In this work, a methodology for the evaluation of enantioselective binding of imazalil (IMA) enantiomers to human serum albumin (HSA) that does not require the separation of free and bound to HSA fractions is developed. This methodology comprises the incubation of IMA-HSA designed mixtures for 30 min directly in the capillary electrophoresis system and the subsequent direct injection and chiral separation of IMA employing highly sulfated β-cyclodextrin as chiral selector and the complete filling technique. Two mathematical approaches were used to estimate apparent affinity constants (K1), protein binding and enantioselectivity (ES) for both enantiomers of IMA. Moderate enantioselective binding of IMA enantiomers to HSA (ES = 2.0) was shown by the 1:1 stoichiometry and log K1 values of 3.4 ± 0.4 and 3.1 ± 0.3 for the first and second eluted enantiomers, respectively.
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http://dx.doi.org/10.1002/bmc.3472 | DOI Listing |
Nature
January 2025
Manchester Institute of Biotechnology, The University of Manchester, Manchester, UK.
Nucleophilic aromatic substitutions (SAr) are amongst the most widely used processes in the pharmaceutical and agrochemical industries, allowing convergent assembly of complex molecules through C-C and C-X (X = O, N, S) bond formation. SAr reactions are typically carried out using forcing conditions, involving polar aprotic solvents, stoichiometric bases and elevated temperatures, which do not allow for control over reaction selectivity. Despite the importance of SAr chemistry, there are only a handful of selective catalytic methods reported that rely on small organic hydrogen-bonding or phase-transfer catalysts.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Exploiting novel noncovalent interactions for catalysis design represents a fascinating direction. For the flexible and relatively weak anion-π interactions, manipulation of two or more π-acidic surfaces for cooperative activation is highly desirable. Here, we demonstrate the strategy of cooperative anion-π catalysis based on chiral molecular cages with V-shaped electron-deficient cavities for synergic binding and activation of dicarbonyl electrophiles toward highly enantioselective desymmetrization transformation.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Laboratory of Inorganic Synthesis and Catalysis, Institute of Chemical Sciences and Engineering, École Polytechnique Fédérale de Lausanne, I, SIC-LSCI, BCH 3305, Lausanne, 1015, Switzerland Website.
Artificial metalloenzymes (ArMs) enable the integration of abiotic cofactors within a native protein scaffold, allowing for non-natural catalytic activities. Previous ArMs, however, have primarily relied on single cofactor systems, limiting them to only one catalytic function. Here we present an approach to construct ArMs embedding two catalytic cofactors based on the biotin-streptavidin technology.
View Article and Find Full Text PDFNatl Sci Rev
January 2025
Laboratory of Chemical Biology and State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
The Mpox virus (MPXV) has emerged as a formidable orthopoxvirus, posing an immense challenge to global public health. An understanding of the regulatory mechanisms of MPXV infection, replication and immune evasion will benefit the development of novel antiviral strategies. Despite the involvement of G-quadruplexes (G4s) in modulating the infection and replication processes of multiple viruses, their roles in the MPXV life cycle remain largely unknown.
View Article and Find Full Text PDFTetrahedron Lett
October 2024
Department of Chemistry, University of California, Berkeley, CA 94720, USA.
Neutral dual hydrogen bond donors (HBDs) are effective catalysts that enhance the electrophilicity of substrates or the Lewis/Brønsted acidity of reagents through an anion-binding mechanism. Despite their success in various enantioselective organocatalytic reactions, their application to transition metal catalysis remains rare. Herein, we report the activation of gold(I) precatalysts by chiral ureas, leading to enantioselective hydroarylation of allenes with indoles.
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