable of simultaneously inhibiting the SH1, SH2, and SH3 domains of PTK6. This strategy opens new possibilities for therapeutic interventions targeting PTK6.

Reference: Y. Zhou and M. W. Wong, Pharm. 17 (2024) 60. DOI: 10.3390/ph17010060

Highlight 7

The commonly accepted mechanism of CO2 fixation of epoxides to cyclic carbonates catalyzed by multifunctional non-halide green organocatalysts is challenged by our computational DFT-D3 study, which revealed a new polymerization-like mechanism comprising alternate epoxide and CO2 activation steps, and a nested CO2 activation pathway. The general applicability of the new polymerization-like mechanism is supported by two multifunctional catalyzed CO2 fixation reactions.

Reference: M. Chen, H. Yang, and M.W. Wong. Chem. Commun. 58 (2022) 8262-8265. DOI: 10.1039/d2cc03409c